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News Roundup: New and Noteworthy Information
Women with Down syndrome who experienced early menopause were almost twice as likely to develop dementia at a younger age than those who entered menopause later, according to research in the January Journal of Alzheimer’s Disease. In a prospective longitudinal cohort study of dementia and mortality in women with Down syndrome, researchers followed 85 postmenopausal subjects for an average of 4.3 years and found a significant correlation between the age at menopause onset and age at diagnosis of dementia. Subjects with an earlier onset of menopause had a 1.8-fold increased risk of dementia. In addition, women who experienced menopause earlier had a twofold increased risk of dying younger.
White, elderly cancer survivors have a reduced risk of developing Alzheimer’s disease, as reported in the January 12 Neurology. Conversely, patients with Alzheimer’s disease have a reduced cancer risk, investigators found. In a prospective cohort study of 3,020 subjects ages 65 and older, the presence of Alzheimer’s disease was associated with a reduced risk of cancer hospitalizations, after adjustments for demographic and other factors. Prevalent cancer was also associated with a reduced risk of Alzheimer’s disease among white subjects after the researchers adjusted for demographics, number of apolipoprotein ε4 alleles, hypertension, diabetes, and coronary heart disease. The opposite was found in minorities, although the sample size was considered too small. No significant association was found between cancer and vascular dementia.
Ginkgo biloba did not preserve cognitive function any better than a placebo, per a study in the December 23, 2009, JAMA. In the randomized, double-blind, placebo-controlled Ginkgo Evaluation of Memory study, researchers at six academic medical centers in the US tracked 3,069 community-dwelling subjects ages 72 to 96 years for an average of 6.1 years. Subjects were given either a twice-daily dose of 120 mg extract of Ginkgo biloba or a placebo. Cognition was measured as rates of change over time in the Modified Mini-Mental State Examination, the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and neuropsychologic domains of memory, attention, visual-spatial construction, language, and executive functions. Investigators found no significant difference in cognitive decline between the herb and placebo.
A decreased ability to smell is common in patients with Alzheimer’s disease and may be a useful early diagnostic tool, researchers reported in the January 13 Journal of Neuroscience. The study linked olfactory dysfunction with an accumulation of amyloid-β protein in Alzheimer’s disease model mice. “The usefulness of olfactory screens to serve as informative indicators of Alzheimer’s is precluded by a lack of knowledge regarding why the disease impacts olfaction,” the study authors stated. The investigators assayed olfactory perception and amyloid-β deposition in the genetically engineered mice and found that amyloid-β pathology first occurred in an area of the brain responsible for smelling. Mice with higher concentrations of amyloid-β also displayed olfactory dysfunction. Researchers noted the “odor cross-habitation test [was] a powerful behavioral assay…[which] may serve to monitor the efficacy of therapies aimed at reducing amyloid-β.”
The Lancet has retracted the 1998 paper by Wakefield et al that suggested a link between autism and the childhood measles, mumps, and rubella (MMR) vaccine. The retraction, published in the February 2 online issue, follows a judgment by the UK General Medical Council’s Fitness to Practice Panel on January 28. “It has become clear that several elements of the 1998 paper by Wakefield et al are incorrect,” the editors wrote. “In particular, the claims in the original paper that children were ‘consecutively referred’ and that investigations were ‘approved’ by the local ethics committee have been proven to be false.” In 2004, 10 of the original authors retracted parts of the study, stating, “in this paper no causal link was established between MMR vaccine and autism as the data were insufficient.”
Advanced maternal age may be linked to an increased risk of autism, researchers reported in the February 8 online Autism Research. In a study of 12,159 cases of autism from a pool of almost 5 million births between 1990 and 1999, the investigators found a monotonic increased risk of autism related to advancing maternal age (40 and older) regardless of paternal age. However, the study authors noted fathers aged 40 and up who mated with women younger than 30 also had an increased risk of autistic offspring, compared with men in their mid- to late-20s. Yet when the mother was older than 30 and the father was 40 or older, the associated autism risk was similar to that of younger men. The investigators also noted that the “recent trend towards delaying childbearing contributed approximately a 4.6% increase in autism diagnoses in California over the decade.”
Depression and migraine headaches appear to share a common genetic factor, a Dutch study of 2,652 people found. As reported in the January 26 Neurology, researchers compared heritability estimates among members of the Erasmus Rucphen family for migraine with and without depression, and depression rates between migraineurs and controls. Of the total study population, 360 had migraines, 151 of whom experienced migraine aura as well. One-quarter of migraineurs also had depression, compared with 13% of the controls. Odds ratios for depression in patients with migraine were 1.29 for those without aura and 1.70 for those with aura. “There is a bidirectional association between depression and migraine, in particular migraine with aura, which can be explained, at least partly, by shared genetic factors,” the study authors noted.
The FDA has approved Ampyra (dalfampridine) extended-release tablets to improve walking in patients with multiple sclerosis (MS). In clinical trials, patients treated with dalfampridine had faster walking speeds than those treated with a placebo. It is the first report in which a drug for MS improved function that was lost as a result of the disease. The most common side effects reported were urinary tract infection, insomnia, dizziness, headache, nausea, and others. When taken in doses greater than 10 mg twice a day, seizures may occur. It should not be used in patients with moderate to severe kidney disease. Dalfampridine is distributed by Acorda Therapeutics Inc of Hawthorne, New York.
Black patients with multiple sclerosis showed increased tissue damage and higher lesion volumes compared with white patients, according to research in the February 16 Neurology. In a study of 567 patients, 488 of whom were white and 79 were black, investigators compared quantitative MRI evaluations including T1-, T2-, and gadolinium contrast-enhancing lesion volumes and contrast-enhancing number, global and tissue-specific brain atrophy, and magnetization transfer ratios (MTR) in lesions and normal-appearing gray matter (NAGM) and white matter (NAWM). The researchers found that MTR values in lesions and in NAGM and NAWM were significantly lower in black subjects than in whites, and T1- and T2- lesion volumes were greater, both of which indicate a more aggressive clinical disease.
Dopamine agonists can cause or exacerbate compulsive behaviors in patients with Parkinson’s, according to research published in the January 14 Neuron. “A constellation of pathological behaviors, including gambling, shopping, binge eating, and hypersexuality is seen in 17% of patients on dopamine agonists,” the study authors wrote. Because reinforcement learning algorithms allow for computation of prediction error, the researchers used a reinforcement learning model to deconstruct decision-making processes dysregulated by dopamine agonists in patients who are susceptible to compulsive behaviors. The investigators found that the medications increased the rate of learning from gain outcomes and increased striatal prediction error activity, signifying a “better than expected” outcome.
Patients with acute ischemic stroke admitted to the hospital on the weekend are more likely to receive t-PA than those admitted on a weekday, a study in the January Archives of Neurology reported. Researchers analyzed rates of t-PA administration, as well as death rates, among 78,657stroke patients admitted to Virginia hospitals between 1998 and 2006 and found weekend patients (n=20,279) were 20% more likely to receive t-PA than weekday patients (n=58,378). There was no statistically significant difference in patient mortality based on day of admission; however, because a greater percentage of weekend patients received t-PA while death rates remained equal, the study authors noted that those treated with t-PA may be more likely to die in the hospital.
Impaired cognitive function in elderly men may be an independent predictor of subsequent stroke, according to a report in the February 2 Neurology. In a study of 930 elderly men (mean age, 70), Swedish researchers found that taking longer to complete the Trail Making Test B increased stroke risk by as much as 300% for those in the highest quartile, compared with those in the lowest quartile. Each time increase of 1 SD was associated with a 1.48 higher risk of stroke. “Our results extend previous findings of cognitive decline as an independent predictor of stroke and indicate that the risk of brain infarction is increased already in the subclinical phase of cognitive deficit,” the study authors wrote.
Women with Down syndrome who experienced early menopause were almost twice as likely to develop dementia at a younger age than those who entered menopause later, according to research in the January Journal of Alzheimer’s Disease. In a prospective longitudinal cohort study of dementia and mortality in women with Down syndrome, researchers followed 85 postmenopausal subjects for an average of 4.3 years and found a significant correlation between the age at menopause onset and age at diagnosis of dementia. Subjects with an earlier onset of menopause had a 1.8-fold increased risk of dementia. In addition, women who experienced menopause earlier had a twofold increased risk of dying younger.
White, elderly cancer survivors have a reduced risk of developing Alzheimer’s disease, as reported in the January 12 Neurology. Conversely, patients with Alzheimer’s disease have a reduced cancer risk, investigators found. In a prospective cohort study of 3,020 subjects ages 65 and older, the presence of Alzheimer’s disease was associated with a reduced risk of cancer hospitalizations, after adjustments for demographic and other factors. Prevalent cancer was also associated with a reduced risk of Alzheimer’s disease among white subjects after the researchers adjusted for demographics, number of apolipoprotein ε4 alleles, hypertension, diabetes, and coronary heart disease. The opposite was found in minorities, although the sample size was considered too small. No significant association was found between cancer and vascular dementia.
Ginkgo biloba did not preserve cognitive function any better than a placebo, per a study in the December 23, 2009, JAMA. In the randomized, double-blind, placebo-controlled Ginkgo Evaluation of Memory study, researchers at six academic medical centers in the US tracked 3,069 community-dwelling subjects ages 72 to 96 years for an average of 6.1 years. Subjects were given either a twice-daily dose of 120 mg extract of Ginkgo biloba or a placebo. Cognition was measured as rates of change over time in the Modified Mini-Mental State Examination, the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and neuropsychologic domains of memory, attention, visual-spatial construction, language, and executive functions. Investigators found no significant difference in cognitive decline between the herb and placebo.
A decreased ability to smell is common in patients with Alzheimer’s disease and may be a useful early diagnostic tool, researchers reported in the January 13 Journal of Neuroscience. The study linked olfactory dysfunction with an accumulation of amyloid-β protein in Alzheimer’s disease model mice. “The usefulness of olfactory screens to serve as informative indicators of Alzheimer’s is precluded by a lack of knowledge regarding why the disease impacts olfaction,” the study authors stated. The investigators assayed olfactory perception and amyloid-β deposition in the genetically engineered mice and found that amyloid-β pathology first occurred in an area of the brain responsible for smelling. Mice with higher concentrations of amyloid-β also displayed olfactory dysfunction. Researchers noted the “odor cross-habitation test [was] a powerful behavioral assay…[which] may serve to monitor the efficacy of therapies aimed at reducing amyloid-β.”
The Lancet has retracted the 1998 paper by Wakefield et al that suggested a link between autism and the childhood measles, mumps, and rubella (MMR) vaccine. The retraction, published in the February 2 online issue, follows a judgment by the UK General Medical Council’s Fitness to Practice Panel on January 28. “It has become clear that several elements of the 1998 paper by Wakefield et al are incorrect,” the editors wrote. “In particular, the claims in the original paper that children were ‘consecutively referred’ and that investigations were ‘approved’ by the local ethics committee have been proven to be false.” In 2004, 10 of the original authors retracted parts of the study, stating, “in this paper no causal link was established between MMR vaccine and autism as the data were insufficient.”
Advanced maternal age may be linked to an increased risk of autism, researchers reported in the February 8 online Autism Research. In a study of 12,159 cases of autism from a pool of almost 5 million births between 1990 and 1999, the investigators found a monotonic increased risk of autism related to advancing maternal age (40 and older) regardless of paternal age. However, the study authors noted fathers aged 40 and up who mated with women younger than 30 also had an increased risk of autistic offspring, compared with men in their mid- to late-20s. Yet when the mother was older than 30 and the father was 40 or older, the associated autism risk was similar to that of younger men. The investigators also noted that the “recent trend towards delaying childbearing contributed approximately a 4.6% increase in autism diagnoses in California over the decade.”
Depression and migraine headaches appear to share a common genetic factor, a Dutch study of 2,652 people found. As reported in the January 26 Neurology, researchers compared heritability estimates among members of the Erasmus Rucphen family for migraine with and without depression, and depression rates between migraineurs and controls. Of the total study population, 360 had migraines, 151 of whom experienced migraine aura as well. One-quarter of migraineurs also had depression, compared with 13% of the controls. Odds ratios for depression in patients with migraine were 1.29 for those without aura and 1.70 for those with aura. “There is a bidirectional association between depression and migraine, in particular migraine with aura, which can be explained, at least partly, by shared genetic factors,” the study authors noted.
The FDA has approved Ampyra (dalfampridine) extended-release tablets to improve walking in patients with multiple sclerosis (MS). In clinical trials, patients treated with dalfampridine had faster walking speeds than those treated with a placebo. It is the first report in which a drug for MS improved function that was lost as a result of the disease. The most common side effects reported were urinary tract infection, insomnia, dizziness, headache, nausea, and others. When taken in doses greater than 10 mg twice a day, seizures may occur. It should not be used in patients with moderate to severe kidney disease. Dalfampridine is distributed by Acorda Therapeutics Inc of Hawthorne, New York.
Black patients with multiple sclerosis showed increased tissue damage and higher lesion volumes compared with white patients, according to research in the February 16 Neurology. In a study of 567 patients, 488 of whom were white and 79 were black, investigators compared quantitative MRI evaluations including T1-, T2-, and gadolinium contrast-enhancing lesion volumes and contrast-enhancing number, global and tissue-specific brain atrophy, and magnetization transfer ratios (MTR) in lesions and normal-appearing gray matter (NAGM) and white matter (NAWM). The researchers found that MTR values in lesions and in NAGM and NAWM were significantly lower in black subjects than in whites, and T1- and T2- lesion volumes were greater, both of which indicate a more aggressive clinical disease.
Dopamine agonists can cause or exacerbate compulsive behaviors in patients with Parkinson’s, according to research published in the January 14 Neuron. “A constellation of pathological behaviors, including gambling, shopping, binge eating, and hypersexuality is seen in 17% of patients on dopamine agonists,” the study authors wrote. Because reinforcement learning algorithms allow for computation of prediction error, the researchers used a reinforcement learning model to deconstruct decision-making processes dysregulated by dopamine agonists in patients who are susceptible to compulsive behaviors. The investigators found that the medications increased the rate of learning from gain outcomes and increased striatal prediction error activity, signifying a “better than expected” outcome.
Patients with acute ischemic stroke admitted to the hospital on the weekend are more likely to receive t-PA than those admitted on a weekday, a study in the January Archives of Neurology reported. Researchers analyzed rates of t-PA administration, as well as death rates, among 78,657stroke patients admitted to Virginia hospitals between 1998 and 2006 and found weekend patients (n=20,279) were 20% more likely to receive t-PA than weekday patients (n=58,378). There was no statistically significant difference in patient mortality based on day of admission; however, because a greater percentage of weekend patients received t-PA while death rates remained equal, the study authors noted that those treated with t-PA may be more likely to die in the hospital.
Impaired cognitive function in elderly men may be an independent predictor of subsequent stroke, according to a report in the February 2 Neurology. In a study of 930 elderly men (mean age, 70), Swedish researchers found that taking longer to complete the Trail Making Test B increased stroke risk by as much as 300% for those in the highest quartile, compared with those in the lowest quartile. Each time increase of 1 SD was associated with a 1.48 higher risk of stroke. “Our results extend previous findings of cognitive decline as an independent predictor of stroke and indicate that the risk of brain infarction is increased already in the subclinical phase of cognitive deficit,” the study authors wrote.
Women with Down syndrome who experienced early menopause were almost twice as likely to develop dementia at a younger age than those who entered menopause later, according to research in the January Journal of Alzheimer’s Disease. In a prospective longitudinal cohort study of dementia and mortality in women with Down syndrome, researchers followed 85 postmenopausal subjects for an average of 4.3 years and found a significant correlation between the age at menopause onset and age at diagnosis of dementia. Subjects with an earlier onset of menopause had a 1.8-fold increased risk of dementia. In addition, women who experienced menopause earlier had a twofold increased risk of dying younger.
White, elderly cancer survivors have a reduced risk of developing Alzheimer’s disease, as reported in the January 12 Neurology. Conversely, patients with Alzheimer’s disease have a reduced cancer risk, investigators found. In a prospective cohort study of 3,020 subjects ages 65 and older, the presence of Alzheimer’s disease was associated with a reduced risk of cancer hospitalizations, after adjustments for demographic and other factors. Prevalent cancer was also associated with a reduced risk of Alzheimer’s disease among white subjects after the researchers adjusted for demographics, number of apolipoprotein ε4 alleles, hypertension, diabetes, and coronary heart disease. The opposite was found in minorities, although the sample size was considered too small. No significant association was found between cancer and vascular dementia.
Ginkgo biloba did not preserve cognitive function any better than a placebo, per a study in the December 23, 2009, JAMA. In the randomized, double-blind, placebo-controlled Ginkgo Evaluation of Memory study, researchers at six academic medical centers in the US tracked 3,069 community-dwelling subjects ages 72 to 96 years for an average of 6.1 years. Subjects were given either a twice-daily dose of 120 mg extract of Ginkgo biloba or a placebo. Cognition was measured as rates of change over time in the Modified Mini-Mental State Examination, the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and neuropsychologic domains of memory, attention, visual-spatial construction, language, and executive functions. Investigators found no significant difference in cognitive decline between the herb and placebo.
A decreased ability to smell is common in patients with Alzheimer’s disease and may be a useful early diagnostic tool, researchers reported in the January 13 Journal of Neuroscience. The study linked olfactory dysfunction with an accumulation of amyloid-β protein in Alzheimer’s disease model mice. “The usefulness of olfactory screens to serve as informative indicators of Alzheimer’s is precluded by a lack of knowledge regarding why the disease impacts olfaction,” the study authors stated. The investigators assayed olfactory perception and amyloid-β deposition in the genetically engineered mice and found that amyloid-β pathology first occurred in an area of the brain responsible for smelling. Mice with higher concentrations of amyloid-β also displayed olfactory dysfunction. Researchers noted the “odor cross-habitation test [was] a powerful behavioral assay…[which] may serve to monitor the efficacy of therapies aimed at reducing amyloid-β.”
The Lancet has retracted the 1998 paper by Wakefield et al that suggested a link between autism and the childhood measles, mumps, and rubella (MMR) vaccine. The retraction, published in the February 2 online issue, follows a judgment by the UK General Medical Council’s Fitness to Practice Panel on January 28. “It has become clear that several elements of the 1998 paper by Wakefield et al are incorrect,” the editors wrote. “In particular, the claims in the original paper that children were ‘consecutively referred’ and that investigations were ‘approved’ by the local ethics committee have been proven to be false.” In 2004, 10 of the original authors retracted parts of the study, stating, “in this paper no causal link was established between MMR vaccine and autism as the data were insufficient.”
Advanced maternal age may be linked to an increased risk of autism, researchers reported in the February 8 online Autism Research. In a study of 12,159 cases of autism from a pool of almost 5 million births between 1990 and 1999, the investigators found a monotonic increased risk of autism related to advancing maternal age (40 and older) regardless of paternal age. However, the study authors noted fathers aged 40 and up who mated with women younger than 30 also had an increased risk of autistic offspring, compared with men in their mid- to late-20s. Yet when the mother was older than 30 and the father was 40 or older, the associated autism risk was similar to that of younger men. The investigators also noted that the “recent trend towards delaying childbearing contributed approximately a 4.6% increase in autism diagnoses in California over the decade.”
Depression and migraine headaches appear to share a common genetic factor, a Dutch study of 2,652 people found. As reported in the January 26 Neurology, researchers compared heritability estimates among members of the Erasmus Rucphen family for migraine with and without depression, and depression rates between migraineurs and controls. Of the total study population, 360 had migraines, 151 of whom experienced migraine aura as well. One-quarter of migraineurs also had depression, compared with 13% of the controls. Odds ratios for depression in patients with migraine were 1.29 for those without aura and 1.70 for those with aura. “There is a bidirectional association between depression and migraine, in particular migraine with aura, which can be explained, at least partly, by shared genetic factors,” the study authors noted.
The FDA has approved Ampyra (dalfampridine) extended-release tablets to improve walking in patients with multiple sclerosis (MS). In clinical trials, patients treated with dalfampridine had faster walking speeds than those treated with a placebo. It is the first report in which a drug for MS improved function that was lost as a result of the disease. The most common side effects reported were urinary tract infection, insomnia, dizziness, headache, nausea, and others. When taken in doses greater than 10 mg twice a day, seizures may occur. It should not be used in patients with moderate to severe kidney disease. Dalfampridine is distributed by Acorda Therapeutics Inc of Hawthorne, New York.
Black patients with multiple sclerosis showed increased tissue damage and higher lesion volumes compared with white patients, according to research in the February 16 Neurology. In a study of 567 patients, 488 of whom were white and 79 were black, investigators compared quantitative MRI evaluations including T1-, T2-, and gadolinium contrast-enhancing lesion volumes and contrast-enhancing number, global and tissue-specific brain atrophy, and magnetization transfer ratios (MTR) in lesions and normal-appearing gray matter (NAGM) and white matter (NAWM). The researchers found that MTR values in lesions and in NAGM and NAWM were significantly lower in black subjects than in whites, and T1- and T2- lesion volumes were greater, both of which indicate a more aggressive clinical disease.
