News Roundup

Aspects of spatial navigation may be particularly sensitive for detecting the earliest cognitive deficits of Alzheimer’s disease, according to a study published April 26 in the Journal of Alzheimer’s Disease. This study included 42 clinically normal people without preclinical Alzheimer’s disease, 13 clinically normal people with preclinical Alzheimer’s disease, and 16 people with early-stage symptomatic Alzheimer’s disease. Preclinical Alzheimer’s disease was defined based on CSF Aβ42 levels below 500 pg/mL. Preclinical Alzheimer’s disease was associated with deficits in the use of a wayfinding strategy, but not in the use of a route-learning strategy. In addition, post hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic Alzheimer’s disease-related deficits in the use of wayfinding and route-learning strategies.

One meal per week of seafood and long-chain omega-3 fatty acids protects against decline in multiple cognitive domains, according to a study published online ahead of print May 4 in Neurology. Researchers examined 915 participants who completed at least one follow-up cognitive assessment and provided dietary data. Scores for global cognitive function and five cognitive domains were assessed using 19 cognitive tests. Consumption of seafood was associated with slower decline in semantic memory and perceptual speed in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain omega-3 intake from food.

Persistent environmental pollutants measured in blood are significantly associated with amyotrophic lateral sclerosis (ALS) and may represent modifiable risk factors, according to a study published online ahead of print May 9 in JAMA Neurology. Participants included 156 cases and 128 controls. Complete demographic and pollutant data were available for 101 cases and 110 controls. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS. A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for two organochlorine pesticides, two polychlorinated biphenyls, and one brominated flame retardant. There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood. Additionally, tau correlation coefficients ranged from –0.18 to 0.24.

Outcomes of sports-related concussion vary according to the level of competition, according to a study published online ahead of print May 2 in JAMA Pediatrics. Three injury surveillance programs recorded 1,429 sports-related concussions between 2012 and 2014 among youth, high school, and college-level football athletes. Across all levels, 15.3% of concussions resulted in return to play at least 30 days after the concussion, and 3.1% resulted in return to play less than 24 hours after the concussion. Compared with youth, a higher number of concussion symptoms were reported in high school athletes. Compared with college athletes, the odds of return to play at least 30 days after injury were larger in youth athletes and high school athletes.

A screening test for newborns identifies infants with Niemann-Pick type C, according to a study published May 4 in Science Translational Medicine. The bile acids most elevated in infants with Niemann-Pick type C were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β,5α,6β-triol. Analysis of dried blood spots from 4,992 controls, 134 Niemann-Pick type C carriers, and 44 subjects with Niemann-Pick type C provided 100% sensitivity and specificity in the study samples. The researchers found that infants with Niemann-Pick type C have about thirtyfold higher amounts of 3β,5α,6β-trihydroxycholanic acid in the blood than healthy individuals. In addition, levels of 3β,5α,6β-trihydroxycholanic acid also could distinguish between patients with Niemann-Pick type C and carriers of the disease who show no symptoms.

The FDA has approved pimavanserin for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. The approval is based on data from a phase III study and other supportive studies. In the phase III study, pimavanserin significantly reduced the frequency and severity of psychotic symptoms, compared with placebo, on the Scale for Assessment of Positive Symptoms—Parkinson’s Disease. This benefit was achieved without impairing motor function. The most common adverse reactions in this study were peripheral edema and confusional state. The drug has a boxed warning alerting health care professionals about an increased risk of death associated with the use of atypical antipsychotics to treat older people with dementia-related psychosis. Acadia Pharmaceuticals, headquartered in San Diego, markets the product under the name Nuplazid.

Compared with the standard dose of t-PA (0.9 mg/kg), a low dose (0.6 mg/kg) is associated with slightly reduced rates of bleeding and mortality, according to a study published online ahead of print May 10 in the New England Journal of Medicine. Using a two-by-two quasi-factorial open-label design, researchers randomly assigned 3,310 patients who were eligible for thrombolytic therapy to low-dose IV t-PA or the standard dose. At 90 days, 53.2% of participants in the low-dose group had died or had disability, compared with 51.1% of participants in the standard-dose group. Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group. Fatal events occurred within seven days in 0.5% and 1.5% of participants, respectively.

Triptans and dihydroergotamine (DHE) are not associated with acute or subacute ischemic vascular events in the abortive treatment of basilar migraine or hemiplegic migraine, according to a study published online ahead of print April 8 in Headache. A retrospective chart review of 80 patients with basilar migraine or hemiplegic migraine who received acute abortive treatment with either triptans or DHE was conducted at four headache centers to assess the frequency of ischemic vascular events after administration. No stroke or myocardial infarction was reported. In the triptan group, five patients reported adverse effects that included gastrointestinal upset, rash, neck dystonia, nightmares, and flushing. In the DHE group, five patients had adverse events that included chest tightness, dystonic reaction, transient asymptomatic anterior T wave inversion, and agitation.

The FDA has approved Fycompa (perampanel) CIII oral suspension as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures, and of primary generalized tonic-clonic seizures in patients with epilepsy age 12 and older. The oral suspension formulation is a bioequivalent, interchangeable alternative to the Fycompa tablet formulation. The approval of Fycompa CIII oral suspension was based on a study that demonstrated bioequivalence between a single dose of perampanel oral suspension and a single dose of perampanel tablet when administered under fasted conditions in healthy subjects. Fycompa is an oral medication and the only FDA-approved noncompetitive AMPA receptor antagonist. Its most common side effects include dizziness, sleepiness, headache, tiredness, and irritability. Eisai, headquartered in Woodcliff Lake, New Jersey, markets the drug.

In patients with acute ischemic stroke or transient ischemic attack, ticagrelor is not superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days, according to a study published online ahead of print May 10 in the New England Journal of Medicine. Included in this study were 13,199 patients with nonsevere ischemic stroke or high-risk transient ischemic attack who had not received IV or intra-arterial thrombolysis and who had not had a cardioembolic stroke. During 90 days of treatment, a primary end point event (ie, stroke, myocardial infarction, or death) occurred in 442 of the 6,589 patients treated with ticagrelor, versus 497 of the 6,610 patients treated with aspirin. Ischemic stroke occurred in 385 patients treated with ticagrelor and in 441 patients treated with aspirin.

Physicians differ substantially when giving prognoses and treatment recommendations for patients with intracerebral hemorrhage, according to a study published online ahead of print April 15 in Neurology. A written survey with two intracerebral hemorrhage scenarios was completed by 742 practicing neurologists and neurosurgeons. Physician predictions of 30-day mortality varied widely, as did treatment recommendations. Responses encompassed the full range of options for each case. No physician demographic or personality characteristics were associated with treatment recommendations. Providing a prognostic score changed treatment recommendations, and the effect differed across cases. When the prognostic score suggested a 0% chance of functional independence, the likelihood of treatment limitations was increased, compared with no prognostic score. Conversely, if the score suggested a 66% chance of independence, treatment limitations were less likely.

Mitoxantrone slightly increases the overall incidence of malignancies and significantly increases the risk of leukemia and colorectal cancer, according to a study published online ahead of print May 11 in Neurology. Researchers retrospectively examined all mitoxantrone-treated patients with multiple sclerosis seen between 1994 and 2007 at one hospital. They collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. The incidence ratio of malignancy was 1.50. The standardized incidence ratio of colorectal cancer was 2.98, and that of acute myeloid leukemia, 10.44. Higher age at treatment initiation was a risk factor, but neither cumulative mitoxantrone dose, treatment with other immunosuppressive drugs, nor sex was. In all, 55 patients died. Twelve deaths resulted from a malignancy, and 43 from other causes.

Tau tangles provide a good indication of cognitive decline in the later stages of Alzheimer’s disease, according to a study published May 11 in Science Translational Medicine. The study suggests that while β-amyloid remains a critical marker for the early detection of Alzheimer’s disease, tau may be more useful for tracking disease progression and, potentially, patient response to therapies. Researchers analyzed PET imaging of tau and β-amyloid in 10 patients with mild Alzheimer’s disease and 36 healthy adults. Compared with amyloid plaques, tau tangles in the temporal lobe more closely correlated with cognitive deficits, as measured by a battery of memory tests. Tau deposits in the temporal lobe also were strongly associated with tau detected in the patients’ CSF. Tau therefore may better predict dementia during Alzheimer’s disease progression than β-amyloid.

—Kimberly Williams

Aspects of spatial navigation may be particularly sensitive for detecting the earliest cognitive deficits of Alzheimer’s disease, according to a study published April 26 in the Journal of Alzheimer’s Disease. This study included 42 clinically normal people without preclinical Alzheimer’s disease, 13 clinically normal people with preclinical Alzheimer’s disease, and 16 people with early-stage symptomatic Alzheimer’s disease. Preclinical Alzheimer’s disease was defined based on CSF Aβ42 levels below 500 pg/mL. Preclinical Alzheimer’s disease was associated with deficits in the use of a wayfinding strategy, but not in the use of a route-learning strategy. In addition, post hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic Alzheimer’s disease-related deficits in the use of wayfinding and route-learning strategies.

One meal per week of seafood and long-chain omega-3 fatty acids protects against decline in multiple cognitive domains, according to a study published online ahead of print May 4 in Neurology. Researchers examined 915 participants who completed at least one follow-up cognitive assessment and provided dietary data. Scores for global cognitive function and five cognitive domains were assessed using 19 cognitive tests. Consumption of seafood was associated with slower decline in semantic memory and perceptual speed in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain omega-3 intake from food.

Persistent environmental pollutants measured in blood are significantly associated with amyotrophic lateral sclerosis (ALS) and may represent modifiable risk factors, according to a study published online ahead of print May 9 in JAMA Neurology. Participants included 156 cases and 128 controls. Complete demographic and pollutant data were available for 101 cases and 110 controls. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS. A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for two organochlorine pesticides, two polychlorinated biphenyls, and one brominated flame retardant. There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood. Additionally, tau correlation coefficients ranged from –0.18 to 0.24.

Outcomes of sports-related concussion vary according to the level of competition, according to a study published online ahead of print May 2 in JAMA Pediatrics. Three injury surveillance programs recorded 1,429 sports-related concussions between 2012 and 2014 among youth, high school, and college-level football athletes. Across all levels, 15.3% of concussions resulted in return to play at least 30 days after the concussion, and 3.1% resulted in return to play less than 24 hours after the concussion. Compared with youth, a higher number of concussion symptoms were reported in high school athletes. Compared with college athletes, the odds of return to play at least 30 days after injury were larger in youth athletes and high school athletes.

A screening test for newborns identifies infants with Niemann-Pick type C, according to a study published May 4 in Science Translational Medicine. The bile acids most elevated in infants with Niemann-Pick type C were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β,5α,6β-triol. Analysis of dried blood spots from 4,992 controls, 134 Niemann-Pick type C carriers, and 44 subjects with Niemann-Pick type C provided 100% sensitivity and specificity in the study samples. The researchers found that infants with Niemann-Pick type C have about thirtyfold higher amounts of 3β,5α,6β-trihydroxycholanic acid in the blood than healthy individuals. In addition, levels of 3β,5α,6β-trihydroxycholanic acid also could distinguish between patients with Niemann-Pick type C and carriers of the disease who show no symptoms.

The FDA has approved pimavanserin for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. The approval is based on data from a phase III study and other supportive studies. In the phase III study, pimavanserin significantly reduced the frequency and severity of psychotic symptoms, compared with placebo, on the Scale for Assessment of Positive Symptoms—Parkinson’s Disease. This benefit was achieved without impairing motor function. The most common adverse reactions in this study were peripheral edema and confusional state. The drug has a boxed warning alerting health care professionals about an increased risk of death associated with the use of atypical antipsychotics to treat older people with dementia-related psychosis. Acadia Pharmaceuticals, headquartered in San Diego, markets the product under the name Nuplazid.

Compared with the standard dose of t-PA (0.9 mg/kg), a low dose (0.6 mg/kg) is associated with slightly reduced rates of bleeding and mortality, according to a study published online ahead of print May 10 in the New England Journal of Medicine. Using a two-by-two quasi-factorial open-label design, researchers randomly assigned 3,310 patients who were eligible for thrombolytic therapy to low-dose IV t-PA or the standard dose. At 90 days, 53.2% of participants in the low-dose group had died or had disability, compared with 51.1% of participants in the standard-dose group. Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group. Fatal events occurred within seven days in 0.5% and 1.5% of participants, respectively.

Triptans and dihydroergotamine (DHE) are not associated with acute or subacute ischemic vascular events in the abortive treatment of basilar migraine or hemiplegic migraine, according to a study published online ahead of print April 8 in Headache. A retrospective chart review of 80 patients with basilar migraine or hemiplegic migraine who received acute abortive treatment with either triptans or DHE was conducted at four headache centers to assess the frequency of ischemic vascular events after administration. No stroke or myocardial infarction was reported. In the triptan group, five patients reported adverse effects that included gastrointestinal upset, rash, neck dystonia, nightmares, and flushing. In the DHE group, five patients had adverse events that included chest tightness, dystonic reaction, transient asymptomatic anterior T wave inversion, and agitation.

The FDA has approved Fycompa (perampanel) CIII oral suspension as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures, and of primary generalized tonic-clonic seizures in patients with epilepsy age 12 and older. The oral suspension formulation is a bioequivalent, interchangeable alternative to the Fycompa tablet formulation. The approval of Fycompa CIII oral suspension was based on a study that demonstrated bioequivalence between a single dose of perampanel oral suspension and a single dose of perampanel tablet when administered under fasted conditions in healthy subjects. Fycompa is an oral medication and the only FDA-approved noncompetitive AMPA receptor antagonist. Its most common side effects include dizziness, sleepiness, headache, tiredness, and irritability. Eisai, headquartered in Woodcliff Lake, New Jersey, markets the drug.

In patients with acute ischemic stroke or transient ischemic attack, ticagrelor is not superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days, according to a study published online ahead of print May 10 in the New England Journal of Medicine. Included in this study were 13,199 patients with nonsevere ischemic stroke or high-risk transient ischemic attack who had not received IV or intra-arterial thrombolysis and who had not had a cardioembolic stroke. During 90 days of treatment, a primary end point event (ie, stroke, myocardial infarction, or death) occurred in 442 of the 6,589 patients treated with ticagrelor, versus 497 of the 6,610 patients treated with aspirin. Ischemic stroke occurred in 385 patients treated with ticagrelor and in 441 patients treated with aspirin.

Physicians differ substantially when giving prognoses and treatment recommendations for patients with intracerebral hemorrhage, according to a study published online ahead of print April 15 in Neurology. A written survey with two intracerebral hemorrhage scenarios was completed by 742 practicing neurologists and neurosurgeons. Physician predictions of 30-day mortality varied widely, as did treatment recommendations. Responses encompassed the full range of options for each case. No physician demographic or personality characteristics were associated with treatment recommendations. Providing a prognostic score changed treatment recommendations, and the effect differed across cases. When the prognostic score suggested a 0% chance of functional independence, the likelihood of treatment limitations was increased, compared with no prognostic score. Conversely, if the score suggested a 66% chance of independence, treatment limitations were less likely.

Mitoxantrone slightly increases the overall incidence of malignancies and significantly increases the risk of leukemia and colorectal cancer, according to a study published online ahead of print May 11 in Neurology. Researchers retrospectively examined all mitoxantrone-treated patients with multiple sclerosis seen between 1994 and 2007 at one hospital. They collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. The incidence ratio of malignancy was 1.50. The standardized incidence ratio of colorectal cancer was 2.98, and that of acute myeloid leukemia, 10.44. Higher age at treatment initiation was a risk factor, but neither cumulative mitoxantrone dose, treatment with other immunosuppressive drugs, nor sex was. In all, 55 patients died. Twelve deaths resulted from a malignancy, and 43 from other causes.

Tau tangles provide a good indication of cognitive decline in the later stages of Alzheimer’s disease, according to a study published May 11 in Science Translational Medicine. The study suggests that while β-amyloid remains a critical marker for the early detection of Alzheimer’s disease, tau may be more useful for tracking disease progression and, potentially, patient response to therapies. Researchers analyzed PET imaging of tau and β-amyloid in 10 patients with mild Alzheimer’s disease and 36 healthy adults. Compared with amyloid plaques, tau tangles in the temporal lobe more closely correlated with cognitive deficits, as measured by a battery of memory tests. Tau deposits in the temporal lobe also were strongly associated with tau detected in the patients’ CSF. Tau therefore may better predict dementia during Alzheimer’s disease progression than β-amyloid.

—Kimberly Williams

Aspects of spatial navigation may be particularly sensitive for detecting the earliest cognitive deficits of Alzheimer’s disease, according to a study published April 26 in the Journal of Alzheimer’s Disease. This study included 42 clinically normal people without preclinical Alzheimer’s disease, 13 clinically normal people with preclinical Alzheimer’s disease, and 16 people with early-stage symptomatic Alzheimer’s disease. Preclinical Alzheimer’s disease was defined based on CSF Aβ42 levels below 500 pg/mL. Preclinical Alzheimer’s disease was associated with deficits in the use of a wayfinding strategy, but not in the use of a route-learning strategy. In addition, post hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic Alzheimer’s disease-related deficits in the use of wayfinding and route-learning strategies.

One meal per week of seafood and long-chain omega-3 fatty acids protects against decline in multiple cognitive domains, according to a study published online ahead of print May 4 in Neurology. Researchers examined 915 participants who completed at least one follow-up cognitive assessment and provided dietary data. Scores for global cognitive function and five cognitive domains were assessed using 19 cognitive tests. Consumption of seafood was associated with slower decline in semantic memory and perceptual speed in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain omega-3 intake from food.

Persistent environmental pollutants measured in blood are significantly associated with amyotrophic lateral sclerosis (ALS) and may represent modifiable risk factors, according to a study published online ahead of print May 9 in JAMA Neurology. Participants included 156 cases and 128 controls. Complete demographic and pollutant data were available for 101 cases and 110 controls. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS. A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for two organochlorine pesticides, two polychlorinated biphenyls, and one brominated flame retardant. There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood. Additionally, tau correlation coefficients ranged from –0.18 to 0.24.

Outcomes of sports-related concussion vary according to the level of competition, according to a study published online ahead of print May 2 in JAMA Pediatrics. Three injury surveillance programs recorded 1,429 sports-related concussions between 2012 and 2014 among youth, high school, and college-level football athletes. Across all levels, 15.3% of concussions resulted in return to play at least 30 days after the concussion, and 3.1% resulted in return to play less than 24 hours after the concussion. Compared with youth, a higher number of concussion symptoms were reported in high school athletes. Compared with college athletes, the odds of return to play at least 30 days after injury were larger in youth athletes and high school athletes.

A screening test for newborns identifies infants with Niemann-Pick type C, according to a study published May 4 in Science Translational Medicine. The bile acids most elevated in infants with Niemann-Pick type C were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β,5α,6β-triol. Analysis of dried blood spots from 4,992 controls, 134 Niemann-Pick type C carriers, and 44 subjects with Niemann-Pick type C provided 100% sensitivity and specificity in the study samples. The researchers found that infants with Niemann-Pick type C have about thirtyfold higher amounts of 3β,5α,6β-trihydroxycholanic acid in the blood than healthy individuals. In addition, levels of 3β,5α,6β-trihydroxycholanic acid also could distinguish between patients with Niemann-Pick type C and carriers of the disease who show no symptoms.

The FDA has approved pimavanserin for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. The approval is based on data from a phase III study and other supportive studies. In the phase III study, pimavanserin significantly reduced the frequency and severity of psychotic symptoms, compared with placebo, on the Scale for Assessment of Positive Symptoms—Parkinson’s Disease. This benefit was achieved without impairing motor function. The most common adverse reactions in this study were peripheral edema and confusional state. The drug has a boxed warning alerting health care professionals about an increased risk of death associated with the use of atypical antipsychotics to treat older people with dementia-related psychosis. Acadia Pharmaceuticals, headquartered in San Diego, markets the product under the name Nuplazid.

Compared with the standard dose of t-PA (0.9 mg/kg), a low dose (0.6 mg/kg) is associated with slightly reduced rates of bleeding and mortality, according to a study published online ahead of print May 10 in the New England Journal of Medicine. Using a two-by-two quasi-factorial open-label design, researchers randomly assigned 3,310 patients who were eligible for thrombolytic therapy to low-dose IV t-PA or the standard dose. At 90 days, 53.2% of participants in the low-dose group had died or had disability, compared with 51.1% of participants in the standard-dose group. Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group. Fatal events occurred within seven days in 0.5% and 1.5% of participants, respectively.

Triptans and dihydroergotamine (DHE) are not associated with acute or subacute ischemic vascular events in the abortive treatment of basilar migraine or hemiplegic migraine, according to a study published online ahead of print April 8 in Headache. A retrospective chart review of 80 patients with basilar migraine or hemiplegic migraine who received acute abortive treatment with either triptans or DHE was conducted at four headache centers to assess the frequency of ischemic vascular events after administration. No stroke or myocardial infarction was reported. In the triptan group, five patients reported adverse effects that included gastrointestinal upset, rash, neck dystonia, nightmares, and flushing. In the DHE group, five patients had adverse events that included chest tightness, dystonic reaction, transient asymptomatic anterior T wave inversion, and agitation.

The FDA has approved Fycompa (perampanel) CIII oral suspension as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures, and of primary generalized tonic-clonic seizures in patients with epilepsy age 12 and older. The oral suspension formulation is a bioequivalent, interchangeable alternative to the Fycompa tablet formulation. The approval of Fycompa CIII oral suspension was based on a study that demonstrated bioequivalence between a single dose of perampanel oral suspension and a single dose of perampanel tablet when administered under fasted conditions in healthy subjects. Fycompa is an oral medication and the only FDA-approved noncompetitive AMPA receptor antagonist. Its most common side effects include dizziness, sleepiness, headache, tiredness, and irritability. Eisai, headquartered in Woodcliff Lake, New Jersey, markets the drug.

In patients with acute ischemic stroke or transient ischemic attack, ticagrelor is not superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days, according to a study published online ahead of print May 10 in the New England Journal of Medicine. Included in this study were 13,199 patients with nonsevere ischemic stroke or high-risk transient ischemic attack who had not received IV or intra-arterial thrombolysis and who had not had a cardioembolic stroke. During 90 days of treatment, a primary end point event (ie, stroke, myocardial infarction, or death) occurred in 442 of the 6,589 patients treated with ticagrelor, versus 497 of the 6,610 patients treated with aspirin. Ischemic stroke occurred in 385 patients treated with ticagrelor and in 441 patients treated with aspirin.

Physicians differ substantially when giving prognoses and treatment recommendations for patients with intracerebral hemorrhage, according to a study published online ahead of print April 15 in Neurology. A written survey with two intracerebral hemorrhage scenarios was completed by 742 practicing neurologists and neurosurgeons. Physician predictions of 30-day mortality varied widely, as did treatment recommendations. Responses encompassed the full range of options for each case. No physician demographic or personality characteristics were associated with treatment recommendations. Providing a prognostic score changed treatment recommendations, and the effect differed across cases. When the prognostic score suggested a 0% chance of functional independence, the likelihood of treatment limitations was increased, compared with no prognostic score. Conversely, if the score suggested a 66% chance of independence, treatment limitations were less likely.

Mitoxantrone slightly increases the overall incidence of malignancies and significantly increases the risk of leukemia and colorectal cancer, according to a study published online ahead of print May 11 in Neurology. Researchers retrospectively examined all mitoxantrone-treated patients with multiple sclerosis seen between 1994 and 2007 at one hospital. They collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. The incidence ratio of malignancy was 1.50. The standardized incidence ratio of colorectal cancer was 2.98, and that of acute myeloid leukemia, 10.44. Higher age at treatment initiation was a risk factor, but neither cumulative mitoxantrone dose, treatment with other immunosuppressive drugs, nor sex was. In all, 55 patients died. Twelve deaths resulted from a malignancy, and 43 from other causes.

Tau tangles provide a good indication of cognitive decline in the later stages of Alzheimer’s disease, according to a study published May 11 in Science Translational Medicine. The study suggests that while β-amyloid remains a critical marker for the early detection of Alzheimer’s disease, tau may be more useful for tracking disease progression and, potentially, patient response to therapies. Researchers analyzed PET imaging of tau and β-amyloid in 10 patients with mild Alzheimer’s disease and 36 healthy adults. Compared with amyloid plaques, tau tangles in the temporal lobe more closely correlated with cognitive deficits, as measured by a battery of memory tests. Tau deposits in the temporal lobe also were strongly associated with tau detected in the patients’ CSF. Tau therefore may better predict dementia during Alzheimer’s disease progression than β-amyloid.

—Kimberly Williams

Patients who have type 1 diabetes have an increased risk of developing epilepsy, according to a study published online ahead of print March 31 in Diabetologia. This study cohort included 2,568 patients with type 1 diabetes, each of whom was frequency-matched by sex, residence, and index year with 10 patients without type 1 diabetes. Cox proportional hazard regression analysis was conducted to estimate the effects of type 1 diabetes on epilepsy risk. After adjusting for potential confounders, the type 1 diabetes cohort was 2.84 times more likely to develop epilepsy than the control cohort. “Metabolic abnormalities of type 1 diabetes, such as hyperglycemia and hypoglycemia, may have a damaging effect on the central nervous system and be associated with significant long-term neurological sequelae,” said the authors.

Antipsychotics are associated with a significantly increased mortality risk in patients with Parkinson’s disease, after adjusting for measurable confounders, according to a study published online ahead of print March 21 in JAMA Neurology. This retrospective matched-cohort study used data from the fiscal years of 1999 to 2010. The rates of 180-day mortality were compared in 7,877 patients initiating antipsychotic therapy and in 7,877 patients who did not initiate antipsychotic therapy. Antipsychotic use was associated with more than twice the hazard ratio of death, compared with nonuse. The hazard ratio was significantly higher for patients who used typical versus atypical antipsychotics. Among the atypical antipsychotics used, hazard ratios relative to nonuse of antipsychotics were, in descending order, 2.79 for olanzapine, 2.46 for risperidone, and 2.16 for quetiapine fumarate.

White matter tracts related to regulation of sleep and wakefulness, and limbic cognitive and sensorimotor regions, are disrupted in the right brain in patients with primary insomnia, according to a study published online ahead of print April 5 in Radiology. Investigators used tract-based spatial statistics to compare changes in diffusion parameters of white matter tracts from 23 patients with primary insomnia and 30 healthy controls. They evaluated how accurately these changes could distinguish patients with insomnia from healthy controls. Patients with primary insomnia had lower fractional anisotropy values mainly in the right anterior limb of the internal capsule, the right posterior limb of the internal capsule, the right anterior corona radiata, the right superior corona radiata, the right superior longitudinal fasciculus, the body of the corpus callosum, and the right thalamus.

Among Chinese adults, a higher level of fruit consumption is associated with lower blood pressure and blood glucose levels and, largely independent of these and other factors, with significantly lower risks of major cardiovascular diseases, according to a study published April 7 in the New England Journal of Medicine. Between 2004 and 2008, researchers recruited 512,891 adults between ages 30 and 79 from 10 locations in China. In all, 5,173 deaths from cardiovascular disease, 2,551 incident major coronary events, 14,579 ischemic strokes, and 3,523 intracerebral hemorrhages were recorded among the 451,665 participants without a history of cardiovascular disease or antihypertensive treatments at baseline. The adjusted hazard ratios for daily consumption versus nonconsumption were 0.75 for ischemic stroke and 0.64 for hemorrhagic stroke.

