News Roundup

Men with diabetes in midlife have an increased risk for Alzheimer’s disease, researchers reported in the April 9 online Neurology. Acute insulin response and glucose tolerance were tested among 2,322 50-year-old men. During a median 32-year follow-up, 102 participants were diagnosed with Alzheimer’s disease, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. The researchers found that patients with a low insulin response at baseline had a higher cumulative risk of Alzheimer’s disease (hazard ratio [HR] per 1-SD decrease, 1.31). The association was stronger in participants without the apolipoprotein ε4 allele. Impaired glucose tolerance increased the risk of vascular dementia (HR per 1-SD decrease, 1.45). “Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment,” added the study authors.

High blood pressure may prevent the onset of headaches, reported researchers in the April 15 Neurology. According to an analysis of data from the large epidemiologic Nord-Trøndelag Health Survey from 1984-1986 and 1995-1997, increasing systolic blood pressure and pulse pressure were both associated with decreasing prevalence of nonmigrainous headache or migraine. The findings were less clear in patients using antihypertensive medication, however. The researchers observed that both increases are related to arterial stiffness and that headache prevalence may be decreased through modulation of the baroreflex arch. “Stimulation of the baroreflex arch in response to increased blood pressure is assumed to inhibit pain transmission at both spinal and supraspinal levels, possibly because of an interaction of the centers modulating nociception and cardiovascular reflexes in the brainstem,” they concluded.

Chronic ingestion of caffeine protects the blood-brain barrier from cholesterol-induced leakage, according to a study in the April Journal of Neuroinflammation. Researchers fed rabbits a 2% cholesterol-enriched diet and administered 3 mg of caffeine daily in the drinking water for 12 weeks. “Caffeine blocked high cholesterol diet-induced increases in extravasation of immunoglobulin G and fibrinogen, increases in leakage of Evan’s blue dye, decreases in levels of the tight junction proteins occludin and zona occludens 1, increases in astrocytes activation, and microglia density where immunoglobulin G extravasation was present,” said the authors. Because high cholesterol is a risk factor for Alzheimer’s disease, they suggested that caffeine and caffeine-like drugs could be useful in its treatment.

A new nano-engineered gel inhibits formation of scar tissue and enables fiber to regenerate and grow after a spinal cord injury, reported researchers in the April 2 Journal of Neuroscience. Peptide amphiphile molecules self-assemble in vivo to form cylindrical nanofibers that display the laminin epitope IKVAV, and the resultant nanofibers have been observed to promote neurite outgrowth from cultured neurons. In the present study, mice treated with peptide amphiphile molecules showed reduced astrogliosis, reduced cell death, and an increased number of oligodendroglia at the site of injury. In addition, the nanofibers promoted regeneration of descending motor fibers and ascending sensory fibers through the lesion site, and significant behavioral improvement was observed, said the researchers.

The increase in autism rates may be attributed to changing diagnostic criteria, according to a study published in the May Developmental Medicine and Child Neurology. Among 38 adults ages 15 to 31 (31 men) who had participated in studies of developmental language disorder during childhood, self-completion of the Autism Diagnostic Observation Schedule–Generic and parent evaluations on the Autism Diagnostic Interview–Revised (based on symptoms present at ages 4 to 5) revealed that eight individuals met criteria for autism and four met criteria for milder forms of autistic spectrum disorder. “Most individuals with autism had been identified with pragmatic impairments in childhood,” said the study authors. They asserted that children who are now diagnosed unambiguously with autistic disorder previously would have been diagnosed with developmental language disorder.

Leaky blood vessels that no longer have the ability to protect the spinal cord from toxins may contribute to the development of amyotrophic lateral sclerosis, as reported in the April Nature Neuroscience. Researchers found that mice with a superoxide dismutase 1 mutation had disruption of the blood–spinal cord barrier and reduced levels of tight junction proteins zona occludens 1, occludin, and claudin 5 between endothelial cells. This resulted in microhemorrhages with release of neurotoxic hemoglobin-derived products, reductions in microcirculation, and hypoperfusion. The damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, however, “indicating that it was a central contributor to disease initiation,” said the authors.

Race and community factors affect the rate of stroke hospitalization among Medicare beneficiaries, according to a report by the CDC and the Centers for Medicare and Medicaid Services. The study showed that the stroke hospitalization rate for African Americans was 27% higher than for the general population, 30% higher than for whites, and 36% higher than for Hispanics. Community conditions, including the availability of affordable healthy food, safe options for physical activity, access to high-quality health care, and antismoking legislation and policies, can influence a person’s risk for stroke, the investigators pointed out. They also reported that counties in the southeastern states had the highest rate of stroke hospitalizations, and 21% of counties did not have a hospital at all, 31% lacked a hospital with an emergency department, and 77% did not have a hospital with neurology services. The study may facilitate quality initiatives and payment reform proposals to address the variations identified and focus more attention on the needs of underserved Medicare populations, noted the authors.