Dopamine agonists can cause or exacerbate compulsive behaviors in patients with Parkinson’s, according to research published in the January 14 Neuron. “A constellation of pathological behaviors, including gambling, shopping, binge eating, and hypersexuality is seen in 17% of patients on dopamine agonists,” the study authors wrote. Because reinforcement learning algorithms allow for computation of prediction error, the researchers used a reinforcement learning model to deconstruct decision-making processes dysregulated by dopamine agonists in patients who are susceptible to compulsive behaviors. The investigators found that the medications increased the rate of learning from gain outcomes and increased striatal prediction error activity, signifying a “better than expected” outcome.
Patients with acute ischemic stroke admitted to the hospital on the weekend are more likely to receive t-PA than those admitted on a weekday, a study in the January Archives of Neurology reported. Researchers analyzed rates of t-PA administration, as well as death rates, among 78,657stroke patients admitted to Virginia hospitals between 1998 and 2006 and found weekend patients (n=20,279) were 20% more likely to receive t-PA than weekday patients (n=58,378). There was no statistically significant difference in patient mortality based on day of admission; however, because a greater percentage of weekend patients received t-PA while death rates remained equal, the study authors noted that those treated with t-PA may be more likely to die in the hospital.
Impaired cognitive function in elderly men may be an independent predictor of subsequent stroke, according to a report in the February 2 Neurology. In a study of 930 elderly men (mean age, 70), Swedish researchers found that taking longer to complete the Trail Making Test B increased stroke risk by as much as 300% for those in the highest quartile, compared with those in the lowest quartile. Each time increase of 1 SD was associated with a 1.48 higher risk of stroke. “Our results extend previous findings of cognitive decline as an independent predictor of stroke and indicate that the risk of brain infarction is increased already in the subclinical phase of cognitive deficit,” the study authors wrote.
News Roundup: New and Noteworthy Information
Increased muscle strength is associated with a reduced risk of Alzheimer’s disease and slower rate of cognitive decline in older persons, according to a report in the November Archives of Neurology. During a mean follow-up of 3.6 years, 138 persons without dementia at baseline developed Alzheimer’s disease. Each 1-U increase in muscle strength at baseline was associated with a 43% decrease for Alzheimer’s disease (hazard ratio [HR], 0.57). The association persisted after adjustment for BMI, physical activity, pulmonary function, vascular risk factors, vascular disease, and apolipoprotein ε 4 status. “In a mixed-effects model adjusted for age, sex, education status, and baseline level of global cognition, increased muscle strength was associated with a slower rate of decline in global cognitive function,” researchers stated. Muscle strength was also associated with a decreased risk of MCI (HR, 0.67).
Patients with early Alzheimer’s disease show decreased gray matter volume in the medial frontal and temporo-parietal cortices that is associated with loss of independence in daily living activities, according to a study in the October 8 online Journal of Alzheimer’s Disease. Researchers observed 56 persons without dementia and 58 patients with early-stage Alzheimer’s disease, using MRI and a comprehensive cognitive and physical evaluation. “Imaging evidence revealed that in Alzheimer’s disease, regional gray matter atrophy measures in medial frontal and temporo-parietal areas were related to decreased cognition, physical function, and independence,” the investigators stated. “Loss of independence in early Alzheimer’s disease is closely related to impaired cognition associated with performing complex behaviors.”
Smoking may be an established risk factor for sporadic amyotrophic lateral sclerosis (ALS), according to a study published in the November 17 Neurology. The study was a follow-up to a 2003 evidenced-based review of exogenous risk factors. The current study, based on a Medline literature search for the terms smoking, ALS (or amyotrophic lateral sclerosis), and MND (or motor neuron disease), conducted between 2003 and April 2009, yielded seven articles meeting inclusion criteria. One study of class II evidence and one of class III evidence showed an increased risk of ALS with smoking. A dose-response effect was seen with the class II study. “Evidence-based analysis of epidemiologic data shows concordance among results of better-designed studies linking smoking to ALS, and lets those results drive the conclusions,” investigators stated.
The FDA has approved a 30-mg dose of Focalin XR (dexmethylphenidate HCl) extended-release capsules for the treatment of patients with ADHD. The increased dose provides physicians with an additional treatment option that offers statistically significant improvement of symptoms for up to 12 hours, compared with placebo. Data regarding doses of 30 mg/day in children and 40 mg/day in adults supported the approval of the new increased dose formulation. A randomized, double-blind, crossover study involving 165 children with ADHD (ages 6 to 12) showed that 30 mg of the drug provided significantly greater improvement in symptoms, compared with a 20-mg dose. The most common adverse events were decreased appetite, increased heart rate, headache, and abdominal pain (28.2% [30 mg]; 21.6% [20 mg]; and 17.6% [placebo]). Focalin XR is manufactured by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Dysport (abobotulinumtoxinA) is now commercially available in the United States for the treatment of cervical dystonia in adults. The FDA approved Dysport in April 2009 based on two phase III studies. Less than 5% of those treated experienced adverse events, which include muscular weakness, dysphagia, dysphonia, and injection site discomfort, among others. Dysport is marketed by the US-based affiliate of Ipsen in Brisbane, California.
Frontotemporal lobar degeneration (FTLD) is a highly heritable disorder, but heritability varies among the different clinical subtypes, researchers reported in the November 3 Neurology. Blood samples were collected from 225 patients with a diagnosis within the FTLD spectrum, and family history scores (1 to 4) were given to each family. “A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had clear autosomal dominant history (score of 1),” the investigators reported. “Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable.” Mutations were found in MAPT and GRN genes (8.9% and 8.4%, respectively), but not in VCP, CHMP2B, or TARDP.
Rates of intrauterine growth restriction and cesarean delivery are only marginally higher for women with epilepsy and multiple sclerosis (MS) than they are for the general obstetric population, according to a study in the November 18 onlineNeurology. In addition, no increase was observed regarding other adverse pregnancy outcomes in these patients. Researchers used the 2003 to 2006 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to determine the number of deliveries to women with MS, epilepsy, diabetes mellitus, and the general obstetric population. “MS was associated with mildly increased odds of antenatal hospitalization (odds ratio [OR], 1.3) intrauterine growth restriction (OR, 1.7), and cesarean delivery (OR, 1.3),” investigators stated. “Similarly, epilepsy was associated with increased rates of antenatal hospitalization (OR, 3.0), intrauterine growth restriction (OR, 1.9), and cesarean delivery (OR, 1.5).”
Obesity in adolescence is associated with an increased risk for multiple sclerosis (MS), according to a study in the November 10 Neurology. Women in the Nurses’ Health Study and the Nurses Health Study II provided information on their weight at age 18, as well as their weight and height at baseline. They then selected silhouettes representing their body at ages 5, 10, and 20. A total of 593 cases of MS were confirmed during 40 years of follow-up in both cohorts. “Obesity at age 18 (BMI >= 30 kg/m2) was associated with a greater than twofold increased risk of MS (multivariate relative risk, pooled = 2.25),” the investigators stated. Large body size at ages 5 or 10 was not associated with risk of MS, but at age 20 it was associated with a 96% increased risk.
The FDA has approved Qutenza (capsaicin) 8% patch, for the management of neuropathic pain due to postherpetic neuralgia that can follow shingles. Qutenza is the first and only product that contains prescription-strength capsaicin. Postherpetic neuralgia pain was reduced for up to 12 weeks following a single one-hour treatment in clinical studies. The drug is locally acting and nonnarcotic, and is unlikely to cause drowsiness or adverse drug-drug interactions. The most common adverse reactions included application site redness, pain, itching, and papules. Qutenza is manufactured by NeurogesX, Inc in San Mateo, California, and will be available in the US in the first half of 2010.
Estrogen replacement therapy is not beneficial to stroke patients who have been without estrogen for a long period, researchers reported in the November 4Journal of Neuroscience. Investigators sought to elucidate the mechanisms of 17 β -estradiol (E2) antioxidant and neuroprotective actions in stroke. It appears that estrogen receptors on brain cells diminish significantly when estrogen therapy is delayed, along with typical neuroprotection effects. “As a whole, the study reveals a novel, membrane-mediated antioxidant mechanism in neurons by E2 provides support and mechanistic insights for a ‘critical period’ of E2 replacement in the hippocampus and demonstrates a heretofore unknown hypersensitivity of the CA3/CA4 to ischemic injury after prolonged hypoestrogenicity,” the researchers concluded.
Moderate to heavy physical activity is protective against the risk of isch emic stroke in men, independent of other risk factors, investigators reported in the November 24 Neurology. In the Northern Manhattan Study, the researchers included a prospective cohort of older, urban-dwelling, multiethnic, stroke-free individuals. In 40.5% of the cohort, physical inactivity was present. Over a median follow-up of 9.1 years, 238 incident ischemic strokes occurred. “Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65). “Engaging in any physical activity versus none (adjusted HR, 1.16), and energy expended in kcal/wk (adjusted HR per 500-unit increase, 1.01) were not associated with ischemic stroke risk,” the authors stated. “There was an interaction of sex with intensity of physical activity, such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR, 0.37), but not in women (adjusted HR, 0.92).”
—Laura Sassano
Increased muscle strength is associated with a reduced risk of Alzheimer’s disease and slower rate of cognitive decline in older persons, according to a report in the November Archives of Neurology. During a mean follow-up of 3.6 years, 138 persons without dementia at baseline developed Alzheimer’s disease. Each 1-U increase in muscle strength at baseline was associated with a 43% decrease for Alzheimer’s disease (hazard ratio [HR], 0.57). The association persisted after adjustment for BMI, physical activity, pulmonary function, vascular risk factors, vascular disease, and apolipoprotein ε 4 status. “In a mixed-effects model adjusted for age, sex, education status, and baseline level of global cognition, increased muscle strength was associated with a slower rate of decline in global cognitive function,” researchers stated. Muscle strength was also associated with a decreased risk of MCI (HR, 0.67).
Patients with early Alzheimer’s disease show decreased gray matter volume in the medial frontal and temporo-parietal cortices that is associated with loss of independence in daily living activities, according to a study in the October 8 online Journal of Alzheimer’s Disease. Researchers observed 56 persons without dementia and 58 patients with early-stage Alzheimer’s disease, using MRI and a comprehensive cognitive and physical evaluation. “Imaging evidence revealed that in Alzheimer’s disease, regional gray matter atrophy measures in medial frontal and temporo-parietal areas were related to decreased cognition, physical function, and independence,” the investigators stated. “Loss of independence in early Alzheimer’s disease is closely related to impaired cognition associated with performing complex behaviors.”
Smoking may be an established risk factor for sporadic amyotrophic lateral sclerosis (ALS), according to a study published in the November 17 Neurology. The study was a follow-up to a 2003 evidenced-based review of exogenous risk factors. The current study, based on a Medline literature search for the terms smoking, ALS (or amyotrophic lateral sclerosis), and MND (or motor neuron disease), conducted between 2003 and April 2009, yielded seven articles meeting inclusion criteria. One study of class II evidence and one of class III evidence showed an increased risk of ALS with smoking. A dose-response effect was seen with the class II study. “Evidence-based analysis of epidemiologic data shows concordance among results of better-designed studies linking smoking to ALS, and lets those results drive the conclusions,” investigators stated.
The FDA has approved a 30-mg dose of Focalin XR (dexmethylphenidate HCl) extended-release capsules for the treatment of patients with ADHD. The increased dose provides physicians with an additional treatment option that offers statistically significant improvement of symptoms for up to 12 hours, compared with placebo. Data regarding doses of 30 mg/day in children and 40 mg/day in adults supported the approval of the new increased dose formulation. A randomized, double-blind, crossover study involving 165 children with ADHD (ages 6 to 12) showed that 30 mg of the drug provided significantly greater improvement in symptoms, compared with a 20-mg dose. The most common adverse events were decreased appetite, increased heart rate, headache, and abdominal pain (28.2% [30 mg]; 21.6% [20 mg]; and 17.6% [placebo]). Focalin XR is manufactured by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Dysport (abobotulinumtoxinA) is now commercially available in the United States for the treatment of cervical dystonia in adults. The FDA approved Dysport in April 2009 based on two phase III studies. Less than 5% of those treated experienced adverse events, which include muscular weakness, dysphagia, dysphonia, and injection site discomfort, among others. Dysport is marketed by the US-based affiliate of Ipsen in Brisbane, California.
Frontotemporal lobar degeneration (FTLD) is a highly heritable disorder, but heritability varies among the different clinical subtypes, researchers reported in the November 3 Neurology. Blood samples were collected from 225 patients with a diagnosis within the FTLD spectrum, and family history scores (1 to 4) were given to each family. “A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had clear autosomal dominant history (score of 1),” the investigators reported. “Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable.” Mutations were found in MAPT and GRN genes (8.9% and 8.4%, respectively), but not in VCP, CHMP2B, or TARDP.
Rates of intrauterine growth restriction and cesarean delivery are only marginally higher for women with epilepsy and multiple sclerosis (MS) than they are for the general obstetric population, according to a study in the November 18 onlineNeurology. In addition, no increase was observed regarding other adverse pregnancy outcomes in these patients. Researchers used the 2003 to 2006 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to determine the number of deliveries to women with MS, epilepsy, diabetes mellitus, and the general obstetric population. “MS was associated with mildly increased odds of antenatal hospitalization (odds ratio [OR], 1.3) intrauterine growth restriction (OR, 1.7), and cesarean delivery (OR, 1.3),” investigators stated. “Similarly, epilepsy was associated with increased rates of antenatal hospitalization (OR, 3.0), intrauterine growth restriction (OR, 1.9), and cesarean delivery (OR, 1.5).”
Obesity in adolescence is associated with an increased risk for multiple sclerosis (MS), according to a study in the November 10 Neurology. Women in the Nurses’ Health Study and the Nurses Health Study II provided information on their weight at age 18, as well as their weight and height at baseline. They then selected silhouettes representing their body at ages 5, 10, and 20. A total of 593 cases of MS were confirmed during 40 years of follow-up in both cohorts. “Obesity at age 18 (BMI >= 30 kg/m2) was associated with a greater than twofold increased risk of MS (multivariate relative risk, pooled = 2.25),” the investigators stated. Large body size at ages 5 or 10 was not associated with risk of MS, but at age 20 it was associated with a 96% increased risk.
The FDA has approved Qutenza (capsaicin) 8% patch, for the management of neuropathic pain due to postherpetic neuralgia that can follow shingles. Qutenza is the first and only product that contains prescription-strength capsaicin. Postherpetic neuralgia pain was reduced for up to 12 weeks following a single one-hour treatment in clinical studies. The drug is locally acting and nonnarcotic, and is unlikely to cause drowsiness or adverse drug-drug interactions. The most common adverse reactions included application site redness, pain, itching, and papules. Qutenza is manufactured by NeurogesX, Inc in San Mateo, California, and will be available in the US in the first half of 2010.
Estrogen replacement therapy is not beneficial to stroke patients who have been without estrogen for a long period, researchers reported in the November 4Journal of Neuroscience. Investigators sought to elucidate the mechanisms of 17 β -estradiol (E2) antioxidant and neuroprotective actions in stroke. It appears that estrogen receptors on brain cells diminish significantly when estrogen therapy is delayed, along with typical neuroprotection effects. “As a whole, the study reveals a novel, membrane-mediated antioxidant mechanism in neurons by E2 provides support and mechanistic insights for a ‘critical period’ of E2 replacement in the hippocampus and demonstrates a heretofore unknown hypersensitivity of the CA3/CA4 to ischemic injury after prolonged hypoestrogenicity,” the researchers concluded.
Moderate to heavy physical activity is protective against the risk of isch emic stroke in men, independent of other risk factors, investigators reported in the November 24 Neurology. In the Northern Manhattan Study, the researchers included a prospective cohort of older, urban-dwelling, multiethnic, stroke-free individuals. In 40.5% of the cohort, physical inactivity was present. Over a median follow-up of 9.1 years, 238 incident ischemic strokes occurred. “Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65). “Engaging in any physical activity versus none (adjusted HR, 1.16), and energy expended in kcal/wk (adjusted HR per 500-unit increase, 1.01) were not associated with ischemic stroke risk,” the authors stated. “There was an interaction of sex with intensity of physical activity, such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR, 0.37), but not in women (adjusted HR, 0.92).”
—Laura Sassano
Increased muscle strength is associated with a reduced risk of Alzheimer’s disease and slower rate of cognitive decline in older persons, according to a report in the November Archives of Neurology. During a mean follow-up of 3.6 years, 138 persons without dementia at baseline developed Alzheimer’s disease. Each 1-U increase in muscle strength at baseline was associated with a 43% decrease for Alzheimer’s disease (hazard ratio [HR], 0.57). The association persisted after adjustment for BMI, physical activity, pulmonary function, vascular risk factors, vascular disease, and apolipoprotein ε 4 status. “In a mixed-effects model adjusted for age, sex, education status, and baseline level of global cognition, increased muscle strength was associated with a slower rate of decline in global cognitive function,” researchers stated. Muscle strength was also associated with a decreased risk of MCI (HR, 0.67).
Patients with early Alzheimer’s disease show decreased gray matter volume in the medial frontal and temporo-parietal cortices that is associated with loss of independence in daily living activities, according to a study in the October 8 online Journal of Alzheimer’s Disease. Researchers observed 56 persons without dementia and 58 patients with early-stage Alzheimer’s disease, using MRI and a comprehensive cognitive and physical evaluation. “Imaging evidence revealed that in Alzheimer’s disease, regional gray matter atrophy measures in medial frontal and temporo-parietal areas were related to decreased cognition, physical function, and independence,” the investigators stated. “Loss of independence in early Alzheimer’s disease is closely related to impaired cognition associated with performing complex behaviors.”
Smoking may be an established risk factor for sporadic amyotrophic lateral sclerosis (ALS), according to a study published in the November 17 Neurology. The study was a follow-up to a 2003 evidenced-based review of exogenous risk factors. The current study, based on a Medline literature search for the terms smoking, ALS (or amyotrophic lateral sclerosis), and MND (or motor neuron disease), conducted between 2003 and April 2009, yielded seven articles meeting inclusion criteria. One study of class II evidence and one of class III evidence showed an increased risk of ALS with smoking. A dose-response effect was seen with the class II study. “Evidence-based analysis of epidemiologic data shows concordance among results of better-designed studies linking smoking to ALS, and lets those results drive the conclusions,” investigators stated.
The FDA has approved a 30-mg dose of Focalin XR (dexmethylphenidate HCl) extended-release capsules for the treatment of patients with ADHD. The increased dose provides physicians with an additional treatment option that offers statistically significant improvement of symptoms for up to 12 hours, compared with placebo. Data regarding doses of 30 mg/day in children and 40 mg/day in adults supported the approval of the new increased dose formulation. A randomized, double-blind, crossover study involving 165 children with ADHD (ages 6 to 12) showed that 30 mg of the drug provided significantly greater improvement in symptoms, compared with a 20-mg dose. The most common adverse events were decreased appetite, increased heart rate, headache, and abdominal pain (28.2% [30 mg]; 21.6% [20 mg]; and 17.6% [placebo]). Focalin XR is manufactured by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Dysport (abobotulinumtoxinA) is now commercially available in the United States for the treatment of cervical dystonia in adults. The FDA approved Dysport in April 2009 based on two phase III studies. Less than 5% of those treated experienced adverse events, which include muscular weakness, dysphagia, dysphonia, and injection site discomfort, among others. Dysport is marketed by the US-based affiliate of Ipsen in Brisbane, California.
Frontotemporal lobar degeneration (FTLD) is a highly heritable disorder, but heritability varies among the different clinical subtypes, researchers reported in the November 3 Neurology. Blood samples were collected from 225 patients with a diagnosis within the FTLD spectrum, and family history scores (1 to 4) were given to each family. “A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had clear autosomal dominant history (score of 1),” the investigators reported. “Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable.” Mutations were found in MAPT and GRN genes (8.9% and 8.4%, respectively), but not in VCP, CHMP2B, or TARDP.
Rates of intrauterine growth restriction and cesarean delivery are only marginally higher for women with epilepsy and multiple sclerosis (MS) than they are for the general obstetric population, according to a study in the November 18 onlineNeurology. In addition, no increase was observed regarding other adverse pregnancy outcomes in these patients. Researchers used the 2003 to 2006 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to determine the number of deliveries to women with MS, epilepsy, diabetes mellitus, and the general obstetric population. “MS was associated with mildly increased odds of antenatal hospitalization (odds ratio [OR], 1.3) intrauterine growth restriction (OR, 1.7), and cesarean delivery (OR, 1.3),” investigators stated. “Similarly, epilepsy was associated with increased rates of antenatal hospitalization (OR, 3.0), intrauterine growth restriction (OR, 1.9), and cesarean delivery (OR, 1.5).”