A low level of leisure-time physical activity is independently associated with greater decline in cognitive performance over time, according to a study published online ahead of print March 23 in Neurology. Researchers assessed cognition in participants in the Northern Manhattan Study using a standard neuropsychologic examination. The neuropsychologic examination was repeated five years later and subcategorized using standardized z scores over validated domains. No or low levels of leisure-time physical activity were associated with worse executive function, semantic memory, and processing speed scores on the first neuropsychologic examination. The associations were slightly attenuated and not significant after adjusting for vascular risk factors. Cognitively unimpaired participants who reported no to low leisure-time physical activity versus moderate to high levels declined more over time in processing speed and episodic memory.

Participation in the “Sleep for Success” education program is associated with significant improvement in children’s sleep and academic performance, according to a study published in Sleep Medicine. Using a community-based participatory research approach, researchers composed a program of four modules that addressed the children, their family and community, the school staff, and decision-makers within the school setting. In all, 71 students participated in the evaluation of the program. The effectiveness of the program was evaluated using nonrandomized, controlled before-and-after study groups that were assessed at two time points. In the intervention group, true sleep was extended by 18.2 minutes per night, sleep efficiency improved by 2.3%, and sleep latency was shortened by 2.3 minutes. Report card grades also improved significantly in English and mathematics.

The combination of rosuvastatin, candesartan, and hydrochlorothiazide is associated with a significantly lower rate of cardiovascular events than dual placebo in people who do not have cardiovascular disease, according to a study published online ahead of print April 2 in the New England Journal of Medicine. Researchers randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to 10 mg/day of rosuvastatin or placebo, and to 16 mg/day of candesartan, plus 12.5 mg/day of hydrochlorothiazide or placebo. The decrease in the low-density lipoprotein cholesterol level was 33.7 mg/dL greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo.

Right hemisphere white matter integrity is related to speech fluency measures in patients with chronic aphasia, according to a study published online ahead of print March 30 in Neurology. The study included 33 people with an average age of 58 who had a stroke on the left side of their brain. Fractional anisotropy values for the right middle temporal gyrus, precentral gyrus, and pars opercularis significantly predicted speech fluency, but fractional anisotropy values of the pars triangularis and superior parietal lobule did not. A multiple regression analysis showed that combining fractional anisotropy of the significant right hemisphere regions with the lesion load of the left arcuate fasciculus provided the best model for predicting speech fluency. Fractional anisotropy of corpus callosum fibers connecting left and right supplementary motor areas was also correlated with speech fluency.

Differences in white matter microstructure may partially account for the variance in functional outcomes among veterans with combat-related mild traumatic brain injury (mTBI), according to a study published online ahead of print March 29 in Radiology. From 2010 to 2013, an initial post deployment evaluation, including clinical assessment and brain MRI with diffusion tensor imaging, was performed in combat veterans who sustained mTBI while deployed. Veterans who did and did not return to work were also compared for differences in clinical variables by using t and χ² tests. After a mean follow-up of 1.4 years, 34 of 57 veterans had returned to work. Cumulative health care visits over time were inversely correlated with diffusion anisotropy of the splenium of the corpus callosum and adjacent parietal white matter.

Cognitive status and intelligibility may be associated with everyday communicative outcomes in Parkinson’s disease, according to a study published online ahead of print March 16 in the Journal of Parkinson’s Disease. Investigators searched five online databases in May 2015 and also conducted supplementary searches. In all, 4,816 records were identified through database searches, and 16 additional records were identified through supplementary searches. Forty-one articles were suitable for full-text screening, and 15 articles met the eligibility criteria. Ten studies assessed the role of cognitive status, and nine found that participants with greater cognitive impairment had greater everyday communication difficulties. Four studies assessed the role of intelligibility, and all found that participants with greater intelligibility impairment had greater everyday communication difficulties. Effects often were weak, however, and not consistent.

Common variants near FOXF2 are associated with increased stroke susceptibility, according to a study published online ahead of print April 7 in the Lancet Neurology. Researchers completed a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts consisting of 84,961 participants, of whom 4,348 had stroke. Investigators completed validation analyses for variants yielding a significant association with all stroke, ischemic stroke, cardioembolic ischemic stroke, or noncardioembolic ischemic stroke. Study authors replicated seven of eight known loci associated with risk for ischemic stroke and identified a novel locus at chromosome 6p25 associated with risk of all stroke. The rs12204590 stroke risk allele was also associated with increased white matter hyperintensity in adults without stroke. Young patients with segmental deletions of FOXF2 showed extensive white matter hyperintensity.

Young women with musculoskeletal pain complaints may have comorbid sleep problems that require treatment, according to a study published in the April issue of Pain. Researchers investigated the cross-sectional and longitudinal relationship between sleep problems and chronic pain, and musculoskeletal pain, headache, and abdominal pain severity in a general population of adults between ages 19 and 22. They studied whether relationships were moderated by sex and whether symptoms of anxiety and depression, fatigue, or physical inactivity mediated these effects. Follow-up data were collected in 1,753 participants. Sleep problems were associated with chronic pain, musculoskeletal pain, headache, and abdominal pain severity. They also predicted chronic pain and an increase in musculoskeletal pain severity at three years of follow-up. The effect was stronger in females than in males.

—Kimberly Williams

Patients who have type 1 diabetes have an increased risk of developing epilepsy, according to a study published online ahead of print March 31 in Diabetologia. This study cohort included 2,568 patients with type 1 diabetes, each of whom was frequency-matched by sex, residence, and index year with 10 patients without type 1 diabetes. Cox proportional hazard regression analysis was conducted to estimate the effects of type 1 diabetes on epilepsy risk. After adjusting for potential confounders, the type 1 diabetes cohort was 2.84 times more likely to develop epilepsy than the control cohort. “Metabolic abnormalities of type 1 diabetes, such as hyperglycemia and hypoglycemia, may have a damaging effect on the central nervous system and be associated with significant long-term neurological sequelae,” said the authors.

Antipsychotics are associated with a significantly increased mortality risk in patients with Parkinson’s disease, after adjusting for measurable confounders, according to a study published online ahead of print March 21 in JAMA Neurology. This retrospective matched-cohort study used data from the fiscal years of 1999 to 2010. The rates of 180-day mortality were compared in 7,877 patients initiating antipsychotic therapy and in 7,877 patients who did not initiate antipsychotic therapy. Antipsychotic use was associated with more than twice the hazard ratio of death, compared with nonuse. The hazard ratio was significantly higher for patients who used typical versus atypical antipsychotics. Among the atypical antipsychotics used, hazard ratios relative to nonuse of antipsychotics were, in descending order, 2.79 for olanzapine, 2.46 for risperidone, and 2.16 for quetiapine fumarate.

White matter tracts related to regulation of sleep and wakefulness, and limbic cognitive and sensorimotor regions, are disrupted in the right brain in patients with primary insomnia, according to a study published online ahead of print April 5 in Radiology. Investigators used tract-based spatial statistics to compare changes in diffusion parameters of white matter tracts from 23 patients with primary insomnia and 30 healthy controls. They evaluated how accurately these changes could distinguish patients with insomnia from healthy controls. Patients with primary insomnia had lower fractional anisotropy values mainly in the right anterior limb of the internal capsule, the right posterior limb of the internal capsule, the right anterior corona radiata, the right superior corona radiata, the right superior longitudinal fasciculus, the body of the corpus callosum, and the right thalamus.

Among Chinese adults, a higher level of fruit consumption is associated with lower blood pressure and blood glucose levels and, largely independent of these and other factors, with significantly lower risks of major cardiovascular diseases, according to a study published April 7 in the New England Journal of Medicine. Between 2004 and 2008, researchers recruited 512,891 adults between ages 30 and 79 from 10 locations in China. In all, 5,173 deaths from cardiovascular disease, 2,551 incident major coronary events, 14,579 ischemic strokes, and 3,523 intracerebral hemorrhages were recorded among the 451,665 participants without a history of cardiovascular disease or antihypertensive treatments at baseline. The adjusted hazard ratios for daily consumption versus nonconsumption were 0.75 for ischemic stroke and 0.64 for hemorrhagic stroke.

A low level of leisure-time physical activity is independently associated with greater decline in cognitive performance over time, according to a study published online ahead of print March 23 in Neurology. Researchers assessed cognition in participants in the Northern Manhattan Study using a standard neuropsychologic examination. The neuropsychologic examination was repeated five years later and subcategorized using standardized z scores over validated domains. No or low levels of leisure-time physical activity were associated with worse executive function, semantic memory, and processing speed scores on the first neuropsychologic examination. The associations were slightly attenuated and not significant after adjusting for vascular risk factors. Cognitively unimpaired participants who reported no to low leisure-time physical activity versus moderate to high levels declined more over time in processing speed and episodic memory.

Participation in the “Sleep for Success” education program is associated with significant improvement in children’s sleep and academic performance, according to a study published in Sleep Medicine. Using a community-based participatory research approach, researchers composed a program of four modules that addressed the children, their family and community, the school staff, and decision-makers within the school setting. In all, 71 students participated in the evaluation of the program. The effectiveness of the program was evaluated using nonrandomized, controlled before-and-after study groups that were assessed at two time points. In the intervention group, true sleep was extended by 18.2 minutes per night, sleep efficiency improved by 2.3%, and sleep latency was shortened by 2.3 minutes. Report card grades also improved significantly in English and mathematics.

The combination of rosuvastatin, candesartan, and hydrochlorothiazide is associated with a significantly lower rate of cardiovascular events than dual placebo in people who do not have cardiovascular disease, according to a study published online ahead of print April 2 in the New England Journal of Medicine. Researchers randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to 10 mg/day of rosuvastatin or placebo, and to 16 mg/day of candesartan, plus 12.5 mg/day of hydrochlorothiazide or placebo. The decrease in the low-density lipoprotein cholesterol level was 33.7 mg/dL greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo.

Right hemisphere white matter integrity is related to speech fluency measures in patients with chronic aphasia, according to a study published online ahead of print March 30 in Neurology. The study included 33 people with an average age of 58 who had a stroke on the left side of their brain. Fractional anisotropy values for the right middle temporal gyrus, precentral gyrus, and pars opercularis significantly predicted speech fluency, but fractional anisotropy values of the pars triangularis and superior parietal lobule did not. A multiple regression analysis showed that combining fractional anisotropy of the significant right hemisphere regions with the lesion load of the left arcuate fasciculus provided the best model for predicting speech fluency. Fractional anisotropy of corpus callosum fibers connecting left and right supplementary motor areas was also correlated with speech fluency.

Differences in white matter microstructure may partially account for the variance in functional outcomes among veterans with combat-related mild traumatic brain injury (mTBI), according to a study published online ahead of print March 29 in Radiology. From 2010 to 2013, an initial post deployment evaluation, including clinical assessment and brain MRI with diffusion tensor imaging, was performed in combat veterans who sustained mTBI while deployed. Veterans who did and did not return to work were also compared for differences in clinical variables by using t and χ² tests. After a mean follow-up of 1.4 years, 34 of 57 veterans had returned to work. Cumulative health care visits over time were inversely correlated with diffusion anisotropy of the splenium of the corpus callosum and adjacent parietal white matter.

Cognitive status and intelligibility may be associated with everyday communicative outcomes in Parkinson’s disease, according to a study published online ahead of print March 16 in the Journal of Parkinson’s Disease. Investigators searched five online databases in May 2015 and also conducted supplementary searches. In all, 4,816 records were identified through database searches, and 16 additional records were identified through supplementary searches. Forty-one articles were suitable for full-text screening, and 15 articles met the eligibility criteria. Ten studies assessed the role of cognitive status, and nine found that participants with greater cognitive impairment had greater everyday communication difficulties. Four studies assessed the role of intelligibility, and all found that participants with greater intelligibility impairment had greater everyday communication difficulties. Effects often were weak, however, and not consistent.

Common variants near FOXF2 are associated with increased stroke susceptibility, according to a study published online ahead of print April 7 in the Lancet Neurology. Researchers completed a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts consisting of 84,961 participants, of whom 4,348 had stroke. Investigators completed validation analyses for variants yielding a significant association with all stroke, ischemic stroke, cardioembolic ischemic stroke, or noncardioembolic ischemic stroke. Study authors replicated seven of eight known loci associated with risk for ischemic stroke and identified a novel locus at chromosome 6p25 associated with risk of all stroke. The rs12204590 stroke risk allele was also associated with increased white matter hyperintensity in adults without stroke. Young patients with segmental deletions of FOXF2 showed extensive white matter hyperintensity.

Young women with musculoskeletal pain complaints may have comorbid sleep problems that require treatment, according to a study published in the April issue of Pain. Researchers investigated the cross-sectional and longitudinal relationship between sleep problems and chronic pain, and musculoskeletal pain, headache, and abdominal pain severity in a general population of adults between ages 19 and 22. They studied whether relationships were moderated by sex and whether symptoms of anxiety and depression, fatigue, or physical inactivity mediated these effects. Follow-up data were collected in 1,753 participants. Sleep problems were associated with chronic pain, musculoskeletal pain, headache, and abdominal pain severity. They also predicted chronic pain and an increase in musculoskeletal pain severity at three years of follow-up. The effect was stronger in females than in males.

—Kimberly Williams

Patients who have type 1 diabetes have an increased risk of developing epilepsy, according to a study published online ahead of print March 31 in Diabetologia. This study cohort included 2,568 patients with type 1 diabetes, each of whom was frequency-matched by sex, residence, and index year with 10 patients without type 1 diabetes. Cox proportional hazard regression analysis was conducted to estimate the effects of type 1 diabetes on epilepsy risk. After adjusting for potential confounders, the type 1 diabetes cohort was 2.84 times more likely to develop epilepsy than the control cohort. “Metabolic abnormalities of type 1 diabetes, such as hyperglycemia and hypoglycemia, may have a damaging effect on the central nervous system and be associated with significant long-term neurological sequelae,” said the authors.

Antipsychotics are associated with a significantly increased mortality risk in patients with Parkinson’s disease, after adjusting for measurable confounders, according to a study published online ahead of print March 21 in JAMA Neurology. This retrospective matched-cohort study used data from the fiscal years of 1999 to 2010. The rates of 180-day mortality were compared in 7,877 patients initiating antipsychotic therapy and in 7,877 patients who did not initiate antipsychotic therapy. Antipsychotic use was associated with more than twice the hazard ratio of death, compared with nonuse. The hazard ratio was significantly higher for patients who used typical versus atypical antipsychotics. Among the atypical antipsychotics used, hazard ratios relative to nonuse of antipsychotics were, in descending order, 2.79 for olanzapine, 2.46 for risperidone, and 2.16 for quetiapine fumarate.

White matter tracts related to regulation of sleep and wakefulness, and limbic cognitive and sensorimotor regions, are disrupted in the right brain in patients with primary insomnia, according to a study published online ahead of print April 5 in Radiology. Investigators used tract-based spatial statistics to compare changes in diffusion parameters of white matter tracts from 23 patients with primary insomnia and 30 healthy controls. They evaluated how accurately these changes could distinguish patients with insomnia from healthy controls. Patients with primary insomnia had lower fractional anisotropy values mainly in the right anterior limb of the internal capsule, the right posterior limb of the internal capsule, the right anterior corona radiata, the right superior corona radiata, the right superior longitudinal fasciculus, the body of the corpus callosum, and the right thalamus.

Among Chinese adults, a higher level of fruit consumption is associated with lower blood pressure and blood glucose levels and, largely independent of these and other factors, with significantly lower risks of major cardiovascular diseases, according to a study published April 7 in the New England Journal of Medicine. Between 2004 and 2008, researchers recruited 512,891 adults between ages 30 and 79 from 10 locations in China. In all, 5,173 deaths from cardiovascular disease, 2,551 incident major coronary events, 14,579 ischemic strokes, and 3,523 intracerebral hemorrhages were recorded among the 451,665 participants without a history of cardiovascular disease or antihypertensive treatments at baseline. The adjusted hazard ratios for daily consumption versus nonconsumption were 0.75 for ischemic stroke and 0.64 for hemorrhagic stroke.

A low level of leisure-time physical activity is independently associated with greater decline in cognitive performance over time, according to a study published online ahead of print March 23 in Neurology. Researchers assessed cognition in participants in the Northern Manhattan Study using a standard neuropsychologic examination. The neuropsychologic examination was repeated five years later and subcategorized using standardized z scores over validated domains. No or low levels of leisure-time physical activity were associated with worse executive function, semantic memory, and processing speed scores on the first neuropsychologic examination. The associations were slightly attenuated and not significant after adjusting for vascular risk factors. Cognitively unimpaired participants who reported no to low leisure-time physical activity versus moderate to high levels declined more over time in processing speed and episodic memory.

Participation in the “Sleep for Success” education program is associated with significant improvement in children’s sleep and academic performance, according to a study published in Sleep Medicine. Using a community-based participatory research approach, researchers composed a program of four modules that addressed the children, their family and community, the school staff, and decision-makers within the school setting. In all, 71 students participated in the evaluation of the program. The effectiveness of the program was evaluated using nonrandomized, controlled before-and-after study groups that were assessed at two time points. In the intervention group, true sleep was extended by 18.2 minutes per night, sleep efficiency improved by 2.3%, and sleep latency was shortened by 2.3 minutes. Report card grades also improved significantly in English and mathematics.

The combination of rosuvastatin, candesartan, and hydrochlorothiazide is associated with a significantly lower rate of cardiovascular events than dual placebo in people who do not have cardiovascular disease, according to a study published online ahead of print April 2 in the New England Journal of Medicine. Researchers randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to 10 mg/day of rosuvastatin or placebo, and to 16 mg/day of candesartan, plus 12.5 mg/day of hydrochlorothiazide or placebo. The decrease in the low-density lipoprotein cholesterol level was 33.7 mg/dL greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo.

Right hemisphere white matter integrity is related to speech fluency measures in patients with chronic aphasia, according to a study published online ahead of print March 30 in Neurology. The study included 33 people with an average age of 58 who had a stroke on the left side of their brain. Fractional anisotropy values for the right middle temporal gyrus, precentral gyrus, and pars opercularis significantly predicted speech fluency, but fractional anisotropy values of the pars triangularis and superior parietal lobule did not. A multiple regression analysis showed that combining fractional anisotropy of the significant right hemisphere regions with the lesion load of the left arcuate fasciculus provided the best model for predicting speech fluency. Fractional anisotropy of corpus callosum fibers connecting left and right supplementary motor areas was also correlated with speech fluency.

Differences in white matter microstructure may partially account for the variance in functional outcomes among veterans with combat-related mild traumatic brain injury (mTBI), according to a study published online ahead of print March 29 in Radiology. From 2010 to 2013, an initial post deployment evaluation, including clinical assessment and brain MRI with diffusion tensor imaging, was performed in combat veterans who sustained mTBI while deployed. Veterans who did and did not return to work were also compared for differences in clinical variables by using t and χ² tests. After a mean follow-up of 1.4 years, 34 of 57 veterans had returned to work. Cumulative health care visits over time were inversely correlated with diffusion anisotropy of the splenium of the corpus callosum and adjacent parietal white matter.

Cognitive status and intelligibility may be associated with everyday communicative outcomes in Parkinson’s disease, according to a study published online ahead of print March 16 in the Journal of Parkinson’s Disease. Investigators searched five online databases in May 2015 and also conducted supplementary searches. In all, 4,816 records were identified through database searches, and 16 additional records were identified through supplementary searches. Forty-one articles were suitable for full-text screening, and 15 articles met the eligibility criteria. Ten studies assessed the role of cognitive status, and nine found that participants with greater cognitive impairment had greater everyday communication difficulties. Four studies assessed the role of intelligibility, and all found that participants with greater intelligibility impairment had greater everyday communication difficulties. Effects often were weak, however, and not consistent.

Common variants near FOXF2 are associated with increased stroke susceptibility, according to a study published online ahead of print April 7 in the Lancet Neurology. Researchers completed a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts consisting of 84,961 participants, of whom 4,348 had stroke. Investigators completed validation analyses for variants yielding a significant association with all stroke, ischemic stroke, cardioembolic ischemic stroke, or noncardioembolic ischemic stroke. Study authors replicated seven of eight known loci associated with risk for ischemic stroke and identified a novel locus at chromosome 6p25 associated with risk of all stroke. The rs12204590 stroke risk allele was also associated with increased white matter hyperintensity in adults without stroke. Young patients with segmental deletions of FOXF2 showed extensive white matter hyperintensity.

Young women with musculoskeletal pain complaints may have comorbid sleep problems that require treatment, according to a study published in the April issue of Pain. Researchers investigated the cross-sectional and longitudinal relationship between sleep problems and chronic pain, and musculoskeletal pain, headache, and abdominal pain severity in a general population of adults between ages 19 and 22. They studied whether relationships were moderated by sex and whether symptoms of anxiety and depression, fatigue, or physical inactivity mediated these effects. Follow-up data were collected in 1,753 participants. Sleep problems were associated with chronic pain, musculoskeletal pain, headache, and abdominal pain severity. They also predicted chronic pain and an increase in musculoskeletal pain severity at three years of follow-up. The effect was stronger in females than in males.

—Kimberly Williams

Carotid endarterectomy is superior to carotid artery stenting in patients age 70 and older with symptomatic carotid stenosis, according to a study published online ahead of print February 12 in the Lancet. Researchers analyzed individual patient data from four randomized controlled trials. In all, 4,754 patients were randomly assigned to carotid endarterectomy or carotid artery stenting. For patients assigned to carotid artery stenting, the periprocedural hazard ratio for stroke and death in patients age 65 to 69, compared with patients younger than 60, was 2.16. The hazard ratio was about 4.0 for patients age 70 or older. There was no evidence of an increased periprocedural risk by age group with carotid endarterectomy. Age was not associated with the postprocedural stroke risk either within treatment group or between treatment groups.

Having a history of major surgery is associated with a negligibly lower level of cognitive functioning, according to a study published in the February issue of Anesthesiology. Using linear regression adjusted for sex and age, investigators compared results from five cognitive tests between twins who had major, minor, hip, knee replacement, or other surgery, and a reference group of twins without surgery. Genetic and shared environmental confounding was addressed in intrapair analysis of 87 monozygotic and 124 dizygotic same-sex twin pairs in whom one had a history of major surgery and the other did not. Compared with the reference group, twins with at least one major surgery had a composite cognitive score that was one tenth of one standard deviation lower.

Alcohol consumption immediately raises cardiovascular risk, but risk remains high only following heavy alcohol consumption, according to a study published March 8 in Circulation. Researchers identified 23 studies including 29,457 participants that assessed the association between alcohol intake and cardiovascular events in the subsequent hours and days. They calculated pooled relative risks for the association between alcohol intake and myocardial infarction, ischemic stroke, and hemorrhagic stroke. Their analysis was based on DerSimonian and Laird random-effects models. Moderate alcohol consumption was associated with a higher cardiovascular risk that was attenuated after 24 hours. Moderate alcohol consumption also was protective against myocardial infarction, hemorrhagic stroke, and ischemic stroke within one week. Heavy alcohol consumption was associated with higher cardiovascular risk during the following day and week.

Hostile attitudes and effortful coping in young adulthood are associated with worse cognition in midlife, according to a study published online ahead of print March 2 in Neurology. Investigators used linear regression to examine the association of these two characteristics at baseline with subsequent cognitive ability in 3,126 black and white people. Baseline hostility and effortful coping were prospectively associated with lower cognitive function 25 years later, controlling for age, sex, race, education, long-term exposure to depression, discrimination, negative life events, and baseline cognitive ability. Compared with the lowest quartile, those in the highest quartile of hostility performed 0.21 standard deviation units lower on cognitive tasks. Those in the highest quartile of effortful coping performed 0.30 standard deviation units lower on cognitive tasks, compared with those in the lowest quartile.

Insufficient amounts of vitamin D during pregnancy may increase the risk of multiple sclerosis (MS) in offspring, according to a study published online ahead of print March 7 in JAMA Neurology. Researchers identified 193 people who received a diagnosis of MS before December 31, 2009, and matched 176 cases with 326 controls. Maternal serum vitamin D levels were measured using a chemiluminescence assay. Mean maternal vitamin D levels were in the insufficient range, but were higher in controls than in cases. Maternal vitamin D deficiency during early pregnancy was associated with a nearly twofold increased risk of MS in the offspring, compared with maternal vitamin D sufficiency. The researchers found no statistically significant association between the risk of MS and increasing serum vitamin D levels.

Comorbidity is more common than expected in multiple sclerosis (MS), even around the time of diagnosis, according to a study published online ahead of print March 9 in Neurology. Using population-based administrative health data, researchers identified 23,382 incident MS cases and 116,638 age-, sex-, and geographically matched controls. Investigators estimated the prevalence of hypertension, diabetes, hyperlipidemia, heart disease, chronic lung disease, epilepsy, fibromyalgia, inflammatory bowel disease, depression, anxiety, bipolar disorder, and schizophrenia at MS diagnosis using validated case definitions. Compared with the matched population, all comorbidities except hyperlipidemia were more common in the MS population. The prevalence of hypertension was 16% higher for women with MS and 48% higher for men with MS, compared with controls. Diabetes, epilepsy, depression, and anxiety were more prevalent among men with MS than women with MS.

Increasing energy output from various physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status, according to a study published online ahead of print March 11 in the Journal of Alzheimer’s Disease. Subjects were recruited from a population-based longitudinal study of cardiovascular health in people age 65 or older. Researchers analyzed a subsample of 876 subjects for whom data about energy output, cognition, and brain volume were available. Higher energy output from various physical activity types was associated with larger gray matter volumes in frontal, temporal, and parietal lobes, as well as in the hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis.

Periodontitis is associated with an increase in cognitive decline in Alzheimer’s disease, independent of baseline cognitive state, according to a study published March 10 in PLoS One. The increase may be mediated through effects on systemic inflammation. In a six-month observational cohort study, 60 participants with mild to moderate Alzheimer’s disease underwent cognitive assessments and blood tests for systemic inflammatory markers. A dental hygienist who was blind to cognitive outcomes assessed participants’ dental health. Participants were followed up at six months, when all assessments were repeated. Periodontitis at baseline was not related to baseline cognitive state, but was associated with a sixfold increase in the rate of cognitive decline, as measured by the Alzheimer’s Disease Assessment Scale–Cognitive subscale, over a six-month follow-up period.

Zika virus infection can cause Guillain-Barré syndrome, according to a study published online ahead of print February 29 in the Lancet. Researchers examined people diagnosed with Guillain-Barré syndrome during an outbreak in French Polynesia, along with two groups of matched controls. In all, 42 patients were diagnosed with Guillain-Barré syndrome during the study period, and 41 of them had anti-Zika virus immunoglobulin M (IgM) or immunoglobulin G. All cases had neutralizing antibodies against Zika virus, compared with 54 of 98 participants in control group 1. Furthermore, 39 cases had Zika virus IgM, and 37 had experienced a transient illness at a median of six days before the onset of neurologic symptoms. Patients with Guillain-Barré syndrome had electrophysiologic findings compatible with acute motor axonal neuropathy type and had rapid evolution of disease.