Treatment for Alzheimer’s disease that clears β-amyloid plaques from the brain does not restore cognitive function, according to the results of a study in the April 2 Journal of Neuroscience. Beagles ages 8.4 to 12.4 years with preexisting β-amyloid pathology had no improvement in learning, spatial attention, or spatial memory when immunized with fibrillar β-amyloid(1-42) formulated with aluminum salt for 2.4 years (25 vaccinations). Brain levels of soluble and insoluble β-amyloid(1-40) and β-amyloid(1-42) and the extent of diffuse plaque accumulation decreased significantly in several cortical regions. “However, the amount of soluble oligomers remained unchanged,” noted the researchers. They suggested that immunization before oligomeric or fibrillar β-amyloid formation may have a greater impact on cognition or that clearing preexisting β-amyloid from the brain may be more beneficial to cognition if combined with a second treatment that restores neuron health.

Serum urate reduces progression of Parkinson’s disease, according to findings published in the April 14 online Archives of Neurology. Investigators studied the progression toward clinical disability warranting dopaminergic therapy in 804 participants with early Parkinson’s disease. Hazard ratios (HRs) of reaching this point declined with increasing baseline concentrations of urate, with subjects in the top quintile reaching this point at half the rate of subjects in the bottom quintile (HR, 0.51); the association was stronger in men than in women (HRs, 0.39 vs 0.77).

The brain structure of children who are prenatally exposed to drugs and alcohol may continue to be affected into early adolescence, reported researchers in the April Pediatrics. Volumetric MRI was performed on 35 children (mean age, 12.3) with intrauterine exposure to cocaine, marijuana, alcohol, or tobacco. Those exposed to cocaine (n = 14) had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than did comparison children, although this lost statistical significance after adjustment for other exposures. Prenatal ethanol exposure and prenatal cigarette exposure were also associated with reductions in cortical gray matter volume, total parenchymal volume, and head circumference.

Men with diabetes in midlife have an increased risk for Alzheimer’s disease, researchers reported in the April 9 online Neurology. Acute insulin response and glucose tolerance were tested among 2,322 50-year-old men. During a median 32-year follow-up, 102 participants were diagnosed with Alzheimer’s disease, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. The researchers found that patients with a low insulin response at baseline had a higher cumulative risk of Alzheimer’s disease (hazard ratio [HR] per 1-SD decrease, 1.31). The association was stronger in participants without the apolipoprotein ε4 allele. Impaired glucose tolerance increased the risk of vascular dementia (HR per 1-SD decrease, 1.45). “Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment,” added the study authors.

High blood pressure may prevent the onset of headaches, reported researchers in the April 15 Neurology. According to an analysis of data from the large epidemiologic Nord-Trøndelag Health Survey from 1984-1986 and 1995-1997, increasing systolic blood pressure and pulse pressure were both associated with decreasing prevalence of nonmigrainous headache or migraine. The findings were less clear in patients using antihypertensive medication, however. The researchers observed that both increases are related to arterial stiffness and that headache prevalence may be decreased through modulation of the baroreflex arch. “Stimulation of the baroreflex arch in response to increased blood pressure is assumed to inhibit pain transmission at both spinal and supraspinal levels, possibly because of an interaction of the centers modulating nociception and cardiovascular reflexes in the brainstem,” they concluded.

Chronic ingestion of caffeine protects the blood-brain barrier from cholesterol-induced leakage, according to a study in the April Journal of Neuroinflammation. Researchers fed rabbits a 2% cholesterol-enriched diet and administered 3 mg of caffeine daily in the drinking water for 12 weeks. “Caffeine blocked high cholesterol diet-induced increases in extravasation of immunoglobulin G and fibrinogen, increases in leakage of Evan’s blue dye, decreases in levels of the tight junction proteins occludin and zona occludens 1, increases in astrocytes activation, and microglia density where immunoglobulin G extravasation was present,” said the authors. Because high cholesterol is a risk factor for Alzheimer’s disease, they suggested that caffeine and caffeine-like drugs could be useful in its treatment.

A new nano-engineered gel inhibits formation of scar tissue and enables fiber to regenerate and grow after a spinal cord injury, reported researchers in the April 2 Journal of Neuroscience. Peptide amphiphile molecules self-assemble in vivo to form cylindrical nanofibers that display the laminin epitope IKVAV, and the resultant nanofibers have been observed to promote neurite outgrowth from cultured neurons. In the present study, mice treated with peptide amphiphile molecules showed reduced astrogliosis, reduced cell death, and an increased number of oligodendroglia at the site of injury. In addition, the nanofibers promoted regeneration of descending motor fibers and ascending sensory fibers through the lesion site, and significant behavioral improvement was observed, said the researchers.

The increase in autism rates may be attributed to changing diagnostic criteria, according to a study published in the May Developmental Medicine and Child Neurology. Among 38 adults ages 15 to 31 (31 men) who had participated in studies of developmental language disorder during childhood, self-completion of the Autism Diagnostic Observation Schedule–Generic and parent evaluations on the Autism Diagnostic Interview–Revised (based on symptoms present at ages 4 to 5) revealed that eight individuals met criteria for autism and four met criteria for milder forms of autistic spectrum disorder. “Most individuals with autism had been identified with pragmatic impairments in childhood,” said the study authors. They asserted that children who are now diagnosed unambiguously with autistic disorder previously would have been diagnosed with developmental language disorder.