Obesity in adolescence is associated with an increased risk for multiple sclerosis (MS), according to a study in the November 10 Neurology. Women in the Nurses’ Health Study and the Nurses Health Study II provided information on their weight at age 18, as well as their weight and height at baseline. They then selected silhouettes representing their body at ages 5, 10, and 20. A total of 593 cases of MS were confirmed during 40 years of follow-up in both cohorts. “Obesity at age 18 (BMI >= 30 kg/m2) was associated with a greater than twofold increased risk of MS (multivariate relative risk, pooled = 2.25),” the investigators stated. Large body size at ages 5 or 10 was not associated with risk of MS, but at age 20 it was associated with a 96% increased risk.
The FDA has approved Qutenza (capsaicin) 8% patch, for the management of neuropathic pain due to postherpetic neuralgia that can follow shingles. Qutenza is the first and only product that contains prescription-strength capsaicin. Postherpetic neuralgia pain was reduced for up to 12 weeks following a single one-hour treatment in clinical studies. The drug is locally acting and nonnarcotic, and is unlikely to cause drowsiness or adverse drug-drug interactions. The most common adverse reactions included application site redness, pain, itching, and papules. Qutenza is manufactured by NeurogesX, Inc in San Mateo, California, and will be available in the US in the first half of 2010.
Estrogen replacement therapy is not beneficial to stroke patients who have been without estrogen for a long period, researchers reported in the November 4Journal of Neuroscience. Investigators sought to elucidate the mechanisms of 17 β -estradiol (E2) antioxidant and neuroprotective actions in stroke. It appears that estrogen receptors on brain cells diminish significantly when estrogen therapy is delayed, along with typical neuroprotection effects. “As a whole, the study reveals a novel, membrane-mediated antioxidant mechanism in neurons by E2 provides support and mechanistic insights for a ‘critical period’ of E2 replacement in the hippocampus and demonstrates a heretofore unknown hypersensitivity of the CA3/CA4 to ischemic injury after prolonged hypoestrogenicity,” the researchers concluded.
Moderate to heavy physical activity is protective against the risk of isch emic stroke in men, independent of other risk factors, investigators reported in the November 24 Neurology. In the Northern Manhattan Study, the researchers included a prospective cohort of older, urban-dwelling, multiethnic, stroke-free individuals. In 40.5% of the cohort, physical inactivity was present. Over a median follow-up of 9.1 years, 238 incident ischemic strokes occurred. “Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65). “Engaging in any physical activity versus none (adjusted HR, 1.16), and energy expended in kcal/wk (adjusted HR per 500-unit increase, 1.01) were not associated with ischemic stroke risk,” the authors stated. “There was an interaction of sex with intensity of physical activity, such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR, 0.37), but not in women (adjusted HR, 0.92).”
—Laura Sassano
News Roundup: New and Noteworthy Information
Higher diastolic blood pressure (DBP) is cross-sectionally and independently associated with cognitive impairment, investigators reported in the August 25 Neurology. The association was found after adjusting for economic factors, depressive symptoms, and current use of any antihyperintensive medication in 30,228 black and white men and women (45 and older). “An increment of 10 mm Hg in DBP was associated with a 7% higher odds of cognitive impairment,” the researchers stated. “No independent association was identified between impaired cognitive status and systolic blood pressure (odds ratio [OR], 1.02) or pulse pressure (OR, 0.99).” No evidence of nonlinear relationships between any blood pressure components and impaired cognitive status was found.
Use of smokeless tobacco products is associated with risk of fatal myocardial infarction and stroke, according to the August 18 online BMJ. Investigators from Sweden and the United States conducted a meta-analysis of 11 observational studies (primarily including men). “Eight risk estimates were available for fatal myocardial infarction: the relative risk for ever use of smokeless tobacco products was 1.13 and the excess risk was restricted to current users,” the investigators stated. “The relative risk of fatal stroke, on the basis of five risk estimates, was 1.40.” Increased risk of fatal myocardial infarction was shown in studies from both geographic locations. “Data on dose-response were limited but did not suggest a strong relation between risk of dying from either disease and frequency or duration of use of smokeless tobacco products,” the researchers noted.
A mutation in transcriptional repressor hDEC2-P385R is associated with a human short sleep phenotype, according to a study in the August 14 issue of Science. Investigators found that within a small extended family, two members with the mutation had lifelong shorter daily sleep requirements than most persons. The researchers then genetically engineered mice and fruit flies to express the mutated human gene and studied its impact on behavior and sleep patterns. “Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner,” the study authors stated. “These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.”
The FDA has approved Extavia for reducing the frequency of clinical exacerbations in patients with relapsing forms of multiple sclerosis (MS). It is also indicated in patients who have had a first clinical episode of MS and have features consistent with the disease as shown by MRI. Extavia is a new branded version of interferon beta-1b and the same medicinal product as Betaseron. Interferon beta-1b has been shown to reduce annualized relapse rates by 34%, with patients nearly twice as likely to remain relapse-free for more than two years, compared with those receiving placebo. Injection site necrosis has been reported in 4% of patients in controlled trials, and anaphylaxis has been reported as a rare complication of interferon use. Extavia is marketed by the Pharmaceuticals Division of Novartis (East Hanover, NJ) and is expected to be available this fall.
White matter hyperintensity (WMH) is more strongly related to amnestic mild cognitive impairment (aMCI), and infarcts are more strongly related to nonamnestic MCI, according to a study in the August 11 issue of Neurology. Researchers investigated the relationship of WMH volume and infarcts in brain per MRI to MCI in 679 elderly persons without dementia. WMH was adjusted for total cranial volume, and MCI was defined using the Peterson criteria. WMH was more strongly related to aMCI (OR, 1.9) than nonamnestic MCI (OR, 1.6). However, infarcts were more strongly related to nonamnestic MCI (OR, 2.7) than aMCI (OR, 1.4). “In secondary analyses using continuous cognitive scores as outcomes, WMH, but not infarcts, were related to memory, while infarcts were more strongly related with nonamnestic domains,” the researchers noted. “The nature of WMH in aMCI requires further study,” they concluded.
Intellectually normal children with seizures had neuropsychologic deficits at seizure onset, per a study published in the August 18 issue of Neurology. Investigators compared 282 children between ages 6 and 14 who had an IQ of 70 or higher and with a first recognized seizure to 147 healthy siblings. “In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychologic deficits at or near onset,” the researchers stated. Risk factors included multiple seizures (ie, second unprovoked seizure, odds ratio [OR], 1.96), use of antiepileptic drugs (OR, 2.27), symptomatic/cryptogenic etiology (OR, 2.15), and epileptiform activity on the initial EEG (OR, 1.96). Increased odds for neuropsychologic impairment were associated with absence epilepsy (OR, 2.00).
The H5N1 avian influenza virus may increase the risk for Parkinson’s disease and other neurologic disorders, according to a report in the August 10 online Proceedings of the National Academy of Sciences. In a mouse model, investigators showed that the virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. “In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection,” the researchers stated. A significant loss in dopaminergic neurons in the substantia nigra pars compacta was also observed, 60 days after infection. “Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson’s and Alzheimer’s diseases,” the investigators concluded.
The FDA has approved Sabril (vigabatrin) tablets and oral solution for two difficult-to-treat epilepsies. Vigabatrin is indicated as monotherapy for pediatric patients ages 1 month to 2 years with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss, and as adjunctive add-on therapy in adults with refractory complex partial seizures who have not responded to alternative treatments, and for whom the potential benefits outweigh the risk of vision loss. Vigabatrin use has been linked to permanent bilateral concentric visual field constriction in 30% or more of patients that ranges in severity from mild to severe. Vigabatrin is manufactured by Lundbeck, Inc (Deerfield, Illinois).
Compared with women without epilepsy, epileptic seizures during pregnancy increased the risk for low-birth-weight infants, preterm delivery, and small for gestational age by 1.36-fold, 1.63-fold, and 1.37-fold, respectively, according to a study in the August Archives of Neurology. Researchers in Taiwan matched 1,016 women with epilepsy with single births from 2001 to 2003 and who had been diagnosed with epilepsy in the two years prior to index delivery with 8,128 women without chronic disease. The authors then compared women with epilepsy who had seizures during pregnancy to women with epilepsy who did not have seizures and found that the risk of infants being small for gestational age increased most significantly (odds ratio, 1.34) among those who had seizures during pregnancy.
P2X7 receptor antagonist, Brilliant blue G (BBG), reduced spinal cord anatomic damage and improved motor recovery in rats without evident toxicity when administered 15 minutes after injury, researchers reported in the July 28 Proceedings of the National Academy of Sciences. Treatment with BBG, a derivative of a commonly used food color (FD&C blue No. 1) that is used to give M&Ms and Gatorade their blue tint, also directly reduced local activation of astrocytes and microglia, in addition to neutrophil infiltration. “These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses,” investigators stated. “Systemic administration of BBG may thus comprise a readily feasible approach by which to treat spinal cord injury in humans.”
Although angiotensin-converting enzyme (ACE) inhibitors as a class do not appear to be associated with dementia risk or cognitive decline in older, hypertensive (HTN) adults, within-class differences may occur regarding these outcomes, suggests a study in the July 13 Archives of Internal Medicine. Investigators identified 158 cases of dementia among 414 participants who were exposed to ACE inhibitors and 640 who were not. There was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01). “However, centrally active ACE inhibitors were associated with 65% less decline in Modified Mini-Mental State Examination scores per year of exposure, and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20) and greater odds of disability in instrumental activities of daily living (adjusted OR, 1.16), compared with other anti-hypertension drugs,” investigators reported.
Researchers have found an association between the cytochrome P450 (CYP) 2C19*2 variant and diminished platelet response to clopidogrel treatment and poor cardiovascular outcomes, according to a study in the August 26 JAMA. Clopidogrel was administered for seven days to 429 healthy Amish persons. “Thirteen single-nucleotide polymorphisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with diminished clopidogrel response, with a high degree of statistical significance,” noted the study authors. “The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention.” In addition, those with the variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death in one year of follow-up.
Intramuscular AVI-4658 induces the expression of dystrophin, benefiting patients with Duchenne muscular dystrophy, according to a study in the August 26 online Lancet Neurology. Investigators assessed the safety of AVI-4658.Two patients received 0.09 mg AVI-4658 in 900 µl (0.9%) saline, and five received 0.9 mg AVI-4658 in 900 µl saline. “In randomly chosen sections of treated EDB muscles, the mean intensity of dystrophin staining ranged from 22% to 32% of the mean intensity of dystrophin in healthy control muscles (mean, 26.4%), and the mean intensity was 17% (range, 11% to 21%) greater than the intensity in the contralateral saline-treated muscle,” the researchers stated. “In the dystrophin-positive fibers, the intensity of dystrophin staining was up to 42% of that in healthy muscle.”
Higher diastolic blood pressure (DBP) is cross-sectionally and independently associated with cognitive impairment, investigators reported in the August 25 Neurology. The association was found after adjusting for economic factors, depressive symptoms, and current use of any antihyperintensive medication in 30,228 black and white men and women (45 and older). “An increment of 10 mm Hg in DBP was associated with a 7% higher odds of cognitive impairment,” the researchers stated. “No independent association was identified between impaired cognitive status and systolic blood pressure (odds ratio [OR], 1.02) or pulse pressure (OR, 0.99).” No evidence of nonlinear relationships between any blood pressure components and impaired cognitive status was found.
Use of smokeless tobacco products is associated with risk of fatal myocardial infarction and stroke, according to the August 18 online BMJ. Investigators from Sweden and the United States conducted a meta-analysis of 11 observational studies (primarily including men). “Eight risk estimates were available for fatal myocardial infarction: the relative risk for ever use of smokeless tobacco products was 1.13 and the excess risk was restricted to current users,” the investigators stated. “The relative risk of fatal stroke, on the basis of five risk estimates, was 1.40.” Increased risk of fatal myocardial infarction was shown in studies from both geographic locations. “Data on dose-response were limited but did not suggest a strong relation between risk of dying from either disease and frequency or duration of use of smokeless tobacco products,” the researchers noted.
A mutation in transcriptional repressor hDEC2-P385R is associated with a human short sleep phenotype, according to a study in the August 14 issue of Science. Investigators found that within a small extended family, two members with the mutation had lifelong shorter daily sleep requirements than most persons. The researchers then genetically engineered mice and fruit flies to express the mutated human gene and studied its impact on behavior and sleep patterns. “Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner,” the study authors stated. “These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.”
The FDA has approved Extavia for reducing the frequency of clinical exacerbations in patients with relapsing forms of multiple sclerosis (MS). It is also indicated in patients who have had a first clinical episode of MS and have features consistent with the disease as shown by MRI. Extavia is a new branded version of interferon beta-1b and the same medicinal product as Betaseron. Interferon beta-1b has been shown to reduce annualized relapse rates by 34%, with patients nearly twice as likely to remain relapse-free for more than two years, compared with those receiving placebo. Injection site necrosis has been reported in 4% of patients in controlled trials, and anaphylaxis has been reported as a rare complication of interferon use. Extavia is marketed by the Pharmaceuticals Division of Novartis (East Hanover, NJ) and is expected to be available this fall.
White matter hyperintensity (WMH) is more strongly related to amnestic mild cognitive impairment (aMCI), and infarcts are more strongly related to nonamnestic MCI, according to a study in the August 11 issue of Neurology. Researchers investigated the relationship of WMH volume and infarcts in brain per MRI to MCI in 679 elderly persons without dementia. WMH was adjusted for total cranial volume, and MCI was defined using the Peterson criteria. WMH was more strongly related to aMCI (OR, 1.9) than nonamnestic MCI (OR, 1.6). However, infarcts were more strongly related to nonamnestic MCI (OR, 2.7) than aMCI (OR, 1.4). “In secondary analyses using continuous cognitive scores as outcomes, WMH, but not infarcts, were related to memory, while infarcts were more strongly related with nonamnestic domains,” the researchers noted. “The nature of WMH in aMCI requires further study,” they concluded.
Intellectually normal children with seizures had neuropsychologic deficits at seizure onset, per a study published in the August 18 issue of Neurology. Investigators compared 282 children between ages 6 and 14 who had an IQ of 70 or higher and with a first recognized seizure to 147 healthy siblings. “In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychologic deficits at or near onset,” the researchers stated. Risk factors included multiple seizures (ie, second unprovoked seizure, odds ratio [OR], 1.96), use of antiepileptic drugs (OR, 2.27), symptomatic/cryptogenic etiology (OR, 2.15), and epileptiform activity on the initial EEG (OR, 1.96). Increased odds for neuropsychologic impairment were associated with absence epilepsy (OR, 2.00).
The H5N1 avian influenza virus may increase the risk for Parkinson’s disease and other neurologic disorders, according to a report in the August 10 online Proceedings of the National Academy of Sciences. In a mouse model, investigators showed that the virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. “In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection,” the researchers stated. A significant loss in dopaminergic neurons in the substantia nigra pars compacta was also observed, 60 days after infection. “Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson’s and Alzheimer’s diseases,” the investigators concluded.
The FDA has approved Sabril (vigabatrin) tablets and oral solution for two difficult-to-treat epilepsies. Vigabatrin is indicated as monotherapy for pediatric patients ages 1 month to 2 years with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss, and as adjunctive add-on therapy in adults with refractory complex partial seizures who have not responded to alternative treatments, and for whom the potential benefits outweigh the risk of vision loss. Vigabatrin use has been linked to permanent bilateral concentric visual field constriction in 30% or more of patients that ranges in severity from mild to severe. Vigabatrin is manufactured by Lundbeck, Inc (Deerfield, Illinois).
Compared with women without epilepsy, epileptic seizures during pregnancy increased the risk for low-birth-weight infants, preterm delivery, and small for gestational age by 1.36-fold, 1.63-fold, and 1.37-fold, respectively, according to a study in the August Archives of Neurology. Researchers in Taiwan matched 1,016 women with epilepsy with single births from 2001 to 2003 and who had been diagnosed with epilepsy in the two years prior to index delivery with 8,128 women without chronic disease. The authors then compared women with epilepsy who had seizures during pregnancy to women with epilepsy who did not have seizures and found that the risk of infants being small for gestational age increased most significantly (odds ratio, 1.34) among those who had seizures during pregnancy.
P2X7 receptor antagonist, Brilliant blue G (BBG), reduced spinal cord anatomic damage and improved motor recovery in rats without evident toxicity when administered 15 minutes after injury, researchers reported in the July 28 Proceedings of the National Academy of Sciences. Treatment with BBG, a derivative of a commonly used food color (FD&C blue No. 1) that is used to give M&Ms and Gatorade their blue tint, also directly reduced local activation of astrocytes and microglia, in addition to neutrophil infiltration. “These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses,” investigators stated. “Systemic administration of BBG may thus comprise a readily feasible approach by which to treat spinal cord injury in humans.”
Although angiotensin-converting enzyme (ACE) inhibitors as a class do not appear to be associated with dementia risk or cognitive decline in older, hypertensive (HTN) adults, within-class differences may occur regarding these outcomes, suggests a study in the July 13 Archives of Internal Medicine. Investigators identified 158 cases of dementia among 414 participants who were exposed to ACE inhibitors and 640 who were not. There was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01). “However, centrally active ACE inhibitors were associated with 65% less decline in Modified Mini-Mental State Examination scores per year of exposure, and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20) and greater odds of disability in instrumental activities of daily living (adjusted OR, 1.16), compared with other anti-hypertension drugs,” investigators reported.
Researchers have found an association between the cytochrome P450 (CYP) 2C19*2 variant and diminished platelet response to clopidogrel treatment and poor cardiovascular outcomes, according to a study in the August 26 JAMA. Clopidogrel was administered for seven days to 429 healthy Amish persons. “Thirteen single-nucleotide polymorphisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with diminished clopidogrel response, with a high degree of statistical significance,” noted the study authors. “The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention.” In addition, those with the variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death in one year of follow-up.
Intramuscular AVI-4658 induces the expression of dystrophin, benefiting patients with Duchenne muscular dystrophy, according to a study in the August 26 online Lancet Neurology. Investigators assessed the safety of AVI-4658.Two patients received 0.09 mg AVI-4658 in 900 µl (0.9%) saline, and five received 0.9 mg AVI-4658 in 900 µl saline. “In randomly chosen sections of treated EDB muscles, the mean intensity of dystrophin staining ranged from 22% to 32% of the mean intensity of dystrophin in healthy control muscles (mean, 26.4%), and the mean intensity was 17% (range, 11% to 21%) greater than the intensity in the contralateral saline-treated muscle,” the researchers stated. “In the dystrophin-positive fibers, the intensity of dystrophin staining was up to 42% of that in healthy muscle.”
Higher diastolic blood pressure (DBP) is cross-sectionally and independently associated with cognitive impairment, investigators reported in the August 25 Neurology. The association was found after adjusting for economic factors, depressive symptoms, and current use of any antihyperintensive medication in 30,228 black and white men and women (45 and older). “An increment of 10 mm Hg in DBP was associated with a 7% higher odds of cognitive impairment,” the researchers stated. “No independent association was identified between impaired cognitive status and systolic blood pressure (odds ratio [OR], 1.02) or pulse pressure (OR, 0.99).” No evidence of nonlinear relationships between any blood pressure components and impaired cognitive status was found.
Use of smokeless tobacco products is associated with risk of fatal myocardial infarction and stroke, according to the August 18 online BMJ. Investigators from Sweden and the United States conducted a meta-analysis of 11 observational studies (primarily including men). “Eight risk estimates were available for fatal myocardial infarction: the relative risk for ever use of smokeless tobacco products was 1.13 and the excess risk was restricted to current users,” the investigators stated. “The relative risk of fatal stroke, on the basis of five risk estimates, was 1.40.” Increased risk of fatal myocardial infarction was shown in studies from both geographic locations. “Data on dose-response were limited but did not suggest a strong relation between risk of dying from either disease and frequency or duration of use of smokeless tobacco products,” the researchers noted.
A mutation in transcriptional repressor hDEC2-P385R is associated with a human short sleep phenotype, according to a study in the August 14 issue of Science. Investigators found that within a small extended family, two members with the mutation had lifelong shorter daily sleep requirements than most persons. The researchers then genetically engineered mice and fruit flies to express the mutated human gene and studied its impact on behavior and sleep patterns. “Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner,” the study authors stated. “These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.”
The FDA has approved Extavia for reducing the frequency of clinical exacerbations in patients with relapsing forms of multiple sclerosis (MS). It is also indicated in patients who have had a first clinical episode of MS and have features consistent with the disease as shown by MRI. Extavia is a new branded version of interferon beta-1b and the same medicinal product as Betaseron. Interferon beta-1b has been shown to reduce annualized relapse rates by 34%, with patients nearly twice as likely to remain relapse-free for more than two years, compared with those receiving placebo. Injection site necrosis has been reported in 4% of patients in controlled trials, and anaphylaxis has been reported as a rare complication of interferon use. Extavia is marketed by the Pharmaceuticals Division of Novartis (East Hanover, NJ) and is expected to be available this fall.