Radiosurgery may benefit some patients with arteriovenous malformations, according to a study published in the February issue of Stroke. Researchers combined cerebral arteriovenous malformation radiosurgery outcome data from seven institutions participating in the International Gamma Knife Research Foundation. The cohort included 509 patients with a mean age of 40. Favorable outcome was defined as obliteration of malformation, no postprocedural hemorrhage, and no permanent radiation-induced changes. Adverse outcome was defined as any new or worsening neurologic symptoms or death. Arteriovenous malformation was obliterated in 75% of patients. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3% of patients, respectively. The rates of favorable outcome, adverse neurologic outcome, permanent neurologic morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively.

A video-game-based cognitive rehabilitation program changes thalamocortical functional connectivity and improves cognition in patients with multiple sclerosis (MS), according to a study published online ahead of print March 8 in Radiology. Researchers randomized 24 patients with MS and cognitive impairment to the cognitive rehabilitation program or a wait-list group. Patients were evaluated with cognitive tests and 3-T resting-state functional MRI at baseline and at eight weeks. Eleven healthy controls also underwent baseline resting-state functional MRI. Patients with MS had lower thalamocortical functional connectivity at baseline than controls. At follow-up, the intervention group had increased functional connectivity in the cingulum, precuneus, and bilateral parietal cortex, and lower functional connectivity in the cerebellum and the left prefrontal cortex, compared with the wait-list group. These changes correlated with cognitive improvement.

Traumatic brain injury (TBI) may be a risk factor for mild cognitive impairment (MCI), but the association between the two may be related to gender and depression, according to a study published online ahead of print February 8 in the Journal of Alzheimer’s Disease. Investigators examined data for 3,187 people with MCI and 3,244 people with normal cognition. TBI was categorized based on lifetime reported TBI with loss of consciousness without chronic deficit. TBI history was a significant predictor of MCI and was associated with increased odds of MCI diagnosis in unadjusted models and adjusted models accounting for age, education, APOE4, and a composite vascular score. The association was largely attenuated after adjustment for history of depression. MCI was diagnosed a mean of 2.3 years earlier among people with TBI.

The FDA has approved Briviact (brivaracetam) as an adjunctive therapy in the treatment of partial-onset seizures in patients age 16 and older with epilepsy. Briviact’s effectiveness was studied in three clinical trials including 1,550 participants. Briviact, taken along with other medications, effectively reduced seizure frequency. The most common side effects reported by people taking Briviact in clinical trials include drowsiness, dizziness, fatigue, nausea, and vomiting. Briviact will be available in film-coated tablets, oral solution, and injection. Briviact injection can be used when oral administration is temporarily not feasible. The recommended starting dosage is 50 mg twice daily. Based on individual patient tolerability and therapeutic response, the dose may be adjusted to 25 mg twice daily or 100 mg twice daily. UCB, headquartered in Brussels, manufactures the drug.

—Kimberly Williams

Carotid endarterectomy is superior to carotid artery stenting in patients age 70 and older with symptomatic carotid stenosis, according to a study published online ahead of print February 12 in the Lancet. Researchers analyzed individual patient data from four randomized controlled trials. In all, 4,754 patients were randomly assigned to carotid endarterectomy or carotid artery stenting. For patients assigned to carotid artery stenting, the periprocedural hazard ratio for stroke and death in patients age 65 to 69, compared with patients younger than 60, was 2.16. The hazard ratio was about 4.0 for patients age 70 or older. There was no evidence of an increased periprocedural risk by age group with carotid endarterectomy. Age was not associated with the postprocedural stroke risk either within treatment group or between treatment groups.

Having a history of major surgery is associated with a negligibly lower level of cognitive functioning, according to a study published in the February issue of Anesthesiology. Using linear regression adjusted for sex and age, investigators compared results from five cognitive tests between twins who had major, minor, hip, knee replacement, or other surgery, and a reference group of twins without surgery. Genetic and shared environmental confounding was addressed in intrapair analysis of 87 monozygotic and 124 dizygotic same-sex twin pairs in whom one had a history of major surgery and the other did not. Compared with the reference group, twins with at least one major surgery had a composite cognitive score that was one tenth of one standard deviation lower.

Alcohol consumption immediately raises cardiovascular risk, but risk remains high only following heavy alcohol consumption, according to a study published March 8 in Circulation. Researchers identified 23 studies including 29,457 participants that assessed the association between alcohol intake and cardiovascular events in the subsequent hours and days. They calculated pooled relative risks for the association between alcohol intake and myocardial infarction, ischemic stroke, and hemorrhagic stroke. Their analysis was based on DerSimonian and Laird random-effects models. Moderate alcohol consumption was associated with a higher cardiovascular risk that was attenuated after 24 hours. Moderate alcohol consumption also was protective against myocardial infarction, hemorrhagic stroke, and ischemic stroke within one week. Heavy alcohol consumption was associated with higher cardiovascular risk during the following day and week.

Hostile attitudes and effortful coping in young adulthood are associated with worse cognition in midlife, according to a study published online ahead of print March 2 in Neurology. Investigators used linear regression to examine the association of these two characteristics at baseline with subsequent cognitive ability in 3,126 black and white people. Baseline hostility and effortful coping were prospectively associated with lower cognitive function 25 years later, controlling for age, sex, race, education, long-term exposure to depression, discrimination, negative life events, and baseline cognitive ability. Compared with the lowest quartile, those in the highest quartile of hostility performed 0.21 standard deviation units lower on cognitive tasks. Those in the highest quartile of effortful coping performed 0.30 standard deviation units lower on cognitive tasks, compared with those in the lowest quartile.

Insufficient amounts of vitamin D during pregnancy may increase the risk of multiple sclerosis (MS) in offspring, according to a study published online ahead of print March 7 in JAMA Neurology. Researchers identified 193 people who received a diagnosis of MS before December 31, 2009, and matched 176 cases with 326 controls. Maternal serum vitamin D levels were measured using a chemiluminescence assay. Mean maternal vitamin D levels were in the insufficient range, but were higher in controls than in cases. Maternal vitamin D deficiency during early pregnancy was associated with a nearly twofold increased risk of MS in the offspring, compared with maternal vitamin D sufficiency. The researchers found no statistically significant association between the risk of MS and increasing serum vitamin D levels.

Comorbidity is more common than expected in multiple sclerosis (MS), even around the time of diagnosis, according to a study published online ahead of print March 9 in Neurology. Using population-based administrative health data, researchers identified 23,382 incident MS cases and 116,638 age-, sex-, and geographically matched controls. Investigators estimated the prevalence of hypertension, diabetes, hyperlipidemia, heart disease, chronic lung disease, epilepsy, fibromyalgia, inflammatory bowel disease, depression, anxiety, bipolar disorder, and schizophrenia at MS diagnosis using validated case definitions. Compared with the matched population, all comorbidities except hyperlipidemia were more common in the MS population. The prevalence of hypertension was 16% higher for women with MS and 48% higher for men with MS, compared with controls. Diabetes, epilepsy, depression, and anxiety were more prevalent among men with MS than women with MS.

Increasing energy output from various physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status, according to a study published online ahead of print March 11 in the Journal of Alzheimer’s Disease. Subjects were recruited from a population-based longitudinal study of cardiovascular health in people age 65 or older. Researchers analyzed a subsample of 876 subjects for whom data about energy output, cognition, and brain volume were available. Higher energy output from various physical activity types was associated with larger gray matter volumes in frontal, temporal, and parietal lobes, as well as in the hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis.

Periodontitis is associated with an increase in cognitive decline in Alzheimer’s disease, independent of baseline cognitive state, according to a study published March 10 in PLoS One. The increase may be mediated through effects on systemic inflammation. In a six-month observational cohort study, 60 participants with mild to moderate Alzheimer’s disease underwent cognitive assessments and blood tests for systemic inflammatory markers. A dental hygienist who was blind to cognitive outcomes assessed participants’ dental health. Participants were followed up at six months, when all assessments were repeated. Periodontitis at baseline was not related to baseline cognitive state, but was associated with a sixfold increase in the rate of cognitive decline, as measured by the Alzheimer’s Disease Assessment Scale–Cognitive subscale, over a six-month follow-up period.

Zika virus infection can cause Guillain-Barré syndrome, according to a study published online ahead of print February 29 in the Lancet. Researchers examined people diagnosed with Guillain-Barré syndrome during an outbreak in French Polynesia, along with two groups of matched controls. In all, 42 patients were diagnosed with Guillain-Barré syndrome during the study period, and 41 of them had anti-Zika virus immunoglobulin M (IgM) or immunoglobulin G. All cases had neutralizing antibodies against Zika virus, compared with 54 of 98 participants in control group 1. Furthermore, 39 cases had Zika virus IgM, and 37 had experienced a transient illness at a median of six days before the onset of neurologic symptoms. Patients with Guillain-Barré syndrome had electrophysiologic findings compatible with acute motor axonal neuropathy type and had rapid evolution of disease.

Radiosurgery may benefit some patients with arteriovenous malformations, according to a study published in the February issue of Stroke. Researchers combined cerebral arteriovenous malformation radiosurgery outcome data from seven institutions participating in the International Gamma Knife Research Foundation. The cohort included 509 patients with a mean age of 40. Favorable outcome was defined as obliteration of malformation, no postprocedural hemorrhage, and no permanent radiation-induced changes. Adverse outcome was defined as any new or worsening neurologic symptoms or death. Arteriovenous malformation was obliterated in 75% of patients. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3% of patients, respectively. The rates of favorable outcome, adverse neurologic outcome, permanent neurologic morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively.

A video-game-based cognitive rehabilitation program changes thalamocortical functional connectivity and improves cognition in patients with multiple sclerosis (MS), according to a study published online ahead of print March 8 in Radiology. Researchers randomized 24 patients with MS and cognitive impairment to the cognitive rehabilitation program or a wait-list group. Patients were evaluated with cognitive tests and 3-T resting-state functional MRI at baseline and at eight weeks. Eleven healthy controls also underwent baseline resting-state functional MRI. Patients with MS had lower thalamocortical functional connectivity at baseline than controls. At follow-up, the intervention group had increased functional connectivity in the cingulum, precuneus, and bilateral parietal cortex, and lower functional connectivity in the cerebellum and the left prefrontal cortex, compared with the wait-list group. These changes correlated with cognitive improvement.

Traumatic brain injury (TBI) may be a risk factor for mild cognitive impairment (MCI), but the association between the two may be related to gender and depression, according to a study published online ahead of print February 8 in the Journal of Alzheimer’s Disease. Investigators examined data for 3,187 people with MCI and 3,244 people with normal cognition. TBI was categorized based on lifetime reported TBI with loss of consciousness without chronic deficit. TBI history was a significant predictor of MCI and was associated with increased odds of MCI diagnosis in unadjusted models and adjusted models accounting for age, education, APOE4, and a composite vascular score. The association was largely attenuated after adjustment for history of depression. MCI was diagnosed a mean of 2.3 years earlier among people with TBI.

The FDA has approved Briviact (brivaracetam) as an adjunctive therapy in the treatment of partial-onset seizures in patients age 16 and older with epilepsy. Briviact’s effectiveness was studied in three clinical trials including 1,550 participants. Briviact, taken along with other medications, effectively reduced seizure frequency. The most common side effects reported by people taking Briviact in clinical trials include drowsiness, dizziness, fatigue, nausea, and vomiting. Briviact will be available in film-coated tablets, oral solution, and injection. Briviact injection can be used when oral administration is temporarily not feasible. The recommended starting dosage is 50 mg twice daily. Based on individual patient tolerability and therapeutic response, the dose may be adjusted to 25 mg twice daily or 100 mg twice daily. UCB, headquartered in Brussels, manufactures the drug.

—Kimberly Williams

Carotid endarterectomy is superior to carotid artery stenting in patients age 70 and older with symptomatic carotid stenosis, according to a study published online ahead of print February 12 in the Lancet. Researchers analyzed individual patient data from four randomized controlled trials. In all, 4,754 patients were randomly assigned to carotid endarterectomy or carotid artery stenting. For patients assigned to carotid artery stenting, the periprocedural hazard ratio for stroke and death in patients age 65 to 69, compared with patients younger than 60, was 2.16. The hazard ratio was about 4.0 for patients age 70 or older. There was no evidence of an increased periprocedural risk by age group with carotid endarterectomy. Age was not associated with the postprocedural stroke risk either within treatment group or between treatment groups.

Having a history of major surgery is associated with a negligibly lower level of cognitive functioning, according to a study published in the February issue of Anesthesiology. Using linear regression adjusted for sex and age, investigators compared results from five cognitive tests between twins who had major, minor, hip, knee replacement, or other surgery, and a reference group of twins without surgery. Genetic and shared environmental confounding was addressed in intrapair analysis of 87 monozygotic and 124 dizygotic same-sex twin pairs in whom one had a history of major surgery and the other did not. Compared with the reference group, twins with at least one major surgery had a composite cognitive score that was one tenth of one standard deviation lower.

Alcohol consumption immediately raises cardiovascular risk, but risk remains high only following heavy alcohol consumption, according to a study published March 8 in Circulation. Researchers identified 23 studies including 29,457 participants that assessed the association between alcohol intake and cardiovascular events in the subsequent hours and days. They calculated pooled relative risks for the association between alcohol intake and myocardial infarction, ischemic stroke, and hemorrhagic stroke. Their analysis was based on DerSimonian and Laird random-effects models. Moderate alcohol consumption was associated with a higher cardiovascular risk that was attenuated after 24 hours. Moderate alcohol consumption also was protective against myocardial infarction, hemorrhagic stroke, and ischemic stroke within one week. Heavy alcohol consumption was associated with higher cardiovascular risk during the following day and week.

Hostile attitudes and effortful coping in young adulthood are associated with worse cognition in midlife, according to a study published online ahead of print March 2 in Neurology. Investigators used linear regression to examine the association of these two characteristics at baseline with subsequent cognitive ability in 3,126 black and white people. Baseline hostility and effortful coping were prospectively associated with lower cognitive function 25 years later, controlling for age, sex, race, education, long-term exposure to depression, discrimination, negative life events, and baseline cognitive ability. Compared with the lowest quartile, those in the highest quartile of hostility performed 0.21 standard deviation units lower on cognitive tasks. Those in the highest quartile of effortful coping performed 0.30 standard deviation units lower on cognitive tasks, compared with those in the lowest quartile.

Insufficient amounts of vitamin D during pregnancy may increase the risk of multiple sclerosis (MS) in offspring, according to a study published online ahead of print March 7 in JAMA Neurology. Researchers identified 193 people who received a diagnosis of MS before December 31, 2009, and matched 176 cases with 326 controls. Maternal serum vitamin D levels were measured using a chemiluminescence assay. Mean maternal vitamin D levels were in the insufficient range, but were higher in controls than in cases. Maternal vitamin D deficiency during early pregnancy was associated with a nearly twofold increased risk of MS in the offspring, compared with maternal vitamin D sufficiency. The researchers found no statistically significant association between the risk of MS and increasing serum vitamin D levels.

Comorbidity is more common than expected in multiple sclerosis (MS), even around the time of diagnosis, according to a study published online ahead of print March 9 in Neurology. Using population-based administrative health data, researchers identified 23,382 incident MS cases and 116,638 age-, sex-, and geographically matched controls. Investigators estimated the prevalence of hypertension, diabetes, hyperlipidemia, heart disease, chronic lung disease, epilepsy, fibromyalgia, inflammatory bowel disease, depression, anxiety, bipolar disorder, and schizophrenia at MS diagnosis using validated case definitions. Compared with the matched population, all comorbidities except hyperlipidemia were more common in the MS population. The prevalence of hypertension was 16% higher for women with MS and 48% higher for men with MS, compared with controls. Diabetes, epilepsy, depression, and anxiety were more prevalent among men with MS than women with MS.

Increasing energy output from various physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status, according to a study published online ahead of print March 11 in the Journal of Alzheimer’s Disease. Subjects were recruited from a population-based longitudinal study of cardiovascular health in people age 65 or older. Researchers analyzed a subsample of 876 subjects for whom data about energy output, cognition, and brain volume were available. Higher energy output from various physical activity types was associated with larger gray matter volumes in frontal, temporal, and parietal lobes, as well as in the hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis.

Periodontitis is associated with an increase in cognitive decline in Alzheimer’s disease, independent of baseline cognitive state, according to a study published March 10 in PLoS One. The increase may be mediated through effects on systemic inflammation. In a six-month observational cohort study, 60 participants with mild to moderate Alzheimer’s disease underwent cognitive assessments and blood tests for systemic inflammatory markers. A dental hygienist who was blind to cognitive outcomes assessed participants’ dental health. Participants were followed up at six months, when all assessments were repeated. Periodontitis at baseline was not related to baseline cognitive state, but was associated with a sixfold increase in the rate of cognitive decline, as measured by the Alzheimer’s Disease Assessment Scale–Cognitive subscale, over a six-month follow-up period.

Zika virus infection can cause Guillain-Barré syndrome, according to a study published online ahead of print February 29 in the Lancet. Researchers examined people diagnosed with Guillain-Barré syndrome during an outbreak in French Polynesia, along with two groups of matched controls. In all, 42 patients were diagnosed with Guillain-Barré syndrome during the study period, and 41 of them had anti-Zika virus immunoglobulin M (IgM) or immunoglobulin G. All cases had neutralizing antibodies against Zika virus, compared with 54 of 98 participants in control group 1. Furthermore, 39 cases had Zika virus IgM, and 37 had experienced a transient illness at a median of six days before the onset of neurologic symptoms. Patients with Guillain-Barré syndrome had electrophysiologic findings compatible with acute motor axonal neuropathy type and had rapid evolution of disease.

Radiosurgery may benefit some patients with arteriovenous malformations, according to a study published in the February issue of Stroke. Researchers combined cerebral arteriovenous malformation radiosurgery outcome data from seven institutions participating in the International Gamma Knife Research Foundation. The cohort included 509 patients with a mean age of 40. Favorable outcome was defined as obliteration of malformation, no postprocedural hemorrhage, and no permanent radiation-induced changes. Adverse outcome was defined as any new or worsening neurologic symptoms or death. Arteriovenous malformation was obliterated in 75% of patients. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3% of patients, respectively. The rates of favorable outcome, adverse neurologic outcome, permanent neurologic morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively.

A video-game-based cognitive rehabilitation program changes thalamocortical functional connectivity and improves cognition in patients with multiple sclerosis (MS), according to a study published online ahead of print March 8 in Radiology. Researchers randomized 24 patients with MS and cognitive impairment to the cognitive rehabilitation program or a wait-list group. Patients were evaluated with cognitive tests and 3-T resting-state functional MRI at baseline and at eight weeks. Eleven healthy controls also underwent baseline resting-state functional MRI. Patients with MS had lower thalamocortical functional connectivity at baseline than controls. At follow-up, the intervention group had increased functional connectivity in the cingulum, precuneus, and bilateral parietal cortex, and lower functional connectivity in the cerebellum and the left prefrontal cortex, compared with the wait-list group. These changes correlated with cognitive improvement.

Traumatic brain injury (TBI) may be a risk factor for mild cognitive impairment (MCI), but the association between the two may be related to gender and depression, according to a study published online ahead of print February 8 in the Journal of Alzheimer’s Disease. Investigators examined data for 3,187 people with MCI and 3,244 people with normal cognition. TBI was categorized based on lifetime reported TBI with loss of consciousness without chronic deficit. TBI history was a significant predictor of MCI and was associated with increased odds of MCI diagnosis in unadjusted models and adjusted models accounting for age, education, APOE4, and a composite vascular score. The association was largely attenuated after adjustment for history of depression. MCI was diagnosed a mean of 2.3 years earlier among people with TBI.

The FDA has approved Briviact (brivaracetam) as an adjunctive therapy in the treatment of partial-onset seizures in patients age 16 and older with epilepsy. Briviact’s effectiveness was studied in three clinical trials including 1,550 participants. Briviact, taken along with other medications, effectively reduced seizure frequency. The most common side effects reported by people taking Briviact in clinical trials include drowsiness, dizziness, fatigue, nausea, and vomiting. Briviact will be available in film-coated tablets, oral solution, and injection. Briviact injection can be used when oral administration is temporarily not feasible. The recommended starting dosage is 50 mg twice daily. Based on individual patient tolerability and therapeutic response, the dose may be adjusted to 25 mg twice daily or 100 mg twice daily. UCB, headquartered in Brussels, manufactures the drug.

—Kimberly Williams

Adults with a diagnosis of concussion have an increased long-term risk of suicide, particularly after concussions on weekends, according to a study published online ahead of print February 8 in the Canadian Medical Association Journal. Researchers performed a longitudinal cohort analysis of adults with a diagnosis of concussion from April 1, 1992 to March 31, 2012. Concussions that resulted in hospital admission were excluded. Investigators identified 235,110 patients with concussion, and 667 subsequent suicides occurring over a median follow-up of 9.3 years, which was three times the expected rate. Weekend concussions were associated with a one-third further increased risk of suicide, compared with weekday concussions. According to the researchers, the increased risk applied regardless of patients’ demographic characteristics, was independent of past psychiatric conditions, became accentuated with time, and exceeded the risk among military personnel.

Imaging with 3-T T2-weighted brain MRI distinguishes perivenous multiple sclerosis (MS) lesions from microangiopathic lesions, according to a study of 40 patients published online ahead of print December 10, 2015, in the Multiple Sclerosis Journal. Initially, a test cohort of 10 patients with MS and 10 patients with microangiopathic white matter lesions underwent T2-weighted brain imaging on a 3T MRI. Anonymized scans were analyzed blind to clinical data, and simple diagnostic rules were devised. These rules were applied to a validation cohort of 20 patients by a blinded observer. Within the test cohort, all patients with MS had central veins visible in more than 45% of brain lesions, while the rest had central veins visible in less than 45% of lesions. By applying diagnostic rules to the validation cohort, all remaining patients were correctly categorized.

In asymptomatic patients with severe carotid stenosis who are not at high risk for surgical complications, stenting is noninferior to endarterectomy with regard to the rates of stroke, death, or myocardial infarction at one year, according to a study published online ahead of print February 17 in the New England Journal of Medicine. Researchers compared carotid-artery stenting with embolic protection and carotid endarterectomy in 1,453 patients age 79 or younger. The rate of stroke or death within 30 days was 2.9% in the stenting group and 1.7% in the endarterectomy group. From 30 days to five years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stenting group and 97.3% in the endarterectomy group, and the overall survival rates were 87.1% and 89.4%, respectively.

Past exposure to marijuana is associated with worsened verbal memory, but does not appear to affect other domains of cognitive function, according to a study published online ahead of print February 1 in JAMA Internal Medicine. Researchers examined data for 5,115 African American and Caucasian men and women ages 18 to 30 at baseline. Participants were followed for 26 years to estimate cumulative exposure to marijuana. Among 3,385 participants with cognitive function measurements at the year 25 visit, 2,852 reported past marijuana use, and 392 continued to use marijuana into middle age. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worsened verbal memory. For each five years of past exposure, verbal memory was 0.13 standardized units lower.

Frequent shifts in sleep timing may impair metabolic health among non-shift-working women of middle age, according to a study published in the February issue of Sleep. A total of 338 Caucasian, African American, and Chinese non-shift-working women ages 48 through 58 who were not taking insulin-related medications participated in the Study of Women’s Health Across the Nation Sleep Study and were examined approximately 5.39 years later. Daily diary-reported bedtimes were used to calculate four measures of sleep timing. BMI and insulin resistance were measured at two time points. In cross-sectional models, greater variability in bedtime and greater bedtime delay were associated with higher homeostatic model assessment-insulin resistance, and greater bedtime advance was associated with higher BMI. Prospectively, greater bedtime delay predicted increased homeostatic model assessment-insulin resistance.

Elderly people with high levels of depressive symptoms on several occasions over a 10-year period have substantially increased risk of coronary heart disease and stroke, according to a study published in the January issue of Journal of the American Geriatrics Society. Researchers examined 9,294 participants at baseline between 1999 and 2001, and during repeated study visits. There were 7,313 participants with an average age of 73.8, with no history of coronary heart disease, stroke, or dementia at baseline. After a median follow-up of 8.4 years, 629 first coronary heart disease or stroke events occurred. After adjustment for sociodemographic characteristics and vascular risk factors, the risk of coronary heart disease and stroke combined increased 1.15-fold per each additional study visit with high levels of depressive symptoms.

Submandibular gland needle biopsies identify phosphorylated alpha-synuclein staining in 74% of patients with early Parkinson’s disease, according to a study published in the February issue of Movement Disorders. Twenty-five patients with early Parkinson’s disease and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein and reviewed blind to clinical diagnosis. Only nerve element staining was considered positive. Mean age was 69.5 for the Parkinson’s disease group and 64.8 for controls, and disease duration was 2.6 years. Six people with Parkinson’s disease and one control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 patients with Parkinson’s disease and two out of nine control subjects. Parkinson’s disease-positive and -negative cases did not differ clinically.

Lower cardiovascular fitness and exaggerated exercise blood pressure heart-rate responses in middle-aged adults are associated with smaller brain volume nearly two decades later, according to a study published online ahead of print February 10 in Neurology. In all, 1,094 people without dementia and cardiovascular disease underwent an exercise treadmill test at a mean age of 40. A second treadmill test and MRI scans of the brain were administered two decades later. Poor cardiovascular fitness and greater diastolic blood pressure and heart-rate response to exercise at baseline were associated with a smaller total cerebral brain volume almost two decades later in multivariable adjusted models. The effect of one standard deviation of lower fitness was equivalent to approximately one additional year of brain aging in individuals free of cardiovascular disease.

The increased risks of falling and hip fracture before the diagnosis of Parkinson’s disease may suggest the presence of clinically relevant neurodegenerative impairment years before the diagnosis of the disease, according to a study published February 2 in PLOS Medicine. Researchers compiled two nested case–control cohorts: In cohort one were individuals diagnosed with Parkinson’s disease; cohort two included individuals with an injurious fall. In cohort one, 18.0% of cases had at least one injurious fall before Parkinson’s disease diagnosis, whereas 11.5% of controls had an injurious fall. In cohort two, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with Parkinson’s disease during follow-up. The risk of Parkinson’s disease was increased for as long as 10 years after an injurious fall.

Increased amyloid β burden is observed in traumatic brain injury (TBI), according to a study published online ahead of print February 3 in Neurology. Patients age 11 months to 17 years with moderate to severe TBI underwent ¹¹C-Pittsburgh compound B (¹¹C-PiB)-PET, structural and diffusion MRI, and neuropsychologic examination. Healthy controls and patients with Alzheimer’s disease underwent PET and structural MRI. In TBI, fractional anisotropy was estimated and correlated with ¹¹C-PiB binding potential. Increased ¹¹C-PiB binding potential was found in TBI versus controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared with Alzheimer’s disease, binding after TBI was lower in neocortical regions, but increased in the cerebellum.

Among participants in the Framingham Heart Study, the incidence of dementia has declined over three decades, according to a study published February 11 in the New England Journal of Medicine. In this analysis, which included 5,205 people age 60 and older, researchers used Cox proportional-hazards models adjusted for age and sex to determine the five-year incidence of dementia during each of four epochs. The five-year age- and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch, 2.8 per 100 persons during the second epoch, 2.2 per 100 persons during the third epoch, and 2.0 per 100 persons during the fourth epoch. During the second through fourth epochs, the incidence of dementia declined by 22%, 38%, and 44%, respectively, compared with the first epoch.