Leaky blood vessels that no longer have the ability to protect the spinal cord from toxins may contribute to the development of amyotrophic lateral sclerosis, as reported in the April Nature Neuroscience. Researchers found that mice with a superoxide dismutase 1 mutation had disruption of the blood–spinal cord barrier and reduced levels of tight junction proteins zona occludens 1, occludin, and claudin 5 between endothelial cells. This resulted in microhemorrhages with release of neurotoxic hemoglobin-derived products, reductions in microcirculation, and hypoperfusion. The damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, however, “indicating that it was a central contributor to disease initiation,” said the authors.

Race and community factors affect the rate of stroke hospitalization among Medicare beneficiaries, according to a report by the CDC and the Centers for Medicare and Medicaid Services. The study showed that the stroke hospitalization rate for African Americans was 27% higher than for the general population, 30% higher than for whites, and 36% higher than for Hispanics. Community conditions, including the availability of affordable healthy food, safe options for physical activity, access to high-quality health care, and antismoking legislation and policies, can influence a person’s risk for stroke, the investigators pointed out. They also reported that counties in the southeastern states had the highest rate of stroke hospitalizations, and 21% of counties did not have a hospital at all, 31% lacked a hospital with an emergency department, and 77% did not have a hospital with neurology services. The study may facilitate quality initiatives and payment reform proposals to address the variations identified and focus more attention on the needs of underserved Medicare populations, noted the authors.

Treatment for Alzheimer’s disease that clears β-amyloid plaques from the brain does not restore cognitive function, according to the results of a study in the April 2 Journal of Neuroscience. Beagles ages 8.4 to 12.4 years with preexisting β-amyloid pathology had no improvement in learning, spatial attention, or spatial memory when immunized with fibrillar β-amyloid(1-42) formulated with aluminum salt for 2.4 years (25 vaccinations). Brain levels of soluble and insoluble β-amyloid(1-40) and β-amyloid(1-42) and the extent of diffuse plaque accumulation decreased significantly in several cortical regions. “However, the amount of soluble oligomers remained unchanged,” noted the researchers. They suggested that immunization before oligomeric or fibrillar β-amyloid formation may have a greater impact on cognition or that clearing preexisting β-amyloid from the brain may be more beneficial to cognition if combined with a second treatment that restores neuron health.

Serum urate reduces progression of Parkinson’s disease, according to findings published in the April 14 online Archives of Neurology. Investigators studied the progression toward clinical disability warranting dopaminergic therapy in 804 participants with early Parkinson’s disease. Hazard ratios (HRs) of reaching this point declined with increasing baseline concentrations of urate, with subjects in the top quintile reaching this point at half the rate of subjects in the bottom quintile (HR, 0.51); the association was stronger in men than in women (HRs, 0.39 vs 0.77).

The brain structure of children who are prenatally exposed to drugs and alcohol may continue to be affected into early adolescence, reported researchers in the April Pediatrics. Volumetric MRI was performed on 35 children (mean age, 12.3) with intrauterine exposure to cocaine, marijuana, alcohol, or tobacco. Those exposed to cocaine (n = 14) had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than did comparison children, although this lost statistical significance after adjustment for other exposures. Prenatal ethanol exposure and prenatal cigarette exposure were also associated with reductions in cortical gray matter volume, total parenchymal volume, and head circumference.

Men with diabetes in midlife have an increased risk for Alzheimer’s disease, researchers reported in the April 9 online Neurology. Acute insulin response and glucose tolerance were tested among 2,322 50-year-old men. During a median 32-year follow-up, 102 participants were diagnosed with Alzheimer’s disease, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. The researchers found that patients with a low insulin response at baseline had a higher cumulative risk of Alzheimer’s disease (hazard ratio [HR] per 1-SD decrease, 1.31). The association was stronger in participants without the apolipoprotein ε4 allele. Impaired glucose tolerance increased the risk of vascular dementia (HR per 1-SD decrease, 1.45). “Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment,” added the study authors.

High blood pressure may prevent the onset of headaches, reported researchers in the April 15 Neurology. According to an analysis of data from the large epidemiologic Nord-Trøndelag Health Survey from 1984-1986 and 1995-1997, increasing systolic blood pressure and pulse pressure were both associated with decreasing prevalence of nonmigrainous headache or migraine. The findings were less clear in patients using antihypertensive medication, however. The researchers observed that both increases are related to arterial stiffness and that headache prevalence may be decreased through modulation of the baroreflex arch. “Stimulation of the baroreflex arch in response to increased blood pressure is assumed to inhibit pain transmission at both spinal and supraspinal levels, possibly because of an interaction of the centers modulating nociception and cardiovascular reflexes in the brainstem,” they concluded.

Chronic ingestion of caffeine protects the blood-brain barrier from cholesterol-induced leakage, according to a study in the April Journal of Neuroinflammation. Researchers fed rabbits a 2% cholesterol-enriched diet and administered 3 mg of caffeine daily in the drinking water for 12 weeks. “Caffeine blocked high cholesterol diet-induced increases in extravasation of immunoglobulin G and fibrinogen, increases in leakage of Evan’s blue dye, decreases in levels of the tight junction proteins occludin and zona occludens 1, increases in astrocytes activation, and microglia density where immunoglobulin G extravasation was present,” said the authors. Because high cholesterol is a risk factor for Alzheimer’s disease, they suggested that caffeine and caffeine-like drugs could be useful in its treatment.