White matter hyperintensity (WMH) is more strongly related to amnestic mild cognitive impairment (aMCI), and infarcts are more strongly related to nonamnestic MCI, according to a study in the August 11 issue of Neurology. Researchers investigated the relationship of WMH volume and infarcts in brain per MRI to MCI in 679 elderly persons without dementia. WMH was adjusted for total cranial volume, and MCI was defined using the Peterson criteria. WMH was more strongly related to aMCI (OR, 1.9) than nonamnestic MCI (OR, 1.6). However, infarcts were more strongly related to nonamnestic MCI (OR, 2.7) than aMCI (OR, 1.4). “In secondary analyses using continuous cognitive scores as outcomes, WMH, but not infarcts, were related to memory, while infarcts were more strongly related with nonamnestic domains,” the researchers noted. “The nature of WMH in aMCI requires further study,” they concluded.
Intellectually normal children with seizures had neuropsychologic deficits at seizure onset, per a study published in the August 18 issue of Neurology. Investigators compared 282 children between ages 6 and 14 who had an IQ of 70 or higher and with a first recognized seizure to 147 healthy siblings. “In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychologic deficits at or near onset,” the researchers stated. Risk factors included multiple seizures (ie, second unprovoked seizure, odds ratio [OR], 1.96), use of antiepileptic drugs (OR, 2.27), symptomatic/cryptogenic etiology (OR, 2.15), and epileptiform activity on the initial EEG (OR, 1.96). Increased odds for neuropsychologic impairment were associated with absence epilepsy (OR, 2.00).
The H5N1 avian influenza virus may increase the risk for Parkinson’s disease and other neurologic disorders, according to a report in the August 10 online Proceedings of the National Academy of Sciences. In a mouse model, investigators showed that the virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. “In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection,” the researchers stated. A significant loss in dopaminergic neurons in the substantia nigra pars compacta was also observed, 60 days after infection. “Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson’s and Alzheimer’s diseases,” the investigators concluded.
The FDA has approved Sabril (vigabatrin) tablets and oral solution for two difficult-to-treat epilepsies. Vigabatrin is indicated as monotherapy for pediatric patients ages 1 month to 2 years with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss, and as adjunctive add-on therapy in adults with refractory complex partial seizures who have not responded to alternative treatments, and for whom the potential benefits outweigh the risk of vision loss. Vigabatrin use has been linked to permanent bilateral concentric visual field constriction in 30% or more of patients that ranges in severity from mild to severe. Vigabatrin is manufactured by Lundbeck, Inc (Deerfield, Illinois).
Compared with women without epilepsy, epileptic seizures during pregnancy increased the risk for low-birth-weight infants, preterm delivery, and small for gestational age by 1.36-fold, 1.63-fold, and 1.37-fold, respectively, according to a study in the August Archives of Neurology. Researchers in Taiwan matched 1,016 women with epilepsy with single births from 2001 to 2003 and who had been diagnosed with epilepsy in the two years prior to index delivery with 8,128 women without chronic disease. The authors then compared women with epilepsy who had seizures during pregnancy to women with epilepsy who did not have seizures and found that the risk of infants being small for gestational age increased most significantly (odds ratio, 1.34) among those who had seizures during pregnancy.
P2X7 receptor antagonist, Brilliant blue G (BBG), reduced spinal cord anatomic damage and improved motor recovery in rats without evident toxicity when administered 15 minutes after injury, researchers reported in the July 28 Proceedings of the National Academy of Sciences. Treatment with BBG, a derivative of a commonly used food color (FD&C blue No. 1) that is used to give M&Ms and Gatorade their blue tint, also directly reduced local activation of astrocytes and microglia, in addition to neutrophil infiltration. “These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses,” investigators stated. “Systemic administration of BBG may thus comprise a readily feasible approach by which to treat spinal cord injury in humans.”
Although angiotensin-converting enzyme (ACE) inhibitors as a class do not appear to be associated with dementia risk or cognitive decline in older, hypertensive (HTN) adults, within-class differences may occur regarding these outcomes, suggests a study in the July 13 Archives of Internal Medicine. Investigators identified 158 cases of dementia among 414 participants who were exposed to ACE inhibitors and 640 who were not. There was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01). “However, centrally active ACE inhibitors were associated with 65% less decline in Modified Mini-Mental State Examination scores per year of exposure, and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20) and greater odds of disability in instrumental activities of daily living (adjusted OR, 1.16), compared with other anti-hypertension drugs,” investigators reported.
Researchers have found an association between the cytochrome P450 (CYP) 2C19*2 variant and diminished platelet response to clopidogrel treatment and poor cardiovascular outcomes, according to a study in the August 26 JAMA. Clopidogrel was administered for seven days to 429 healthy Amish persons. “Thirteen single-nucleotide polymorphisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with diminished clopidogrel response, with a high degree of statistical significance,” noted the study authors. “The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention.” In addition, those with the variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death in one year of follow-up.
Intramuscular AVI-4658 induces the expression of dystrophin, benefiting patients with Duchenne muscular dystrophy, according to a study in the August 26 online Lancet Neurology. Investigators assessed the safety of AVI-4658.Two patients received 0.09 mg AVI-4658 in 900 µl (0.9%) saline, and five received 0.9 mg AVI-4658 in 900 µl saline. “In randomly chosen sections of treated EDB muscles, the mean intensity of dystrophin staining ranged from 22% to 32% of the mean intensity of dystrophin in healthy control muscles (mean, 26.4%), and the mean intensity was 17% (range, 11% to 21%) greater than the intensity in the contralateral saline-treated muscle,” the researchers stated. “In the dystrophin-positive fibers, the intensity of dystrophin staining was up to 42% of that in healthy muscle.”
News Roundup: New and Noteworthy Information
Patients previously treated with IV immunoglobulin (IVIg) showed a reduced risk of developing Alzheimer’s disease and related disorders (ADRD), according to a study published in the July 21 Neurology. Investigators conducted a retrospective case-control analysis of medical claims for patients 65 or older from a national database. “Treated patients in the Kaplan-Meier analysis had lower ADRD incidence with an estimated 2.6% of the 847 IVIg-treated vs. 4.6% of 84,700 controls diagnosed with ADRD at 60 months after index date,” the researchers stated. Of those treated in a Cox proportional hazard model, 42% had a lower risk of being diagnosed with ADRD, and an estimated 2.8% of treated versus 4.8% of controls were diagnosed with ADRD at 60 months after index date.
Most adolescents with chronic daily headache (CDH) will experience a decline in headache frequency over time, according to a study in the July 15 online Neurology. A total of 103 adolescents (mean age, 21.6; 26 males) with CDH were followed up from 2000 to 2008. Headache frequency, presence of CDH in 2008, and Migraine Disability Assessment scores were outcome measures. Moderate or severe headache disability was reported by 28 (27.2%) subjects. Twelve (12%) participants met CDH criteria; chronic migraine was the most common subtype (n = 10, 83%). Medication overuse was noted in two (2%) patients. “Presence of migraine at baseline predicted poorer outcome of all three measures,” investigators stated. CDH onset at 13 or younger lasting at least two years and medication overuse predicted more frequent headaches or presence of CDH in 2008.
Select biomarkers may be used to predict cardiovascular events but have minimal gain in comparison to conventional risk factors, researchers reported in the July 1JAMA. A cohort of 5,067 subjects (mean age, 58; 60% women) without cardiovascular disease were followed up for a median of 12.8 years. A total of 418 cardiovascular and 230 coronary events occurred. “Models with conventional risk factors had C statistics of 0.758 and 0.760 for cardiovascular and coronary events, respectively,” the investigators stated. In backward-elimination models, C-reactive protein and N-terminal pro-B type natriuretic peptide (N-BNP) for cardiovascular events and midregional proadrenomedullin and N-BNP for coronary events were retained, which increased the C statistic by 0.007 and 0.009, respectively. “Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.”
Persistent cognitive impairment is a better predictor of white matter hyperintensity (WMH) volumes than baseline WMH burden, reported investigators in the July 14Neurology. Researchers observed 98 cognitively intact elderly subjects (49 with three brain MRIs and annual cognitive and neurologic assessments until persistent cognitive impairment diagnosis). Cognitive impairment risk was assessed with Cox proportional hazards survival analyses. Higher risk of persistent cognitive impairment was associated with total WMH volume (hazard ratio [HR], 1.84) and periventricular WMH volume (HR, 1.94), but not with baseline WMH volumes. “Greater periventricular WMH burden progression is associated with the development of persistent cognitive impairment, a potential precursor to Alzheimer’s or vascular dementia,” researchers stated. “Identification of factors that decrease WMH accumulation over time is needed to maintain cognitive health in our growing elderly population,” stated the authors.
Cambia, a diclofenac-based NSAID combined with potassium bicarbonate, has been approved by the FDA for the treatment of acute migraine with or without aura in adults. In clinical trials, Cambia effectively treated migraine pain, photophobia, phonophobia, and nausea. Significant onset of relief from pain was achieved within 15 to 30 minutes. Cambia is marketed by Novartis Pharma AG, headquartered in Basel, Switzerland, through a license from Kowa Pharmaceuticals America (KPA), Inc, in Montgomery, Alabama.
The FDA has approved a New Drug Application for Sumavel DosePro (sumatriptan injection), a needle-free delivery system to treat acute migraine with or without aura, and cluster headache. Sumavel DosePro provides migraine relief within 10 minutes for some patients. The system should only be used when diagnosis of migraine or cluster headaches has been established. It should not be administered to patients with cerebrovascular symptoms, peripheral vascular disease, or uncontrolled hypertension. Sumavel DosePro is marketed by Zogenix, Inc, in San Diego.
Cigarette smoking accelerates MS from a relapsing-remitting to a progressive course, according to a report in the July Archives of Neurology. Included in the study were 1,465 subjects with clinically definite MS (25% men; mean age, 42 at baseline; disease duration, 9.4 years); 780 patients (53.2%) were never-smokers, 428 (29.2%) were ex-smokers , and 257 (17.5%) were current smokers. At baseline, current smokers showed significantly worse disease than did never-smokers. “In addition, current smokers were significantly more likely to have primary progressive MS (adjusted odds ratio, 2.41),” investigators stated. “At longitudinal analysis, MS in smokers progressed from relapsing-remitting to secondary progressive disease faster than in never-smokers (hazard ratio for current smokers vs. never smokers, 2.50).” Also, T2-weighted lesion volume increased faster in smokers, while brain parenchymal fraction decreased faster.
Greater impairment and disability and higher education level are independently associated with an earlier need for symptomatic treatment in early Parkinson’s disease, according to a study that was reported in the July 13 online Archives of Neurology. Patients (n = 413) were randomized into treatment groups: creatine (n = 67), minocycline (n =66), coenzyme Q10 (n = 71), GPI-1485 (n = 71), and placebo (n = 138). The time between baseline assessment and need for the initiation of symptomatic treatment for Parkinson’s disease was the main outcome measure. Within 12 months, approximately half (48.5%) of the participants had reached end point. “Higher baseline impairment and disability, as determined by the Unified Parkinson’s Disease Rating Scale (UPDRS) III (motor section), UPDRS II (activities of daily living section, participant rating), and Modified Rankin Scale scores and level of education were independently associated with an earlier need for symptomatic treatment,” investigators stated.
Neuronal hypertrophy may reflect compensatory mechanisms that prevent cognitive impairment despite substantial Alzheimer’s disease lesions, according to a study that was published in the July 8 online issue of Neurology. Researchers termed the presence of neuritic beta-amyloid plaques and neurofibrillary tangles in the autopsied brains of subjects who were deemed cognitively normal before death as asymptomatic Alzheimer’s disease (ASYMAD). The study authors observed four subject groups—those with ASYMAD (n = 10), those with mild cognitive impairment (MCI, n = 5), those with Alzheimer’s disease (n = 10), and age-matched controls (n = 13). “A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in the ASYMAD compared with MCI,” the investigators stated. “Furthermore, significant higher idea density scores in early life were observed in controls and the ASYMAD group compared to the MCI and Alzheimer’s disease groups.”
—Laura Sassano
Patients previously treated with IV immunoglobulin (IVIg) showed a reduced risk of developing Alzheimer’s disease and related disorders (ADRD), according to a study published in the July 21 Neurology. Investigators conducted a retrospective case-control analysis of medical claims for patients 65 or older from a national database. “Treated patients in the Kaplan-Meier analysis had lower ADRD incidence with an estimated 2.6% of the 847 IVIg-treated vs. 4.6% of 84,700 controls diagnosed with ADRD at 60 months after index date,” the researchers stated. Of those treated in a Cox proportional hazard model, 42% had a lower risk of being diagnosed with ADRD, and an estimated 2.8% of treated versus 4.8% of controls were diagnosed with ADRD at 60 months after index date.
Most adolescents with chronic daily headache (CDH) will experience a decline in headache frequency over time, according to a study in the July 15 online Neurology. A total of 103 adolescents (mean age, 21.6; 26 males) with CDH were followed up from 2000 to 2008. Headache frequency, presence of CDH in 2008, and Migraine Disability Assessment scores were outcome measures. Moderate or severe headache disability was reported by 28 (27.2%) subjects. Twelve (12%) participants met CDH criteria; chronic migraine was the most common subtype (n = 10, 83%). Medication overuse was noted in two (2%) patients. “Presence of migraine at baseline predicted poorer outcome of all three measures,” investigators stated. CDH onset at 13 or younger lasting at least two years and medication overuse predicted more frequent headaches or presence of CDH in 2008.
Select biomarkers may be used to predict cardiovascular events but have minimal gain in comparison to conventional risk factors, researchers reported in the July 1JAMA. A cohort of 5,067 subjects (mean age, 58; 60% women) without cardiovascular disease were followed up for a median of 12.8 years. A total of 418 cardiovascular and 230 coronary events occurred. “Models with conventional risk factors had C statistics of 0.758 and 0.760 for cardiovascular and coronary events, respectively,” the investigators stated. In backward-elimination models, C-reactive protein and N-terminal pro-B type natriuretic peptide (N-BNP) for cardiovascular events and midregional proadrenomedullin and N-BNP for coronary events were retained, which increased the C statistic by 0.007 and 0.009, respectively. “Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.”
Persistent cognitive impairment is a better predictor of white matter hyperintensity (WMH) volumes than baseline WMH burden, reported investigators in the July 14Neurology. Researchers observed 98 cognitively intact elderly subjects (49 with three brain MRIs and annual cognitive and neurologic assessments until persistent cognitive impairment diagnosis). Cognitive impairment risk was assessed with Cox proportional hazards survival analyses. Higher risk of persistent cognitive impairment was associated with total WMH volume (hazard ratio [HR], 1.84) and periventricular WMH volume (HR, 1.94), but not with baseline WMH volumes. “Greater periventricular WMH burden progression is associated with the development of persistent cognitive impairment, a potential precursor to Alzheimer’s or vascular dementia,” researchers stated. “Identification of factors that decrease WMH accumulation over time is needed to maintain cognitive health in our growing elderly population,” stated the authors.
Cambia, a diclofenac-based NSAID combined with potassium bicarbonate, has been approved by the FDA for the treatment of acute migraine with or without aura in adults. In clinical trials, Cambia effectively treated migraine pain, photophobia, phonophobia, and nausea. Significant onset of relief from pain was achieved within 15 to 30 minutes. Cambia is marketed by Novartis Pharma AG, headquartered in Basel, Switzerland, through a license from Kowa Pharmaceuticals America (KPA), Inc, in Montgomery, Alabama.
The FDA has approved a New Drug Application for Sumavel DosePro (sumatriptan injection), a needle-free delivery system to treat acute migraine with or without aura, and cluster headache. Sumavel DosePro provides migraine relief within 10 minutes for some patients. The system should only be used when diagnosis of migraine or cluster headaches has been established. It should not be administered to patients with cerebrovascular symptoms, peripheral vascular disease, or uncontrolled hypertension. Sumavel DosePro is marketed by Zogenix, Inc, in San Diego.
Cigarette smoking accelerates MS from a relapsing-remitting to a progressive course, according to a report in the July Archives of Neurology. Included in the study were 1,465 subjects with clinically definite MS (25% men; mean age, 42 at baseline; disease duration, 9.4 years); 780 patients (53.2%) were never-smokers, 428 (29.2%) were ex-smokers , and 257 (17.5%) were current smokers. At baseline, current smokers showed significantly worse disease than did never-smokers. “In addition, current smokers were significantly more likely to have primary progressive MS (adjusted odds ratio, 2.41),” investigators stated. “At longitudinal analysis, MS in smokers progressed from relapsing-remitting to secondary progressive disease faster than in never-smokers (hazard ratio for current smokers vs. never smokers, 2.50).” Also, T2-weighted lesion volume increased faster in smokers, while brain parenchymal fraction decreased faster.
Greater impairment and disability and higher education level are independently associated with an earlier need for symptomatic treatment in early Parkinson’s disease, according to a study that was reported in the July 13 online Archives of Neurology. Patients (n = 413) were randomized into treatment groups: creatine (n = 67), minocycline (n =66), coenzyme Q10 (n = 71), GPI-1485 (n = 71), and placebo (n = 138). The time between baseline assessment and need for the initiation of symptomatic treatment for Parkinson’s disease was the main outcome measure. Within 12 months, approximately half (48.5%) of the participants had reached end point. “Higher baseline impairment and disability, as determined by the Unified Parkinson’s Disease Rating Scale (UPDRS) III (motor section), UPDRS II (activities of daily living section, participant rating), and Modified Rankin Scale scores and level of education were independently associated with an earlier need for symptomatic treatment,” investigators stated.
Neuronal hypertrophy may reflect compensatory mechanisms that prevent cognitive impairment despite substantial Alzheimer’s disease lesions, according to a study that was published in the July 8 online issue of Neurology. Researchers termed the presence of neuritic beta-amyloid plaques and neurofibrillary tangles in the autopsied brains of subjects who were deemed cognitively normal before death as asymptomatic Alzheimer’s disease (ASYMAD). The study authors observed four subject groups—those with ASYMAD (n = 10), those with mild cognitive impairment (MCI, n = 5), those with Alzheimer’s disease (n = 10), and age-matched controls (n = 13). “A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in the ASYMAD compared with MCI,” the investigators stated. “Furthermore, significant higher idea density scores in early life were observed in controls and the ASYMAD group compared to the MCI and Alzheimer’s disease groups.”
—Laura Sassano
Patients previously treated with IV immunoglobulin (IVIg) showed a reduced risk of developing Alzheimer’s disease and related disorders (ADRD), according to a study published in the July 21 Neurology. Investigators conducted a retrospective case-control analysis of medical claims for patients 65 or older from a national database. “Treated patients in the Kaplan-Meier analysis had lower ADRD incidence with an estimated 2.6% of the 847 IVIg-treated vs. 4.6% of 84,700 controls diagnosed with ADRD at 60 months after index date,” the researchers stated. Of those treated in a Cox proportional hazard model, 42% had a lower risk of being diagnosed with ADRD, and an estimated 2.8% of treated versus 4.8% of controls were diagnosed with ADRD at 60 months after index date.
Most adolescents with chronic daily headache (CDH) will experience a decline in headache frequency over time, according to a study in the July 15 online Neurology. A total of 103 adolescents (mean age, 21.6; 26 males) with CDH were followed up from 2000 to 2008. Headache frequency, presence of CDH in 2008, and Migraine Disability Assessment scores were outcome measures. Moderate or severe headache disability was reported by 28 (27.2%) subjects. Twelve (12%) participants met CDH criteria; chronic migraine was the most common subtype (n = 10, 83%). Medication overuse was noted in two (2%) patients. “Presence of migraine at baseline predicted poorer outcome of all three measures,” investigators stated. CDH onset at 13 or younger lasting at least two years and medication overuse predicted more frequent headaches or presence of CDH in 2008.
Select biomarkers may be used to predict cardiovascular events but have minimal gain in comparison to conventional risk factors, researchers reported in the July 1JAMA. A cohort of 5,067 subjects (mean age, 58; 60% women) without cardiovascular disease were followed up for a median of 12.8 years. A total of 418 cardiovascular and 230 coronary events occurred. “Models with conventional risk factors had C statistics of 0.758 and 0.760 for cardiovascular and coronary events, respectively,” the investigators stated. In backward-elimination models, C-reactive protein and N-terminal pro-B type natriuretic peptide (N-BNP) for cardiovascular events and midregional proadrenomedullin and N-BNP for coronary events were retained, which increased the C statistic by 0.007 and 0.009, respectively. “Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.”
Persistent cognitive impairment is a better predictor of white matter hyperintensity (WMH) volumes than baseline WMH burden, reported investigators in the July 14Neurology. Researchers observed 98 cognitively intact elderly subjects (49 with three brain MRIs and annual cognitive and neurologic assessments until persistent cognitive impairment diagnosis). Cognitive impairment risk was assessed with Cox proportional hazards survival analyses. Higher risk of persistent cognitive impairment was associated with total WMH volume (hazard ratio [HR], 1.84) and periventricular WMH volume (HR, 1.94), but not with baseline WMH volumes. “Greater periventricular WMH burden progression is associated with the development of persistent cognitive impairment, a potential precursor to Alzheimer’s or vascular dementia,” researchers stated. “Identification of factors that decrease WMH accumulation over time is needed to maintain cognitive health in our growing elderly population,” stated the authors.