The FDA has approved Onzetra Xsail (sumatriptan nasal powder), formerly known as AVP-825, for the acute treatment of migraine with or without aura in adults. The approval is based on data from phase II and phase III trials, safety data from more than 300 patients, and reference data from the extensive clinical use of sumatriptan over the past 20 years. In one trial, 230 patients with migraine were randomized to self-administer either Onzetra Xsail or placebo, using the Xsail Breath Powered Delivery Device when they had moderate to severe migraine pain. A significantly greater proportion of patients on the study drug reported headache relief at 30 minutes and at every time point up to two hours post dose. Avanir Pharmaceuticals manufactures the drug.

The FDA has approved Medtronic Deep Brain Stimulation (DBS) Therapy for use in patients with Parkinson’s disease of at least four-years duration and with recent onset of motor complications, or motor complications of longer-standing duration that are not adequately controlled with medication. In 2002, the FDA initially approved Medtronic DBS Therapy for use in patients with advanced Parkinson’s disease. This new approval expands the population of patients who may benefit from this therapy. The approval is based on data from the EARLYSTIM study published in the New England Journal of Medicine in 2012.

—Kimberly Williams

Adults with a diagnosis of concussion have an increased long-term risk of suicide, particularly after concussions on weekends, according to a study published online ahead of print February 8 in the Canadian Medical Association Journal. Researchers performed a longitudinal cohort analysis of adults with a diagnosis of concussion from April 1, 1992 to March 31, 2012. Concussions that resulted in hospital admission were excluded. Investigators identified 235,110 patients with concussion, and 667 subsequent suicides occurring over a median follow-up of 9.3 years, which was three times the expected rate. Weekend concussions were associated with a one-third further increased risk of suicide, compared with weekday concussions. According to the researchers, the increased risk applied regardless of patients’ demographic characteristics, was independent of past psychiatric conditions, became accentuated with time, and exceeded the risk among military personnel.

Imaging with 3-T T2-weighted brain MRI distinguishes perivenous multiple sclerosis (MS) lesions from microangiopathic lesions, according to a study of 40 patients published online ahead of print December 10, 2015, in the Multiple Sclerosis Journal. Initially, a test cohort of 10 patients with MS and 10 patients with microangiopathic white matter lesions underwent T2-weighted brain imaging on a 3T MRI. Anonymized scans were analyzed blind to clinical data, and simple diagnostic rules were devised. These rules were applied to a validation cohort of 20 patients by a blinded observer. Within the test cohort, all patients with MS had central veins visible in more than 45% of brain lesions, while the rest had central veins visible in less than 45% of lesions. By applying diagnostic rules to the validation cohort, all remaining patients were correctly categorized.

In asymptomatic patients with severe carotid stenosis who are not at high risk for surgical complications, stenting is noninferior to endarterectomy with regard to the rates of stroke, death, or myocardial infarction at one year, according to a study published online ahead of print February 17 in the New England Journal of Medicine. Researchers compared carotid-artery stenting with embolic protection and carotid endarterectomy in 1,453 patients age 79 or younger. The rate of stroke or death within 30 days was 2.9% in the stenting group and 1.7% in the endarterectomy group. From 30 days to five years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stenting group and 97.3% in the endarterectomy group, and the overall survival rates were 87.1% and 89.4%, respectively.

Past exposure to marijuana is associated with worsened verbal memory, but does not appear to affect other domains of cognitive function, according to a study published online ahead of print February 1 in JAMA Internal Medicine. Researchers examined data for 5,115 African American and Caucasian men and women ages 18 to 30 at baseline. Participants were followed for 26 years to estimate cumulative exposure to marijuana. Among 3,385 participants with cognitive function measurements at the year 25 visit, 2,852 reported past marijuana use, and 392 continued to use marijuana into middle age. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worsened verbal memory. For each five years of past exposure, verbal memory was 0.13 standardized units lower.

Frequent shifts in sleep timing may impair metabolic health among non-shift-working women of middle age, according to a study published in the February issue of Sleep. A total of 338 Caucasian, African American, and Chinese non-shift-working women ages 48 through 58 who were not taking insulin-related medications participated in the Study of Women’s Health Across the Nation Sleep Study and were examined approximately 5.39 years later. Daily diary-reported bedtimes were used to calculate four measures of sleep timing. BMI and insulin resistance were measured at two time points. In cross-sectional models, greater variability in bedtime and greater bedtime delay were associated with higher homeostatic model assessment-insulin resistance, and greater bedtime advance was associated with higher BMI. Prospectively, greater bedtime delay predicted increased homeostatic model assessment-insulin resistance.

Elderly people with high levels of depressive symptoms on several occasions over a 10-year period have substantially increased risk of coronary heart disease and stroke, according to a study published in the January issue of Journal of the American Geriatrics Society. Researchers examined 9,294 participants at baseline between 1999 and 2001, and during repeated study visits. There were 7,313 participants with an average age of 73.8, with no history of coronary heart disease, stroke, or dementia at baseline. After a median follow-up of 8.4 years, 629 first coronary heart disease or stroke events occurred. After adjustment for sociodemographic characteristics and vascular risk factors, the risk of coronary heart disease and stroke combined increased 1.15-fold per each additional study visit with high levels of depressive symptoms.

Submandibular gland needle biopsies identify phosphorylated alpha-synuclein staining in 74% of patients with early Parkinson’s disease, according to a study published in the February issue of Movement Disorders. Twenty-five patients with early Parkinson’s disease and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein and reviewed blind to clinical diagnosis. Only nerve element staining was considered positive. Mean age was 69.5 for the Parkinson’s disease group and 64.8 for controls, and disease duration was 2.6 years. Six people with Parkinson’s disease and one control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 patients with Parkinson’s disease and two out of nine control subjects. Parkinson’s disease-positive and -negative cases did not differ clinically.

Lower cardiovascular fitness and exaggerated exercise blood pressure heart-rate responses in middle-aged adults are associated with smaller brain volume nearly two decades later, according to a study published online ahead of print February 10 in Neurology. In all, 1,094 people without dementia and cardiovascular disease underwent an exercise treadmill test at a mean age of 40. A second treadmill test and MRI scans of the brain were administered two decades later. Poor cardiovascular fitness and greater diastolic blood pressure and heart-rate response to exercise at baseline were associated with a smaller total cerebral brain volume almost two decades later in multivariable adjusted models. The effect of one standard deviation of lower fitness was equivalent to approximately one additional year of brain aging in individuals free of cardiovascular disease.

The increased risks of falling and hip fracture before the diagnosis of Parkinson’s disease may suggest the presence of clinically relevant neurodegenerative impairment years before the diagnosis of the disease, according to a study published February 2 in PLOS Medicine. Researchers compiled two nested case–control cohorts: In cohort one were individuals diagnosed with Parkinson’s disease; cohort two included individuals with an injurious fall. In cohort one, 18.0% of cases had at least one injurious fall before Parkinson’s disease diagnosis, whereas 11.5% of controls had an injurious fall. In cohort two, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with Parkinson’s disease during follow-up. The risk of Parkinson’s disease was increased for as long as 10 years after an injurious fall.

Increased amyloid β burden is observed in traumatic brain injury (TBI), according to a study published online ahead of print February 3 in Neurology. Patients age 11 months to 17 years with moderate to severe TBI underwent ¹¹C-Pittsburgh compound B (¹¹C-PiB)-PET, structural and diffusion MRI, and neuropsychologic examination. Healthy controls and patients with Alzheimer’s disease underwent PET and structural MRI. In TBI, fractional anisotropy was estimated and correlated with ¹¹C-PiB binding potential. Increased ¹¹C-PiB binding potential was found in TBI versus controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared with Alzheimer’s disease, binding after TBI was lower in neocortical regions, but increased in the cerebellum.

Among participants in the Framingham Heart Study, the incidence of dementia has declined over three decades, according to a study published February 11 in the New England Journal of Medicine. In this analysis, which included 5,205 people age 60 and older, researchers used Cox proportional-hazards models adjusted for age and sex to determine the five-year incidence of dementia during each of four epochs. The five-year age- and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch, 2.8 per 100 persons during the second epoch, 2.2 per 100 persons during the third epoch, and 2.0 per 100 persons during the fourth epoch. During the second through fourth epochs, the incidence of dementia declined by 22%, 38%, and 44%, respectively, compared with the first epoch.

The FDA has approved Onzetra Xsail (sumatriptan nasal powder), formerly known as AVP-825, for the acute treatment of migraine with or without aura in adults. The approval is based on data from phase II and phase III trials, safety data from more than 300 patients, and reference data from the extensive clinical use of sumatriptan over the past 20 years. In one trial, 230 patients with migraine were randomized to self-administer either Onzetra Xsail or placebo, using the Xsail Breath Powered Delivery Device when they had moderate to severe migraine pain. A significantly greater proportion of patients on the study drug reported headache relief at 30 minutes and at every time point up to two hours post dose. Avanir Pharmaceuticals manufactures the drug.

The FDA has approved Medtronic Deep Brain Stimulation (DBS) Therapy for use in patients with Parkinson’s disease of at least four-years duration and with recent onset of motor complications, or motor complications of longer-standing duration that are not adequately controlled with medication. In 2002, the FDA initially approved Medtronic DBS Therapy for use in patients with advanced Parkinson’s disease. This new approval expands the population of patients who may benefit from this therapy. The approval is based on data from the EARLYSTIM study published in the New England Journal of Medicine in 2012.

—Kimberly Williams

Adults with a diagnosis of concussion have an increased long-term risk of suicide, particularly after concussions on weekends, according to a study published online ahead of print February 8 in the Canadian Medical Association Journal. Researchers performed a longitudinal cohort analysis of adults with a diagnosis of concussion from April 1, 1992 to March 31, 2012. Concussions that resulted in hospital admission were excluded. Investigators identified 235,110 patients with concussion, and 667 subsequent suicides occurring over a median follow-up of 9.3 years, which was three times the expected rate. Weekend concussions were associated with a one-third further increased risk of suicide, compared with weekday concussions. According to the researchers, the increased risk applied regardless of patients’ demographic characteristics, was independent of past psychiatric conditions, became accentuated with time, and exceeded the risk among military personnel.

Imaging with 3-T T2-weighted brain MRI distinguishes perivenous multiple sclerosis (MS) lesions from microangiopathic lesions, according to a study of 40 patients published online ahead of print December 10, 2015, in the Multiple Sclerosis Journal. Initially, a test cohort of 10 patients with MS and 10 patients with microangiopathic white matter lesions underwent T2-weighted brain imaging on a 3T MRI. Anonymized scans were analyzed blind to clinical data, and simple diagnostic rules were devised. These rules were applied to a validation cohort of 20 patients by a blinded observer. Within the test cohort, all patients with MS had central veins visible in more than 45% of brain lesions, while the rest had central veins visible in less than 45% of lesions. By applying diagnostic rules to the validation cohort, all remaining patients were correctly categorized.

In asymptomatic patients with severe carotid stenosis who are not at high risk for surgical complications, stenting is noninferior to endarterectomy with regard to the rates of stroke, death, or myocardial infarction at one year, according to a study published online ahead of print February 17 in the New England Journal of Medicine. Researchers compared carotid-artery stenting with embolic protection and carotid endarterectomy in 1,453 patients age 79 or younger. The rate of stroke or death within 30 days was 2.9% in the stenting group and 1.7% in the endarterectomy group. From 30 days to five years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stenting group and 97.3% in the endarterectomy group, and the overall survival rates were 87.1% and 89.4%, respectively.

Past exposure to marijuana is associated with worsened verbal memory, but does not appear to affect other domains of cognitive function, according to a study published online ahead of print February 1 in JAMA Internal Medicine. Researchers examined data for 5,115 African American and Caucasian men and women ages 18 to 30 at baseline. Participants were followed for 26 years to estimate cumulative exposure to marijuana. Among 3,385 participants with cognitive function measurements at the year 25 visit, 2,852 reported past marijuana use, and 392 continued to use marijuana into middle age. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worsened verbal memory. For each five years of past exposure, verbal memory was 0.13 standardized units lower.

Frequent shifts in sleep timing may impair metabolic health among non-shift-working women of middle age, according to a study published in the February issue of Sleep. A total of 338 Caucasian, African American, and Chinese non-shift-working women ages 48 through 58 who were not taking insulin-related medications participated in the Study of Women’s Health Across the Nation Sleep Study and were examined approximately 5.39 years later. Daily diary-reported bedtimes were used to calculate four measures of sleep timing. BMI and insulin resistance were measured at two time points. In cross-sectional models, greater variability in bedtime and greater bedtime delay were associated with higher homeostatic model assessment-insulin resistance, and greater bedtime advance was associated with higher BMI. Prospectively, greater bedtime delay predicted increased homeostatic model assessment-insulin resistance.

Elderly people with high levels of depressive symptoms on several occasions over a 10-year period have substantially increased risk of coronary heart disease and stroke, according to a study published in the January issue of Journal of the American Geriatrics Society. Researchers examined 9,294 participants at baseline between 1999 and 2001, and during repeated study visits. There were 7,313 participants with an average age of 73.8, with no history of coronary heart disease, stroke, or dementia at baseline. After a median follow-up of 8.4 years, 629 first coronary heart disease or stroke events occurred. After adjustment for sociodemographic characteristics and vascular risk factors, the risk of coronary heart disease and stroke combined increased 1.15-fold per each additional study visit with high levels of depressive symptoms.

Submandibular gland needle biopsies identify phosphorylated alpha-synuclein staining in 74% of patients with early Parkinson’s disease, according to a study published in the February issue of Movement Disorders. Twenty-five patients with early Parkinson’s disease and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein and reviewed blind to clinical diagnosis. Only nerve element staining was considered positive. Mean age was 69.5 for the Parkinson’s disease group and 64.8 for controls, and disease duration was 2.6 years. Six people with Parkinson’s disease and one control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 patients with Parkinson’s disease and two out of nine control subjects. Parkinson’s disease-positive and -negative cases did not differ clinically.

Lower cardiovascular fitness and exaggerated exercise blood pressure heart-rate responses in middle-aged adults are associated with smaller brain volume nearly two decades later, according to a study published online ahead of print February 10 in Neurology. In all, 1,094 people without dementia and cardiovascular disease underwent an exercise treadmill test at a mean age of 40. A second treadmill test and MRI scans of the brain were administered two decades later. Poor cardiovascular fitness and greater diastolic blood pressure and heart-rate response to exercise at baseline were associated with a smaller total cerebral brain volume almost two decades later in multivariable adjusted models. The effect of one standard deviation of lower fitness was equivalent to approximately one additional year of brain aging in individuals free of cardiovascular disease.

The increased risks of falling and hip fracture before the diagnosis of Parkinson’s disease may suggest the presence of clinically relevant neurodegenerative impairment years before the diagnosis of the disease, according to a study published February 2 in PLOS Medicine. Researchers compiled two nested case–control cohorts: In cohort one were individuals diagnosed with Parkinson’s disease; cohort two included individuals with an injurious fall. In cohort one, 18.0% of cases had at least one injurious fall before Parkinson’s disease diagnosis, whereas 11.5% of controls had an injurious fall. In cohort two, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with Parkinson’s disease during follow-up. The risk of Parkinson’s disease was increased for as long as 10 years after an injurious fall.

Increased amyloid β burden is observed in traumatic brain injury (TBI), according to a study published online ahead of print February 3 in Neurology. Patients age 11 months to 17 years with moderate to severe TBI underwent ¹¹C-Pittsburgh compound B (¹¹C-PiB)-PET, structural and diffusion MRI, and neuropsychologic examination. Healthy controls and patients with Alzheimer’s disease underwent PET and structural MRI. In TBI, fractional anisotropy was estimated and correlated with ¹¹C-PiB binding potential. Increased ¹¹C-PiB binding potential was found in TBI versus controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared with Alzheimer’s disease, binding after TBI was lower in neocortical regions, but increased in the cerebellum.

Among participants in the Framingham Heart Study, the incidence of dementia has declined over three decades, according to a study published February 11 in the New England Journal of Medicine. In this analysis, which included 5,205 people age 60 and older, researchers used Cox proportional-hazards models adjusted for age and sex to determine the five-year incidence of dementia during each of four epochs. The five-year age- and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch, 2.8 per 100 persons during the second epoch, 2.2 per 100 persons during the third epoch, and 2.0 per 100 persons during the fourth epoch. During the second through fourth epochs, the incidence of dementia declined by 22%, 38%, and 44%, respectively, compared with the first epoch.

The FDA has approved Onzetra Xsail (sumatriptan nasal powder), formerly known as AVP-825, for the acute treatment of migraine with or without aura in adults. The approval is based on data from phase II and phase III trials, safety data from more than 300 patients, and reference data from the extensive clinical use of sumatriptan over the past 20 years. In one trial, 230 patients with migraine were randomized to self-administer either Onzetra Xsail or placebo, using the Xsail Breath Powered Delivery Device when they had moderate to severe migraine pain. A significantly greater proportion of patients on the study drug reported headache relief at 30 minutes and at every time point up to two hours post dose. Avanir Pharmaceuticals manufactures the drug.

The FDA has approved Medtronic Deep Brain Stimulation (DBS) Therapy for use in patients with Parkinson’s disease of at least four-years duration and with recent onset of motor complications, or motor complications of longer-standing duration that are not adequately controlled with medication. In 2002, the FDA initially approved Medtronic DBS Therapy for use in patients with advanced Parkinson’s disease. This new approval expands the population of patients who may benefit from this therapy. The approval is based on data from the EARLYSTIM study published in the New England Journal of Medicine in 2012.

—Kimberly Williams

Herpes zoster is associated with a short-term increased risk of stroke, and preventing infection may prevent this increased risk, according to a study published online ahead of print December 9, 2015, in Mayo Clinic Proceedings. In a community cohort study, researchers compared the risk of stroke and myocardial infarction at four time points in 4,862 adults with and without herpes zoster. People with herpes zoster had more risk or confounding factors for myocardial infarction and stroke, suggesting that they had worse health status overall. People with herpes zoster were at increased risk for stroke at three months after infection, compared with those without a history of herpes zoster. Herpes zoster was not associated with an increased risk of stroke or myocardial infarction at any point beyond three months.

Supplementation with 10,400 IU of vitamin D3 daily is safe and well-tolerated in patients with multiple sclerosis (MS), according to a study published online ahead of print December 30, 2015, in Neurology. Supplementation also may mitigate patients’ hyperactive immune response. In a double-blind, single-center study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU of vitamin D3 daily for six months. Blood tests were performed at baseline and three and six months. In the high-dose group, researchers found a reduction in the proportion of interleukin-17+CD4+ T cells, CD161+CD4+ T cells, and effector memory CD4+ T cells, with a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. These effects were not observed in the low-dose group.

Weight loss is associated with rapid progression of Parkinson’s disease, according to a study published online ahead of print January 11 in JAMA Neurology. Researchers analyzed data for 1,673 participants in the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1. Of this cohort, 158 people lost weight, whereas 233 gained weight. After adjusting for covariates, researchers found that mean motor score increased by 1.48 more points per visit among people who lost weight than among people whose weight was stable. Mean motor score decreased by 0.51 points per visit for people who gained weight, relative to participants with stable weight. The observed difference in survival between the three BMI groups was not a significant outcome after data were adjusted for covariates.

Distal flow status is associated with risk for subsequent stroke in patients with symptomatic atherosclerotic vertebrobasilar occlusive disease, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. Researchers conducted a prospective, blinded, longitudinal cohort study of 82 patients with recent vertebrobasilar transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Distal flow status was low in 18 of the 72 participants included in the analysis and was significantly associated with risk for a subsequent vertebrobasilar stroke. The 12- and 24-month event-free survival rates were 78% and 70%, respectively, in the low-flow group, compared with 96% and 87%, respectively, in the normal-flow group. Hazard ratio for stroke was 11.55 among people with low distal flow.

The FDA has approved incobotulinumtoxinA for the treatment of upper limb spasticity in adult patients. The approval is based on the results of a randomized, multicenter, placebo-controlled trial. Treatment with incobotulinumtoxinA for adult upper limb spasticity resulted in statistically and clinically significant improvements in muscle tone. The product’s safety and efficacy were evaluated in multiple phase III clinical studies that included more than 400 patients. The safety profile for this indication is similar to that observed for other indications. FDA first approved incobotulinumtoxinA in August 2010 for the treatment of adults with cervical dystonia and blepharospasm. The most common adverse reactions include seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection. Merz Pharma Group, headquartered in Raleigh, North Carolina, markets the product under the name Xeomin.

Cannabidiol may reduce seizure frequency and have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy, according to a study published online ahead of print December 23, 2015, in Lancet Neurology. Patients received 2 to 5 mg/kg/day of oral cannabidiol, and the dose was increased until intolerance or to a maximum dose of 25 mg/kg/day or 50 mg/kg/day. Adverse events included somnolence, decreased appetite, diarrhea, fatigue, and convulsion. Five patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 patients, including one death regarded as unrelated to the study drug. Twenty patients had severe adverse events possibly related to cannabidiol use, the most common being status epilepticus. The median reduction in monthly motor seizures was 36.5%.

For every hour of reperfusion delay, the benefit of intra-arterial treatment for ischemic stroke decreases and the absolute risk difference for a good outcome is reduced by 6%, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) compared intra-arterial treatment with no intra-arterial treatment in 500 patients. The median time to treatment was 260 minutes. Median time from treatment to reperfusion was 340 minutes. The researchers found an interaction between time from treatment to reperfusion and treatment effect, but not between time to treatment and treatment effect. The adjusted risk difference was 25.9% when reperfusion was achieved at three hours, 18.8% at four hours, and 6.7% at six hours.

Anticholinergic drugs are not associated with impaired cognitive performance among patients with Parkinson’s disease, according to a study published October 2, 2015, in Journal of Parkinson’s Disease. Using data from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation—Parkinson’s Disease study, the researchers studied 195 patients with Parkinson’s disease and 84 controls. Patients’ detailed medication history, including over-the-counter drugs, was evaluated using the Anticholinergic Drug Scale (ADS). Each drug’s anticholinergic activity was classified on a scale from 0 to 3. Follow-up lasted 18 months. The investigators found no differences in global cognition, attention, memory, or executive function between patients with Parkinson’s disease who used anticholinergic drugs and those who did not. The proportion of patients with mild cognitive impairment was similar in both groups.

Anxiety symptoms are associated with an increased risk of dementia, according to a study published online ahead of print November 6, 2015, in Alzheimer’s & Dementia. The study included 1,082 fraternal and identical twins without dementia. Participants completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. The twins also completed in-person tests every three years, answered questionnaires, and were screened for dementia throughout the study. Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up. There was a 48% increased risk of dementia for people who had experienced high anxiety at any time, compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic, compared with monozygotic twins.

Common variants of MS4A6A and ABCA7 are associated with atrophy in cortical and hippocampal regions of the brain, according to a study published online ahead of print November 5, 2015, in Neurobiology of Aging. Researchers studied the relationship between the top 10 genetic variants associated with Alzheimer’s disease risk, excluding APOE, with cortical and hippocampal atrophy. They performed 1.5-T MRI to measure brain size and conducted genetic analyses for 50 cognitively normal participants and 98 participants with mild cognitive impairment. After explicit matching of cortical and hippocampal morphology, investigators computed in 3D the cortical thickness and hippocampal radial distance measures for each participant. MS4A6A rs610932 and ABCA7 rs3764650 had significant associations with cortical and hippocampal atrophy. The study may be the first to report the effect of these variants on neurodegeneration.

Anemia is associated with an increased risk of mild cognitive impairment (MCI), independent of traditional cardiovascular risk factors, according to a study published November 21, 2015, in Journal of Alzheimer’s Disease. Researchers examined 4,033 participants in a cohort study with available hemoglobin data and complete cognitive assessments. Participants’ age ranged between 50 and 80, and they were assessed between 2000 and 2003. Participants with anemia (ie, hemoglobin level less than 13 g/dl in men and less than 12 g/dl in women) had poorer cognitive performance in verbal memory and executive function, compared with people without anemia. The fully adjusted odds ratios for MCI, amnestic MCI, and nonamnestic MCI in anemic versus nonanemic participants were 1.92, 1.96, and 1.88, respectively.

By manipulating the WNT pathway, researchers efficiently differentiated human pluripotent stem cells to cells resembling central serotonin neurons, according to a study published in the January issue of Nature Biotechnology. For their investigation, the researchers used stem cells derived from embryos and stem cells derived from adult cells. The resulting serotonin neurons resembled those located in the rhombomeric segments 2-3 of the rostral raphe. They expressed a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2. The cells also exhibited typical electrophysiologic properties and released serotonin in an activity-dependent manner. When treated with tramadol and escitalopram oxalate, the serotonin neurons released or took up serotonin in a dose- and time-dependent manner. These cells may help researchers to evaluate drug candidates, according to the investigators.

Vascular and Lewy body pathologies and vascular risk factors modify the risk of psychosis in Alzheimer’s disease, according to a study published November 30, 2015, in Journal of Alzheimer’s Disease. Researchers reviewed a group of patients with clinically diagnosed Alzheimer’s disease who had neuropathology data, as well as a group of neuropathologically definite cases of Alzheimer’s disease. They investigated the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. In all, 1,073 participants were included in this study. A total of 34% of clinically diagnosed patients and 37% of neuropathologically definite cases had psychotic symptoms during their illness. Overall, Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis.

—Kimberly Williams

Herpes zoster is associated with a short-term increased risk of stroke, and preventing infection may prevent this increased risk, according to a study published online ahead of print December 9, 2015, in Mayo Clinic Proceedings. In a community cohort study, researchers compared the risk of stroke and myocardial infarction at four time points in 4,862 adults with and without herpes zoster. People with herpes zoster had more risk or confounding factors for myocardial infarction and stroke, suggesting that they had worse health status overall. People with herpes zoster were at increased risk for stroke at three months after infection, compared with those without a history of herpes zoster. Herpes zoster was not associated with an increased risk of stroke or myocardial infarction at any point beyond three months.

Supplementation with 10,400 IU of vitamin D3 daily is safe and well-tolerated in patients with multiple sclerosis (MS), according to a study published online ahead of print December 30, 2015, in Neurology. Supplementation also may mitigate patients’ hyperactive immune response. In a double-blind, single-center study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU of vitamin D3 daily for six months. Blood tests were performed at baseline and three and six months. In the high-dose group, researchers found a reduction in the proportion of interleukin-17+CD4+ T cells, CD161+CD4+ T cells, and effector memory CD4+ T cells, with a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. These effects were not observed in the low-dose group.

Weight loss is associated with rapid progression of Parkinson’s disease, according to a study published online ahead of print January 11 in JAMA Neurology. Researchers analyzed data for 1,673 participants in the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1. Of this cohort, 158 people lost weight, whereas 233 gained weight. After adjusting for covariates, researchers found that mean motor score increased by 1.48 more points per visit among people who lost weight than among people whose weight was stable. Mean motor score decreased by 0.51 points per visit for people who gained weight, relative to participants with stable weight. The observed difference in survival between the three BMI groups was not a significant outcome after data were adjusted for covariates.