A new nano-engineered gel inhibits formation of scar tissue and enables fiber to regenerate and grow after a spinal cord injury, reported researchers in the April 2 Journal of Neuroscience. Peptide amphiphile molecules self-assemble in vivo to form cylindrical nanofibers that display the laminin epitope IKVAV, and the resultant nanofibers have been observed to promote neurite outgrowth from cultured neurons. In the present study, mice treated with peptide amphiphile molecules showed reduced astrogliosis, reduced cell death, and an increased number of oligodendroglia at the site of injury. In addition, the nanofibers promoted regeneration of descending motor fibers and ascending sensory fibers through the lesion site, and significant behavioral improvement was observed, said the researchers.

The increase in autism rates may be attributed to changing diagnostic criteria, according to a study published in the May Developmental Medicine and Child Neurology. Among 38 adults ages 15 to 31 (31 men) who had participated in studies of developmental language disorder during childhood, self-completion of the Autism Diagnostic Observation Schedule–Generic and parent evaluations on the Autism Diagnostic Interview–Revised (based on symptoms present at ages 4 to 5) revealed that eight individuals met criteria for autism and four met criteria for milder forms of autistic spectrum disorder. “Most individuals with autism had been identified with pragmatic impairments in childhood,” said the study authors. They asserted that children who are now diagnosed unambiguously with autistic disorder previously would have been diagnosed with developmental language disorder.

Leaky blood vessels that no longer have the ability to protect the spinal cord from toxins may contribute to the development of amyotrophic lateral sclerosis, as reported in the April Nature Neuroscience. Researchers found that mice with a superoxide dismutase 1 mutation had disruption of the blood–spinal cord barrier and reduced levels of tight junction proteins zona occludens 1, occludin, and claudin 5 between endothelial cells. This resulted in microhemorrhages with release of neurotoxic hemoglobin-derived products, reductions in microcirculation, and hypoperfusion. The damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, however, “indicating that it was a central contributor to disease initiation,” said the authors.

Race and community factors affect the rate of stroke hospitalization among Medicare beneficiaries, according to a report by the CDC and the Centers for Medicare and Medicaid Services. The study showed that the stroke hospitalization rate for African Americans was 27% higher than for the general population, 30% higher than for whites, and 36% higher than for Hispanics. Community conditions, including the availability of affordable healthy food, safe options for physical activity, access to high-quality health care, and antismoking legislation and policies, can influence a person’s risk for stroke, the investigators pointed out. They also reported that counties in the southeastern states had the highest rate of stroke hospitalizations, and 21% of counties did not have a hospital at all, 31% lacked a hospital with an emergency department, and 77% did not have a hospital with neurology services. The study may facilitate quality initiatives and payment reform proposals to address the variations identified and focus more attention on the needs of underserved Medicare populations, noted the authors.

Treatment for Alzheimer’s disease that clears β-amyloid plaques from the brain does not restore cognitive function, according to the results of a study in the April 2 Journal of Neuroscience. Beagles ages 8.4 to 12.4 years with preexisting β-amyloid pathology had no improvement in learning, spatial attention, or spatial memory when immunized with fibrillar β-amyloid(1-42) formulated with aluminum salt for 2.4 years (25 vaccinations). Brain levels of soluble and insoluble β-amyloid(1-40) and β-amyloid(1-42) and the extent of diffuse plaque accumulation decreased significantly in several cortical regions. “However, the amount of soluble oligomers remained unchanged,” noted the researchers. They suggested that immunization before oligomeric or fibrillar β-amyloid formation may have a greater impact on cognition or that clearing preexisting β-amyloid from the brain may be more beneficial to cognition if combined with a second treatment that restores neuron health.

Serum urate reduces progression of Parkinson’s disease, according to findings published in the April 14 online Archives of Neurology. Investigators studied the progression toward clinical disability warranting dopaminergic therapy in 804 participants with early Parkinson’s disease. Hazard ratios (HRs) of reaching this point declined with increasing baseline concentrations of urate, with subjects in the top quintile reaching this point at half the rate of subjects in the bottom quintile (HR, 0.51); the association was stronger in men than in women (HRs, 0.39 vs 0.77).

The brain structure of children who are prenatally exposed to drugs and alcohol may continue to be affected into early adolescence, reported researchers in the April Pediatrics. Volumetric MRI was performed on 35 children (mean age, 12.3) with intrauterine exposure to cocaine, marijuana, alcohol, or tobacco. Those exposed to cocaine (n = 14) had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than did comparison children, although this lost statistical significance after adjustment for other exposures. Prenatal ethanol exposure and prenatal cigarette exposure were also associated with reductions in cortical gray matter volume, total parenchymal volume, and head circumference.

The net benefit of IV t-PA treatment in patients with ischemic stroke was greater in patients also using antiplatelet drugs, despite an increased risk of symptomatic intracerebral hemorrhage, reported researchers in the March 10 online Archives of Neurology. Of 301 consecutive ischemic stroke patients treated with IV t-PA at a single university hospital, 89 also used antiplatelet drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 13.5% of patients who received antiplatelet drugs and in 2.8% of those who did not, and was independently predicted by antiplatelet drug use (odds ratio, 6.0). However, prior antiplatelet therapy was also independently associated with a favorable outcome, defined as a modified Rankin Scale score of 2 or less at three months (odds ratio, 2.0).