Cambia, a diclofenac-based NSAID combined with potassium bicarbonate, has been approved by the FDA for the treatment of acute migraine with or without aura in adults. In clinical trials, Cambia effectively treated migraine pain, photophobia, phonophobia, and nausea. Significant onset of relief from pain was achieved within 15 to 30 minutes. Cambia is marketed by Novartis Pharma AG, headquartered in Basel, Switzerland, through a license from Kowa Pharmaceuticals America (KPA), Inc, in Montgomery, Alabama.
The FDA has approved a New Drug Application for Sumavel DosePro (sumatriptan injection), a needle-free delivery system to treat acute migraine with or without aura, and cluster headache. Sumavel DosePro provides migraine relief within 10 minutes for some patients. The system should only be used when diagnosis of migraine or cluster headaches has been established. It should not be administered to patients with cerebrovascular symptoms, peripheral vascular disease, or uncontrolled hypertension. Sumavel DosePro is marketed by Zogenix, Inc, in San Diego.
Cigarette smoking accelerates MS from a relapsing-remitting to a progressive course, according to a report in the July Archives of Neurology. Included in the study were 1,465 subjects with clinically definite MS (25% men; mean age, 42 at baseline; disease duration, 9.4 years); 780 patients (53.2%) were never-smokers, 428 (29.2%) were ex-smokers , and 257 (17.5%) were current smokers. At baseline, current smokers showed significantly worse disease than did never-smokers. “In addition, current smokers were significantly more likely to have primary progressive MS (adjusted odds ratio, 2.41),” investigators stated. “At longitudinal analysis, MS in smokers progressed from relapsing-remitting to secondary progressive disease faster than in never-smokers (hazard ratio for current smokers vs. never smokers, 2.50).” Also, T2-weighted lesion volume increased faster in smokers, while brain parenchymal fraction decreased faster.
Greater impairment and disability and higher education level are independently associated with an earlier need for symptomatic treatment in early Parkinson’s disease, according to a study that was reported in the July 13 online Archives of Neurology. Patients (n = 413) were randomized into treatment groups: creatine (n = 67), minocycline (n =66), coenzyme Q10 (n = 71), GPI-1485 (n = 71), and placebo (n = 138). The time between baseline assessment and need for the initiation of symptomatic treatment for Parkinson’s disease was the main outcome measure. Within 12 months, approximately half (48.5%) of the participants had reached end point. “Higher baseline impairment and disability, as determined by the Unified Parkinson’s Disease Rating Scale (UPDRS) III (motor section), UPDRS II (activities of daily living section, participant rating), and Modified Rankin Scale scores and level of education were independently associated with an earlier need for symptomatic treatment,” investigators stated.
Neuronal hypertrophy may reflect compensatory mechanisms that prevent cognitive impairment despite substantial Alzheimer’s disease lesions, according to a study that was published in the July 8 online issue of Neurology. Researchers termed the presence of neuritic beta-amyloid plaques and neurofibrillary tangles in the autopsied brains of subjects who were deemed cognitively normal before death as asymptomatic Alzheimer’s disease (ASYMAD). The study authors observed four subject groups—those with ASYMAD (n = 10), those with mild cognitive impairment (MCI, n = 5), those with Alzheimer’s disease (n = 10), and age-matched controls (n = 13). “A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in the ASYMAD compared with MCI,” the investigators stated. “Furthermore, significant higher idea density scores in early life were observed in controls and the ASYMAD group compared to the MCI and Alzheimer’s disease groups.”
—Laura Sassano
News Roundup: New and Noteworthy Information
Researchers have identified two new locations of genes that might be implicated in susceptibility to multiple sclerosis (MS), according to a report in the June 14 onlineNature Genetics. The genome-wide association study included 1,618 cases and shared data for 3,413 controls. Replication was performed in an independent set of 2,256 cases and 2,310 controls. Risk-associated single-nucleotide polymorphisms (SNPs) were identified on chromosome 12q13-14 (rs703842, rs10876994, and rs12368653), as well as upstream of CD40 on chromosome 20q13 (rs6074022 and rs1569723). These loci are also associated with other autoimmune diseases. A statistical interaction was observed between SNPs in EVI5-RPL5 and HLA-DR15. The investigators stated that future research will focus on mapping the discovered regions and identifying how changes in the target genes affect development of MS.
Depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease, and donepezil may delay that progression, according to a study in the June 16 Neurology. Investigators studied 756 subjects with aMCI in a three-year, double-blind, placebo-controlled trial of donepezil and vitamin E. Depressive symptoms were assessed at baseline using the Beck Depression Inventory (BDI). Participants were followed up until the end of the study or until the primary end point of progression to probable or possible Alzheimer’s disease. Higher BDI scores were associated with progression to Alzheimer’s disease. “Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to Alzheimer’s disease was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years, and remained marginally lower at 2.7 years,” the authors stated. “Donepezil appears to modulate the increased risk of Alzheimer’s disease conferred by the presence of depressive symptoms,” they concluded.
Approximately half of all recurrent strokes within seven days after transient ischemic attack (TIA) occur during the first 24 hours, investigators reported in the June 2Neurology. Investigators determined the risk of recurrent stroke, defined as new neurologic symptoms of sudden onset after initial recovery, at six, 12, and 24 hours. “Of 1,247 first TIA or strokes, 35 had recurrent strokes within 24 hours, all in the same arterial territory,” the researchers reported. In 25 cases, the initial event subsided prior to the recurrent stroke. “The six-, 12-, and 24-hour stroke risks after 488 first TIAs were 1.2%, 2.1%, and 5.1%, with 42% of all strokes during the 30 days after a first TIA occurring within the first 24 hours,” the investigators stated. Risk at 12 and 24 hours strongly correlated with ABCD2 score. “Sixteen patients (64%) sought urgent medical attention prior to the recurrent stroke, although none received acute antiplatelet treatment.”
The use of thigh-length graduated compression stockings (GCS) is not advised for acute stroke patients, according to a study in the June 6 Lancet. Patients admitted to the hospital within one week of acute stroke were randomized to routine care plus thigh-length GCS (n = 1,256) or routine care only (n = 1,262). The primary outcome, occurrence of symptomatic or asymptomatic deep vein thrombosis in the popliteal or femoral veins, “occurred in 126 patients (10.0%) allocated to the thigh-length GCS and 133 (10.5%) allocated to avoid GCS, resulting in a nonsignificant absolute reduction in risk of 0.5%,” investigators reported. Patients in the GCS group also experienced more skin breaks, ulcers, blisters, and skin necrosis than those in the avoidance group (64 [5%] vs 16 [1%]; odds ratio, 4.18). The study authors concluded that “national guidelines for stroke might need to be revised on the basis of these results.”
Vitamin D can reduce the risk for dementia, per a study published in the May Journal of Alzheimer’s Disease. “The observational evidence includes that low serum 25-hydroxyvitamin D [25(OH)D] has been associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which are either considered risk factors for dementia or have preceded incidence of dementia,” the investigators stated. “The laboratory evidence includes several findings on the role of vitamin D in neuroprotection and reducing inflammation.” The authors noted that observational studies of incidence of dementia in relation to prediagnostic serum 25(OH)D or vitamin D supplementation are warranted.
The FDA has approved Cambia (diclofenac potassium for oral solution) for the treatment of acute migraine in adults. The drug is a diclofenac-based NSAID combined with potassium bicarbonate and can be used in adult migraineurs with or without aura. In randomized clinical trials, diclofenac potassium for oral solution provided statistically significant onset of relief from migraine pain within 15 to 30 minutes. In addition, it was effective in providing relief from photophobia, phonophobia, and nausea. Diclofenac potassium for oral solution is marketed by Kowa Pharmaceuticals America, Inc., in Montgomery, Alabama, and will be available in late 2009.
Patients with subjective cognitive impairment (SCI) might be in the early stages of Alzheimer’s disease, suggests a report in the July Lancet Neurology. Investigators observed patients with SCI, amnestic mild cognitive impairment (aMCI), and nonamnestic mild cognitive impairment (naMCI). A CSF Alzheimer’s disease profile was defined as an abnormal ratio of β-amyloid 42 to tau. Outcome measures included changes in memory, overall cognition, Mini-Mental State Examination score, daily function, and progression to dementia of the Alzheimer’s disease type. “The CSF Alzheimer’s disease profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]), than in healthy controls (28 of 89 [31%]),” the researchers stated. In addition, the CSF Alzheimer’s disease profile was predictive of Alzheimer’s disease–type dementia in subjects with MCI.
NR
—Laura Sassano
Researchers have identified two new locations of genes that might be implicated in susceptibility to multiple sclerosis (MS), according to a report in the June 14 onlineNature Genetics. The genome-wide association study included 1,618 cases and shared data for 3,413 controls. Replication was performed in an independent set of 2,256 cases and 2,310 controls. Risk-associated single-nucleotide polymorphisms (SNPs) were identified on chromosome 12q13-14 (rs703842, rs10876994, and rs12368653), as well as upstream of CD40 on chromosome 20q13 (rs6074022 and rs1569723). These loci are also associated with other autoimmune diseases. A statistical interaction was observed between SNPs in EVI5-RPL5 and HLA-DR15. The investigators stated that future research will focus on mapping the discovered regions and identifying how changes in the target genes affect development of MS.
Depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease, and donepezil may delay that progression, according to a study in the June 16 Neurology. Investigators studied 756 subjects with aMCI in a three-year, double-blind, placebo-controlled trial of donepezil and vitamin E. Depressive symptoms were assessed at baseline using the Beck Depression Inventory (BDI). Participants were followed up until the end of the study or until the primary end point of progression to probable or possible Alzheimer’s disease. Higher BDI scores were associated with progression to Alzheimer’s disease. “Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to Alzheimer’s disease was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years, and remained marginally lower at 2.7 years,” the authors stated. “Donepezil appears to modulate the increased risk of Alzheimer’s disease conferred by the presence of depressive symptoms,” they concluded.
Approximately half of all recurrent strokes within seven days after transient ischemic attack (TIA) occur during the first 24 hours, investigators reported in the June 2Neurology. Investigators determined the risk of recurrent stroke, defined as new neurologic symptoms of sudden onset after initial recovery, at six, 12, and 24 hours. “Of 1,247 first TIA or strokes, 35 had recurrent strokes within 24 hours, all in the same arterial territory,” the researchers reported. In 25 cases, the initial event subsided prior to the recurrent stroke. “The six-, 12-, and 24-hour stroke risks after 488 first TIAs were 1.2%, 2.1%, and 5.1%, with 42% of all strokes during the 30 days after a first TIA occurring within the first 24 hours,” the investigators stated. Risk at 12 and 24 hours strongly correlated with ABCD2 score. “Sixteen patients (64%) sought urgent medical attention prior to the recurrent stroke, although none received acute antiplatelet treatment.”
The use of thigh-length graduated compression stockings (GCS) is not advised for acute stroke patients, according to a study in the June 6 Lancet. Patients admitted to the hospital within one week of acute stroke were randomized to routine care plus thigh-length GCS (n = 1,256) or routine care only (n = 1,262). The primary outcome, occurrence of symptomatic or asymptomatic deep vein thrombosis in the popliteal or femoral veins, “occurred in 126 patients (10.0%) allocated to the thigh-length GCS and 133 (10.5%) allocated to avoid GCS, resulting in a nonsignificant absolute reduction in risk of 0.5%,” investigators reported. Patients in the GCS group also experienced more skin breaks, ulcers, blisters, and skin necrosis than those in the avoidance group (64 [5%] vs 16 [1%]; odds ratio, 4.18). The study authors concluded that “national guidelines for stroke might need to be revised on the basis of these results.”
Vitamin D can reduce the risk for dementia, per a study published in the May Journal of Alzheimer’s Disease. “The observational evidence includes that low serum 25-hydroxyvitamin D [25(OH)D] has been associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which are either considered risk factors for dementia or have preceded incidence of dementia,” the investigators stated. “The laboratory evidence includes several findings on the role of vitamin D in neuroprotection and reducing inflammation.” The authors noted that observational studies of incidence of dementia in relation to prediagnostic serum 25(OH)D or vitamin D supplementation are warranted.
The FDA has approved Cambia (diclofenac potassium for oral solution) for the treatment of acute migraine in adults. The drug is a diclofenac-based NSAID combined with potassium bicarbonate and can be used in adult migraineurs with or without aura. In randomized clinical trials, diclofenac potassium for oral solution provided statistically significant onset of relief from migraine pain within 15 to 30 minutes. In addition, it was effective in providing relief from photophobia, phonophobia, and nausea. Diclofenac potassium for oral solution is marketed by Kowa Pharmaceuticals America, Inc., in Montgomery, Alabama, and will be available in late 2009.
Patients with subjective cognitive impairment (SCI) might be in the early stages of Alzheimer’s disease, suggests a report in the July Lancet Neurology. Investigators observed patients with SCI, amnestic mild cognitive impairment (aMCI), and nonamnestic mild cognitive impairment (naMCI). A CSF Alzheimer’s disease profile was defined as an abnormal ratio of β-amyloid 42 to tau. Outcome measures included changes in memory, overall cognition, Mini-Mental State Examination score, daily function, and progression to dementia of the Alzheimer’s disease type. “The CSF Alzheimer’s disease profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]), than in healthy controls (28 of 89 [31%]),” the researchers stated. In addition, the CSF Alzheimer’s disease profile was predictive of Alzheimer’s disease–type dementia in subjects with MCI.
NR
—Laura Sassano
Researchers have identified two new locations of genes that might be implicated in susceptibility to multiple sclerosis (MS), according to a report in the June 14 onlineNature Genetics. The genome-wide association study included 1,618 cases and shared data for 3,413 controls. Replication was performed in an independent set of 2,256 cases and 2,310 controls. Risk-associated single-nucleotide polymorphisms (SNPs) were identified on chromosome 12q13-14 (rs703842, rs10876994, and rs12368653), as well as upstream of CD40 on chromosome 20q13 (rs6074022 and rs1569723). These loci are also associated with other autoimmune diseases. A statistical interaction was observed between SNPs in EVI5-RPL5 and HLA-DR15. The investigators stated that future research will focus on mapping the discovered regions and identifying how changes in the target genes affect development of MS.
Depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease, and donepezil may delay that progression, according to a study in the June 16 Neurology. Investigators studied 756 subjects with aMCI in a three-year, double-blind, placebo-controlled trial of donepezil and vitamin E. Depressive symptoms were assessed at baseline using the Beck Depression Inventory (BDI). Participants were followed up until the end of the study or until the primary end point of progression to probable or possible Alzheimer’s disease. Higher BDI scores were associated with progression to Alzheimer’s disease. “Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to Alzheimer’s disease was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years, and remained marginally lower at 2.7 years,” the authors stated. “Donepezil appears to modulate the increased risk of Alzheimer’s disease conferred by the presence of depressive symptoms,” they concluded.
Approximately half of all recurrent strokes within seven days after transient ischemic attack (TIA) occur during the first 24 hours, investigators reported in the June 2Neurology. Investigators determined the risk of recurrent stroke, defined as new neurologic symptoms of sudden onset after initial recovery, at six, 12, and 24 hours. “Of 1,247 first TIA or strokes, 35 had recurrent strokes within 24 hours, all in the same arterial territory,” the researchers reported. In 25 cases, the initial event subsided prior to the recurrent stroke. “The six-, 12-, and 24-hour stroke risks after 488 first TIAs were 1.2%, 2.1%, and 5.1%, with 42% of all strokes during the 30 days after a first TIA occurring within the first 24 hours,” the investigators stated. Risk at 12 and 24 hours strongly correlated with ABCD2 score. “Sixteen patients (64%) sought urgent medical attention prior to the recurrent stroke, although none received acute antiplatelet treatment.”
The use of thigh-length graduated compression stockings (GCS) is not advised for acute stroke patients, according to a study in the June 6 Lancet. Patients admitted to the hospital within one week of acute stroke were randomized to routine care plus thigh-length GCS (n = 1,256) or routine care only (n = 1,262). The primary outcome, occurrence of symptomatic or asymptomatic deep vein thrombosis in the popliteal or femoral veins, “occurred in 126 patients (10.0%) allocated to the thigh-length GCS and 133 (10.5%) allocated to avoid GCS, resulting in a nonsignificant absolute reduction in risk of 0.5%,” investigators reported. Patients in the GCS group also experienced more skin breaks, ulcers, blisters, and skin necrosis than those in the avoidance group (64 [5%] vs 16 [1%]; odds ratio, 4.18). The study authors concluded that “national guidelines for stroke might need to be revised on the basis of these results.”
Vitamin D can reduce the risk for dementia, per a study published in the May Journal of Alzheimer’s Disease. “The observational evidence includes that low serum 25-hydroxyvitamin D [25(OH)D] has been associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which are either considered risk factors for dementia or have preceded incidence of dementia,” the investigators stated. “The laboratory evidence includes several findings on the role of vitamin D in neuroprotection and reducing inflammation.” The authors noted that observational studies of incidence of dementia in relation to prediagnostic serum 25(OH)D or vitamin D supplementation are warranted.
The FDA has approved Cambia (diclofenac potassium for oral solution) for the treatment of acute migraine in adults. The drug is a diclofenac-based NSAID combined with potassium bicarbonate and can be used in adult migraineurs with or without aura. In randomized clinical trials, diclofenac potassium for oral solution provided statistically significant onset of relief from migraine pain within 15 to 30 minutes. In addition, it was effective in providing relief from photophobia, phonophobia, and nausea. Diclofenac potassium for oral solution is marketed by Kowa Pharmaceuticals America, Inc., in Montgomery, Alabama, and will be available in late 2009.
Patients with subjective cognitive impairment (SCI) might be in the early stages of Alzheimer’s disease, suggests a report in the July Lancet Neurology. Investigators observed patients with SCI, amnestic mild cognitive impairment (aMCI), and nonamnestic mild cognitive impairment (naMCI). A CSF Alzheimer’s disease profile was defined as an abnormal ratio of β-amyloid 42 to tau. Outcome measures included changes in memory, overall cognition, Mini-Mental State Examination score, daily function, and progression to dementia of the Alzheimer’s disease type. “The CSF Alzheimer’s disease profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]), than in healthy controls (28 of 89 [31%]),” the researchers stated. In addition, the CSF Alzheimer’s disease profile was predictive of Alzheimer’s disease–type dementia in subjects with MCI.
NR
—Laura Sassano
News Roundup: New and Noteworthy Information
First-ever stroke patients who are prescribed statin therapy after hospital discharge have a lower risk of 10-year stroke recurrence and improved survival, according to a study in the May 26 Neurology. Investigators observed a cohort of 794 consecutive, first-ever acute stroke patients from the Athenian Stroke Registry who were admitted since January 1997 and for whom information covering a 10-year follow-up period was available. The recurrence rate among patients who did not receive statins after hospital discharge was 16.3%, compared with 7.5% among those who did receive statins. “Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio, 0.65),” the researchers stated. “Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event.”
The trajectory of cognitive decline is accelerated by delirium in patients with Alzheimer’s disease, according to a report in the May 5 Neurology. A secondary analysis of data from the Massachusetts Alzheimer’s Disease Research Center examined cognitive performance over time for patients who developed (n = 72) and did not develop (n = 336) delirium. “Among patients who developed delirium, the average decline at baseline for performance on the Information-Memory-Concentration was 2.5 points per year, but after an episode of delirium there was a further decline to an average of 4.9 points per year,” investigators stated. The rate of change occurred approximately three times faster in those who had delirium across groups.
The specificity and sensitivity of self-reported stroke is inaccurate among adults of varying ethnicities, according to a report in the May 11 online Archives of Neurology. High-resolution MRIs were conducted in a community-based cohort study of 717 persons without dementia. “In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%,” the investigators commented. “In analyses stratified by median age (80.1), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: P = .02).” False-negative results were associated with impaired memory, cognitive skills, language ability, hypertension, and myocardial infarction.
The late-life dementia risk index accurately stratifies older adults into categories of low, moderate, and high risk for dementia, according to a study in the May 13 onlineNeurology. Researchers developed a point system based on logistic regression coefficients to identify predictive factors of developing incident dementia within six years. Within that time, 14% of subjects (mean age, 76) developed dementia. The final index included older age (1 to 2 points), poor cognitive performance (2 to 4 points), and BMI less than 18.5 (2 points), as well as one or more apolipoprotein E ┖ alleles, cerebral MRI findings of white matter disease, ventricular enlargement, and other factors (1 point each). “Four percent of subjects with low scores developed dementia over six years compared with 23% of subjects with moderate scores and 56% of subjects with high scores,” the researchers stated.
Lamictal (lamotrigine) ODT (orally disintegrating tablets) has been approved by the FDA for long-term treatment of bipolar 1 disorder to lengthen the time between mood episodes in patients 18 and older who have been treated with other medication. Lamotrigine ODT demonstrated bioequivalence to lamotrigine and can also be used as monotherapy for patients 16 and older who are switching from other drugs used to treat partial seizures, or in combination with other drugs to treat certain types of seizures in patients 2 and older. The new formulation offers an option to patients who have difficulty swalling tablets. Lamictal ODT is expected to be available in 25-mg, 50-mg, 100-mg, and 200-mg doses in early July. Lamictal ODT is marketed by GlaxoSmithKline.