Distal flow status is associated with risk for subsequent stroke in patients with symptomatic atherosclerotic vertebrobasilar occlusive disease, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. Researchers conducted a prospective, blinded, longitudinal cohort study of 82 patients with recent vertebrobasilar transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Distal flow status was low in 18 of the 72 participants included in the analysis and was significantly associated with risk for a subsequent vertebrobasilar stroke. The 12- and 24-month event-free survival rates were 78% and 70%, respectively, in the low-flow group, compared with 96% and 87%, respectively, in the normal-flow group. Hazard ratio for stroke was 11.55 among people with low distal flow.

The FDA has approved incobotulinumtoxinA for the treatment of upper limb spasticity in adult patients. The approval is based on the results of a randomized, multicenter, placebo-controlled trial. Treatment with incobotulinumtoxinA for adult upper limb spasticity resulted in statistically and clinically significant improvements in muscle tone. The product’s safety and efficacy were evaluated in multiple phase III clinical studies that included more than 400 patients. The safety profile for this indication is similar to that observed for other indications. FDA first approved incobotulinumtoxinA in August 2010 for the treatment of adults with cervical dystonia and blepharospasm. The most common adverse reactions include seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection. Merz Pharma Group, headquartered in Raleigh, North Carolina, markets the product under the name Xeomin.

Cannabidiol may reduce seizure frequency and have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy, according to a study published online ahead of print December 23, 2015, in Lancet Neurology. Patients received 2 to 5 mg/kg/day of oral cannabidiol, and the dose was increased until intolerance or to a maximum dose of 25 mg/kg/day or 50 mg/kg/day. Adverse events included somnolence, decreased appetite, diarrhea, fatigue, and convulsion. Five patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 patients, including one death regarded as unrelated to the study drug. Twenty patients had severe adverse events possibly related to cannabidiol use, the most common being status epilepticus. The median reduction in monthly motor seizures was 36.5%.

For every hour of reperfusion delay, the benefit of intra-arterial treatment for ischemic stroke decreases and the absolute risk difference for a good outcome is reduced by 6%, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) compared intra-arterial treatment with no intra-arterial treatment in 500 patients. The median time to treatment was 260 minutes. Median time from treatment to reperfusion was 340 minutes. The researchers found an interaction between time from treatment to reperfusion and treatment effect, but not between time to treatment and treatment effect. The adjusted risk difference was 25.9% when reperfusion was achieved at three hours, 18.8% at four hours, and 6.7% at six hours.

Anticholinergic drugs are not associated with impaired cognitive performance among patients with Parkinson’s disease, according to a study published October 2, 2015, in Journal of Parkinson’s Disease. Using data from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation—Parkinson’s Disease study, the researchers studied 195 patients with Parkinson’s disease and 84 controls. Patients’ detailed medication history, including over-the-counter drugs, was evaluated using the Anticholinergic Drug Scale (ADS). Each drug’s anticholinergic activity was classified on a scale from 0 to 3. Follow-up lasted 18 months. The investigators found no differences in global cognition, attention, memory, or executive function between patients with Parkinson’s disease who used anticholinergic drugs and those who did not. The proportion of patients with mild cognitive impairment was similar in both groups.

Anxiety symptoms are associated with an increased risk of dementia, according to a study published online ahead of print November 6, 2015, in Alzheimer’s & Dementia. The study included 1,082 fraternal and identical twins without dementia. Participants completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. The twins also completed in-person tests every three years, answered questionnaires, and were screened for dementia throughout the study. Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up. There was a 48% increased risk of dementia for people who had experienced high anxiety at any time, compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic, compared with monozygotic twins.

Common variants of MS4A6A and ABCA7 are associated with atrophy in cortical and hippocampal regions of the brain, according to a study published online ahead of print November 5, 2015, in Neurobiology of Aging. Researchers studied the relationship between the top 10 genetic variants associated with Alzheimer’s disease risk, excluding APOE, with cortical and hippocampal atrophy. They performed 1.5-T MRI to measure brain size and conducted genetic analyses for 50 cognitively normal participants and 98 participants with mild cognitive impairment. After explicit matching of cortical and hippocampal morphology, investigators computed in 3D the cortical thickness and hippocampal radial distance measures for each participant. MS4A6A rs610932 and ABCA7 rs3764650 had significant associations with cortical and hippocampal atrophy. The study may be the first to report the effect of these variants on neurodegeneration.

Anemia is associated with an increased risk of mild cognitive impairment (MCI), independent of traditional cardiovascular risk factors, according to a study published November 21, 2015, in Journal of Alzheimer’s Disease. Researchers examined 4,033 participants in a cohort study with available hemoglobin data and complete cognitive assessments. Participants’ age ranged between 50 and 80, and they were assessed between 2000 and 2003. Participants with anemia (ie, hemoglobin level less than 13 g/dl in men and less than 12 g/dl in women) had poorer cognitive performance in verbal memory and executive function, compared with people without anemia. The fully adjusted odds ratios for MCI, amnestic MCI, and nonamnestic MCI in anemic versus nonanemic participants were 1.92, 1.96, and 1.88, respectively.

By manipulating the WNT pathway, researchers efficiently differentiated human pluripotent stem cells to cells resembling central serotonin neurons, according to a study published in the January issue of Nature Biotechnology. For their investigation, the researchers used stem cells derived from embryos and stem cells derived from adult cells. The resulting serotonin neurons resembled those located in the rhombomeric segments 2-3 of the rostral raphe. They expressed a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2. The cells also exhibited typical electrophysiologic properties and released serotonin in an activity-dependent manner. When treated with tramadol and escitalopram oxalate, the serotonin neurons released or took up serotonin in a dose- and time-dependent manner. These cells may help researchers to evaluate drug candidates, according to the investigators.

Vascular and Lewy body pathologies and vascular risk factors modify the risk of psychosis in Alzheimer’s disease, according to a study published November 30, 2015, in Journal of Alzheimer’s Disease. Researchers reviewed a group of patients with clinically diagnosed Alzheimer’s disease who had neuropathology data, as well as a group of neuropathologically definite cases of Alzheimer’s disease. They investigated the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. In all, 1,073 participants were included in this study. A total of 34% of clinically diagnosed patients and 37% of neuropathologically definite cases had psychotic symptoms during their illness. Overall, Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis.

—Kimberly Williams

Herpes zoster is associated with a short-term increased risk of stroke, and preventing infection may prevent this increased risk, according to a study published online ahead of print December 9, 2015, in Mayo Clinic Proceedings. In a community cohort study, researchers compared the risk of stroke and myocardial infarction at four time points in 4,862 adults with and without herpes zoster. People with herpes zoster had more risk or confounding factors for myocardial infarction and stroke, suggesting that they had worse health status overall. People with herpes zoster were at increased risk for stroke at three months after infection, compared with those without a history of herpes zoster. Herpes zoster was not associated with an increased risk of stroke or myocardial infarction at any point beyond three months.

Supplementation with 10,400 IU of vitamin D3 daily is safe and well-tolerated in patients with multiple sclerosis (MS), according to a study published online ahead of print December 30, 2015, in Neurology. Supplementation also may mitigate patients’ hyperactive immune response. In a double-blind, single-center study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU of vitamin D3 daily for six months. Blood tests were performed at baseline and three and six months. In the high-dose group, researchers found a reduction in the proportion of interleukin-17+CD4+ T cells, CD161+CD4+ T cells, and effector memory CD4+ T cells, with a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. These effects were not observed in the low-dose group.

Weight loss is associated with rapid progression of Parkinson’s disease, according to a study published online ahead of print January 11 in JAMA Neurology. Researchers analyzed data for 1,673 participants in the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1. Of this cohort, 158 people lost weight, whereas 233 gained weight. After adjusting for covariates, researchers found that mean motor score increased by 1.48 more points per visit among people who lost weight than among people whose weight was stable. Mean motor score decreased by 0.51 points per visit for people who gained weight, relative to participants with stable weight. The observed difference in survival between the three BMI groups was not a significant outcome after data were adjusted for covariates.

Distal flow status is associated with risk for subsequent stroke in patients with symptomatic atherosclerotic vertebrobasilar occlusive disease, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. Researchers conducted a prospective, blinded, longitudinal cohort study of 82 patients with recent vertebrobasilar transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Distal flow status was low in 18 of the 72 participants included in the analysis and was significantly associated with risk for a subsequent vertebrobasilar stroke. The 12- and 24-month event-free survival rates were 78% and 70%, respectively, in the low-flow group, compared with 96% and 87%, respectively, in the normal-flow group. Hazard ratio for stroke was 11.55 among people with low distal flow.

The FDA has approved incobotulinumtoxinA for the treatment of upper limb spasticity in adult patients. The approval is based on the results of a randomized, multicenter, placebo-controlled trial. Treatment with incobotulinumtoxinA for adult upper limb spasticity resulted in statistically and clinically significant improvements in muscle tone. The product’s safety and efficacy were evaluated in multiple phase III clinical studies that included more than 400 patients. The safety profile for this indication is similar to that observed for other indications. FDA first approved incobotulinumtoxinA in August 2010 for the treatment of adults with cervical dystonia and blepharospasm. The most common adverse reactions include seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection. Merz Pharma Group, headquartered in Raleigh, North Carolina, markets the product under the name Xeomin.

Cannabidiol may reduce seizure frequency and have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy, according to a study published online ahead of print December 23, 2015, in Lancet Neurology. Patients received 2 to 5 mg/kg/day of oral cannabidiol, and the dose was increased until intolerance or to a maximum dose of 25 mg/kg/day or 50 mg/kg/day. Adverse events included somnolence, decreased appetite, diarrhea, fatigue, and convulsion. Five patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 patients, including one death regarded as unrelated to the study drug. Twenty patients had severe adverse events possibly related to cannabidiol use, the most common being status epilepticus. The median reduction in monthly motor seizures was 36.5%.

For every hour of reperfusion delay, the benefit of intra-arterial treatment for ischemic stroke decreases and the absolute risk difference for a good outcome is reduced by 6%, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) compared intra-arterial treatment with no intra-arterial treatment in 500 patients. The median time to treatment was 260 minutes. Median time from treatment to reperfusion was 340 minutes. The researchers found an interaction between time from treatment to reperfusion and treatment effect, but not between time to treatment and treatment effect. The adjusted risk difference was 25.9% when reperfusion was achieved at three hours, 18.8% at four hours, and 6.7% at six hours.

Anticholinergic drugs are not associated with impaired cognitive performance among patients with Parkinson’s disease, according to a study published October 2, 2015, in Journal of Parkinson’s Disease. Using data from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation—Parkinson’s Disease study, the researchers studied 195 patients with Parkinson’s disease and 84 controls. Patients’ detailed medication history, including over-the-counter drugs, was evaluated using the Anticholinergic Drug Scale (ADS). Each drug’s anticholinergic activity was classified on a scale from 0 to 3. Follow-up lasted 18 months. The investigators found no differences in global cognition, attention, memory, or executive function between patients with Parkinson’s disease who used anticholinergic drugs and those who did not. The proportion of patients with mild cognitive impairment was similar in both groups.

Anxiety symptoms are associated with an increased risk of dementia, according to a study published online ahead of print November 6, 2015, in Alzheimer’s & Dementia. The study included 1,082 fraternal and identical twins without dementia. Participants completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. The twins also completed in-person tests every three years, answered questionnaires, and were screened for dementia throughout the study. Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up. There was a 48% increased risk of dementia for people who had experienced high anxiety at any time, compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic, compared with monozygotic twins.

Common variants of MS4A6A and ABCA7 are associated with atrophy in cortical and hippocampal regions of the brain, according to a study published online ahead of print November 5, 2015, in Neurobiology of Aging. Researchers studied the relationship between the top 10 genetic variants associated with Alzheimer’s disease risk, excluding APOE, with cortical and hippocampal atrophy. They performed 1.5-T MRI to measure brain size and conducted genetic analyses for 50 cognitively normal participants and 98 participants with mild cognitive impairment. After explicit matching of cortical and hippocampal morphology, investigators computed in 3D the cortical thickness and hippocampal radial distance measures for each participant. MS4A6A rs610932 and ABCA7 rs3764650 had significant associations with cortical and hippocampal atrophy. The study may be the first to report the effect of these variants on neurodegeneration.

Anemia is associated with an increased risk of mild cognitive impairment (MCI), independent of traditional cardiovascular risk factors, according to a study published November 21, 2015, in Journal of Alzheimer’s Disease. Researchers examined 4,033 participants in a cohort study with available hemoglobin data and complete cognitive assessments. Participants’ age ranged between 50 and 80, and they were assessed between 2000 and 2003. Participants with anemia (ie, hemoglobin level less than 13 g/dl in men and less than 12 g/dl in women) had poorer cognitive performance in verbal memory and executive function, compared with people without anemia. The fully adjusted odds ratios for MCI, amnestic MCI, and nonamnestic MCI in anemic versus nonanemic participants were 1.92, 1.96, and 1.88, respectively.

By manipulating the WNT pathway, researchers efficiently differentiated human pluripotent stem cells to cells resembling central serotonin neurons, according to a study published in the January issue of Nature Biotechnology. For their investigation, the researchers used stem cells derived from embryos and stem cells derived from adult cells. The resulting serotonin neurons resembled those located in the rhombomeric segments 2-3 of the rostral raphe. They expressed a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2. The cells also exhibited typical electrophysiologic properties and released serotonin in an activity-dependent manner. When treated with tramadol and escitalopram oxalate, the serotonin neurons released or took up serotonin in a dose- and time-dependent manner. These cells may help researchers to evaluate drug candidates, according to the investigators.

Vascular and Lewy body pathologies and vascular risk factors modify the risk of psychosis in Alzheimer’s disease, according to a study published November 30, 2015, in Journal of Alzheimer’s Disease. Researchers reviewed a group of patients with clinically diagnosed Alzheimer’s disease who had neuropathology data, as well as a group of neuropathologically definite cases of Alzheimer’s disease. They investigated the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. In all, 1,073 participants were included in this study. A total of 34% of clinically diagnosed patients and 37% of neuropathologically definite cases had psychotic symptoms during their illness. Overall, Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis.

—Kimberly Williams

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

The risk of epilepsy is increased in children with hospital-diagnosed pertussis infections, compared with the general population, but the absolute risk is low, according to a Danish study published in the November 3 issue of JAMA. Researchers used data from population-based medical registries covering all Danish hospitals to identify all patients with pertussis born between 1978 and 2011 and followed up through 2011. Investigators used the Civil Registration System to identify 10 individuals from the general population for each patient with pertussis, matched on sex and year of birth. They identified 4,700 patients with pertussis, of whom 90 developed epilepsy during the follow-up. The cumulative incidence of epilepsy at age 10 was 1.7% for patients with pertussis and 0.9% for the matched comparison cohort.

Chronic users of antiepileptic drugs have poorer standing balance, compared with nonusers, according to a longitudinal twin and sibling study published in the November issue of Epilepsia. Researchers studied 26 twin and sibling pairs. Siblings were of the same gender, but only one in each pair had exposure to antiepileptic drugs. Clinical and laboratory balance examinations were conducted twice, and at least one year elapsed between examinations. The mean within-pair differences in balance measures were calculated cross-sectionally at baseline and follow-up, and longitudinally. Researchers found no significant mean within-pair difference at baseline in age (mean, 44), weight, and height. Cross-sectional sway measures from posturography and clinical static balance tests showed poorer performance in antiepileptic drug users, compared with nonusers, on several test conditions at baseline and follow-up.

Treatment for symptomatic intracerebral hemorrhage (sICH) after thrombolysis for stroke does not significantly reduce the likelihood of in-hospital mortality or hematoma expansion, according to a retrospective study published online ahead of print October 26 in JAMA Neurology. Of 3,894 patients treated with IV rt-PA within 4.5 hours after onset of ischemic stroke symptoms, 128 had sICH. The median time from initiation of rt-PA to sICH diagnosis was 470 minutes, and the median time from diagnosis to treatment of sICH was 112 minutes. The in-hospital mortality rate was 52.3%, and 26.8% of participants had hematoma expansion. In multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality. Severe hypofibrinogenemia was associated with hematoma expansion and occurred in 36.3% of patients without hematoma expansion.

Gaucher disease or mutations in the β-glucocerebrosidase gene (GBA) may protect individuals from deficiency in visual color discrimination, according to a study published September 14 in Journal of Parkinson’s Disease. Investigators tested groups of patients on the Farnsworth-Munsell 100 hue test (FMHT) and calculated their mean Total Error Scores (TES). Patients were classified as having Parkinson’s disease only, Gaucher disease only, Parkinson’s disease and Gaucher disease, GBA mutations, GBA mutations and Parkinson’s disease, or as controls. Patients with Parkinson’s disease only had the highest mean TES, and patients with Gaucher disease only had the lowest mean TES. GBA carriers without Parkinson’s disease made more errors than patients with Gaucher disease only, which was approximately the same number of errors as healthy controls.

Brain scans of people in a coma may help predict who will regain consciousness, according to a study published online ahead of print November 11 in Neurology. Researchers compared 27 prospectively recruited comatose patients who had severe brain injury (14 with traumatic injury and 13 with anoxic injury) with 14 age-matched healthy participants. Standardized clinical assessment and functional MRI were performed at an average of four days after withdrawal of sedation. Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with posterior cingulate cortex, regardless of etiology of injury. The functional connectivity strength between the posterior cingulate cortex and the medial prefrontal cortex was significantly different between comatose patients who subsequently recovered and those who subsequently scored an unfavorable outcome three months after brain injury.

Raloxifene does not have a significant cognitive effect for women with Alzheimer’s disease, according to a study published online ahead of print November 4 in Neurology. Investigators conducted a randomized, double-blind, placebo-controlled pilot study with a planned treatment period of 12 months. Women with mild to moderate late-onset Alzheimer’s disease were randomized to high-dose (ie, 120 mg) oral raloxifene or identical placebo provided once daily. Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses, and 39 women contributed 12-month outcomes. Results on the Alzheimer’s Disease Assessment Scale, cognitive subscale showed no cognitive benefits in the raloxifene-treated group. Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score.

Nonpharmacologic sleep interventions may help optimize outcomes in patients with chronic pain, according to data published in the November issue of Sleep. Investigators analyzed 11 randomized controlled trials, involving 1,066 participants, that evaluated the effect of nonpharmacologic sleep treatments on self-reported sleep quality, pain, and well-being in patients with long-term pain. They extracted means and standard deviations of sleep quality, pain, fatigue, depression, anxiety, and physical and psychologic functioning for the treatment and control groups at baseline, post treatment, and final follow-up. Nonpharmacologic sleep treatments in patients with chronic pain were associated with a large improvement in sleep quality, a small reduction in pain, and moderate improvement in fatigue at post treatment. The effects on sleep quality and fatigue were maintained for as long as one year, when a moderate reduction in depression also was observed.

CSF biomarkers of angiogenesis are increased in Parkinson’s disease and associated with gait difficulties, blood–­brain barrier dysfunction, white matter lesions, and cerebral microbleeds, according to a study published online ahead of print October 28 in Neurology. This cross-sectional analysis included 38 elderly controls and 100 patients with Parkinson’s disease. Patients with Parkinson’s disease without dementia displayed higher CSF levels of vascular endothelial growth factor, placental growth factor, and vascular endothelial growth factor 2, and lower levels of angiopoietin 2, compared with controls. Similar alterations in vascular endothelial growth factor, placental growth factor, and angiopoietin 2 levels were observed in patients with Parkinson’s disease with dementia. Abnormal angiogenesis may be important in Parkinson’s disease pathogenesis and contribute to dopa-resistant symptoms, said the researchers.

Despite comparable reductions in total sleep time, partial sleep loss from sleep continuity disruption is more detrimental to positive mood than partial sleep loss from delaying bedtime, even when controlling for concomitant increases in negative mood, according to a study published in the November issue of Sleep. Participants were randomized to receive three consecutive nights of sleep continuity disruption by forced nocturnal awakenings, or one of the following two control conditions: restricted sleep opportunity or uninterrupted sleep. Compared with controls with restricted sleep opportunity, participants who underwent forced awakenings had significantly less slow wave sleep after the first night of sleep deprivation, and significantly lower positive mood after the second night of sleep deprivation. The differential change in slow wave sleep statistically mediated the observed group differences in positive mood.

Among patients who underwent transcatheter atrial septal defect closure (ASD), the use of clopidogrel and aspirin, compared with aspirin plus placebo, resulted in a lower monthly frequency of migraine attacks over three months, according to a study published online ahead of print November 9 in JAMA. A total of 171 patients without migraine were randomized to receive dual antiplatelet therapy or single antiplatelet therapy (ie, aspirin and placebo) for three months following transcatheter ASD closure. The mean age of the participants was 49, and 62% were women. Among patients with migraines following the procedure, those who received clopidogrel had less-severe migraine attacks. No patients who received clopidogrel had moderately or severely disabling migraine attacks, and 37% of the placebo group had such attacks.

The Consortium of Multiple Sclerosis Centers (CMSC) has issued a statement asserting that prescribers must retain the right to decide on the best treatment and medication for each patient with MS. “The varied and individualized course of MS mandates full access to symptomatic management as well as disease-modifying therapies, which, in the best judgment of the prescriber, offer optimal treatment outcomes. Medications to treat symptoms are carefully decided on an individual basis and by best-practice regimens,” said the CMSC. “Lack of understanding of the disease course and the challenges of MS treatment result in poor decision making practices by the insurance plans and specialty pharmacies and subsequent denial of prescribed medications.... CMSC proposes a collaborative care model in which providers, patients, and insurers work together to address these concerns.”

APOE4 greatly increases the likelihood of microbleeds in some men, according to a study published online ahead of print October 16 in Neurobiology of Aging. These microbleeds contribute to memory loss. Investigators examined brain scans of 658 participants (ages 48 to 91) in the Alzheimer’s Disease Neuroimaging Initiative. Of those subjects, 402 had mild cognitive impairment (MCI), 90 had early-stage Alzheimer’s disease, and 166 were cognitively normal. Researchers also analyzed scans of 448 other subjects (ages 36 to 88). Of those people, 152 had MCI, 152 had Alzheimer’s disease, and 144 were cognitively normal. Male carriers of APOE4 with MCI or Alzheimer’s disease had twice as many microbleeds in their brains as women with similar diagnoses. Researchers should evaluate whether sex steroids can reduce the microbleeds, said the authors.

The Lewy Body Composite Risk Score (LBCRS) increases the diagnostic probability that Lewy body pathology is contributing to dementia and may improve clinical detection and enrollment for clinical trials, according to a study published September 1 in Alzheimer’s Dementia. The LBCRS was tested in a consecutive series of 256 patients and compared with the Clinical Dementia Rating and gold-standard measures of cognition, motor symptoms, function, and behavior. Mean LBCRS scores were significantly different between patients with dementia with Lewy bodies and those with Alzheimer’s disease. Mean LBCRS scores also were significantly different between patients with mild cognitive impairment (MCI) due to dementia with Lewy bodies and patients with MCI due to Alzheimer’s disease. The LBCRS also was able to discriminate between dementia with Lewy bodies and other causes of dementia.

—Kimberly Williams

The risk of epilepsy is increased in children with hospital-diagnosed pertussis infections, compared with the general population, but the absolute risk is low, according to a Danish study published in the November 3 issue of JAMA. Researchers used data from population-based medical registries covering all Danish hospitals to identify all patients with pertussis born between 1978 and 2011 and followed up through 2011. Investigators used the Civil Registration System to identify 10 individuals from the general population for each patient with pertussis, matched on sex and year of birth. They identified 4,700 patients with pertussis, of whom 90 developed epilepsy during the follow-up. The cumulative incidence of epilepsy at age 10 was 1.7% for patients with pertussis and 0.9% for the matched comparison cohort.

Chronic users of antiepileptic drugs have poorer standing balance, compared with nonusers, according to a longitudinal twin and sibling study published in the November issue of Epilepsia. Researchers studied 26 twin and sibling pairs. Siblings were of the same gender, but only one in each pair had exposure to antiepileptic drugs. Clinical and laboratory balance examinations were conducted twice, and at least one year elapsed between examinations. The mean within-pair differences in balance measures were calculated cross-sectionally at baseline and follow-up, and longitudinally. Researchers found no significant mean within-pair difference at baseline in age (mean, 44), weight, and height. Cross-sectional sway measures from posturography and clinical static balance tests showed poorer performance in antiepileptic drug users, compared with nonusers, on several test conditions at baseline and follow-up.

Treatment for symptomatic intracerebral hemorrhage (sICH) after thrombolysis for stroke does not significantly reduce the likelihood of in-hospital mortality or hematoma expansion, according to a retrospective study published online ahead of print October 26 in JAMA Neurology. Of 3,894 patients treated with IV rt-PA within 4.5 hours after onset of ischemic stroke symptoms, 128 had sICH. The median time from initiation of rt-PA to sICH diagnosis was 470 minutes, and the median time from diagnosis to treatment of sICH was 112 minutes. The in-hospital mortality rate was 52.3%, and 26.8% of participants had hematoma expansion. In multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality. Severe hypofibrinogenemia was associated with hematoma expansion and occurred in 36.3% of patients without hematoma expansion.

Gaucher disease or mutations in the β-glucocerebrosidase gene (GBA) may protect individuals from deficiency in visual color discrimination, according to a study published September 14 in Journal of Parkinson’s Disease. Investigators tested groups of patients on the Farnsworth-Munsell 100 hue test (FMHT) and calculated their mean Total Error Scores (TES). Patients were classified as having Parkinson’s disease only, Gaucher disease only, Parkinson’s disease and Gaucher disease, GBA mutations, GBA mutations and Parkinson’s disease, or as controls. Patients with Parkinson’s disease only had the highest mean TES, and patients with Gaucher disease only had the lowest mean TES. GBA carriers without Parkinson’s disease made more errors than patients with Gaucher disease only, which was approximately the same number of errors as healthy controls.

Brain scans of people in a coma may help predict who will regain consciousness, according to a study published online ahead of print November 11 in Neurology. Researchers compared 27 prospectively recruited comatose patients who had severe brain injury (14 with traumatic injury and 13 with anoxic injury) with 14 age-matched healthy participants. Standardized clinical assessment and functional MRI were performed at an average of four days after withdrawal of sedation. Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with posterior cingulate cortex, regardless of etiology of injury. The functional connectivity strength between the posterior cingulate cortex and the medial prefrontal cortex was significantly different between comatose patients who subsequently recovered and those who subsequently scored an unfavorable outcome three months after brain injury.

Raloxifene does not have a significant cognitive effect for women with Alzheimer’s disease, according to a study published online ahead of print November 4 in Neurology. Investigators conducted a randomized, double-blind, placebo-controlled pilot study with a planned treatment period of 12 months. Women with mild to moderate late-onset Alzheimer’s disease were randomized to high-dose (ie, 120 mg) oral raloxifene or identical placebo provided once daily. Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses, and 39 women contributed 12-month outcomes. Results on the Alzheimer’s Disease Assessment Scale, cognitive subscale showed no cognitive benefits in the raloxifene-treated group. Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score.