The prevalence of cerebral microbleeds is high, increases with age, and may be indicative of an increased risk of cerebrovascular problems, reported researchers in the April 1 Neurology. Among 1,062 study participants 60 and older (mean age, 69.6), the MRI-detected prevalence of cerebral microbleeds increased from 17.8% in those ages 60 to 69 to 38.3% in those older than 80. “APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers,” said the authors, while cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location.

Pesticide exposure may increase the risk of Parkinson’s disease, according to the results of a family-based case-control study reported in the March 28 BMC Neurology. The 319 patients with Parkinson’s disease were significantly more likely to report direct pesticide application than were their unaffected relatives (odds ratio, 1.61). There was also a dose-response pattern between frequency, duration, and cumulative exposure and Parkinson’s disease. Additional analyses found that insecticides and herbicides increased the risk of Parkinson’s disease, and that two insecticide classes—organochlorines and organophosphorus compounds—were significantly associated with Parkinson’s disease. Consuming well water and living or working on a farm did not appear to increase risk of disease, however.

There may be an association between the severity of age-related white matter changes and the severity of gait and motor compromise, researchers reported in the March 18 Neurology. In the Leukoaraiosis and Disability Study, 639 nondisabled individuals older than 65 were followed for three years. Mean scores on the Short Physical Performance Battery and walking speeds decreased with severity of age-related white matter changes, and balance was best among those with mild age-related white matter changes compared with moderate or severe changes. A history of falls was also twice as likely in those participants with severe versus mild age-related white matter changes, and 1.5 times as likely in those with moderate changes. “Physical activity might have the potential to reduce the risk of limitations in mobility,” noted the authors, as physically inactive individuals had a higher risk of pathologic Short Physical Performance Battery scores.

High intake of magnesium—but not calcium, potassium, or sodium—appeared to reduce the risk of cerebral infarction in male smokers, reported researchers in the March 10 Archives of Internal Medicine. In a study of 26,556 Finnish male smokers ages 50 to 69 at baseline, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages occurred during a mean follow-up of 13.6 years. Men in the highest quintile of magnesium intake had a 0.85 relative risk of cerebral infarction compared with those in the lowest quintile; the inverse association was stronger in men younger than 60 (relative risk, 0.76). No other minerals were significantly associated with risk of any subtype of stroke. The researchers suggested that high magnesium intake may play a role in the primary prevention of cerebral infarction.

Disclosure of a dementia diagnosis resulted in relief rather than a “catastrophic emotional reaction” among 90 individuals with suspected Alzheimer’s disease and their companions. As reported in the March Journal of the American Geriatrics Society, 69% of the participants were diagnosed with dementia; however, Geriatric Depression Scale scores did not change significantly compared with prediagnosis scores. Instead, a substantial decrease in State-Trait Anxiety Inventory was observed, even among those patients who were only mildly cognitively impaired. The authors suggested that patients and their families may appreciate the explanation of symptoms and the development of a treatment plan that comes with a diagnosis.

Overexpression of the cdk5 activator p25 led to increased amyloidogenic processing of amyloid precursor protein, which may have implications for Alzheimer’s disease pathogenesis, reported researchers in the March 13 Neuron. Mice that overexpressed p25 showed elevated levels of BACE1 mRNA and protein pSTAT3, whereas cdk5-deficient mice had reduced levels; a targeted mutation to the STAT3 cdk5 responsive site also led to lower levels of BACE1. The authors noted that transcriptional control of BACE1 could have implications for Alzheimer’s disease. As a cdk5 inhibitor reversed BACE-driven amyloidgenic processing, it may provide a therapeutic candidate for Alzheimer’s disease.

Maximum carotid plaque thickness was associated with an increased risk of vascular outcomes, especially among Hispanics, in an analysis of 2,189 subjects in a population-based cohort, as reported in the April 1 Neurology. Carotid plaque was present in 58% of the participants. During the mean 6.9 years of follow-up, vascular events occurred among 319 subjects: 121 had ischemic strokes, 118 had myocardial infarctions, and 166 died of vascular causes. Although there was a 2.8-fold increased risk of combined vascular events among those with carotid plaque thickness greater than the prespecified cutoff of 1.9 mm compared with those with no carotid plaque, the association was only significant among Hispanics after full adjustment. “Approximately 44% of the low-risk individuals … had a 10-year vascular risk of 18.3% if having carotid plaque,” said the researchers. They concluded that maximum carotid plaque thickness may be a useful risk stratification tool and a surrogate end point in clinical trials.

Parenchymal volumetric loss dose-dependently correlated with severity of traumatic brain injury (TBI), according to the results of a study of 69 chronic-phase TBI patients reported in the March 4 Neurology. A minimum of one year after TBI, high-resolution structural MRI also detected a spatially extensive pattern of volume loss that covaried with TBI severity, “with particularly widespread effects in white matter volume and sulcal/subdural CSF.” Of the 38 brain regions imaged, the most reliable effects were observed in the frontal, temporal, and cingulate regions, stated the researchers. They noted that the pattern of volume loss was independent of contributions of focal and diffuse injury, as focal lesions were associated with greater frontal and temporal volume loss, but the loss remained marked when analyses were restricted to patients with diffuse injury.

