New and Noteworthy Information—October 2015

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 Researchers performed a meta-analysis of published studies and unpublished individual-level data examining the effects of longer working hours on cardiovascular disease.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