Nonpharmacologic sleep interventions may help optimize outcomes in patients with chronic pain, according to data published in the November issue of Sleep. Investigators analyzed 11 randomized controlled trials, involving 1,066 participants, that evaluated the effect of nonpharmacologic sleep treatments on self-reported sleep quality, pain, and well-being in patients with long-term pain. They extracted means and standard deviations of sleep quality, pain, fatigue, depression, anxiety, and physical and psychologic functioning for the treatment and control groups at baseline, post treatment, and final follow-up. Nonpharmacologic sleep treatments in patients with chronic pain were associated with a large improvement in sleep quality, a small reduction in pain, and moderate improvement in fatigue at post treatment. The effects on sleep quality and fatigue were maintained for as long as one year, when a moderate reduction in depression also was observed.

CSF biomarkers of angiogenesis are increased in Parkinson’s disease and associated with gait difficulties, blood–­brain barrier dysfunction, white matter lesions, and cerebral microbleeds, according to a study published online ahead of print October 28 in Neurology. This cross-sectional analysis included 38 elderly controls and 100 patients with Parkinson’s disease. Patients with Parkinson’s disease without dementia displayed higher CSF levels of vascular endothelial growth factor, placental growth factor, and vascular endothelial growth factor 2, and lower levels of angiopoietin 2, compared with controls. Similar alterations in vascular endothelial growth factor, placental growth factor, and angiopoietin 2 levels were observed in patients with Parkinson’s disease with dementia. Abnormal angiogenesis may be important in Parkinson’s disease pathogenesis and contribute to dopa-resistant symptoms, said the researchers.

Despite comparable reductions in total sleep time, partial sleep loss from sleep continuity disruption is more detrimental to positive mood than partial sleep loss from delaying bedtime, even when controlling for concomitant increases in negative mood, according to a study published in the November issue of Sleep. Participants were randomized to receive three consecutive nights of sleep continuity disruption by forced nocturnal awakenings, or one of the following two control conditions: restricted sleep opportunity or uninterrupted sleep. Compared with controls with restricted sleep opportunity, participants who underwent forced awakenings had significantly less slow wave sleep after the first night of sleep deprivation, and significantly lower positive mood after the second night of sleep deprivation. The differential change in slow wave sleep statistically mediated the observed group differences in positive mood.

Among patients who underwent transcatheter atrial septal defect closure (ASD), the use of clopidogrel and aspirin, compared with aspirin plus placebo, resulted in a lower monthly frequency of migraine attacks over three months, according to a study published online ahead of print November 9 in JAMA. A total of 171 patients without migraine were randomized to receive dual antiplatelet therapy or single antiplatelet therapy (ie, aspirin and placebo) for three months following transcatheter ASD closure. The mean age of the participants was 49, and 62% were women. Among patients with migraines following the procedure, those who received clopidogrel had less-severe migraine attacks. No patients who received clopidogrel had moderately or severely disabling migraine attacks, and 37% of the placebo group had such attacks.

The Consortium of Multiple Sclerosis Centers (CMSC) has issued a statement asserting that prescribers must retain the right to decide on the best treatment and medication for each patient with MS. “The varied and individualized course of MS mandates full access to symptomatic management as well as disease-modifying therapies, which, in the best judgment of the prescriber, offer optimal treatment outcomes. Medications to treat symptoms are carefully decided on an individual basis and by best-practice regimens,” said the CMSC. “Lack of understanding of the disease course and the challenges of MS treatment result in poor decision making practices by the insurance plans and specialty pharmacies and subsequent denial of prescribed medications.... CMSC proposes a collaborative care model in which providers, patients, and insurers work together to address these concerns.”

APOE4 greatly increases the likelihood of microbleeds in some men, according to a study published online ahead of print October 16 in Neurobiology of Aging. These microbleeds contribute to memory loss. Investigators examined brain scans of 658 participants (ages 48 to 91) in the Alzheimer’s Disease Neuroimaging Initiative. Of those subjects, 402 had mild cognitive impairment (MCI), 90 had early-stage Alzheimer’s disease, and 166 were cognitively normal. Researchers also analyzed scans of 448 other subjects (ages 36 to 88). Of those people, 152 had MCI, 152 had Alzheimer’s disease, and 144 were cognitively normal. Male carriers of APOE4 with MCI or Alzheimer’s disease had twice as many microbleeds in their brains as women with similar diagnoses. Researchers should evaluate whether sex steroids can reduce the microbleeds, said the authors.

The Lewy Body Composite Risk Score (LBCRS) increases the diagnostic probability that Lewy body pathology is contributing to dementia and may improve clinical detection and enrollment for clinical trials, according to a study published September 1 in Alzheimer’s Dementia. The LBCRS was tested in a consecutive series of 256 patients and compared with the Clinical Dementia Rating and gold-standard measures of cognition, motor symptoms, function, and behavior. Mean LBCRS scores were significantly different between patients with dementia with Lewy bodies and those with Alzheimer’s disease. Mean LBCRS scores also were significantly different between patients with mild cognitive impairment (MCI) due to dementia with Lewy bodies and patients with MCI due to Alzheimer’s disease. The LBCRS also was able to discriminate between dementia with Lewy bodies and other causes of dementia.

—Kimberly Williams

The risk of epilepsy is increased in children with hospital-diagnosed pertussis infections, compared with the general population, but the absolute risk is low, according to a Danish study published in the November 3 issue of JAMA. Researchers used data from population-based medical registries covering all Danish hospitals to identify all patients with pertussis born between 1978 and 2011 and followed up through 2011. Investigators used the Civil Registration System to identify 10 individuals from the general population for each patient with pertussis, matched on sex and year of birth. They identified 4,700 patients with pertussis, of whom 90 developed epilepsy during the follow-up. The cumulative incidence of epilepsy at age 10 was 1.7% for patients with pertussis and 0.9% for the matched comparison cohort.

Chronic users of antiepileptic drugs have poorer standing balance, compared with nonusers, according to a longitudinal twin and sibling study published in the November issue of Epilepsia. Researchers studied 26 twin and sibling pairs. Siblings were of the same gender, but only one in each pair had exposure to antiepileptic drugs. Clinical and laboratory balance examinations were conducted twice, and at least one year elapsed between examinations. The mean within-pair differences in balance measures were calculated cross-sectionally at baseline and follow-up, and longitudinally. Researchers found no significant mean within-pair difference at baseline in age (mean, 44), weight, and height. Cross-sectional sway measures from posturography and clinical static balance tests showed poorer performance in antiepileptic drug users, compared with nonusers, on several test conditions at baseline and follow-up.

Treatment for symptomatic intracerebral hemorrhage (sICH) after thrombolysis for stroke does not significantly reduce the likelihood of in-hospital mortality or hematoma expansion, according to a retrospective study published online ahead of print October 26 in JAMA Neurology. Of 3,894 patients treated with IV rt-PA within 4.5 hours after onset of ischemic stroke symptoms, 128 had sICH. The median time from initiation of rt-PA to sICH diagnosis was 470 minutes, and the median time from diagnosis to treatment of sICH was 112 minutes. The in-hospital mortality rate was 52.3%, and 26.8% of participants had hematoma expansion. In multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality. Severe hypofibrinogenemia was associated with hematoma expansion and occurred in 36.3% of patients without hematoma expansion.

Gaucher disease or mutations in the β-glucocerebrosidase gene (GBA) may protect individuals from deficiency in visual color discrimination, according to a study published September 14 in Journal of Parkinson’s Disease. Investigators tested groups of patients on the Farnsworth-Munsell 100 hue test (FMHT) and calculated their mean Total Error Scores (TES). Patients were classified as having Parkinson’s disease only, Gaucher disease only, Parkinson’s disease and Gaucher disease, GBA mutations, GBA mutations and Parkinson’s disease, or as controls. Patients with Parkinson’s disease only had the highest mean TES, and patients with Gaucher disease only had the lowest mean TES. GBA carriers without Parkinson’s disease made more errors than patients with Gaucher disease only, which was approximately the same number of errors as healthy controls.

Brain scans of people in a coma may help predict who will regain consciousness, according to a study published online ahead of print November 11 in Neurology. Researchers compared 27 prospectively recruited comatose patients who had severe brain injury (14 with traumatic injury and 13 with anoxic injury) with 14 age-matched healthy participants. Standardized clinical assessment and functional MRI were performed at an average of four days after withdrawal of sedation. Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with posterior cingulate cortex, regardless of etiology of injury. The functional connectivity strength between the posterior cingulate cortex and the medial prefrontal cortex was significantly different between comatose patients who subsequently recovered and those who subsequently scored an unfavorable outcome three months after brain injury.

Raloxifene does not have a significant cognitive effect for women with Alzheimer’s disease, according to a study published online ahead of print November 4 in Neurology. Investigators conducted a randomized, double-blind, placebo-controlled pilot study with a planned treatment period of 12 months. Women with mild to moderate late-onset Alzheimer’s disease were randomized to high-dose (ie, 120 mg) oral raloxifene or identical placebo provided once daily. Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses, and 39 women contributed 12-month outcomes. Results on the Alzheimer’s Disease Assessment Scale, cognitive subscale showed no cognitive benefits in the raloxifene-treated group. Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score.

Nonpharmacologic sleep interventions may help optimize outcomes in patients with chronic pain, according to data published in the November issue of Sleep. Investigators analyzed 11 randomized controlled trials, involving 1,066 participants, that evaluated the effect of nonpharmacologic sleep treatments on self-reported sleep quality, pain, and well-being in patients with long-term pain. They extracted means and standard deviations of sleep quality, pain, fatigue, depression, anxiety, and physical and psychologic functioning for the treatment and control groups at baseline, post treatment, and final follow-up. Nonpharmacologic sleep treatments in patients with chronic pain were associated with a large improvement in sleep quality, a small reduction in pain, and moderate improvement in fatigue at post treatment. The effects on sleep quality and fatigue were maintained for as long as one year, when a moderate reduction in depression also was observed.

CSF biomarkers of angiogenesis are increased in Parkinson’s disease and associated with gait difficulties, blood–­brain barrier dysfunction, white matter lesions, and cerebral microbleeds, according to a study published online ahead of print October 28 in Neurology. This cross-sectional analysis included 38 elderly controls and 100 patients with Parkinson’s disease. Patients with Parkinson’s disease without dementia displayed higher CSF levels of vascular endothelial growth factor, placental growth factor, and vascular endothelial growth factor 2, and lower levels of angiopoietin 2, compared with controls. Similar alterations in vascular endothelial growth factor, placental growth factor, and angiopoietin 2 levels were observed in patients with Parkinson’s disease with dementia. Abnormal angiogenesis may be important in Parkinson’s disease pathogenesis and contribute to dopa-resistant symptoms, said the researchers.

Despite comparable reductions in total sleep time, partial sleep loss from sleep continuity disruption is more detrimental to positive mood than partial sleep loss from delaying bedtime, even when controlling for concomitant increases in negative mood, according to a study published in the November issue of Sleep. Participants were randomized to receive three consecutive nights of sleep continuity disruption by forced nocturnal awakenings, or one of the following two control conditions: restricted sleep opportunity or uninterrupted sleep. Compared with controls with restricted sleep opportunity, participants who underwent forced awakenings had significantly less slow wave sleep after the first night of sleep deprivation, and significantly lower positive mood after the second night of sleep deprivation. The differential change in slow wave sleep statistically mediated the observed group differences in positive mood.

Among patients who underwent transcatheter atrial septal defect closure (ASD), the use of clopidogrel and aspirin, compared with aspirin plus placebo, resulted in a lower monthly frequency of migraine attacks over three months, according to a study published online ahead of print November 9 in JAMA. A total of 171 patients without migraine were randomized to receive dual antiplatelet therapy or single antiplatelet therapy (ie, aspirin and placebo) for three months following transcatheter ASD closure. The mean age of the participants was 49, and 62% were women. Among patients with migraines following the procedure, those who received clopidogrel had less-severe migraine attacks. No patients who received clopidogrel had moderately or severely disabling migraine attacks, and 37% of the placebo group had such attacks.

The Consortium of Multiple Sclerosis Centers (CMSC) has issued a statement asserting that prescribers must retain the right to decide on the best treatment and medication for each patient with MS. “The varied and individualized course of MS mandates full access to symptomatic management as well as disease-modifying therapies, which, in the best judgment of the prescriber, offer optimal treatment outcomes. Medications to treat symptoms are carefully decided on an individual basis and by best-practice regimens,” said the CMSC. “Lack of understanding of the disease course and the challenges of MS treatment result in poor decision making practices by the insurance plans and specialty pharmacies and subsequent denial of prescribed medications.... CMSC proposes a collaborative care model in which providers, patients, and insurers work together to address these concerns.”

APOE4 greatly increases the likelihood of microbleeds in some men, according to a study published online ahead of print October 16 in Neurobiology of Aging. These microbleeds contribute to memory loss. Investigators examined brain scans of 658 participants (ages 48 to 91) in the Alzheimer’s Disease Neuroimaging Initiative. Of those subjects, 402 had mild cognitive impairment (MCI), 90 had early-stage Alzheimer’s disease, and 166 were cognitively normal. Researchers also analyzed scans of 448 other subjects (ages 36 to 88). Of those people, 152 had MCI, 152 had Alzheimer’s disease, and 144 were cognitively normal. Male carriers of APOE4 with MCI or Alzheimer’s disease had twice as many microbleeds in their brains as women with similar diagnoses. Researchers should evaluate whether sex steroids can reduce the microbleeds, said the authors.

The Lewy Body Composite Risk Score (LBCRS) increases the diagnostic probability that Lewy body pathology is contributing to dementia and may improve clinical detection and enrollment for clinical trials, according to a study published September 1 in Alzheimer’s Dementia. The LBCRS was tested in a consecutive series of 256 patients and compared with the Clinical Dementia Rating and gold-standard measures of cognition, motor symptoms, function, and behavior. Mean LBCRS scores were significantly different between patients with dementia with Lewy bodies and those with Alzheimer’s disease. Mean LBCRS scores also were significantly different between patients with mild cognitive impairment (MCI) due to dementia with Lewy bodies and patients with MCI due to Alzheimer’s disease. The LBCRS also was able to discriminate between dementia with Lewy bodies and other causes of dementia.

—Kimberly Williams

HLA-DRB1*1501, adolescent summer sun habits, and BMI at the age of 20 independently affect age of multiple sclerosis (MS) onset, according to a study published online ahead of print October 7 in Neurology. This cross-sectional study included 1,161 Danish patients with MS. Lifestyle questionnaires and blood samples for genotyping were collected from all participants from 2009 to 2012. Information on age at onset was obtained from the Danish MS Treatment Registry. Younger age at onset was significantly associated with low exposure to summer sun in adolescence, higher BMI at age 20, and the HLA-DRB1*1501 risk allele in both univariate analyses and in a multivariable regression analysis. No association was found between age at onset and other single-nucleotide polymorphisms studied or vitamin D-associated environmental factors.

Treatment responses for autoimmune ataxia are more likely in patients with nonparaneoplastic disorders and those with exclusively plasma membrane protein (PMP) antibodies, according to a study published online ahead of print September 28 in JAMA Neurology. Investigators examined 118 patients with ataxia who were 18 or older, were seropositive for at least one neural autoantibody, had received at least one immunotherapy or cancer therapy, and had neurologist-reported outcomes documented from January 1, 1989, through December 31, 2013. Fifty-four patients had neurologic improvements. Kaplan-Meier analyses revealed that progression to wheelchair dependence occurred significantly faster among patients with neuronal nuclear or cytoplasmic antibody positivity only, although those with glutamic acid decarboxylase 65-kDa isoform autoimmunity progressed to wheelchair dependence at a rate similar to those with PMP autoimmunity.

Patients with celiac disease are not at increased risk for dementia overall, though they may be at increased risk for vascular dementia, according to a study published online ahead of print September 29 in Journal of Alzheimer’s Disease. Researchers compared the incidence of a subsequent dementia diagnosis among 8,846 older adults with celiac disease to that among 43,474 age- and gender-matched controls. The median age of the study population was 63, and 56% of participants were female. During a median follow-up time of 8.4 years, dementia was diagnosed in 4.3% of patients with celiac disease and 4.4% of controls. The researchers observed an increased risk of dementia in the first year following a diagnosis of celiac disease, but the increased risk was restricted to vascular dementia and was not present for Alzheimer’s dementia.

Infection may trigger childhood arterial ischemic stroke, while routine vaccinations appear to protect against it, according to a study published online ahead of print September 30 in Neurology. This international case–control study included 355 children with confirmed cases of arterial ischemic stroke and 354 controls without stroke. Median age was 7.6 for cases and 9.3 for controls. Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases versus 3% of controls. Infection thus conferred a 6.3-fold increased risk of arterial ischemic stroke. Children with some, few, or no routine vaccinations were at higher stroke risk than those receiving all or most vaccinations. Risk factors for arterial ischemic stroke included infection in the prior week, undervaccination, black race, and rural residence.

Amyloid PET and CSF biomarkers identify early Alzheimer’s disease with equal accuracy, according to a study published October 6 in Neurology. Researchers examined 122 healthy elderly people and 34 patients with mild cognitive impairment who developed Alzheimer’s disease dementia within three years (MCI-AD). They examined β-amyloid deposition in nine brain regions with [¹⁸F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. CSF samples and PET scans each identified approximately 90% of patients who later received a diagnosis of Alzheimer’s disease. The best CSF measures for identifying MCI-AD were Aβ42/total tau and Aβ42/hyperphosphorylated tau, which performed better than CSF Aβ42 and Aβ42/40. CSF Aβ42/total tau had the highest accuracy of all CSF and PET biomarkers. The combination of CSF and PET was not better than either individual biomarker.

A combination of dextromethorphan and quinidine demonstrated clinically relevant efficacy for agitation in patients with probable Alzheimer’s disease and was generally well tolerated, according to a study published September 22 in JAMA. A total of 194 patients completed a preliminary 10-week phase II randomized clinical trial. In the sequential parallel comparison design, 152 patients received dextromethorphan–quinidine, and 127 received placebo. Analysis combining all patients and rerandomized placebo nonresponders showed significantly reduced agitation and aggression scores for dextromethorphan–quinidine versus placebo. Among all patients, mean agitation and aggression scores were reduced from 7.1 to 3.8 with dextromethorphan–quinidine and from 7.0 to 5.3 with placebo. Between-group treatment differences were significant. Among rerandomized placebo nonresponders, agitation and aggression scores were reduced from 5.8 to 3.8 with dextromethorphan–quinidine and from 6.7 to 5.8 with placebo.

The FDA has approved Betaconnect, an electronic autoinjector for the treatment of relapsing-remitting multiple sclerosis. Bayer HealthCare (Whippany, NJ) manufactures Betaconnect, which will be available to patients receiving Betaseron beginning in early 2016. The autoinjector, which was created based on feedback from patients and caregivers, offers customizable injection speed and depth settings that allow patients to administer injections quietly and precisely. Betaconnect also has an optional backup reminder function that tells patients the time of their next injection. In addition, the automatic needle insertion and retraction and a visual and audio end-of-dose indication tell patients when the injection is complete. Patients should speak with a healthcare provider before making any changes to injection depth or speed settings.

In patients with an intracranial pressure of more than 20 mmHg after traumatic brain injury (TBI), therapeutic hypothermia plus standard care to reduce intracranial pressure do not result in outcomes better than those associated with standard care alone, according to a study published online ahead of print October 7 in New England Journal of Medicine. Investigators enrolled 387 patients with TBI from November 2009 through October 2014 in a study. Barbiturates and decompressive craniectomy were required to control intracranial pressure in 54% of patients who received standard care and in 44% of patients who received hypothermia and standard care. The hypothermia group had worse outcomes in general than the standard-care group. A favorable outcome occurred in 26% of patients in the hypothermia group and in 37% of patients in the control group.

Differing manifestations of postconcussion symptoms on functional MRI (fMRI) between younger and older patients indicate that age influences the activation, modulation, and allocation of working memory processing resources after mild traumatic brain injury (MTBI), according to a study published online ahead of print October 6 in Radiology. Researchers performed fMRI exams on 13 young adults and 13 older adults with MTBI and 26 age- and gender-matched controls. Younger patients performing working-memory tasks had initial hyperactivation in the right precuneus and right inferior parietal gyrus, compared with younger controls. Older patients performing these tasks had hypoactivation in the right precuneus and right inferior frontal gyrus, compared with older controls. Younger patients, but not older patients, had partial recovery of activation pattern and decreased postconcussion symptoms at follow-up.

An immune system gene is associated with higher rates of amyloid plaque buildup in the brains of patients with Alzheimer’s disease and older adults at risk for the disease, according to a study published in the October issue of Brain. Investigators performed a genome-wide association study of longitudinal change in brain amyloid burden measured by ¹⁸F-florbetapir PET. They found that interleukin-1 receptor accessory protein (IL1RAP) was associated with higher rates of amyloid accumulation, independent of APOE ε4 status. This novel association was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer’s disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts, rs12053868-G was associated with accelerated cognitive decline and lower cortical ¹¹C-PBR28 PET signal.

For children with tuberous sclerosis complex and medically intractable epilepsy, a greater extent of resection is associated with a greater probability of seizure freedom, according to a study published in the October issue of Neurosurgery. Seventy-four patients were included in this retrospective chart review, and their median age at the time of surgery was 120 months. Engel Class I outcome was achieved in 65% and in 50% of patients at the one- and two-year follow-up, respectively. On univariate analyses, younger age at seizure onset, larger size of predominant tuber, and resection larger than a tuberectomy were associated with a longer duration of seizure freedom. In multivariate analyses, resection larger than a tuberectomy was independently associated with a longer duration of seizure freedom.

A new imaging method that uses a 7-T magnet shows promise in locating hard-to-find epileptic foci by visualizing the neurotransmitter glutamate, according to a study published October 14 in Science Translational Medicine. In a pilot study, researchers applied glutamate chemical exchange saturation transfer (GluCEST) to patients with nonlesional temporal lobe epilepsy based on conventional MRI. GluCEST correctly lateralized the temporal lobe seizure focus on visual and quantitative analyses in all patients. Hippocampal volumes were not significantly different between hemispheres. GluCEST allowed high-resolution functional imaging of brain glutamate and has the potential to identify the epileptic focus in patients previously deemed nonlesional. This method may lead to improved clinical outcomes for temporal lobe epilepsy as well as other localization-related epilepsies, according to the researchers.

—Kimberly Williams

HLA-DRB1*1501, adolescent summer sun habits, and BMI at the age of 20 independently affect age of multiple sclerosis (MS) onset, according to a study published online ahead of print October 7 in Neurology. This cross-sectional study included 1,161 Danish patients with MS. Lifestyle questionnaires and blood samples for genotyping were collected from all participants from 2009 to 2012. Information on age at onset was obtained from the Danish MS Treatment Registry. Younger age at onset was significantly associated with low exposure to summer sun in adolescence, higher BMI at age 20, and the HLA-DRB1*1501 risk allele in both univariate analyses and in a multivariable regression analysis. No association was found between age at onset and other single-nucleotide polymorphisms studied or vitamin D-associated environmental factors.

Treatment responses for autoimmune ataxia are more likely in patients with nonparaneoplastic disorders and those with exclusively plasma membrane protein (PMP) antibodies, according to a study published online ahead of print September 28 in JAMA Neurology. Investigators examined 118 patients with ataxia who were 18 or older, were seropositive for at least one neural autoantibody, had received at least one immunotherapy or cancer therapy, and had neurologist-reported outcomes documented from January 1, 1989, through December 31, 2013. Fifty-four patients had neurologic improvements. Kaplan-Meier analyses revealed that progression to wheelchair dependence occurred significantly faster among patients with neuronal nuclear or cytoplasmic antibody positivity only, although those with glutamic acid decarboxylase 65-kDa isoform autoimmunity progressed to wheelchair dependence at a rate similar to those with PMP autoimmunity.

Patients with celiac disease are not at increased risk for dementia overall, though they may be at increased risk for vascular dementia, according to a study published online ahead of print September 29 in Journal of Alzheimer’s Disease. Researchers compared the incidence of a subsequent dementia diagnosis among 8,846 older adults with celiac disease to that among 43,474 age- and gender-matched controls. The median age of the study population was 63, and 56% of participants were female. During a median follow-up time of 8.4 years, dementia was diagnosed in 4.3% of patients with celiac disease and 4.4% of controls. The researchers observed an increased risk of dementia in the first year following a diagnosis of celiac disease, but the increased risk was restricted to vascular dementia and was not present for Alzheimer’s dementia.

Infection may trigger childhood arterial ischemic stroke, while routine vaccinations appear to protect against it, according to a study published online ahead of print September 30 in Neurology. This international case–control study included 355 children with confirmed cases of arterial ischemic stroke and 354 controls without stroke. Median age was 7.6 for cases and 9.3 for controls. Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases versus 3% of controls. Infection thus conferred a 6.3-fold increased risk of arterial ischemic stroke. Children with some, few, or no routine vaccinations were at higher stroke risk than those receiving all or most vaccinations. Risk factors for arterial ischemic stroke included infection in the prior week, undervaccination, black race, and rural residence.

Amyloid PET and CSF biomarkers identify early Alzheimer’s disease with equal accuracy, according to a study published October 6 in Neurology. Researchers examined 122 healthy elderly people and 34 patients with mild cognitive impairment who developed Alzheimer’s disease dementia within three years (MCI-AD). They examined β-amyloid deposition in nine brain regions with [¹⁸F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. CSF samples and PET scans each identified approximately 90% of patients who later received a diagnosis of Alzheimer’s disease. The best CSF measures for identifying MCI-AD were Aβ42/total tau and Aβ42/hyperphosphorylated tau, which performed better than CSF Aβ42 and Aβ42/40. CSF Aβ42/total tau had the highest accuracy of all CSF and PET biomarkers. The combination of CSF and PET was not better than either individual biomarker.

A combination of dextromethorphan and quinidine demonstrated clinically relevant efficacy for agitation in patients with probable Alzheimer’s disease and was generally well tolerated, according to a study published September 22 in JAMA. A total of 194 patients completed a preliminary 10-week phase II randomized clinical trial. In the sequential parallel comparison design, 152 patients received dextromethorphan–quinidine, and 127 received placebo. Analysis combining all patients and rerandomized placebo nonresponders showed significantly reduced agitation and aggression scores for dextromethorphan–quinidine versus placebo. Among all patients, mean agitation and aggression scores were reduced from 7.1 to 3.8 with dextromethorphan–quinidine and from 7.0 to 5.3 with placebo. Between-group treatment differences were significant. Among rerandomized placebo nonresponders, agitation and aggression scores were reduced from 5.8 to 3.8 with dextromethorphan–quinidine and from 6.7 to 5.8 with placebo.

The FDA has approved Betaconnect, an electronic autoinjector for the treatment of relapsing-remitting multiple sclerosis. Bayer HealthCare (Whippany, NJ) manufactures Betaconnect, which will be available to patients receiving Betaseron beginning in early 2016. The autoinjector, which was created based on feedback from patients and caregivers, offers customizable injection speed and depth settings that allow patients to administer injections quietly and precisely. Betaconnect also has an optional backup reminder function that tells patients the time of their next injection. In addition, the automatic needle insertion and retraction and a visual and audio end-of-dose indication tell patients when the injection is complete. Patients should speak with a healthcare provider before making any changes to injection depth or speed settings.