Patients with peripheral artery disease who took aspirin alone or with dipyridamole had a significant reduction in nonfatal stroke, as well as a statistically nonsignificant decrease in the primary end point of cardiovascular events, according to a study in the May 13 JAMA. Investigators identified 18 prospective, randomized controlled trials (5,269 individuals) of aspirin therapy with and without dipyridamole that reported cardiovascular event rates. Nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death were primary endpoints. A total of 251 (8.9%) of 2,823 patients taking aspirin, either alone or with dipyridamole, experienced cardiovascular events, compared with 269 (11%) of 2,446 controls. A reduction in nonfatal stroke was associated with aspirin therapy (52 of 2,823 vs 76 of 2,446; relative risk, 0.66). “Additional randomized controlled trials of aspirin therapy are needed to establish the net benefit and bleeding risks in peripheral artery disease,” researchers stated.
Mutations of the KCNJ10 gene cause what investigators have called the EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy), according to a study in the May 7 New England Journal of Medicine. Investigators performed whole-genome linkage analysis in four children from one family. Heterologous expression system was used to evaluate newly identified mutations. The KCNJ10 gene encodes a potassium channel expressed in the brain, inner ear, and kidney. A single significant locus was found on chromosome 1q23.2 (logarithm of odds score, 4.98). Sequencing revealed homozygous missense mutations in affected persons from each family. “These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents,” the researchers stated. “Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.”
The FDA has announced that safety label changes are necessary for all botulinum toxin products, after reports emerged that the effects of the drug may spread to other areas of the body from the injection site. Changes include addition of a boxed warning and a Risk Evaluation and Mitigation Strategy (REMS). Symptoms including loss of strength, muscle weakness, hoarseness, loss of bladder control, breathing trouble, and vision problems have been mainly reported in children with cerebral palsy who were being treated for muscle spasticity, which is not an approved use of the products. Botulinum toxin type A, botulinum toxin type B, and abobotulinumtoxinA are required to add the new label. The REMS will include a medication guide and communication plan, which are given to patients when the medication is dispensed.
The FDA has required manufacturers of antiepileptic drugs (AEDs) or anticonvulsant drugs to update product labeling to include a warning about the increased risk of suicidal thoughts or actions, as well as develop a medication guide. The changes affect all approved AEDs except those that are indicated for short-term use only. All medication guides are expected to be available by the end of 2009. Patients currently taking or starting any AED should be monitored for behavioral changes.
Lower levels of 25-hydroxyvitamin D (25[OH]D) are associated with poorer cognitive function, according to a report in the May 21 online Journal of Neurology, Neurosurgery, and Psychiatry. A total of 3,369 men (ages 40 to 79) from eight centers in the European Male Ageing Study were assessed for cognitive function with use of three tests. Serum 25(OH)D levels were measured using radioimmunoassay, and associations were observed with locally weighted and linear regression models. “After adjusting for additional confounders, 25(OH)D levels were associated with the Digital Symbol Substitution Test only (beta per 10 nmol/L = 0.152),” investigators stated. “Locally weighted and spline regressions suggested the relationship between 25(OH)D and cognitive function was most pronounced at 25(OH)D concentrations below 35 nmol/L.”
Two years after beginning antidepressant therapy, patients have a higher risk of Parkinson’s disease, which suggests that depressive symptoms could be an early manifestation of the disease, according to a study in the June Journal of Neurology, Neurosurgery and Psychiatry. Cases of Parkinson’s disease (999) were selected from the General Practice Research Database cohort from 1995 to 2001 and matched with up to 10 controls (6,261) by age, sex, and practice. The rate ratio (RR) of Parkinson’s disease in initiators of antidepressant therapy compared with noninitiators was 1.85. “The association was stronger during the first two years after initiation of medication use (RR, 2.19) than later (RR, 1.23),” researchers stated. “Results were similar for selective serotonin reuptake inhibitors and tricyclic antidepressants separately.”
Vimpat (lacosamide), an antiepileptic drug (AED) approved by the FDA as add-on therapy in the treatment of partial-onset seizures in patients 17 and older, is now available in the United States. Vimpat is indicated for patients who have not yet achieved seizure control with their current therapy, as well as for those who have tried various other medications and are still having frequent seizures. No clinically significant pharmacokinetic drug interactions were observed with Vimpat when it was studied in combination with other AEDs. Vimpat is marketed by UCB.
Narcolepsy is associated with T-cell receptor alpha polymorphisms, according to a study in the May 3 online Nature Genetics. Following genome-wide association in Caucasians and replication in three other ethnic groups (1,830 cases, 2,164 controls), the highest significance was observed at rs1154155 (average allelic odds ratio [OR], 1.69; genotypic ORs, 1.94 and 2.55). “This is the first documented genetic involvement of the TRAα locus, encoding the major receptor for HLA-peptide presentation, in any disease,” researchers commented. How specific HLA alleles confer susceptibility to more than 100 HLA-associated disorders is still unclear. The investigators believe that narcolepsy might serve as a model for other HLA-associated disorders and provide new insight on how HLA-TCR interactions contribute to organ-specific autoimmune targeting.”
NR
—Laura Sassano
First-ever stroke patients who are prescribed statin therapy after hospital discharge have a lower risk of 10-year stroke recurrence and improved survival, according to a study in the May 26 Neurology. Investigators observed a cohort of 794 consecutive, first-ever acute stroke patients from the Athenian Stroke Registry who were admitted since January 1997 and for whom information covering a 10-year follow-up period was available. The recurrence rate among patients who did not receive statins after hospital discharge was 16.3%, compared with 7.5% among those who did receive statins. “Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio, 0.65),” the researchers stated. “Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event.”
The trajectory of cognitive decline is accelerated by delirium in patients with Alzheimer’s disease, according to a report in the May 5 Neurology. A secondary analysis of data from the Massachusetts Alzheimer’s Disease Research Center examined cognitive performance over time for patients who developed (n = 72) and did not develop (n = 336) delirium. “Among patients who developed delirium, the average decline at baseline for performance on the Information-Memory-Concentration was 2.5 points per year, but after an episode of delirium there was a further decline to an average of 4.9 points per year,” investigators stated. The rate of change occurred approximately three times faster in those who had delirium across groups.
The specificity and sensitivity of self-reported stroke is inaccurate among adults of varying ethnicities, according to a report in the May 11 online Archives of Neurology. High-resolution MRIs were conducted in a community-based cohort study of 717 persons without dementia. “In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%,” the investigators commented. “In analyses stratified by median age (80.1), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: P = .02).” False-negative results were associated with impaired memory, cognitive skills, language ability, hypertension, and myocardial infarction.
The late-life dementia risk index accurately stratifies older adults into categories of low, moderate, and high risk for dementia, according to a study in the May 13 onlineNeurology. Researchers developed a point system based on logistic regression coefficients to identify predictive factors of developing incident dementia within six years. Within that time, 14% of subjects (mean age, 76) developed dementia. The final index included older age (1 to 2 points), poor cognitive performance (2 to 4 points), and BMI less than 18.5 (2 points), as well as one or more apolipoprotein E ┖ alleles, cerebral MRI findings of white matter disease, ventricular enlargement, and other factors (1 point each). “Four percent of subjects with low scores developed dementia over six years compared with 23% of subjects with moderate scores and 56% of subjects with high scores,” the researchers stated.
Lamictal (lamotrigine) ODT (orally disintegrating tablets) has been approved by the FDA for long-term treatment of bipolar 1 disorder to lengthen the time between mood episodes in patients 18 and older who have been treated with other medication. Lamotrigine ODT demonstrated bioequivalence to lamotrigine and can also be used as monotherapy for patients 16 and older who are switching from other drugs used to treat partial seizures, or in combination with other drugs to treat certain types of seizures in patients 2 and older. The new formulation offers an option to patients who have difficulty swalling tablets. Lamictal ODT is expected to be available in 25-mg, 50-mg, 100-mg, and 200-mg doses in early July. Lamictal ODT is marketed by GlaxoSmithKline.
Patients with peripheral artery disease who took aspirin alone or with dipyridamole had a significant reduction in nonfatal stroke, as well as a statistically nonsignificant decrease in the primary end point of cardiovascular events, according to a study in the May 13 JAMA. Investigators identified 18 prospective, randomized controlled trials (5,269 individuals) of aspirin therapy with and without dipyridamole that reported cardiovascular event rates. Nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death were primary endpoints. A total of 251 (8.9%) of 2,823 patients taking aspirin, either alone or with dipyridamole, experienced cardiovascular events, compared with 269 (11%) of 2,446 controls. A reduction in nonfatal stroke was associated with aspirin therapy (52 of 2,823 vs 76 of 2,446; relative risk, 0.66). “Additional randomized controlled trials of aspirin therapy are needed to establish the net benefit and bleeding risks in peripheral artery disease,” researchers stated.
Mutations of the KCNJ10 gene cause what investigators have called the EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy), according to a study in the May 7 New England Journal of Medicine. Investigators performed whole-genome linkage analysis in four children from one family. Heterologous expression system was used to evaluate newly identified mutations. The KCNJ10 gene encodes a potassium channel expressed in the brain, inner ear, and kidney. A single significant locus was found on chromosome 1q23.2 (logarithm of odds score, 4.98). Sequencing revealed homozygous missense mutations in affected persons from each family. “These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents,” the researchers stated. “Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.”
The FDA has announced that safety label changes are necessary for all botulinum toxin products, after reports emerged that the effects of the drug may spread to other areas of the body from the injection site. Changes include addition of a boxed warning and a Risk Evaluation and Mitigation Strategy (REMS). Symptoms including loss of strength, muscle weakness, hoarseness, loss of bladder control, breathing trouble, and vision problems have been mainly reported in children with cerebral palsy who were being treated for muscle spasticity, which is not an approved use of the products. Botulinum toxin type A, botulinum toxin type B, and abobotulinumtoxinA are required to add the new label. The REMS will include a medication guide and communication plan, which are given to patients when the medication is dispensed.
The FDA has required manufacturers of antiepileptic drugs (AEDs) or anticonvulsant drugs to update product labeling to include a warning about the increased risk of suicidal thoughts or actions, as well as develop a medication guide. The changes affect all approved AEDs except those that are indicated for short-term use only. All medication guides are expected to be available by the end of 2009. Patients currently taking or starting any AED should be monitored for behavioral changes.
Lower levels of 25-hydroxyvitamin D (25[OH]D) are associated with poorer cognitive function, according to a report in the May 21 online Journal of Neurology, Neurosurgery, and Psychiatry. A total of 3,369 men (ages 40 to 79) from eight centers in the European Male Ageing Study were assessed for cognitive function with use of three tests. Serum 25(OH)D levels were measured using radioimmunoassay, and associations were observed with locally weighted and linear regression models. “After adjusting for additional confounders, 25(OH)D levels were associated with the Digital Symbol Substitution Test only (beta per 10 nmol/L = 0.152),” investigators stated. “Locally weighted and spline regressions suggested the relationship between 25(OH)D and cognitive function was most pronounced at 25(OH)D concentrations below 35 nmol/L.”
Two years after beginning antidepressant therapy, patients have a higher risk of Parkinson’s disease, which suggests that depressive symptoms could be an early manifestation of the disease, according to a study in the June Journal of Neurology, Neurosurgery and Psychiatry. Cases of Parkinson’s disease (999) were selected from the General Practice Research Database cohort from 1995 to 2001 and matched with up to 10 controls (6,261) by age, sex, and practice. The rate ratio (RR) of Parkinson’s disease in initiators of antidepressant therapy compared with noninitiators was 1.85. “The association was stronger during the first two years after initiation of medication use (RR, 2.19) than later (RR, 1.23),” researchers stated. “Results were similar for selective serotonin reuptake inhibitors and tricyclic antidepressants separately.”
Vimpat (lacosamide), an antiepileptic drug (AED) approved by the FDA as add-on therapy in the treatment of partial-onset seizures in patients 17 and older, is now available in the United States. Vimpat is indicated for patients who have not yet achieved seizure control with their current therapy, as well as for those who have tried various other medications and are still having frequent seizures. No clinically significant pharmacokinetic drug interactions were observed with Vimpat when it was studied in combination with other AEDs. Vimpat is marketed by UCB.
Narcolepsy is associated with T-cell receptor alpha polymorphisms, according to a study in the May 3 online Nature Genetics. Following genome-wide association in Caucasians and replication in three other ethnic groups (1,830 cases, 2,164 controls), the highest significance was observed at rs1154155 (average allelic odds ratio [OR], 1.69; genotypic ORs, 1.94 and 2.55). “This is the first documented genetic involvement of the TRAα locus, encoding the major receptor for HLA-peptide presentation, in any disease,” researchers commented. How specific HLA alleles confer susceptibility to more than 100 HLA-associated disorders is still unclear. The investigators believe that narcolepsy might serve as a model for other HLA-associated disorders and provide new insight on how HLA-TCR interactions contribute to organ-specific autoimmune targeting.”
NR
—Laura Sassano
First-ever stroke patients who are prescribed statin therapy after hospital discharge have a lower risk of 10-year stroke recurrence and improved survival, according to a study in the May 26 Neurology. Investigators observed a cohort of 794 consecutive, first-ever acute stroke patients from the Athenian Stroke Registry who were admitted since January 1997 and for whom information covering a 10-year follow-up period was available. The recurrence rate among patients who did not receive statins after hospital discharge was 16.3%, compared with 7.5% among those who did receive statins. “Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio, 0.65),” the researchers stated. “Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event.”
The trajectory of cognitive decline is accelerated by delirium in patients with Alzheimer’s disease, according to a report in the May 5 Neurology. A secondary analysis of data from the Massachusetts Alzheimer’s Disease Research Center examined cognitive performance over time for patients who developed (n = 72) and did not develop (n = 336) delirium. “Among patients who developed delirium, the average decline at baseline for performance on the Information-Memory-Concentration was 2.5 points per year, but after an episode of delirium there was a further decline to an average of 4.9 points per year,” investigators stated. The rate of change occurred approximately three times faster in those who had delirium across groups.
The specificity and sensitivity of self-reported stroke is inaccurate among adults of varying ethnicities, according to a report in the May 11 online Archives of Neurology. High-resolution MRIs were conducted in a community-based cohort study of 717 persons without dementia. “In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%,” the investigators commented. “In analyses stratified by median age (80.1), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: P = .02).” False-negative results were associated with impaired memory, cognitive skills, language ability, hypertension, and myocardial infarction.
The late-life dementia risk index accurately stratifies older adults into categories of low, moderate, and high risk for dementia, according to a study in the May 13 onlineNeurology. Researchers developed a point system based on logistic regression coefficients to identify predictive factors of developing incident dementia within six years. Within that time, 14% of subjects (mean age, 76) developed dementia. The final index included older age (1 to 2 points), poor cognitive performance (2 to 4 points), and BMI less than 18.5 (2 points), as well as one or more apolipoprotein E ┖ alleles, cerebral MRI findings of white matter disease, ventricular enlargement, and other factors (1 point each). “Four percent of subjects with low scores developed dementia over six years compared with 23% of subjects with moderate scores and 56% of subjects with high scores,” the researchers stated.
Lamictal (lamotrigine) ODT (orally disintegrating tablets) has been approved by the FDA for long-term treatment of bipolar 1 disorder to lengthen the time between mood episodes in patients 18 and older who have been treated with other medication. Lamotrigine ODT demonstrated bioequivalence to lamotrigine and can also be used as monotherapy for patients 16 and older who are switching from other drugs used to treat partial seizures, or in combination with other drugs to treat certain types of seizures in patients 2 and older. The new formulation offers an option to patients who have difficulty swalling tablets. Lamictal ODT is expected to be available in 25-mg, 50-mg, 100-mg, and 200-mg doses in early July. Lamictal ODT is marketed by GlaxoSmithKline.
Patients with peripheral artery disease who took aspirin alone or with dipyridamole had a significant reduction in nonfatal stroke, as well as a statistically nonsignificant decrease in the primary end point of cardiovascular events, according to a study in the May 13 JAMA. Investigators identified 18 prospective, randomized controlled trials (5,269 individuals) of aspirin therapy with and without dipyridamole that reported cardiovascular event rates. Nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death were primary endpoints. A total of 251 (8.9%) of 2,823 patients taking aspirin, either alone or with dipyridamole, experienced cardiovascular events, compared with 269 (11%) of 2,446 controls. A reduction in nonfatal stroke was associated with aspirin therapy (52 of 2,823 vs 76 of 2,446; relative risk, 0.66). “Additional randomized controlled trials of aspirin therapy are needed to establish the net benefit and bleeding risks in peripheral artery disease,” researchers stated.
Mutations of the KCNJ10 gene cause what investigators have called the EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy), according to a study in the May 7 New England Journal of Medicine. Investigators performed whole-genome linkage analysis in four children from one family. Heterologous expression system was used to evaluate newly identified mutations. The KCNJ10 gene encodes a potassium channel expressed in the brain, inner ear, and kidney. A single significant locus was found on chromosome 1q23.2 (logarithm of odds score, 4.98). Sequencing revealed homozygous missense mutations in affected persons from each family. “These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents,” the researchers stated. “Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.”
The FDA has announced that safety label changes are necessary for all botulinum toxin products, after reports emerged that the effects of the drug may spread to other areas of the body from the injection site. Changes include addition of a boxed warning and a Risk Evaluation and Mitigation Strategy (REMS). Symptoms including loss of strength, muscle weakness, hoarseness, loss of bladder control, breathing trouble, and vision problems have been mainly reported in children with cerebral palsy who were being treated for muscle spasticity, which is not an approved use of the products. Botulinum toxin type A, botulinum toxin type B, and abobotulinumtoxinA are required to add the new label. The REMS will include a medication guide and communication plan, which are given to patients when the medication is dispensed.
The FDA has required manufacturers of antiepileptic drugs (AEDs) or anticonvulsant drugs to update product labeling to include a warning about the increased risk of suicidal thoughts or actions, as well as develop a medication guide. The changes affect all approved AEDs except those that are indicated for short-term use only. All medication guides are expected to be available by the end of 2009. Patients currently taking or starting any AED should be monitored for behavioral changes.
Lower levels of 25-hydroxyvitamin D (25[OH]D) are associated with poorer cognitive function, according to a report in the May 21 online Journal of Neurology, Neurosurgery, and Psychiatry. A total of 3,369 men (ages 40 to 79) from eight centers in the European Male Ageing Study were assessed for cognitive function with use of three tests. Serum 25(OH)D levels were measured using radioimmunoassay, and associations were observed with locally weighted and linear regression models. “After adjusting for additional confounders, 25(OH)D levels were associated with the Digital Symbol Substitution Test only (beta per 10 nmol/L = 0.152),” investigators stated. “Locally weighted and spline regressions suggested the relationship between 25(OH)D and cognitive function was most pronounced at 25(OH)D concentrations below 35 nmol/L.”
Two years after beginning antidepressant therapy, patients have a higher risk of Parkinson’s disease, which suggests that depressive symptoms could be an early manifestation of the disease, according to a study in the June Journal of Neurology, Neurosurgery and Psychiatry. Cases of Parkinson’s disease (999) were selected from the General Practice Research Database cohort from 1995 to 2001 and matched with up to 10 controls (6,261) by age, sex, and practice. The rate ratio (RR) of Parkinson’s disease in initiators of antidepressant therapy compared with noninitiators was 1.85. “The association was stronger during the first two years after initiation of medication use (RR, 2.19) than later (RR, 1.23),” researchers stated. “Results were similar for selective serotonin reuptake inhibitors and tricyclic antidepressants separately.”
Vimpat (lacosamide), an antiepileptic drug (AED) approved by the FDA as add-on therapy in the treatment of partial-onset seizures in patients 17 and older, is now available in the United States. Vimpat is indicated for patients who have not yet achieved seizure control with their current therapy, as well as for those who have tried various other medications and are still having frequent seizures. No clinically significant pharmacokinetic drug interactions were observed with Vimpat when it was studied in combination with other AEDs. Vimpat is marketed by UCB.
Narcolepsy is associated with T-cell receptor alpha polymorphisms, according to a study in the May 3 online Nature Genetics. Following genome-wide association in Caucasians and replication in three other ethnic groups (1,830 cases, 2,164 controls), the highest significance was observed at rs1154155 (average allelic odds ratio [OR], 1.69; genotypic ORs, 1.94 and 2.55). “This is the first documented genetic involvement of the TRAα locus, encoding the major receptor for HLA-peptide presentation, in any disease,” researchers commented. How specific HLA alleles confer susceptibility to more than 100 HLA-associated disorders is still unclear. The investigators believe that narcolepsy might serve as a model for other HLA-associated disorders and provide new insight on how HLA-TCR interactions contribute to organ-specific autoimmune targeting.”