Researchers have proposed a mechanism for the brain’s conversion to epilepsy following injury. As reported in the March 28 online Proceedings of the National Academy of Sciences, the researchers used a large-scale, biophysically realistic model of the epileptic rat dentate gyrus to reconnect the aberrant recurrent granule cell network. Although the investigators noted that network activity in the dentate gyrus was robust after a number of major changes, “the incorporation of a small number of highly interconnected granule cell hubs greatly increase[d] network activity, resulting in a hyperexcitable, potentially seizure-prone circuit.” They suggested that these neural hub cells may be a therapeutic target for epilepsy.

Impaired olfaction may predate clinical Parkinson’s disease in men by at least four years, reported researchers in the February Annals of Neurology. Olfaction was tested in 2,267 Parkinson’s disease– and dementia-free men ages 71 to 95 for up to eight years. Thirty-five men were diagnosed with Parkinson’s disease at an average age of 82.9. During the first four years of follow-up, age-adjusted incidence of Parkinson’s disease declined from the lowest to the highest quartiles of odor identification; the odds ratio for Parkinson’s disease in the lowest quartile compared with the two highest quartiles was 5.2. The researchers suggested that tests of olfaction may be a useful screening tool for risk of Parkinson’s disease in men.

The net benefit of IV t-PA treatment in patients with ischemic stroke was greater in patients also using antiplatelet drugs, despite an increased risk of symptomatic intracerebral hemorrhage, reported researchers in the March 10 online Archives of Neurology. Of 301 consecutive ischemic stroke patients treated with IV t-PA at a single university hospital, 89 also used antiplatelet drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 13.5% of patients who received antiplatelet drugs and in 2.8% of those who did not, and was independently predicted by antiplatelet drug use (odds ratio, 6.0). However, prior antiplatelet therapy was also independently associated with a favorable outcome, defined as a modified Rankin Scale score of 2 or less at three months (odds ratio, 2.0).

The prevalence of cerebral microbleeds is high, increases with age, and may be indicative of an increased risk of cerebrovascular problems, reported researchers in the April 1 Neurology. Among 1,062 study participants 60 and older (mean age, 69.6), the MRI-detected prevalence of cerebral microbleeds increased from 17.8% in those ages 60 to 69 to 38.3% in those older than 80. “APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers,” said the authors, while cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location.

Pesticide exposure may increase the risk of Parkinson’s disease, according to the results of a family-based case-control study reported in the March 28 BMC Neurology. The 319 patients with Parkinson’s disease were significantly more likely to report direct pesticide application than were their unaffected relatives (odds ratio, 1.61). There was also a dose-response pattern between frequency, duration, and cumulative exposure and Parkinson’s disease. Additional analyses found that insecticides and herbicides increased the risk of Parkinson’s disease, and that two insecticide classes—organochlorines and organophosphorus compounds—were significantly associated with Parkinson’s disease. Consuming well water and living or working on a farm did not appear to increase risk of disease, however.

There may be an association between the severity of age-related white matter changes and the severity of gait and motor compromise, researchers reported in the March 18 Neurology. In the Leukoaraiosis and Disability Study, 639 nondisabled individuals older than 65 were followed for three years. Mean scores on the Short Physical Performance Battery and walking speeds decreased with severity of age-related white matter changes, and balance was best among those with mild age-related white matter changes compared with moderate or severe changes. A history of falls was also twice as likely in those participants with severe versus mild age-related white matter changes, and 1.5 times as likely in those with moderate changes. “Physical activity might have the potential to reduce the risk of limitations in mobility,” noted the authors, as physically inactive individuals had a higher risk of pathologic Short Physical Performance Battery scores.

High intake of magnesium—but not calcium, potassium, or sodium—appeared to reduce the risk of cerebral infarction in male smokers, reported researchers in the March 10 Archives of Internal Medicine. In a study of 26,556 Finnish male smokers ages 50 to 69 at baseline, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages occurred during a mean follow-up of 13.6 years. Men in the highest quintile of magnesium intake had a 0.85 relative risk of cerebral infarction compared with those in the lowest quintile; the inverse association was stronger in men younger than 60 (relative risk, 0.76). No other minerals were significantly associated with risk of any subtype of stroke. The researchers suggested that high magnesium intake may play a role in the primary prevention of cerebral infarction.

Disclosure of a dementia diagnosis resulted in relief rather than a “catastrophic emotional reaction” among 90 individuals with suspected Alzheimer’s disease and their companions. As reported in the March Journal of the American Geriatrics Society, 69% of the participants were diagnosed with dementia; however, Geriatric Depression Scale scores did not change significantly compared with prediagnosis scores. Instead, a substantial decrease in State-Trait Anxiety Inventory was observed, even among those patients who were only mildly cognitively impaired. The authors suggested that patients and their families may appreciate the explanation of symptoms and the development of a treatment plan that comes with a diagnosis.