In patients with an intracranial pressure of more than 20 mmHg after traumatic brain injury (TBI), therapeutic hypothermia plus standard care to reduce intracranial pressure do not result in outcomes better than those associated with standard care alone, according to a study published online ahead of print October 7 in New England Journal of Medicine. Investigators enrolled 387 patients with TBI from November 2009 through October 2014 in a study. Barbiturates and decompressive craniectomy were required to control intracranial pressure in 54% of patients who received standard care and in 44% of patients who received hypothermia and standard care. The hypothermia group had worse outcomes in general than the standard-care group. A favorable outcome occurred in 26% of patients in the hypothermia group and in 37% of patients in the control group.

Differing manifestations of postconcussion symptoms on functional MRI (fMRI) between younger and older patients indicate that age influences the activation, modulation, and allocation of working memory processing resources after mild traumatic brain injury (MTBI), according to a study published online ahead of print October 6 in Radiology. Researchers performed fMRI exams on 13 young adults and 13 older adults with MTBI and 26 age- and gender-matched controls. Younger patients performing working-memory tasks had initial hyperactivation in the right precuneus and right inferior parietal gyrus, compared with younger controls. Older patients performing these tasks had hypoactivation in the right precuneus and right inferior frontal gyrus, compared with older controls. Younger patients, but not older patients, had partial recovery of activation pattern and decreased postconcussion symptoms at follow-up.

An immune system gene is associated with higher rates of amyloid plaque buildup in the brains of patients with Alzheimer’s disease and older adults at risk for the disease, according to a study published in the October issue of Brain. Investigators performed a genome-wide association study of longitudinal change in brain amyloid burden measured by ¹⁸F-florbetapir PET. They found that interleukin-1 receptor accessory protein (IL1RAP) was associated with higher rates of amyloid accumulation, independent of APOE ε4 status. This novel association was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer’s disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts, rs12053868-G was associated with accelerated cognitive decline and lower cortical ¹¹C-PBR28 PET signal.

For children with tuberous sclerosis complex and medically intractable epilepsy, a greater extent of resection is associated with a greater probability of seizure freedom, according to a study published in the October issue of Neurosurgery. Seventy-four patients were included in this retrospective chart review, and their median age at the time of surgery was 120 months. Engel Class I outcome was achieved in 65% and in 50% of patients at the one- and two-year follow-up, respectively. On univariate analyses, younger age at seizure onset, larger size of predominant tuber, and resection larger than a tuberectomy were associated with a longer duration of seizure freedom. In multivariate analyses, resection larger than a tuberectomy was independently associated with a longer duration of seizure freedom.

A new imaging method that uses a 7-T magnet shows promise in locating hard-to-find epileptic foci by visualizing the neurotransmitter glutamate, according to a study published October 14 in Science Translational Medicine. In a pilot study, researchers applied glutamate chemical exchange saturation transfer (GluCEST) to patients with nonlesional temporal lobe epilepsy based on conventional MRI. GluCEST correctly lateralized the temporal lobe seizure focus on visual and quantitative analyses in all patients. Hippocampal volumes were not significantly different between hemispheres. GluCEST allowed high-resolution functional imaging of brain glutamate and has the potential to identify the epileptic focus in patients previously deemed nonlesional. This method may lead to improved clinical outcomes for temporal lobe epilepsy as well as other localization-related epilepsies, according to the researchers.

—Kimberly Williams

HLA-DRB1*1501, adolescent summer sun habits, and BMI at the age of 20 independently affect age of multiple sclerosis (MS) onset, according to a study published online ahead of print October 7 in Neurology. This cross-sectional study included 1,161 Danish patients with MS. Lifestyle questionnaires and blood samples for genotyping were collected from all participants from 2009 to 2012. Information on age at onset was obtained from the Danish MS Treatment Registry. Younger age at onset was significantly associated with low exposure to summer sun in adolescence, higher BMI at age 20, and the HLA-DRB1*1501 risk allele in both univariate analyses and in a multivariable regression analysis. No association was found between age at onset and other single-nucleotide polymorphisms studied or vitamin D-associated environmental factors.

Treatment responses for autoimmune ataxia are more likely in patients with nonparaneoplastic disorders and those with exclusively plasma membrane protein (PMP) antibodies, according to a study published online ahead of print September 28 in JAMA Neurology. Investigators examined 118 patients with ataxia who were 18 or older, were seropositive for at least one neural autoantibody, had received at least one immunotherapy or cancer therapy, and had neurologist-reported outcomes documented from January 1, 1989, through December 31, 2013. Fifty-four patients had neurologic improvements. Kaplan-Meier analyses revealed that progression to wheelchair dependence occurred significantly faster among patients with neuronal nuclear or cytoplasmic antibody positivity only, although those with glutamic acid decarboxylase 65-kDa isoform autoimmunity progressed to wheelchair dependence at a rate similar to those with PMP autoimmunity.

Patients with celiac disease are not at increased risk for dementia overall, though they may be at increased risk for vascular dementia, according to a study published online ahead of print September 29 in Journal of Alzheimer’s Disease. Researchers compared the incidence of a subsequent dementia diagnosis among 8,846 older adults with celiac disease to that among 43,474 age- and gender-matched controls. The median age of the study population was 63, and 56% of participants were female. During a median follow-up time of 8.4 years, dementia was diagnosed in 4.3% of patients with celiac disease and 4.4% of controls. The researchers observed an increased risk of dementia in the first year following a diagnosis of celiac disease, but the increased risk was restricted to vascular dementia and was not present for Alzheimer’s dementia.

Infection may trigger childhood arterial ischemic stroke, while routine vaccinations appear to protect against it, according to a study published online ahead of print September 30 in Neurology. This international case–control study included 355 children with confirmed cases of arterial ischemic stroke and 354 controls without stroke. Median age was 7.6 for cases and 9.3 for controls. Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases versus 3% of controls. Infection thus conferred a 6.3-fold increased risk of arterial ischemic stroke. Children with some, few, or no routine vaccinations were at higher stroke risk than those receiving all or most vaccinations. Risk factors for arterial ischemic stroke included infection in the prior week, undervaccination, black race, and rural residence.

Amyloid PET and CSF biomarkers identify early Alzheimer’s disease with equal accuracy, according to a study published October 6 in Neurology. Researchers examined 122 healthy elderly people and 34 patients with mild cognitive impairment who developed Alzheimer’s disease dementia within three years (MCI-AD). They examined β-amyloid deposition in nine brain regions with [¹⁸F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. CSF samples and PET scans each identified approximately 90% of patients who later received a diagnosis of Alzheimer’s disease. The best CSF measures for identifying MCI-AD were Aβ42/total tau and Aβ42/hyperphosphorylated tau, which performed better than CSF Aβ42 and Aβ42/40. CSF Aβ42/total tau had the highest accuracy of all CSF and PET biomarkers. The combination of CSF and PET was not better than either individual biomarker.

A combination of dextromethorphan and quinidine demonstrated clinically relevant efficacy for agitation in patients with probable Alzheimer’s disease and was generally well tolerated, according to a study published September 22 in JAMA. A total of 194 patients completed a preliminary 10-week phase II randomized clinical trial. In the sequential parallel comparison design, 152 patients received dextromethorphan–quinidine, and 127 received placebo. Analysis combining all patients and rerandomized placebo nonresponders showed significantly reduced agitation and aggression scores for dextromethorphan–quinidine versus placebo. Among all patients, mean agitation and aggression scores were reduced from 7.1 to 3.8 with dextromethorphan–quinidine and from 7.0 to 5.3 with placebo. Between-group treatment differences were significant. Among rerandomized placebo nonresponders, agitation and aggression scores were reduced from 5.8 to 3.8 with dextromethorphan–quinidine and from 6.7 to 5.8 with placebo.

The FDA has approved Betaconnect, an electronic autoinjector for the treatment of relapsing-remitting multiple sclerosis. Bayer HealthCare (Whippany, NJ) manufactures Betaconnect, which will be available to patients receiving Betaseron beginning in early 2016. The autoinjector, which was created based on feedback from patients and caregivers, offers customizable injection speed and depth settings that allow patients to administer injections quietly and precisely. Betaconnect also has an optional backup reminder function that tells patients the time of their next injection. In addition, the automatic needle insertion and retraction and a visual and audio end-of-dose indication tell patients when the injection is complete. Patients should speak with a healthcare provider before making any changes to injection depth or speed settings.

In patients with an intracranial pressure of more than 20 mmHg after traumatic brain injury (TBI), therapeutic hypothermia plus standard care to reduce intracranial pressure do not result in outcomes better than those associated with standard care alone, according to a study published online ahead of print October 7 in New England Journal of Medicine. Investigators enrolled 387 patients with TBI from November 2009 through October 2014 in a study. Barbiturates and decompressive craniectomy were required to control intracranial pressure in 54% of patients who received standard care and in 44% of patients who received hypothermia and standard care. The hypothermia group had worse outcomes in general than the standard-care group. A favorable outcome occurred in 26% of patients in the hypothermia group and in 37% of patients in the control group.

Differing manifestations of postconcussion symptoms on functional MRI (fMRI) between younger and older patients indicate that age influences the activation, modulation, and allocation of working memory processing resources after mild traumatic brain injury (MTBI), according to a study published online ahead of print October 6 in Radiology. Researchers performed fMRI exams on 13 young adults and 13 older adults with MTBI and 26 age- and gender-matched controls. Younger patients performing working-memory tasks had initial hyperactivation in the right precuneus and right inferior parietal gyrus, compared with younger controls. Older patients performing these tasks had hypoactivation in the right precuneus and right inferior frontal gyrus, compared with older controls. Younger patients, but not older patients, had partial recovery of activation pattern and decreased postconcussion symptoms at follow-up.

An immune system gene is associated with higher rates of amyloid plaque buildup in the brains of patients with Alzheimer’s disease and older adults at risk for the disease, according to a study published in the October issue of Brain. Investigators performed a genome-wide association study of longitudinal change in brain amyloid burden measured by ¹⁸F-florbetapir PET. They found that interleukin-1 receptor accessory protein (IL1RAP) was associated with higher rates of amyloid accumulation, independent of APOE ε4 status. This novel association was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer’s disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts, rs12053868-G was associated with accelerated cognitive decline and lower cortical ¹¹C-PBR28 PET signal.

For children with tuberous sclerosis complex and medically intractable epilepsy, a greater extent of resection is associated with a greater probability of seizure freedom, according to a study published in the October issue of Neurosurgery. Seventy-four patients were included in this retrospective chart review, and their median age at the time of surgery was 120 months. Engel Class I outcome was achieved in 65% and in 50% of patients at the one- and two-year follow-up, respectively. On univariate analyses, younger age at seizure onset, larger size of predominant tuber, and resection larger than a tuberectomy were associated with a longer duration of seizure freedom. In multivariate analyses, resection larger than a tuberectomy was independently associated with a longer duration of seizure freedom.

A new imaging method that uses a 7-T magnet shows promise in locating hard-to-find epileptic foci by visualizing the neurotransmitter glutamate, according to a study published October 14 in Science Translational Medicine. In a pilot study, researchers applied glutamate chemical exchange saturation transfer (GluCEST) to patients with nonlesional temporal lobe epilepsy based on conventional MRI. GluCEST correctly lateralized the temporal lobe seizure focus on visual and quantitative analyses in all patients. Hippocampal volumes were not significantly different between hemispheres. GluCEST allowed high-resolution functional imaging of brain glutamate and has the potential to identify the epileptic focus in patients previously deemed nonlesional. This method may lead to improved clinical outcomes for temporal lobe epilepsy as well as other localization-related epilepsies, according to the researchers.

—Kimberly Williams

Low vitamin D status was associated with accelerated decline in cognitive function in an ethnically diverse older population, according to data published online ahead of print September 14 in JAMA Neurology. Individuals with low vitamin D declined, on average, at a rate two to three times faster than those with adequate vitamin D levels, said the researchers. Serum 25-hydroxyvitamin D was measured at baseline and at five yearly follow-up visits in a longitudinal, multiethnic cohort of 382 patients in an outpatient clinic. Mean age was 75.5. “Independent of race or ethnicity, baseline cognitive abilities, and a host of other risk factors, vitamin D insufficiency was associated with significantly faster declines in both episodic memory and executive function performance,” the researchers reported. “This work, and that of others, suggests that there is enough evidence to recommend that people in their 60s and older discuss taking a daily vitamin D supplement with their physicians.”

Being overweight or obese may be linked to an increased risk of meningioma, according to a meta-analysis published online ahead of print September 16 in Neurology. The meta-analysis looked at available research on BMI, physical activity, and the two most common types of brain tumors—meningioma and glioma. A total of 12 studies on BMI and six on physical activity were analyzed, involving 2,982 meningioma cases and 3,057 glioma cases. Compared with people with a normal weight, overweight people were 21% more likely to develop a meningioma, and obese people were 54% more likely to develop one. “This is an important finding, since there are few known risk 
factors for meningioma, and the ones we do know about are not things a person can change,” said the investigators. No relationship was found between excess weight and glioma.

Working long hours is linked to an increased risk of stroke and coronary heart disease, compared with working a standard work week, according to research published online ahead of print August 19 in Lancet. Researchers performed a meta-analysis of published studies and unpublished individual-level data examining the effects of longer working hours on cardiovascular disease. Analysis of data from 25 studies involving 603,838 men and women from Europe, the USA, and Australia found a 13% increased risk of incident coronary heart disease in people working 55 or more hours per week, compared with those working a 35- to 40-hour work week. Analysis of data from 17 studies involving 528,908 men and women found a 1.3-times higher risk of stroke in individuals working longer hours per week, compared with those working standard hours. The association remained after controlling for smoking, alcohol consumption, and physical activity, as well as cardiovascular risk factors such as hypertension and high cholesterol.

FDA approved a new indication for Sunovion’s Aptiom (eslicarbazepine acetate): monotherapy for the treatment of partial-onset seizures. Aptiom was approved in 2013 as adjunctive therapy for partial-onset seizures. The new indication approval is based on the results of two phase III trials. Data from the monotherapy trials, in addition to the data generated from the adjunctive trials, confirm that the drug is efficacious and well-tolerated as adjunctive or monotherapy treatment within a daily dose range of 800 to 1,600 mg. The phase III trials evaluated eslicarbazepine acetate (1,600 mg/day or 1,200 mg/day) as monotherapy for partial-onset seizures in patients age 16 or older whose seizures were not well controlled with other antiepileptic drugs (AEDs). Conversion to eslicarbazepine acetate monotherapy was associated with favorable seizure control, compared with historical controls in patients with partial-onset seizures not well controlled by one or two AEDs.

Results of a hospital-based study published online ahead of print August 19 in Neurology offer clinical recommendations regarding acute headache in pregnant women. The investigators conducted a five-year, single-center, retrospective study of consecutive pregnant women presenting to acute care with headache and receiving a neurologic consultation. Their study cohort included 140 women (mean age, 29) who often presented in the third trimester (56.4%). Diagnoses included primary (65%) and secondary (35%) headache disorders. The most common primary headache disorder was migraine (91.2%), and secondary headache disorders were hypertensive disorders. The authors recommend that diagnostic vigilance be heightened in the absence of a headache history and if seizures, hypertension, or fever are present. Attack features may not adequately distinguish primary versus secondary disorders, and low thresholds for neuroimaging and monitoring for preeclampsia are justified, 
they said.

Short sleepers are four times more likely to catch a cold when exposed to the virus, compared with those who sleep longer, according to a study published in the September issue of Sleep. Researchers recruited 164 volunteers between 2007 and 2011. The recruits underwent two months of health screening, interviews, and questionnaires to establish baselines for stress, temperament, and alcohol and cigarette use. Researchers also measured participants’ normal sleep habits one week prior to sequestering them and administering the cold virus. Subjects who slept less than six hours per night were 4.2 times more likely to catch the cold, compared with those who got more than seven hours of sleep, and those who slept less than five hours were 4.5 times more likely to get sick.

Over the long term, a high dose of a purified form of resveratrol stabilizes a biomarker of Alzheimer’s disease progression, according to clinical trial results published online ahead of print September 11 in Neurology. Resveratrol is a naturally occurring compound found in foods such as red grapes, raspberries, dark chocolate, and some red wines. The randomized, phase II, placebo-controlled, double-blind study enrolled 119 patients with mild to moderate Alzheimer’s disease. The highest dose tested was 1 g orally twice per day. Patients who were treated with increasing doses of resveratrol over 12 months showed little or no change in amyloid-beta40 levels in blood and CSF. Those taking placebo had a decrease in the their levels of amyloid-beta40 over baseline. “We can’t conclude from this study that the effects of resveratrol treatment are beneficial,” said the investigators, but “it does appear that resveratrol was able to penetrate the blood–brain barrier, which is an important observation.”

Survivors of an intracerebral hemorrhage (ICH) who had inadequate blood pressure control during follow-up had a higher risk of ICH recurrence, according to a study in the September 1 issue of JAMA. This association was stronger with worsening severity of hypertension. Investigators studied 1,145 patients with ICH who survived at least 90 days. Median follow-up was 37 months. Blood pressure measurements were obtained at three, six, nine, and 12 months, and every six months thereafter. There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up, adequate blood pressure control was achieved on at least one measurement by 625 patients (55%) and consistently by 495 patients (43%). The ICH event rate for lobar and nonlobar ICH was higher among patients with inadequate blood pressure control, compared with patients with adequate blood pressure control.

Genetic findings support observational evidence that lower vitamin D levels are associated with increased risk of multiple sclerosis (MS), according to a study published online August 25 in PLOS Medicine. Using Mendelian randomization to reduce the possibility of confounding, the researchers examined whether there was an association between genetically reduced vitamin D levels and susceptibility to MS among participants in the International MS Genetics Consortium Study, which involves 14,498 patients with MS and 24,091 healthy controls. A genetic decrease in the natural-log-transformed vitamin D level by one standard deviation was associated with a twofold increased risk of MS. According to the researchers, “genetically lowered vitamin D levels are strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay or prevent MS onset merits further investigation.”

Diabetes may be linked to the buildup of tangles or tau in the brain, separate from Alzheimer’s disease, according to a study published online ahead of print September 2 in Neurology. The study involved 816 people (average age, 74). Of those, 397 had mild cognitive impairment, 191 had Alzheimer’s disease dementia, and 228 people had no memory or cognitive problems. A total of 124 people had diabetes. The researchers examined the relationship between type 2 diabetes, the loss of brain cells and their connections, levels of beta amyloid, and tau in the spinal fluid of the participants. Those with diabetes had on average 16 pg/mL greater levels of tau in the spinal and brain fluid, irrespective of the diagnosis of dementia. In addition, patients with diabetes had cortical tissue that was an average of 0.03 mm thinner than that of those who did not have diabetes, regardless of their cognitive abilities or dementia status.

Survivors of childhood cancer who have had a stroke have double the risk of a recurrent stroke when compared with noncancer stroke survivors, according to a study published online ahead of print August 26 in Neurology. The main predictors of recurrent stroke were cranial radiation therapy, hypertension, and older age at first stroke. Researchers analyzed retrospective data from the Childhood Cancer Survivor Study, which followed 14,358 survivors of pediatric cancer. Stroke rates were established through surveys and self-report. Of the 271 respondents who reported having a stroke, 70 also reported a second stroke. Overall, the rate of recurrence within the first 10 years after an initial stroke was 21%, which is double the rate in the general population of stroke survivors. The rate was 33% for patients who had received cranial radiation therapy.

—Glenn S. Williams

Low vitamin D status was associated with accelerated decline in cognitive function in an ethnically diverse older population, according to data published online ahead of print September 14 in JAMA Neurology. Individuals with low vitamin D declined, on average, at a rate two to three times faster than those with adequate vitamin D levels, said the researchers. Serum 25-hydroxyvitamin D was measured at baseline and at five yearly follow-up visits in a longitudinal, multiethnic cohort of 382 patients in an outpatient clinic. Mean age was 75.5. “Independent of race or ethnicity, baseline cognitive abilities, and a host of other risk factors, vitamin D insufficiency was associated with significantly faster declines in both episodic memory and executive function performance,” the researchers reported. “This work, and that of others, suggests that there is enough evidence to recommend that people in their 60s and older discuss taking a daily vitamin D supplement with their physicians.”

Being overweight or obese may be linked to an increased risk of meningioma, according to a meta-analysis published online ahead of print September 16 in Neurology. The meta-analysis looked at available research on BMI, physical activity, and the two most common types of brain tumors—meningioma and glioma. A total of 12 studies on BMI and six on physical activity were analyzed, involving 2,982 meningioma cases and 3,057 glioma cases. Compared with people with a normal weight, overweight people were 21% more likely to develop a meningioma, and obese people were 54% more likely to develop one. “This is an important finding, since there are few known risk 
factors for meningioma, and the ones we do know about are not things a person can change,” said the investigators. No relationship was found between excess weight and glioma.

Working long hours is linked to an increased risk of stroke and coronary heart disease, compared with working a standard work week, according to research published online ahead of print August 19 in Lancet. Researchers performed a meta-analysis of published studies and unpublished individual-level data examining the effects of longer working hours on cardiovascular disease. Analysis of data from 25 studies involving 603,838 men and women from Europe, the USA, and Australia found a 13% increased risk of incident coronary heart disease in people working 55 or more hours per week, compared with those working a 35- to 40-hour work week. Analysis of data from 17 studies involving 528,908 men and women found a 1.3-times higher risk of stroke in individuals working longer hours per week, compared with those working standard hours. The association remained after controlling for smoking, alcohol consumption, and physical activity, as well as cardiovascular risk factors such as hypertension and high cholesterol.

FDA approved a new indication for Sunovion’s Aptiom (eslicarbazepine acetate): monotherapy for the treatment of partial-onset seizures. Aptiom was approved in 2013 as adjunctive therapy for partial-onset seizures. The new indication approval is based on the results of two phase III trials. Data from the monotherapy trials, in addition to the data generated from the adjunctive trials, confirm that the drug is efficacious and well-tolerated as adjunctive or monotherapy treatment within a daily dose range of 800 to 1,600 mg. The phase III trials evaluated eslicarbazepine acetate (1,600 mg/day or 1,200 mg/day) as monotherapy for partial-onset seizures in patients age 16 or older whose seizures were not well controlled with other antiepileptic drugs (AEDs). Conversion to eslicarbazepine acetate monotherapy was associated with favorable seizure control, compared with historical controls in patients with partial-onset seizures not well controlled by one or two AEDs.

Results of a hospital-based study published online ahead of print August 19 in Neurology offer clinical recommendations regarding acute headache in pregnant women. The investigators conducted a five-year, single-center, retrospective study of consecutive pregnant women presenting to acute care with headache and receiving a neurologic consultation. Their study cohort included 140 women (mean age, 29) who often presented in the third trimester (56.4%). Diagnoses included primary (65%) and secondary (35%) headache disorders. The most common primary headache disorder was migraine (91.2%), and secondary headache disorders were hypertensive disorders. The authors recommend that diagnostic vigilance be heightened in the absence of a headache history and if seizures, hypertension, or fever are present. Attack features may not adequately distinguish primary versus secondary disorders, and low thresholds for neuroimaging and monitoring for preeclampsia are justified, 
they said.

Short sleepers are four times more likely to catch a cold when exposed to the virus, compared with those who sleep longer, according to a study published in the September issue of Sleep. Researchers recruited 164 volunteers between 2007 and 2011. The recruits underwent two months of health screening, interviews, and questionnaires to establish baselines for stress, temperament, and alcohol and cigarette use. Researchers also measured participants’ normal sleep habits one week prior to sequestering them and administering the cold virus. Subjects who slept less than six hours per night were 4.2 times more likely to catch the cold, compared with those who got more than seven hours of sleep, and those who slept less than five hours were 4.5 times more likely to get sick.

Over the long term, a high dose of a purified form of resveratrol stabilizes a biomarker of Alzheimer’s disease progression, according to clinical trial results published online ahead of print September 11 in Neurology. Resveratrol is a naturally occurring compound found in foods such as red grapes, raspberries, dark chocolate, and some red wines. The randomized, phase II, placebo-controlled, double-blind study enrolled 119 patients with mild to moderate Alzheimer’s disease. The highest dose tested was 1 g orally twice per day. Patients who were treated with increasing doses of resveratrol over 12 months showed little or no change in amyloid-beta40 levels in blood and CSF. Those taking placebo had a decrease in the their levels of amyloid-beta40 over baseline. “We can’t conclude from this study that the effects of resveratrol treatment are beneficial,” said the investigators, but “it does appear that resveratrol was able to penetrate the blood–brain barrier, which is an important observation.”

Survivors of an intracerebral hemorrhage (ICH) who had inadequate blood pressure control during follow-up had a higher risk of ICH recurrence, according to a study in the September 1 issue of JAMA. This association was stronger with worsening severity of hypertension. Investigators studied 1,145 patients with ICH who survived at least 90 days. Median follow-up was 37 months. Blood pressure measurements were obtained at three, six, nine, and 12 months, and every six months thereafter. There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up, adequate blood pressure control was achieved on at least one measurement by 625 patients (55%) and consistently by 495 patients (43%). The ICH event rate for lobar and nonlobar ICH was higher among patients with inadequate blood pressure control, compared with patients with adequate blood pressure control.

Genetic findings support observational evidence that lower vitamin D levels are associated with increased risk of multiple sclerosis (MS), according to a study published online August 25 in PLOS Medicine. Using Mendelian randomization to reduce the possibility of confounding, the researchers examined whether there was an association between genetically reduced vitamin D levels and susceptibility to MS among participants in the International MS Genetics Consortium Study, which involves 14,498 patients with MS and 24,091 healthy controls. A genetic decrease in the natural-log-transformed vitamin D level by one standard deviation was associated with a twofold increased risk of MS. According to the researchers, “genetically lowered vitamin D levels are strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay or prevent MS onset merits further investigation.”

Diabetes may be linked to the buildup of tangles or tau in the brain, separate from Alzheimer’s disease, according to a study published online ahead of print September 2 in Neurology. The study involved 816 people (average age, 74). Of those, 397 had mild cognitive impairment, 191 had Alzheimer’s disease dementia, and 228 people had no memory or cognitive problems. A total of 124 people had diabetes. The researchers examined the relationship between type 2 diabetes, the loss of brain cells and their connections, levels of beta amyloid, and tau in the spinal fluid of the participants. Those with diabetes had on average 16 pg/mL greater levels of tau in the spinal and brain fluid, irrespective of the diagnosis of dementia. In addition, patients with diabetes had cortical tissue that was an average of 0.03 mm thinner than that of those who did not have diabetes, regardless of their cognitive abilities or dementia status.

Survivors of childhood cancer who have had a stroke have double the risk of a recurrent stroke when compared with noncancer stroke survivors, according to a study published online ahead of print August 26 in Neurology. The main predictors of recurrent stroke were cranial radiation therapy, hypertension, and older age at first stroke. Researchers analyzed retrospective data from the Childhood Cancer Survivor Study, which followed 14,358 survivors of pediatric cancer. Stroke rates were established through surveys and self-report. Of the 271 respondents who reported having a stroke, 70 also reported a second stroke. Overall, the rate of recurrence within the first 10 years after an initial stroke was 21%, which is double the rate in the general population of stroke survivors. The rate was 33% for patients who had received cranial radiation therapy.