NR
—Laura Sassano
News Roundup: New and Noteworthy Information
Both higher overall and abdominal adiposity are associated with an increased risk for restless legs syndrome (RLS), researchers reported in the April 7 Neurology. A total of 65,554 women and 23,119 men without diabetes, arthritis, and pregnancy were included in the analysis. Participants were considered to have RLS if they experienced restless legs five or more times a month and met four diagnostic criteria per the International RLS Study Group. RLS was diagnosed in 6.4% of the women and in 4.1% of the men. Multivariate adjusted odds ratios for RLS were 1.42 for participants with a BMI greater than 30 versus less than 23 and 1.60 for highest versus lowest waist circumference quintiles. “Greater BMI in early adulthood and weight gain were also associated with a higher prevalence of RLS,” stated the investigators.
In utero exposure to valproate is associated with an increased risk of impaired cognitive function at age 3, according to a study in the online April 16 New England Journal of Medicine. Researchers compared neurodevelopmental outcomes at age 3 in 309 children exposed to various antiepileptic drugs. “At three years of age, children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs,” the authors stated. IQ scores for children exposed to valproate were, on average, nine points lower than those exposed to lamotrigine, seven points lower than those exposed to phenytoin, and six points lower than those exposed to carbamazepine. “This finding supports a recommendation that valproate not be used as the first-choice drug in women of childbearing potential,” the investigators concluded.
Older patients with type 2 diabetes and a history of severe hypoglycemic episodes have a greater risk of dementia, per a report in the April 15 JAMA. Researchers collected data on hypoglycemic events that occurred between 1980 and 2002; patients with no prior diagnosis of dementia, mild cognitive impairment, or general memory complaints were followed up through January 15, 2007, for dementia diagnosis. “At least one episode of hypoglycemia was diagnosed in 1,465 patients (8.8%), and dementia was diagnosed in 1,822 patients (11%) during follow-up; 250 patients had both dementia and at least one episode of hypoglycemia (16.95%),” the investigators stated. Compared with patients without hypoglycemia, patients with single or multiple episodes of hypoglycemia had a graded increase in risk, with fully adjusted hazard ratios of 1.26, 1.80, and 1.94 for one, two, and three or more episodes, respectively.
Certain Parkinson’s disease drugs have pathologic syndrome–inducing effects that can be mistaken for primary psychotic disease, according to a report in the April Mayo Clinic Proceedings. Researchers retrospectively reviewed the medical records of 267 patients with Parkinson’s disease. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to Parkinson’s disease drug use. Sixty-six patients (10.6%) were taking a dopamine agonist; of these, seven (2.6%) met the main outcome measure. All seven patients were also among a group of 38 patients taking therapeutic doses > 2 mg pramipexole or 6 mg ropinirole daily). “Behaviors were clearly pathologic and disabling in five: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses,” the investigators noted.
Children with prenatal methamphetamine exposure have altered white matter maturation, researchers reported in the April 15 online Neurology. Twenty-nine methamphetamine-exposed children and 37 unexposed children (ages 3 to 4) underwent 12-direction diffusion tensor imaging on a 3-Tesla MRI scanner. Children with prenatal methamphetamine exposure had lower apparent diffusion coefficient in the frontal (right, -2.1%; left, -2.0%) and parietal white matter (right, -3.9%; left, -3.3%). In addition, methamphetamine-exposed children showed a trend for higher fractional anisotropy in left frontal white matter (+ 4.9%). “Since less myelination and higher dendritic or spine density have been reported in animals exposed to methamphetamine, lower diffusion in our children may reflect more compact axons or greater dendritic or spine density associated with prenatal methamphetamine exposure,” investigators commented.
Use of transcranial Doppler (TCD) ultrasonography screening to help prevent stroke in children with sickle cell disease increased sixfold, according to a study in the April 14Neurology. Prior to 1998, the average annual rate of TCD screening in 157 children with sickle cell disease was 1.8 per 100 person-years. From 1998 through 1999, that rate increased to 5.0. From 2000 through 2005, the rate increased to 11.4. Physical proximity to the vascular laboratory was the only independent predictor of screening. “The annualized stroke rate pre-TCD was 0.44 per 100 person-years, compared to 0.19 post TCD,” investigators stated. “Increased availability of TCD screening could improve the utilization of this effective primary stroke prevention strategy.”
Stable isotope labeling of CNS proteins can be used to assess the effects of potential disease-modifying treatments for Alzheimer’s disease and other CNS disorders, as reported in the March 18 online Annals of Neurology. The study was conducted in healthy men, ages 21 to 50. The γ-secretase inhibitor “LY450139 significantly decreased the production of CNS β-amyloid in a dose-dependent fashion, with inhibition of β-amyloid generation of 47%, 52%, and 84% over a 12-hour period with doses of 100, 140, and 280 mg, respectively,” researchers stated. No difference in β-amyloid clearance was observed. “Results from this approach can assist in making decisions about drug dosing and frequency in the design of larger and longer clinical trials for diseases such as Alzheimer’s disease, and may accelerate effective drug validation,” the researchers concluded.
Use of platelet aggregation inhibitors is associated with the presence of cerebral microbleeds, according to findings in the April 13 online Archives of Neurology. In the Rotterdam Scan Study, researchers used MRI to assess the location of possible microbleeds in 1,062 persons ages 60 and older who were free of dementia. “Compared with nonusers of antithrombotic drugs, cerebral microbleeds were more prevalent among users of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71),” investigators commented. Aspirin users had a higher prevalence of strictly lobular microbleeds (adjusted OR compared with nonusers, 2.70) than those using carbasalate calcium (adjusted OR, 1.16). “This difference was even more pronounced when comparing persons who had used similar dosages of both drugs,” the researchers stated.”
Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α could become a novel therapeutic target for patients with Alzheimer’s disease, researchers reported in the March Archives of Neurology. “Using genome-wide complementary DNA microarray analysis, we found that PGC-1α messenger RNA expression was significantly decreased as a function of progression of clinical dementia in the Alzheimer’s disease brain,” the investigators stated. “Most importantly, we found that the reconstitution of exogenous PGC-1α expression in Tg2576 neurons attenuated the hyperglycemic-mediated β-amyloidogenesis through mechanisms involving the promotion of the ‘nonamyloidogenic' α-secretase processing of amyloid precursor protein through the attenuation of the forkheadlike transcription factor 1 (FoxO3a) expression.”
Investigators have identified a common brain-derived neurotrophic factor (BDNF) polymorphism that is a genetic modifier of Rett syndrome severity, according to a report in the April 7 Neurology. The researchers evaluated the association between disease severity and BDNF polymorphism in 125 mutation-positive patients with Rett syndrome from the Australian Rett Syndrome Database and an Israeli cohort. “Those who were heterozygous (Val/Met) had significantly more severe disease than those who were homozygous for the wild-type (Val/Val) BDNF polymorphism (increased severity score, 2.1),” the study authors stated. “In those with p.R168X, a commonly occurring MECP2 mutation in Rett syndrome, there was a six-point increase in severity score for those who were heterozygous for the BDNF polymorphism, both unadjusted and adjusted for age.”
The apolipoprotein E (APOE) ε 4 allele, a risk factor for early- and late-onset Alzheimer’s disease and age-related cognitive impairment, modulates brain function long before any clinical or neurophysiologic expression of neurodegenerative processes is observed, according to findings in the April 8 online edition of Proceedings of the National Academy of Sciences. Investigators assessed structural and functional effects of the APOE polymorphism in 18 healthy APOE ε 4 carriers and 18 matched controls (ages 20 to 35). Blood oxygen level–dependent fMRI was used to study the brain at rest and during an encoding memory paradigm. “Resting fMRI revealed increased ‘default mode network’ … coactivation in ε 4 carriers relative to noncarriers,” researchers stated. “The encoding task produced greater hippocampal activation in ε 4 carriers relative to noncarriers.”
A genetic locus on chromosome 12p14 is associated with an increased risk for stroke, according to data published in the April 15 New England Journal of Medicine. Investigators analyzed genomewide association data from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, which included 19,602 white persons (mean age, 63) in whom 1,544 incident strokes (1,164 of which were ischemic strokes) occurred during an average of 11 years. Markers most strongly associated with stroke were tested in a replication cohort of 2,430 black persons with 215 incident strokes (191 ischemic strokes), 574 black persons with 85 incident strokes (68 ischemic strokes), 652 Dutch persons with ischemic stroke, and 3,613 unaffected participants. “Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke,” the investigators stated.
Statins have no preventative effect for Alzheimer’s disease or dementia when given to at-risk individuals in late life, per results reported in the April 15 Cochrane Database of Systematic Reviews. In the Heart Protection Study (patients 70 and older), no difference in incidence of dementia (31 cases in the simvastatin group and 31 cases in the placebo group) nor on the modified Telephone Interview for Cognitive Status at final follow-up (23.7% in the simvastatin group were cognitively impaired vs 24.2% in the placebo group) was shown. There was no difference between groups in cognition in relation to age at study entry or history of cerebrovascular disease. In the Prospective Study of Pravastatin in the Elderly at Risk (patients aged 70 to 82), cognitive function declined at the same rate in both treatment cohorts.
NR
—Laura Sassano
Both higher overall and abdominal adiposity are associated with an increased risk for restless legs syndrome (RLS), researchers reported in the April 7 Neurology. A total of 65,554 women and 23,119 men without diabetes, arthritis, and pregnancy were included in the analysis. Participants were considered to have RLS if they experienced restless legs five or more times a month and met four diagnostic criteria per the International RLS Study Group. RLS was diagnosed in 6.4% of the women and in 4.1% of the men. Multivariate adjusted odds ratios for RLS were 1.42 for participants with a BMI greater than 30 versus less than 23 and 1.60 for highest versus lowest waist circumference quintiles. “Greater BMI in early adulthood and weight gain were also associated with a higher prevalence of RLS,” stated the investigators.
In utero exposure to valproate is associated with an increased risk of impaired cognitive function at age 3, according to a study in the online April 16 New England Journal of Medicine. Researchers compared neurodevelopmental outcomes at age 3 in 309 children exposed to various antiepileptic drugs. “At three years of age, children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs,” the authors stated. IQ scores for children exposed to valproate were, on average, nine points lower than those exposed to lamotrigine, seven points lower than those exposed to phenytoin, and six points lower than those exposed to carbamazepine. “This finding supports a recommendation that valproate not be used as the first-choice drug in women of childbearing potential,” the investigators concluded.
Older patients with type 2 diabetes and a history of severe hypoglycemic episodes have a greater risk of dementia, per a report in the April 15 JAMA. Researchers collected data on hypoglycemic events that occurred between 1980 and 2002; patients with no prior diagnosis of dementia, mild cognitive impairment, or general memory complaints were followed up through January 15, 2007, for dementia diagnosis. “At least one episode of hypoglycemia was diagnosed in 1,465 patients (8.8%), and dementia was diagnosed in 1,822 patients (11%) during follow-up; 250 patients had both dementia and at least one episode of hypoglycemia (16.95%),” the investigators stated. Compared with patients without hypoglycemia, patients with single or multiple episodes of hypoglycemia had a graded increase in risk, with fully adjusted hazard ratios of 1.26, 1.80, and 1.94 for one, two, and three or more episodes, respectively.
Certain Parkinson’s disease drugs have pathologic syndrome–inducing effects that can be mistaken for primary psychotic disease, according to a report in the April Mayo Clinic Proceedings. Researchers retrospectively reviewed the medical records of 267 patients with Parkinson’s disease. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to Parkinson’s disease drug use. Sixty-six patients (10.6%) were taking a dopamine agonist; of these, seven (2.6%) met the main outcome measure. All seven patients were also among a group of 38 patients taking therapeutic doses > 2 mg pramipexole or 6 mg ropinirole daily). “Behaviors were clearly pathologic and disabling in five: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses,” the investigators noted.
Children with prenatal methamphetamine exposure have altered white matter maturation, researchers reported in the April 15 online Neurology. Twenty-nine methamphetamine-exposed children and 37 unexposed children (ages 3 to 4) underwent 12-direction diffusion tensor imaging on a 3-Tesla MRI scanner. Children with prenatal methamphetamine exposure had lower apparent diffusion coefficient in the frontal (right, -2.1%; left, -2.0%) and parietal white matter (right, -3.9%; left, -3.3%). In addition, methamphetamine-exposed children showed a trend for higher fractional anisotropy in left frontal white matter (+ 4.9%). “Since less myelination and higher dendritic or spine density have been reported in animals exposed to methamphetamine, lower diffusion in our children may reflect more compact axons or greater dendritic or spine density associated with prenatal methamphetamine exposure,” investigators commented.
Use of transcranial Doppler (TCD) ultrasonography screening to help prevent stroke in children with sickle cell disease increased sixfold, according to a study in the April 14Neurology. Prior to 1998, the average annual rate of TCD screening in 157 children with sickle cell disease was 1.8 per 100 person-years. From 1998 through 1999, that rate increased to 5.0. From 2000 through 2005, the rate increased to 11.4. Physical proximity to the vascular laboratory was the only independent predictor of screening. “The annualized stroke rate pre-TCD was 0.44 per 100 person-years, compared to 0.19 post TCD,” investigators stated. “Increased availability of TCD screening could improve the utilization of this effective primary stroke prevention strategy.”
Stable isotope labeling of CNS proteins can be used to assess the effects of potential disease-modifying treatments for Alzheimer’s disease and other CNS disorders, as reported in the March 18 online Annals of Neurology. The study was conducted in healthy men, ages 21 to 50. The γ-secretase inhibitor “LY450139 significantly decreased the production of CNS β-amyloid in a dose-dependent fashion, with inhibition of β-amyloid generation of 47%, 52%, and 84% over a 12-hour period with doses of 100, 140, and 280 mg, respectively,” researchers stated. No difference in β-amyloid clearance was observed. “Results from this approach can assist in making decisions about drug dosing and frequency in the design of larger and longer clinical trials for diseases such as Alzheimer’s disease, and may accelerate effective drug validation,” the researchers concluded.
Use of platelet aggregation inhibitors is associated with the presence of cerebral microbleeds, according to findings in the April 13 online Archives of Neurology. In the Rotterdam Scan Study, researchers used MRI to assess the location of possible microbleeds in 1,062 persons ages 60 and older who were free of dementia. “Compared with nonusers of antithrombotic drugs, cerebral microbleeds were more prevalent among users of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71),” investigators commented. Aspirin users had a higher prevalence of strictly lobular microbleeds (adjusted OR compared with nonusers, 2.70) than those using carbasalate calcium (adjusted OR, 1.16). “This difference was even more pronounced when comparing persons who had used similar dosages of both drugs,” the researchers stated.”
Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α could become a novel therapeutic target for patients with Alzheimer’s disease, researchers reported in the March Archives of Neurology. “Using genome-wide complementary DNA microarray analysis, we found that PGC-1α messenger RNA expression was significantly decreased as a function of progression of clinical dementia in the Alzheimer’s disease brain,” the investigators stated. “Most importantly, we found that the reconstitution of exogenous PGC-1α expression in Tg2576 neurons attenuated the hyperglycemic-mediated β-amyloidogenesis through mechanisms involving the promotion of the ‘nonamyloidogenic' α-secretase processing of amyloid precursor protein through the attenuation of the forkheadlike transcription factor 1 (FoxO3a) expression.”
Investigators have identified a common brain-derived neurotrophic factor (BDNF) polymorphism that is a genetic modifier of Rett syndrome severity, according to a report in the April 7 Neurology. The researchers evaluated the association between disease severity and BDNF polymorphism in 125 mutation-positive patients with Rett syndrome from the Australian Rett Syndrome Database and an Israeli cohort. “Those who were heterozygous (Val/Met) had significantly more severe disease than those who were homozygous for the wild-type (Val/Val) BDNF polymorphism (increased severity score, 2.1),” the study authors stated. “In those with p.R168X, a commonly occurring MECP2 mutation in Rett syndrome, there was a six-point increase in severity score for those who were heterozygous for the BDNF polymorphism, both unadjusted and adjusted for age.”
The apolipoprotein E (APOE) ε 4 allele, a risk factor for early- and late-onset Alzheimer’s disease and age-related cognitive impairment, modulates brain function long before any clinical or neurophysiologic expression of neurodegenerative processes is observed, according to findings in the April 8 online edition of Proceedings of the National Academy of Sciences. Investigators assessed structural and functional effects of the APOE polymorphism in 18 healthy APOE ε 4 carriers and 18 matched controls (ages 20 to 35). Blood oxygen level–dependent fMRI was used to study the brain at rest and during an encoding memory paradigm. “Resting fMRI revealed increased ‘default mode network’ … coactivation in ε 4 carriers relative to noncarriers,” researchers stated. “The encoding task produced greater hippocampal activation in ε 4 carriers relative to noncarriers.”
A genetic locus on chromosome 12p14 is associated with an increased risk for stroke, according to data published in the April 15 New England Journal of Medicine. Investigators analyzed genomewide association data from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, which included 19,602 white persons (mean age, 63) in whom 1,544 incident strokes (1,164 of which were ischemic strokes) occurred during an average of 11 years. Markers most strongly associated with stroke were tested in a replication cohort of 2,430 black persons with 215 incident strokes (191 ischemic strokes), 574 black persons with 85 incident strokes (68 ischemic strokes), 652 Dutch persons with ischemic stroke, and 3,613 unaffected participants. “Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke,” the investigators stated.
Statins have no preventative effect for Alzheimer’s disease or dementia when given to at-risk individuals in late life, per results reported in the April 15 Cochrane Database of Systematic Reviews. In the Heart Protection Study (patients 70 and older), no difference in incidence of dementia (31 cases in the simvastatin group and 31 cases in the placebo group) nor on the modified Telephone Interview for Cognitive Status at final follow-up (23.7% in the simvastatin group were cognitively impaired vs 24.2% in the placebo group) was shown. There was no difference between groups in cognition in relation to age at study entry or history of cerebrovascular disease. In the Prospective Study of Pravastatin in the Elderly at Risk (patients aged 70 to 82), cognitive function declined at the same rate in both treatment cohorts.
NR
—Laura Sassano
Both higher overall and abdominal adiposity are associated with an increased risk for restless legs syndrome (RLS), researchers reported in the April 7 Neurology. A total of 65,554 women and 23,119 men without diabetes, arthritis, and pregnancy were included in the analysis. Participants were considered to have RLS if they experienced restless legs five or more times a month and met four diagnostic criteria per the International RLS Study Group. RLS was diagnosed in 6.4% of the women and in 4.1% of the men. Multivariate adjusted odds ratios for RLS were 1.42 for participants with a BMI greater than 30 versus less than 23 and 1.60 for highest versus lowest waist circumference quintiles. “Greater BMI in early adulthood and weight gain were also associated with a higher prevalence of RLS,” stated the investigators.
In utero exposure to valproate is associated with an increased risk of impaired cognitive function at age 3, according to a study in the online April 16 New England Journal of Medicine. Researchers compared neurodevelopmental outcomes at age 3 in 309 children exposed to various antiepileptic drugs. “At three years of age, children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs,” the authors stated. IQ scores for children exposed to valproate were, on average, nine points lower than those exposed to lamotrigine, seven points lower than those exposed to phenytoin, and six points lower than those exposed to carbamazepine. “This finding supports a recommendation that valproate not be used as the first-choice drug in women of childbearing potential,” the investigators concluded.
Older patients with type 2 diabetes and a history of severe hypoglycemic episodes have a greater risk of dementia, per a report in the April 15 JAMA. Researchers collected data on hypoglycemic events that occurred between 1980 and 2002; patients with no prior diagnosis of dementia, mild cognitive impairment, or general memory complaints were followed up through January 15, 2007, for dementia diagnosis. “At least one episode of hypoglycemia was diagnosed in 1,465 patients (8.8%), and dementia was diagnosed in 1,822 patients (11%) during follow-up; 250 patients had both dementia and at least one episode of hypoglycemia (16.95%),” the investigators stated. Compared with patients without hypoglycemia, patients with single or multiple episodes of hypoglycemia had a graded increase in risk, with fully adjusted hazard ratios of 1.26, 1.80, and 1.94 for one, two, and three or more episodes, respectively.
Certain Parkinson’s disease drugs have pathologic syndrome–inducing effects that can be mistaken for primary psychotic disease, according to a report in the April Mayo Clinic Proceedings. Researchers retrospectively reviewed the medical records of 267 patients with Parkinson’s disease. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to Parkinson’s disease drug use. Sixty-six patients (10.6%) were taking a dopamine agonist; of these, seven (2.6%) met the main outcome measure. All seven patients were also among a group of 38 patients taking therapeutic doses > 2 mg pramipexole or 6 mg ropinirole daily). “Behaviors were clearly pathologic and disabling in five: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses,” the investigators noted.
Children with prenatal methamphetamine exposure have altered white matter maturation, researchers reported in the April 15 online Neurology. Twenty-nine methamphetamine-exposed children and 37 unexposed children (ages 3 to 4) underwent 12-direction diffusion tensor imaging on a 3-Tesla MRI scanner. Children with prenatal methamphetamine exposure had lower apparent diffusion coefficient in the frontal (right, -2.1%; left, -2.0%) and parietal white matter (right, -3.9%; left, -3.3%). In addition, methamphetamine-exposed children showed a trend for higher fractional anisotropy in left frontal white matter (+ 4.9%). “Since less myelination and higher dendritic or spine density have been reported in animals exposed to methamphetamine, lower diffusion in our children may reflect more compact axons or greater dendritic or spine density associated with prenatal methamphetamine exposure,” investigators commented.