Overexpression of the cdk5 activator p25 led to increased amyloidogenic processing of amyloid precursor protein, which may have implications for Alzheimer’s disease pathogenesis, reported researchers in the March 13 Neuron. Mice that overexpressed p25 showed elevated levels of BACE1 mRNA and protein pSTAT3, whereas cdk5-deficient mice had reduced levels; a targeted mutation to the STAT3 cdk5 responsive site also led to lower levels of BACE1. The authors noted that transcriptional control of BACE1 could have implications for Alzheimer’s disease. As a cdk5 inhibitor reversed BACE-driven amyloidgenic processing, it may provide a therapeutic candidate for Alzheimer’s disease.

Maximum carotid plaque thickness was associated with an increased risk of vascular outcomes, especially among Hispanics, in an analysis of 2,189 subjects in a population-based cohort, as reported in the April 1 Neurology. Carotid plaque was present in 58% of the participants. During the mean 6.9 years of follow-up, vascular events occurred among 319 subjects: 121 had ischemic strokes, 118 had myocardial infarctions, and 166 died of vascular causes. Although there was a 2.8-fold increased risk of combined vascular events among those with carotid plaque thickness greater than the prespecified cutoff of 1.9 mm compared with those with no carotid plaque, the association was only significant among Hispanics after full adjustment. “Approximately 44% of the low-risk individuals … had a 10-year vascular risk of 18.3% if having carotid plaque,” said the researchers. They concluded that maximum carotid plaque thickness may be a useful risk stratification tool and a surrogate end point in clinical trials.

Parenchymal volumetric loss dose-dependently correlated with severity of traumatic brain injury (TBI), according to the results of a study of 69 chronic-phase TBI patients reported in the March 4 Neurology. A minimum of one year after TBI, high-resolution structural MRI also detected a spatially extensive pattern of volume loss that covaried with TBI severity, “with particularly widespread effects in white matter volume and sulcal/subdural CSF.” Of the 38 brain regions imaged, the most reliable effects were observed in the frontal, temporal, and cingulate regions, stated the researchers. They noted that the pattern of volume loss was independent of contributions of focal and diffuse injury, as focal lesions were associated with greater frontal and temporal volume loss, but the loss remained marked when analyses were restricted to patients with diffuse injury.

Researchers have proposed a mechanism for the brain’s conversion to epilepsy following injury. As reported in the March 28 online Proceedings of the National Academy of Sciences, the researchers used a large-scale, biophysically realistic model of the epileptic rat dentate gyrus to reconnect the aberrant recurrent granule cell network. Although the investigators noted that network activity in the dentate gyrus was robust after a number of major changes, “the incorporation of a small number of highly interconnected granule cell hubs greatly increase[d] network activity, resulting in a hyperexcitable, potentially seizure-prone circuit.” They suggested that these neural hub cells may be a therapeutic target for epilepsy.

Impaired olfaction may predate clinical Parkinson’s disease in men by at least four years, reported researchers in the February Annals of Neurology. Olfaction was tested in 2,267 Parkinson’s disease– and dementia-free men ages 71 to 95 for up to eight years. Thirty-five men were diagnosed with Parkinson’s disease at an average age of 82.9. During the first four years of follow-up, age-adjusted incidence of Parkinson’s disease declined from the lowest to the highest quartiles of odor identification; the odds ratio for Parkinson’s disease in the lowest quartile compared with the two highest quartiles was 5.2. The researchers suggested that tests of olfaction may be a useful screening tool for risk of Parkinson’s disease in men.

The net benefit of IV t-PA treatment in patients with ischemic stroke was greater in patients also using antiplatelet drugs, despite an increased risk of symptomatic intracerebral hemorrhage, reported researchers in the March 10 online Archives of Neurology. Of 301 consecutive ischemic stroke patients treated with IV t-PA at a single university hospital, 89 also used antiplatelet drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 13.5% of patients who received antiplatelet drugs and in 2.8% of those who did not, and was independently predicted by antiplatelet drug use (odds ratio, 6.0). However, prior antiplatelet therapy was also independently associated with a favorable outcome, defined as a modified Rankin Scale score of 2 or less at three months (odds ratio, 2.0).

The prevalence of cerebral microbleeds is high, increases with age, and may be indicative of an increased risk of cerebrovascular problems, reported researchers in the April 1 Neurology. Among 1,062 study participants 60 and older (mean age, 69.6), the MRI-detected prevalence of cerebral microbleeds increased from 17.8% in those ages 60 to 69 to 38.3% in those older than 80. “APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers,” said the authors, while cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location.

Pesticide exposure may increase the risk of Parkinson’s disease, according to the results of a family-based case-control study reported in the March 28 BMC Neurology. The 319 patients with Parkinson’s disease were significantly more likely to report direct pesticide application than were their unaffected relatives (odds ratio, 1.61). There was also a dose-response pattern between frequency, duration, and cumulative exposure and Parkinson’s disease. Additional analyses found that insecticides and herbicides increased the risk of Parkinson’s disease, and that two insecticide classes—organochlorines and organophosphorus compounds—were significantly associated with Parkinson’s disease. Consuming well water and living or working on a farm did not appear to increase risk of disease, however.