—Glenn S. Williams

Low vitamin D status was associated with accelerated decline in cognitive function in an ethnically diverse older population, according to data published online ahead of print September 14 in JAMA Neurology. Individuals with low vitamin D declined, on average, at a rate two to three times faster than those with adequate vitamin D levels, said the researchers. Serum 25-hydroxyvitamin D was measured at baseline and at five yearly follow-up visits in a longitudinal, multiethnic cohort of 382 patients in an outpatient clinic. Mean age was 75.5. “Independent of race or ethnicity, baseline cognitive abilities, and a host of other risk factors, vitamin D insufficiency was associated with significantly faster declines in both episodic memory and executive function performance,” the researchers reported. “This work, and that of others, suggests that there is enough evidence to recommend that people in their 60s and older discuss taking a daily vitamin D supplement with their physicians.”

Being overweight or obese may be linked to an increased risk of meningioma, according to a meta-analysis published online ahead of print September 16 in Neurology. The meta-analysis looked at available research on BMI, physical activity, and the two most common types of brain tumors—meningioma and glioma. A total of 12 studies on BMI and six on physical activity were analyzed, involving 2,982 meningioma cases and 3,057 glioma cases. Compared with people with a normal weight, overweight people were 21% more likely to develop a meningioma, and obese people were 54% more likely to develop one. “This is an important finding, since there are few known risk 
factors for meningioma, and the ones we do know about are not things a person can change,” said the investigators. No relationship was found between excess weight and glioma.

Working long hours is linked to an increased risk of stroke and coronary heart disease, compared with working a standard work week, according to research published online ahead of print August 19 in Lancet. Researchers performed a meta-analysis of published studies and unpublished individual-level data examining the effects of longer working hours on cardiovascular disease. Analysis of data from 25 studies involving 603,838 men and women from Europe, the USA, and Australia found a 13% increased risk of incident coronary heart disease in people working 55 or more hours per week, compared with those working a 35- to 40-hour work week. Analysis of data from 17 studies involving 528,908 men and women found a 1.3-times higher risk of stroke in individuals working longer hours per week, compared with those working standard hours. The association remained after controlling for smoking, alcohol consumption, and physical activity, as well as cardiovascular risk factors such as hypertension and high cholesterol.

FDA approved a new indication for Sunovion’s Aptiom (eslicarbazepine acetate): monotherapy for the treatment of partial-onset seizures. Aptiom was approved in 2013 as adjunctive therapy for partial-onset seizures. The new indication approval is based on the results of two phase III trials. Data from the monotherapy trials, in addition to the data generated from the adjunctive trials, confirm that the drug is efficacious and well-tolerated as adjunctive or monotherapy treatment within a daily dose range of 800 to 1,600 mg. The phase III trials evaluated eslicarbazepine acetate (1,600 mg/day or 1,200 mg/day) as monotherapy for partial-onset seizures in patients age 16 or older whose seizures were not well controlled with other antiepileptic drugs (AEDs). Conversion to eslicarbazepine acetate monotherapy was associated with favorable seizure control, compared with historical controls in patients with partial-onset seizures not well controlled by one or two AEDs.

Results of a hospital-based study published online ahead of print August 19 in Neurology offer clinical recommendations regarding acute headache in pregnant women. The investigators conducted a five-year, single-center, retrospective study of consecutive pregnant women presenting to acute care with headache and receiving a neurologic consultation. Their study cohort included 140 women (mean age, 29) who often presented in the third trimester (56.4%). Diagnoses included primary (65%) and secondary (35%) headache disorders. The most common primary headache disorder was migraine (91.2%), and secondary headache disorders were hypertensive disorders. The authors recommend that diagnostic vigilance be heightened in the absence of a headache history and if seizures, hypertension, or fever are present. Attack features may not adequately distinguish primary versus secondary disorders, and low thresholds for neuroimaging and monitoring for preeclampsia are justified, 
they said.

Short sleepers are four times more likely to catch a cold when exposed to the virus, compared with those who sleep longer, according to a study published in the September issue of Sleep. Researchers recruited 164 volunteers between 2007 and 2011. The recruits underwent two months of health screening, interviews, and questionnaires to establish baselines for stress, temperament, and alcohol and cigarette use. Researchers also measured participants’ normal sleep habits one week prior to sequestering them and administering the cold virus. Subjects who slept less than six hours per night were 4.2 times more likely to catch the cold, compared with those who got more than seven hours of sleep, and those who slept less than five hours were 4.5 times more likely to get sick.

Over the long term, a high dose of a purified form of resveratrol stabilizes a biomarker of Alzheimer’s disease progression, according to clinical trial results published online ahead of print September 11 in Neurology. Resveratrol is a naturally occurring compound found in foods such as red grapes, raspberries, dark chocolate, and some red wines. The randomized, phase II, placebo-controlled, double-blind study enrolled 119 patients with mild to moderate Alzheimer’s disease. The highest dose tested was 1 g orally twice per day. Patients who were treated with increasing doses of resveratrol over 12 months showed little or no change in amyloid-beta40 levels in blood and CSF. Those taking placebo had a decrease in the their levels of amyloid-beta40 over baseline. “We can’t conclude from this study that the effects of resveratrol treatment are beneficial,” said the investigators, but “it does appear that resveratrol was able to penetrate the blood–brain barrier, which is an important observation.”

Survivors of an intracerebral hemorrhage (ICH) who had inadequate blood pressure control during follow-up had a higher risk of ICH recurrence, according to a study in the September 1 issue of JAMA. This association was stronger with worsening severity of hypertension. Investigators studied 1,145 patients with ICH who survived at least 90 days. Median follow-up was 37 months. Blood pressure measurements were obtained at three, six, nine, and 12 months, and every six months thereafter. There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up, adequate blood pressure control was achieved on at least one measurement by 625 patients (55%) and consistently by 495 patients (43%). The ICH event rate for lobar and nonlobar ICH was higher among patients with inadequate blood pressure control, compared with patients with adequate blood pressure control.

Genetic findings support observational evidence that lower vitamin D levels are associated with increased risk of multiple sclerosis (MS), according to a study published online August 25 in PLOS Medicine. Using Mendelian randomization to reduce the possibility of confounding, the researchers examined whether there was an association between genetically reduced vitamin D levels and susceptibility to MS among participants in the International MS Genetics Consortium Study, which involves 14,498 patients with MS and 24,091 healthy controls. A genetic decrease in the natural-log-transformed vitamin D level by one standard deviation was associated with a twofold increased risk of MS. According to the researchers, “genetically lowered vitamin D levels are strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay or prevent MS onset merits further investigation.”

Diabetes may be linked to the buildup of tangles or tau in the brain, separate from Alzheimer’s disease, according to a study published online ahead of print September 2 in Neurology. The study involved 816 people (average age, 74). Of those, 397 had mild cognitive impairment, 191 had Alzheimer’s disease dementia, and 228 people had no memory or cognitive problems. A total of 124 people had diabetes. The researchers examined the relationship between type 2 diabetes, the loss of brain cells and their connections, levels of beta amyloid, and tau in the spinal fluid of the participants. Those with diabetes had on average 16 pg/mL greater levels of tau in the spinal and brain fluid, irrespective of the diagnosis of dementia. In addition, patients with diabetes had cortical tissue that was an average of 0.03 mm thinner than that of those who did not have diabetes, regardless of their cognitive abilities or dementia status.

Survivors of childhood cancer who have had a stroke have double the risk of a recurrent stroke when compared with noncancer stroke survivors, according to a study published online ahead of print August 26 in Neurology. The main predictors of recurrent stroke were cranial radiation therapy, hypertension, and older age at first stroke. Researchers analyzed retrospective data from the Childhood Cancer Survivor Study, which followed 14,358 survivors of pediatric cancer. Stroke rates were established through surveys and self-report. Of the 271 respondents who reported having a stroke, 70 also reported a second stroke. Overall, the rate of recurrence within the first 10 years after an initial stroke was 21%, which is double the rate in the general population of stroke survivors. The rate was 33% for patients who had received cranial radiation therapy.

—Glenn S. Williams

Emergency medical services (EMS) use for stroke differs by race, ethnicity, and sex, according to a study published in the August issue of the Journal of the American Heart Association. Data were analyzed from 398,798 stroke patients who were admitted to 1,613 Get With The Guidelines–Stroke participating hospitals between October 2011 and March 2014. Multivariable logistic regression was used to evaluate the associations between combinations of racial, ethnic, and sex groups with EMS use, adjusting for potential confounders including demographics, medical history, and stroke symptoms. White women were most likely to use EMS to get to the hospital (62%). Hispanic men were least likely to use EMS (52%). Hispanic and Asian men and women had 20% to 29% lower adjusted odds of using EMS compared with their white counterparts. Black women were less likely than white women to use EMS.

For patients who take sleeping pills to treat chronic insomnia, new study findings suggest that they may be able to get relief from as little as half of the drugs, and may even be helped by including placebos in the treatment plan. The study was published online July 7 in Sleep Medicine. In all, 74 subjects with chronic insomnia were treated with 10 mg of zolpidem for four weeks. Treatment responders were then randomized to nightly dosing with 10 mg or 5 mg, intermittent dosing (3 to 5 days weekly) with 10 mg, or partial reinforcement dosing (nightly pills with 50% active meds and 50% placebo) with 10 mg for 12 weeks. In compliant subjects, all of the treatment strategies maintained treatment response. For the subjects that remained in remission, the subjects in the intermittent dosing group exhibited poorer sleep continuity. “Our research found that changing the industry standard for maintenance therapy can maintain treatment responses and lower the incidence of side effects,” said the researchers.

Hospitals often overestimate their ability to deliver timely t-PA to treated patients, according to a study published in the July issue of the Journal of the American Heart Association. Researchers surveyed staff in 141 hospitals that treated 48,201 stroke patients in 2009 and 2010. Data included the onset of stroke symptoms, hospital arrival time, treatments, initiation of t-PA, and complications from the drug. Hospital performance was based on “door-to-needle” time. Only 29% of hospital staff accurately identified their door-to-needle performance; 42% of middle-performing hospitals and 85% of low-performing hospitals overestimated their abilities to quickly administer t-PA and nearly 20% of low-performing hospitals believed their door-to-needle time was above the national average. Hospitals that overestimated their performance had lower volumes of t-PA administration.

Incidence rates for Alzheimer’s disease and other dementias among African Americans age 70 or older have decreased over the last two decades, but the incidence rates for these conditions among Africans has remained unchanged over the same time period. According to a study published online ahead of print July 23 in Alzheimer’s & Dementia, dementia and Alzheimer’s disease incidence rates among African Americans were significantly lower in 2001 than in 1992, except for the oldest group. The cohorts consisted of 1,440 African Americans residing in Indianapolis and 1,774 Yoruba in Ibadan, Nigeria, in 1992, and 1,835 African Americans and 1,895 Yoruba in 2001. The overall dementia incidence rates among the African Americans were 3.6% in the 1992 cohort and 1.4% in the 2001 cohort. “The reason for the significant decline in new cases of Alzheimer’s disease and other dementias in the African Americans we studied is not yet entirely clear but we believe it may be possible that medications for cardiovascular conditions contributed to the decline,” the study authors said.

Lower executive function, but not memory, is associated with higher risk of coronary heart disease and stroke, according to a study published online ahead of print August 5 in Neurology. Included in this study were 3,926 participants with a mean age of 75, who were 44% male, and at risk for cardiovascular diseases. During 3.2 years of follow-up, incidence rates of coronary heart disease and stroke were 30.5 and 12.4 per 1,000 person-years, respectively. In multivariable models, participants in the lowest third of executive function, compared with participants in the highest third, had 1.85-fold higher risk of coronary heart disease and 1.51-fold higher risk of stroke. Participants in the lowest third of memory had no increased risk of coronary heart disease or stroke.

The Quick Dementia Rating System (QDRS) differentiates between individuals with and without dementia, accurately stages dementia without extensive tester training or clinician input, and is highly correlated with gold standard measures, according to a study published in the June issue of Alzheimer’s & Dementia. The QDRS was used in 267 patient-caregiver dyads compared with Clinical Dementia Ratings (CDR), neuropsychologic testing, and gold standard measures of function, mood, and behavior. The QDRS scores increased with higher CDR staging and poorer neuropsychologic performance. The QDRS demonstrated low floor and ceiling effects; excellent known-groups validity across CDR stages; construct validity against cognitive, behavioral, and functional measures; and reliability. The QDRS demonstrated differential scores across different dementia etiologies. The QDRS is copyrighted and permission is required to use it. The QDRS is available at no cost to clinicians, researchers, and not-for-profit organizations.

A drug used to treat diabetes may also reduce the risk of Parkinson’s disease, according to a study published July 21 in PLOS Medicine. Researchers conducted a retrospective cohort study in which individuals with diabetes who were prescribed glitazone antidiabetes drugs (rosiglitazone or pioglitazone) were matched by age, sex, practice, and diabetes treatment stage with up to five people who were taking other diabetes treatments. Patients were followed up from 1999 until the first recording of a Parkinson’s disease diagnosis, end of observation in the database, or the end of the study (August 1, 2013). In all, 44,597 glitazone-exposed individuals were matched to 120,373 other antidiabetic users. The incidence rate of Parkinson’s disease in the glitazone-exposed group was 6.4 per 10,000 patient years compared with 8.8 per 10,000 years in those prescribed other antidiabetic treatments.

Day-of-injury serum brain-derived neurotrophic factor (BDNF) is associated with traumatic brain injury (TBI) diagnosis and provides six-month prognostic information regarding recovery, according to a study published online ahead of print July 10 in the Journal of Neurotrauma. Researchers examined BDNF in 300 patients drawn from two independent cohorts of TBI cases presenting to two emergency departments and 150 patients without brain injuries. Among Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) pilot study subjects, median BDNF concentrations were higher in mild than in moderate or severe TBI. In the TRACK-TBI cohort, the subjects with very low BDNF values had higher odds of incomplete recovery than those without very low values. According to the researchers, their results suggest that a test for BDNF levels, administered in the emergency department, could help stratify patients.

Children with multiple sclerosis (MS) are less physically active than children with monophasic acquired demyelinating syndrome, according to a study published online ahead of print August 12 in Neurology. In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, researchers administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. A total of 110 patients were included. Patients with MS reported less strenuous and total physical activity than those with monophasic acquired demyelinating syndrome. Patients with MS who reported greater amounts of moderate physical activity metabolic equivalents had fewer sleep/rest fatigue symptoms. Participation in strenuous physical activity was associated with smaller T2 lesion volumes and lower annualized relapse rate.

—Kimberly Williams

Emergency medical services (EMS) use for stroke differs by race, ethnicity, and sex, according to a study published in the August issue of the Journal of the American Heart Association. Data were analyzed from 398,798 stroke patients who were admitted to 1,613 Get With The Guidelines–Stroke participating hospitals between October 2011 and March 2014. Multivariable logistic regression was used to evaluate the associations between combinations of racial, ethnic, and sex groups with EMS use, adjusting for potential confounders including demographics, medical history, and stroke symptoms. White women were most likely to use EMS to get to the hospital (62%). Hispanic men were least likely to use EMS (52%). Hispanic and Asian men and women had 20% to 29% lower adjusted odds of using EMS compared with their white counterparts. Black women were less likely than white women to use EMS.

For patients who take sleeping pills to treat chronic insomnia, new study findings suggest that they may be able to get relief from as little as half of the drugs, and may even be helped by including placebos in the treatment plan. The study was published online July 7 in Sleep Medicine. In all, 74 subjects with chronic insomnia were treated with 10 mg of zolpidem for four weeks. Treatment responders were then randomized to nightly dosing with 10 mg or 5 mg, intermittent dosing (3 to 5 days weekly) with 10 mg, or partial reinforcement dosing (nightly pills with 50% active meds and 50% placebo) with 10 mg for 12 weeks. In compliant subjects, all of the treatment strategies maintained treatment response. For the subjects that remained in remission, the subjects in the intermittent dosing group exhibited poorer sleep continuity. “Our research found that changing the industry standard for maintenance therapy can maintain treatment responses and lower the incidence of side effects,” said the researchers.

Hospitals often overestimate their ability to deliver timely t-PA to treated patients, according to a study published in the July issue of the Journal of the American Heart Association. Researchers surveyed staff in 141 hospitals that treated 48,201 stroke patients in 2009 and 2010. Data included the onset of stroke symptoms, hospital arrival time, treatments, initiation of t-PA, and complications from the drug. Hospital performance was based on “door-to-needle” time. Only 29% of hospital staff accurately identified their door-to-needle performance; 42% of middle-performing hospitals and 85% of low-performing hospitals overestimated their abilities to quickly administer t-PA and nearly 20% of low-performing hospitals believed their door-to-needle time was above the national average. Hospitals that overestimated their performance had lower volumes of t-PA administration.

Incidence rates for Alzheimer’s disease and other dementias among African Americans age 70 or older have decreased over the last two decades, but the incidence rates for these conditions among Africans has remained unchanged over the same time period. According to a study published online ahead of print July 23 in Alzheimer’s & Dementia, dementia and Alzheimer’s disease incidence rates among African Americans were significantly lower in 2001 than in 1992, except for the oldest group. The cohorts consisted of 1,440 African Americans residing in Indianapolis and 1,774 Yoruba in Ibadan, Nigeria, in 1992, and 1,835 African Americans and 1,895 Yoruba in 2001. The overall dementia incidence rates among the African Americans were 3.6% in the 1992 cohort and 1.4% in the 2001 cohort. “The reason for the significant decline in new cases of Alzheimer’s disease and other dementias in the African Americans we studied is not yet entirely clear but we believe it may be possible that medications for cardiovascular conditions contributed to the decline,” the study authors said.

Lower executive function, but not memory, is associated with higher risk of coronary heart disease and stroke, according to a study published online ahead of print August 5 in Neurology. Included in this study were 3,926 participants with a mean age of 75, who were 44% male, and at risk for cardiovascular diseases. During 3.2 years of follow-up, incidence rates of coronary heart disease and stroke were 30.5 and 12.4 per 1,000 person-years, respectively. In multivariable models, participants in the lowest third of executive function, compared with participants in the highest third, had 1.85-fold higher risk of coronary heart disease and 1.51-fold higher risk of stroke. Participants in the lowest third of memory had no increased risk of coronary heart disease or stroke.

The Quick Dementia Rating System (QDRS) differentiates between individuals with and without dementia, accurately stages dementia without extensive tester training or clinician input, and is highly correlated with gold standard measures, according to a study published in the June issue of Alzheimer’s & Dementia. The QDRS was used in 267 patient-caregiver dyads compared with Clinical Dementia Ratings (CDR), neuropsychologic testing, and gold standard measures of function, mood, and behavior. The QDRS scores increased with higher CDR staging and poorer neuropsychologic performance. The QDRS demonstrated low floor and ceiling effects; excellent known-groups validity across CDR stages; construct validity against cognitive, behavioral, and functional measures; and reliability. The QDRS demonstrated differential scores across different dementia etiologies. The QDRS is copyrighted and permission is required to use it. The QDRS is available at no cost to clinicians, researchers, and not-for-profit organizations.

A drug used to treat diabetes may also reduce the risk of Parkinson’s disease, according to a study published July 21 in PLOS Medicine. Researchers conducted a retrospective cohort study in which individuals with diabetes who were prescribed glitazone antidiabetes drugs (rosiglitazone or pioglitazone) were matched by age, sex, practice, and diabetes treatment stage with up to five people who were taking other diabetes treatments. Patients were followed up from 1999 until the first recording of a Parkinson’s disease diagnosis, end of observation in the database, or the end of the study (August 1, 2013). In all, 44,597 glitazone-exposed individuals were matched to 120,373 other antidiabetic users. The incidence rate of Parkinson’s disease in the glitazone-exposed group was 6.4 per 10,000 patient years compared with 8.8 per 10,000 years in those prescribed other antidiabetic treatments.

Day-of-injury serum brain-derived neurotrophic factor (BDNF) is associated with traumatic brain injury (TBI) diagnosis and provides six-month prognostic information regarding recovery, according to a study published online ahead of print July 10 in the Journal of Neurotrauma. Researchers examined BDNF in 300 patients drawn from two independent cohorts of TBI cases presenting to two emergency departments and 150 patients without brain injuries. Among Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) pilot study subjects, median BDNF concentrations were higher in mild than in moderate or severe TBI. In the TRACK-TBI cohort, the subjects with very low BDNF values had higher odds of incomplete recovery than those without very low values. According to the researchers, their results suggest that a test for BDNF levels, administered in the emergency department, could help stratify patients.

Children with multiple sclerosis (MS) are less physically active than children with monophasic acquired demyelinating syndrome, according to a study published online ahead of print August 12 in Neurology. In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, researchers administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. A total of 110 patients were included. Patients with MS reported less strenuous and total physical activity than those with monophasic acquired demyelinating syndrome. Patients with MS who reported greater amounts of moderate physical activity metabolic equivalents had fewer sleep/rest fatigue symptoms. Participation in strenuous physical activity was associated with smaller T2 lesion volumes and lower annualized relapse rate.

—Kimberly Williams

Emergency medical services (EMS) use for stroke differs by race, ethnicity, and sex, according to a study published in the August issue of the Journal of the American Heart Association. Data were analyzed from 398,798 stroke patients who were admitted to 1,613 Get With The Guidelines–Stroke participating hospitals between October 2011 and March 2014. Multivariable logistic regression was used to evaluate the associations between combinations of racial, ethnic, and sex groups with EMS use, adjusting for potential confounders including demographics, medical history, and stroke symptoms. White women were most likely to use EMS to get to the hospital (62%). Hispanic men were least likely to use EMS (52%). Hispanic and Asian men and women had 20% to 29% lower adjusted odds of using EMS compared with their white counterparts. Black women were less likely than white women to use EMS.

For patients who take sleeping pills to treat chronic insomnia, new study findings suggest that they may be able to get relief from as little as half of the drugs, and may even be helped by including placebos in the treatment plan. The study was published online July 7 in Sleep Medicine. In all, 74 subjects with chronic insomnia were treated with 10 mg of zolpidem for four weeks. Treatment responders were then randomized to nightly dosing with 10 mg or 5 mg, intermittent dosing (3 to 5 days weekly) with 10 mg, or partial reinforcement dosing (nightly pills with 50% active meds and 50% placebo) with 10 mg for 12 weeks. In compliant subjects, all of the treatment strategies maintained treatment response. For the subjects that remained in remission, the subjects in the intermittent dosing group exhibited poorer sleep continuity. “Our research found that changing the industry standard for maintenance therapy can maintain treatment responses and lower the incidence of side effects,” said the researchers.

Hospitals often overestimate their ability to deliver timely t-PA to treated patients, according to a study published in the July issue of the Journal of the American Heart Association. Researchers surveyed staff in 141 hospitals that treated 48,201 stroke patients in 2009 and 2010. Data included the onset of stroke symptoms, hospital arrival time, treatments, initiation of t-PA, and complications from the drug. Hospital performance was based on “door-to-needle” time. Only 29% of hospital staff accurately identified their door-to-needle performance; 42% of middle-performing hospitals and 85% of low-performing hospitals overestimated their abilities to quickly administer t-PA and nearly 20% of low-performing hospitals believed their door-to-needle time was above the national average. Hospitals that overestimated their performance had lower volumes of t-PA administration.

Incidence rates for Alzheimer’s disease and other dementias among African Americans age 70 or older have decreased over the last two decades, but the incidence rates for these conditions among Africans has remained unchanged over the same time period. According to a study published online ahead of print July 23 in Alzheimer’s & Dementia, dementia and Alzheimer’s disease incidence rates among African Americans were significantly lower in 2001 than in 1992, except for the oldest group. The cohorts consisted of 1,440 African Americans residing in Indianapolis and 1,774 Yoruba in Ibadan, Nigeria, in 1992, and 1,835 African Americans and 1,895 Yoruba in 2001. The overall dementia incidence rates among the African Americans were 3.6% in the 1992 cohort and 1.4% in the 2001 cohort. “The reason for the significant decline in new cases of Alzheimer’s disease and other dementias in the African Americans we studied is not yet entirely clear but we believe it may be possible that medications for cardiovascular conditions contributed to the decline,” the study authors said.

Lower executive function, but not memory, is associated with higher risk of coronary heart disease and stroke, according to a study published online ahead of print August 5 in Neurology. Included in this study were 3,926 participants with a mean age of 75, who were 44% male, and at risk for cardiovascular diseases. During 3.2 years of follow-up, incidence rates of coronary heart disease and stroke were 30.5 and 12.4 per 1,000 person-years, respectively. In multivariable models, participants in the lowest third of executive function, compared with participants in the highest third, had 1.85-fold higher risk of coronary heart disease and 1.51-fold higher risk of stroke. Participants in the lowest third of memory had no increased risk of coronary heart disease or stroke.

The Quick Dementia Rating System (QDRS) differentiates between individuals with and without dementia, accurately stages dementia without extensive tester training or clinician input, and is highly correlated with gold standard measures, according to a study published in the June issue of Alzheimer’s & Dementia. The QDRS was used in 267 patient-caregiver dyads compared with Clinical Dementia Ratings (CDR), neuropsychologic testing, and gold standard measures of function, mood, and behavior. The QDRS scores increased with higher CDR staging and poorer neuropsychologic performance. The QDRS demonstrated low floor and ceiling effects; excellent known-groups validity across CDR stages; construct validity against cognitive, behavioral, and functional measures; and reliability. The QDRS demonstrated differential scores across different dementia etiologies. The QDRS is copyrighted and permission is required to use it. The QDRS is available at no cost to clinicians, researchers, and not-for-profit organizations.

A drug used to treat diabetes may also reduce the risk of Parkinson’s disease, according to a study published July 21 in PLOS Medicine. Researchers conducted a retrospective cohort study in which individuals with diabetes who were prescribed glitazone antidiabetes drugs (rosiglitazone or pioglitazone) were matched by age, sex, practice, and diabetes treatment stage with up to five people who were taking other diabetes treatments. Patients were followed up from 1999 until the first recording of a Parkinson’s disease diagnosis, end of observation in the database, or the end of the study (August 1, 2013). In all, 44,597 glitazone-exposed individuals were matched to 120,373 other antidiabetic users. The incidence rate of Parkinson’s disease in the glitazone-exposed group was 6.4 per 10,000 patient years compared with 8.8 per 10,000 years in those prescribed other antidiabetic treatments.

Day-of-injury serum brain-derived neurotrophic factor (BDNF) is associated with traumatic brain injury (TBI) diagnosis and provides six-month prognostic information regarding recovery, according to a study published online ahead of print July 10 in the Journal of Neurotrauma. Researchers examined BDNF in 300 patients drawn from two independent cohorts of TBI cases presenting to two emergency departments and 150 patients without brain injuries. Among Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) pilot study subjects, median BDNF concentrations were higher in mild than in moderate or severe TBI. In the TRACK-TBI cohort, the subjects with very low BDNF values had higher odds of incomplete recovery than those without very low values. According to the researchers, their results suggest that a test for BDNF levels, administered in the emergency department, could help stratify patients.

Children with multiple sclerosis (MS) are less physically active than children with monophasic acquired demyelinating syndrome, according to a study published online ahead of print August 12 in Neurology. In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, researchers administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. A total of 110 patients were included. Patients with MS reported less strenuous and total physical activity than those with monophasic acquired demyelinating syndrome. Patients with MS who reported greater amounts of moderate physical activity metabolic equivalents had fewer sleep/rest fatigue symptoms. Participation in strenuous physical activity was associated with smaller T2 lesion volumes and lower annualized relapse rate.

—Kimberly Williams