There may be an association between the severity of age-related white matter changes and the severity of gait and motor compromise, researchers reported in the March 18 Neurology. In the Leukoaraiosis and Disability Study, 639 nondisabled individuals older than 65 were followed for three years. Mean scores on the Short Physical Performance Battery and walking speeds decreased with severity of age-related white matter changes, and balance was best among those with mild age-related white matter changes compared with moderate or severe changes. A history of falls was also twice as likely in those participants with severe versus mild age-related white matter changes, and 1.5 times as likely in those with moderate changes. “Physical activity might have the potential to reduce the risk of limitations in mobility,” noted the authors, as physically inactive individuals had a higher risk of pathologic Short Physical Performance Battery scores.

High intake of magnesium—but not calcium, potassium, or sodium—appeared to reduce the risk of cerebral infarction in male smokers, reported researchers in the March 10 Archives of Internal Medicine. In a study of 26,556 Finnish male smokers ages 50 to 69 at baseline, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages occurred during a mean follow-up of 13.6 years. Men in the highest quintile of magnesium intake had a 0.85 relative risk of cerebral infarction compared with those in the lowest quintile; the inverse association was stronger in men younger than 60 (relative risk, 0.76). No other minerals were significantly associated with risk of any subtype of stroke. The researchers suggested that high magnesium intake may play a role in the primary prevention of cerebral infarction.

Disclosure of a dementia diagnosis resulted in relief rather than a “catastrophic emotional reaction” among 90 individuals with suspected Alzheimer’s disease and their companions. As reported in the March Journal of the American Geriatrics Society, 69% of the participants were diagnosed with dementia; however, Geriatric Depression Scale scores did not change significantly compared with prediagnosis scores. Instead, a substantial decrease in State-Trait Anxiety Inventory was observed, even among those patients who were only mildly cognitively impaired. The authors suggested that patients and their families may appreciate the explanation of symptoms and the development of a treatment plan that comes with a diagnosis.

Overexpression of the cdk5 activator p25 led to increased amyloidogenic processing of amyloid precursor protein, which may have implications for Alzheimer’s disease pathogenesis, reported researchers in the March 13 Neuron. Mice that overexpressed p25 showed elevated levels of BACE1 mRNA and protein pSTAT3, whereas cdk5-deficient mice had reduced levels; a targeted mutation to the STAT3 cdk5 responsive site also led to lower levels of BACE1. The authors noted that transcriptional control of BACE1 could have implications for Alzheimer’s disease. As a cdk5 inhibitor reversed BACE-driven amyloidgenic processing, it may provide a therapeutic candidate for Alzheimer’s disease.

Maximum carotid plaque thickness was associated with an increased risk of vascular outcomes, especially among Hispanics, in an analysis of 2,189 subjects in a population-based cohort, as reported in the April 1 Neurology. Carotid plaque was present in 58% of the participants. During the mean 6.9 years of follow-up, vascular events occurred among 319 subjects: 121 had ischemic strokes, 118 had myocardial infarctions, and 166 died of vascular causes. Although there was a 2.8-fold increased risk of combined vascular events among those with carotid plaque thickness greater than the prespecified cutoff of 1.9 mm compared with those with no carotid plaque, the association was only significant among Hispanics after full adjustment. “Approximately 44% of the low-risk individuals … had a 10-year vascular risk of 18.3% if having carotid plaque,” said the researchers. They concluded that maximum carotid plaque thickness may be a useful risk stratification tool and a surrogate end point in clinical trials.

Parenchymal volumetric loss dose-dependently correlated with severity of traumatic brain injury (TBI), according to the results of a study of 69 chronic-phase TBI patients reported in the March 4 Neurology. A minimum of one year after TBI, high-resolution structural MRI also detected a spatially extensive pattern of volume loss that covaried with TBI severity, “with particularly widespread effects in white matter volume and sulcal/subdural CSF.” Of the 38 brain regions imaged, the most reliable effects were observed in the frontal, temporal, and cingulate regions, stated the researchers. They noted that the pattern of volume loss was independent of contributions of focal and diffuse injury, as focal lesions were associated with greater frontal and temporal volume loss, but the loss remained marked when analyses were restricted to patients with diffuse injury.

Researchers have proposed a mechanism for the brain’s conversion to epilepsy following injury. As reported in the March 28 online Proceedings of the National Academy of Sciences, the researchers used a large-scale, biophysically realistic model of the epileptic rat dentate gyrus to reconnect the aberrant recurrent granule cell network. Although the investigators noted that network activity in the dentate gyrus was robust after a number of major changes, “the incorporation of a small number of highly interconnected granule cell hubs greatly increase[d] network activity, resulting in a hyperexcitable, potentially seizure-prone circuit.” They suggested that these neural hub cells may be a therapeutic target for epilepsy.

Impaired olfaction may predate clinical Parkinson’s disease in men by at least four years, reported researchers in the February Annals of Neurology. Olfaction was tested in 2,267 Parkinson’s disease– and dementia-free men ages 71 to 95 for up to eight years. Thirty-five men were diagnosed with Parkinson’s disease at an average age of 82.9. During the first four years of follow-up, age-adjusted incidence of Parkinson’s disease declined from the lowest to the highest quartiles of odor identification; the odds ratio for Parkinson’s disease in the lowest quartile compared with the two highest quartiles was 5.2. The researchers suggested that tests of olfaction may be a useful screening tool for risk of Parkinson’s disease in men.