Use of transcranial Doppler (TCD) ultrasonography screening to help prevent stroke in children with sickle cell disease increased sixfold, according to a study in the April 14Neurology. Prior to 1998, the average annual rate of TCD screening in 157 children with sickle cell disease was 1.8 per 100 person-years. From 1998 through 1999, that rate increased to 5.0. From 2000 through 2005, the rate increased to 11.4. Physical proximity to the vascular laboratory was the only independent predictor of screening. “The annualized stroke rate pre-TCD was 0.44 per 100 person-years, compared to 0.19 post TCD,” investigators stated. “Increased availability of TCD screening could improve the utilization of this effective primary stroke prevention strategy.”
Stable isotope labeling of CNS proteins can be used to assess the effects of potential disease-modifying treatments for Alzheimer’s disease and other CNS disorders, as reported in the March 18 online Annals of Neurology. The study was conducted in healthy men, ages 21 to 50. The γ-secretase inhibitor “LY450139 significantly decreased the production of CNS β-amyloid in a dose-dependent fashion, with inhibition of β-amyloid generation of 47%, 52%, and 84% over a 12-hour period with doses of 100, 140, and 280 mg, respectively,” researchers stated. No difference in β-amyloid clearance was observed. “Results from this approach can assist in making decisions about drug dosing and frequency in the design of larger and longer clinical trials for diseases such as Alzheimer’s disease, and may accelerate effective drug validation,” the researchers concluded.
Use of platelet aggregation inhibitors is associated with the presence of cerebral microbleeds, according to findings in the April 13 online Archives of Neurology. In the Rotterdam Scan Study, researchers used MRI to assess the location of possible microbleeds in 1,062 persons ages 60 and older who were free of dementia. “Compared with nonusers of antithrombotic drugs, cerebral microbleeds were more prevalent among users of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71),” investigators commented. Aspirin users had a higher prevalence of strictly lobular microbleeds (adjusted OR compared with nonusers, 2.70) than those using carbasalate calcium (adjusted OR, 1.16). “This difference was even more pronounced when comparing persons who had used similar dosages of both drugs,” the researchers stated.”
Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α could become a novel therapeutic target for patients with Alzheimer’s disease, researchers reported in the March Archives of Neurology. “Using genome-wide complementary DNA microarray analysis, we found that PGC-1α messenger RNA expression was significantly decreased as a function of progression of clinical dementia in the Alzheimer’s disease brain,” the investigators stated. “Most importantly, we found that the reconstitution of exogenous PGC-1α expression in Tg2576 neurons attenuated the hyperglycemic-mediated β-amyloidogenesis through mechanisms involving the promotion of the ‘nonamyloidogenic' α-secretase processing of amyloid precursor protein through the attenuation of the forkheadlike transcription factor 1 (FoxO3a) expression.”
Investigators have identified a common brain-derived neurotrophic factor (BDNF) polymorphism that is a genetic modifier of Rett syndrome severity, according to a report in the April 7 Neurology. The researchers evaluated the association between disease severity and BDNF polymorphism in 125 mutation-positive patients with Rett syndrome from the Australian Rett Syndrome Database and an Israeli cohort. “Those who were heterozygous (Val/Met) had significantly more severe disease than those who were homozygous for the wild-type (Val/Val) BDNF polymorphism (increased severity score, 2.1),” the study authors stated. “In those with p.R168X, a commonly occurring MECP2 mutation in Rett syndrome, there was a six-point increase in severity score for those who were heterozygous for the BDNF polymorphism, both unadjusted and adjusted for age.”
The apolipoprotein E (APOE) ε 4 allele, a risk factor for early- and late-onset Alzheimer’s disease and age-related cognitive impairment, modulates brain function long before any clinical or neurophysiologic expression of neurodegenerative processes is observed, according to findings in the April 8 online edition of Proceedings of the National Academy of Sciences. Investigators assessed structural and functional effects of the APOE polymorphism in 18 healthy APOE ε 4 carriers and 18 matched controls (ages 20 to 35). Blood oxygen level–dependent fMRI was used to study the brain at rest and during an encoding memory paradigm. “Resting fMRI revealed increased ‘default mode network’ … coactivation in ε 4 carriers relative to noncarriers,” researchers stated. “The encoding task produced greater hippocampal activation in ε 4 carriers relative to noncarriers.”
A genetic locus on chromosome 12p14 is associated with an increased risk for stroke, according to data published in the April 15 New England Journal of Medicine. Investigators analyzed genomewide association data from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, which included 19,602 white persons (mean age, 63) in whom 1,544 incident strokes (1,164 of which were ischemic strokes) occurred during an average of 11 years. Markers most strongly associated with stroke were tested in a replication cohort of 2,430 black persons with 215 incident strokes (191 ischemic strokes), 574 black persons with 85 incident strokes (68 ischemic strokes), 652 Dutch persons with ischemic stroke, and 3,613 unaffected participants. “Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke,” the investigators stated.
Statins have no preventative effect for Alzheimer’s disease or dementia when given to at-risk individuals in late life, per results reported in the April 15 Cochrane Database of Systematic Reviews. In the Heart Protection Study (patients 70 and older), no difference in incidence of dementia (31 cases in the simvastatin group and 31 cases in the placebo group) nor on the modified Telephone Interview for Cognitive Status at final follow-up (23.7% in the simvastatin group were cognitively impaired vs 24.2% in the placebo group) was shown. There was no difference between groups in cognition in relation to age at study entry or history of cerebrovascular disease. In the Prospective Study of Pravastatin in the Elderly at Risk (patients aged 70 to 82), cognitive function declined at the same rate in both treatment cohorts.
NR
—Laura Sassano
News Roundup: New and Noteworthy Information
Carotid artery stenting is as efficacious as endarterectomy for the prevention of recurrent ipsilateral ischemic stroke, but safety concerns during the 30-day period following surgery need to be addressed, according to two studies in the October Lancet Neurology. In the Stent-Protected Angioplasty versus Carotid Endarterectomy study, patients underwent either carotid angioplasty with stenting (n = 613) or carotid endarterectomy (n = 601). After two years, the rate of recurrent ipsilateral ischemic stroke was similar in both treatment groups. In the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, researchers compared outcome after stenting with outcome after endarterectomy after four years in 527 subjects who had carotid stenosis of at least 60% that had recently become symptomatic. The probability of periprocedural stroke or death and nonprocedural ipsilateral stroke was higher in those who received stenting than in those who received endarterectomy (11.1% vs 6.2%, respectively; hazard ratio, 1.97). The differences were attributed to “the higher periprocedural risk of stenting compared with endarterectomy,” said the researchers. After the periprocedural period, however, risks for ipsilateral stroke were similar in both treatment groups.
Fetal aneuploidy can be detected using a noninvasive maternal blood test, according to a study in the October 21 Proceedings of the National Academy of Sciences. Researchers used high-throughput shotgun technology to sequence cell-free DNA from the plasma of pregnant women, obtaining an average of five million sequence tags per patient sample. “The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy,” the investigators stated. Nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edwards syndrome), and one case of trisomy 13 (Patau syndrome) were observed among 12 women with aneuploid pregnancies and six women with normal pregnancies. Trisomy was detected as early as the 14th week of gestation. “Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA,” the study authors added, “and we found evidence that this DNA is enriched for sequences from nucleosomes.”
The FDA has approved two new dosage strengths for Stalevo (carbidopa, levodopa, and entacapone) tablets: 75 (18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg entacapone) and 125 (31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone). The new dosage strengths are in addition to the already existing Stalevo 50, 100, 150, and 200 tablets. Stalevo is indicated for patients with Parkinson’s disease who experience end-of-dose “wearing off.” It combines levodopa with the enzyme inhibitors carbidopa and entacapone to provide greater and more sustained levels of levodopa in the blood and improve bodily movement control. The most common side effects include dyskinesia, hypokinesia, hyperkinesia, nausea, diarrhea, discoloration of urine, sweat, and/or saliva, abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Stalevo was originally approved by the FDA in June 2003 and is marketed by Novartis Pharmaceuticals Corporation in East Hanover, New Jersey.
Vitamin D deficiency may have a role in Parkinson’s disease, reported researchers in the October Archives of Neurology. Patients with Parkinson’s disease were matched by age to healthy controls and patients with Alzheimer’s disease. More patients with Parkinson’s disease (55%) had insufficient vitamin D, compared with controls (36%) and patients with Alzheimer’s disease (41%). The Parkinson’s disease subjects also had significantly lower mean plasma 25-hydroxyvitamin D concentration than the Alzheimer’s disease and control cohorts (31.9 vs 34.8 and 37.0 ng/mL, respectively). “Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of Parkinson’s disease,” suggested the investigators.
Treatment with valproic acid was associated with improved memory and reduced brain lesions in a mouse model, reported researchers in the October 27 online Journal of Experimental Medicine. Valproic acid decreased β-amyloid protein production by inhibiting glycogen synthase kinase 3β–mediated γ-secretase cleavage of β-amyloid precursor protein in vitro and in vivo. “Valproic acid treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic Alzheimer’s disease model mice,” observed the investigators. In addition, treatment with valproic acid in the early stages of Alzheimer’s disease alleviated memory deficits in the mice.
Education and occupation may reduce the severity and delay the clinical expression of Alzheimer’s disease, according to a study in the October 21 Neurology. The researchers assessed 242 patients with probable Alzheimer’s disease for the impact of education and occupation on brain glucose metabolism (rCMRglc) in patients with amnestic mild cognitive impairment (aMCI). A significant association was shown between higher education and occupation and lower rCMRglc in the posterior temporoparietal cortex and precuneus in those with probable Alzheimer’s disease and aMCI converters; no such correlation was found in aMCI nonconverters or the control group. “This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer’s disease pathology,” the researchers concluded.
A high level of physical activity is associated with less severe first stroke and improved long-term outcome, according to a report in the October 21 Neurology. Researchers compiled data on 265 subjects (mean age, 68) who represented a subset of patients with first-ever stroke enrolled in the ExStroke Pilot Trial. Prestroke level of physical activity was measured retrospectively using the Physical Activity Scale for the Elderly questionnaire. Stroke severity was measured with the Scandinavian Stroke Scale, and long-term outcome was assessed after two years with the modified Rankin Scale. Patients in the lowest quartile of physical activity had the poorest outcome, as well as a more severe stroke. Higher physical activity was associated with a less severe stroke (odds ratio [OR], 2.54) and a decreased likelihood of poor long-term outcome (OR, 0.46).
Multiplex ligation-dependent probe amplification (MLPA) is an efficient and inexpensive tool for screening chromosomal abnormalities present in autism spectrum disorders, researchers reported in the October BMC Medical Genomics. A screening of 279 unrelated subjects showed duplications of the 15q11-q13 region in two subjects, as well as duplications of the 22q11 region in two subjects. In an additional two patients, smaller de novo duplications were identified. Genes in these novel duplications included GABRB3 and ATP10A in one case and MKRN3, MAGEL2, and NDN in the other. These duplications likely exacerbate symptoms and/or increase liability for autism spectrum disorders. The researchers also found a partial duplication of the ASMT gene in 6% to 7% of cases, compared with 2% of controls, indicating that further study is needed to determine its potential impact on autism spectrum disorders. “MLPA proves to be an efficient method to screen for chromosomal abnormalities,” they stated.
Brain microbleeds are more prevalent in black patients than in white patients, according to a report in the October 7 Neurology. A total of 87 subjects (42 black, 45 white) with intracerebral hemorrhage (ICH) were analyzed. Black subjects were younger and had a greater rate of hypertension but did not have other vascular risk factors. Seventy-four percent of black patients had one or more microbleeds, compared with 42% of white patients. “The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%),” the researchers observed. Race remained an independent predictor of microbleeds (odds ratio, 3.3), after adjusting for age, hypertension, and alcohol use. “Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression,” the investigators concluded.
Patients with acute ischemic stroke who require aggressive measures to lower blood pressure should not be excluded from receiving intravenous t-PA therapy, according to a study in the September Archives of Neurology. Medical records of 178 patients with acute ischemic stroke who were treated with t-PA therapy were reviewed. Fifty patients required blood pressure–lowering treatment before receiving t-PA therapy; of these, 24 patients received nicardipine as first-line therapy or after receiving labetalol. There were no significant differences in adverse events between those treated with nicardipine or labetalol and those who did not receive blood pressure–lowering treatment. “Data suggest that patients with acute ischemic stroke requiring aggressive treatment to lower blood pressure should not be excluded from receiving t-PA therapy,” the authors concluded, noting that a prospective study is needed.
Carotid artery stenting is as efficacious as endarterectomy for the prevention of recurrent ipsilateral ischemic stroke, but safety concerns during the 30-day period following surgery need to be addressed, according to two studies in the October Lancet Neurology. In the Stent-Protected Angioplasty versus Carotid Endarterectomy study, patients underwent either carotid angioplasty with stenting (n = 613) or carotid endarterectomy (n = 601). After two years, the rate of recurrent ipsilateral ischemic stroke was similar in both treatment groups. In the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, researchers compared outcome after stenting with outcome after endarterectomy after four years in 527 subjects who had carotid stenosis of at least 60% that had recently become symptomatic. The probability of periprocedural stroke or death and nonprocedural ipsilateral stroke was higher in those who received stenting than in those who received endarterectomy (11.1% vs 6.2%, respectively; hazard ratio, 1.97). The differences were attributed to “the higher periprocedural risk of stenting compared with endarterectomy,” said the researchers. After the periprocedural period, however, risks for ipsilateral stroke were similar in both treatment groups.
Fetal aneuploidy can be detected using a noninvasive maternal blood test, according to a study in the October 21 Proceedings of the National Academy of Sciences. Researchers used high-throughput shotgun technology to sequence cell-free DNA from the plasma of pregnant women, obtaining an average of five million sequence tags per patient sample. “The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy,” the investigators stated. Nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edwards syndrome), and one case of trisomy 13 (Patau syndrome) were observed among 12 women with aneuploid pregnancies and six women with normal pregnancies. Trisomy was detected as early as the 14th week of gestation. “Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA,” the study authors added, “and we found evidence that this DNA is enriched for sequences from nucleosomes.”
The FDA has approved two new dosage strengths for Stalevo (carbidopa, levodopa, and entacapone) tablets: 75 (18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg entacapone) and 125 (31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone). The new dosage strengths are in addition to the already existing Stalevo 50, 100, 150, and 200 tablets. Stalevo is indicated for patients with Parkinson’s disease who experience end-of-dose “wearing off.” It combines levodopa with the enzyme inhibitors carbidopa and entacapone to provide greater and more sustained levels of levodopa in the blood and improve bodily movement control. The most common side effects include dyskinesia, hypokinesia, hyperkinesia, nausea, diarrhea, discoloration of urine, sweat, and/or saliva, abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Stalevo was originally approved by the FDA in June 2003 and is marketed by Novartis Pharmaceuticals Corporation in East Hanover, New Jersey.
Vitamin D deficiency may have a role in Parkinson’s disease, reported researchers in the October Archives of Neurology. Patients with Parkinson’s disease were matched by age to healthy controls and patients with Alzheimer’s disease. More patients with Parkinson’s disease (55%) had insufficient vitamin D, compared with controls (36%) and patients with Alzheimer’s disease (41%). The Parkinson’s disease subjects also had significantly lower mean plasma 25-hydroxyvitamin D concentration than the Alzheimer’s disease and control cohorts (31.9 vs 34.8 and 37.0 ng/mL, respectively). “Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of Parkinson’s disease,” suggested the investigators.
Treatment with valproic acid was associated with improved memory and reduced brain lesions in a mouse model, reported researchers in the October 27 online Journal of Experimental Medicine. Valproic acid decreased β-amyloid protein production by inhibiting glycogen synthase kinase 3β–mediated γ-secretase cleavage of β-amyloid precursor protein in vitro and in vivo. “Valproic acid treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic Alzheimer’s disease model mice,” observed the investigators. In addition, treatment with valproic acid in the early stages of Alzheimer’s disease alleviated memory deficits in the mice.
Education and occupation may reduce the severity and delay the clinical expression of Alzheimer’s disease, according to a study in the October 21 Neurology. The researchers assessed 242 patients with probable Alzheimer’s disease for the impact of education and occupation on brain glucose metabolism (rCMRglc) in patients with amnestic mild cognitive impairment (aMCI). A significant association was shown between higher education and occupation and lower rCMRglc in the posterior temporoparietal cortex and precuneus in those with probable Alzheimer’s disease and aMCI converters; no such correlation was found in aMCI nonconverters or the control group. “This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer’s disease pathology,” the researchers concluded.
A high level of physical activity is associated with less severe first stroke and improved long-term outcome, according to a report in the October 21 Neurology. Researchers compiled data on 265 subjects (mean age, 68) who represented a subset of patients with first-ever stroke enrolled in the ExStroke Pilot Trial. Prestroke level of physical activity was measured retrospectively using the Physical Activity Scale for the Elderly questionnaire. Stroke severity was measured with the Scandinavian Stroke Scale, and long-term outcome was assessed after two years with the modified Rankin Scale. Patients in the lowest quartile of physical activity had the poorest outcome, as well as a more severe stroke. Higher physical activity was associated with a less severe stroke (odds ratio [OR], 2.54) and a decreased likelihood of poor long-term outcome (OR, 0.46).
Multiplex ligation-dependent probe amplification (MLPA) is an efficient and inexpensive tool for screening chromosomal abnormalities present in autism spectrum disorders, researchers reported in the October BMC Medical Genomics. A screening of 279 unrelated subjects showed duplications of the 15q11-q13 region in two subjects, as well as duplications of the 22q11 region in two subjects. In an additional two patients, smaller de novo duplications were identified. Genes in these novel duplications included GABRB3 and ATP10A in one case and MKRN3, MAGEL2, and NDN in the other. These duplications likely exacerbate symptoms and/or increase liability for autism spectrum disorders. The researchers also found a partial duplication of the ASMT gene in 6% to 7% of cases, compared with 2% of controls, indicating that further study is needed to determine its potential impact on autism spectrum disorders. “MLPA proves to be an efficient method to screen for chromosomal abnormalities,” they stated.
Brain microbleeds are more prevalent in black patients than in white patients, according to a report in the October 7 Neurology. A total of 87 subjects (42 black, 45 white) with intracerebral hemorrhage (ICH) were analyzed. Black subjects were younger and had a greater rate of hypertension but did not have other vascular risk factors. Seventy-four percent of black patients had one or more microbleeds, compared with 42% of white patients. “The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%),” the researchers observed. Race remained an independent predictor of microbleeds (odds ratio, 3.3), after adjusting for age, hypertension, and alcohol use. “Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression,” the investigators concluded.
Patients with acute ischemic stroke who require aggressive measures to lower blood pressure should not be excluded from receiving intravenous t-PA therapy, according to a study in the September Archives of Neurology. Medical records of 178 patients with acute ischemic stroke who were treated with t-PA therapy were reviewed. Fifty patients required blood pressure–lowering treatment before receiving t-PA therapy; of these, 24 patients received nicardipine as first-line therapy or after receiving labetalol. There were no significant differences in adverse events between those treated with nicardipine or labetalol and those who did not receive blood pressure–lowering treatment. “Data suggest that patients with acute ischemic stroke requiring aggressive treatment to lower blood pressure should not be excluded from receiving t-PA therapy,” the authors concluded, noting that a prospective study is needed.
Carotid artery stenting is as efficacious as endarterectomy for the prevention of recurrent ipsilateral ischemic stroke, but safety concerns during the 30-day period following surgery need to be addressed, according to two studies in the October Lancet Neurology. In the Stent-Protected Angioplasty versus Carotid Endarterectomy study, patients underwent either carotid angioplasty with stenting (n = 613) or carotid endarterectomy (n = 601). After two years, the rate of recurrent ipsilateral ischemic stroke was similar in both treatment groups. In the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, researchers compared outcome after stenting with outcome after endarterectomy after four years in 527 subjects who had carotid stenosis of at least 60% that had recently become symptomatic. The probability of periprocedural stroke or death and nonprocedural ipsilateral stroke was higher in those who received stenting than in those who received endarterectomy (11.1% vs 6.2%, respectively; hazard ratio, 1.97). The differences were attributed to “the higher periprocedural risk of stenting compared with endarterectomy,” said the researchers. After the periprocedural period, however, risks for ipsilateral stroke were similar in both treatment groups.
Fetal aneuploidy can be detected using a noninvasive maternal blood test, according to a study in the October 21 Proceedings of the National Academy of Sciences. Researchers used high-throughput shotgun technology to sequence cell-free DNA from the plasma of pregnant women, obtaining an average of five million sequence tags per patient sample. “The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy,” the investigators stated. Nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edwards syndrome), and one case of trisomy 13 (Patau syndrome) were observed among 12 women with aneuploid pregnancies and six women with normal pregnancies. Trisomy was detected as early as the 14th week of gestation. “Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA,” the study authors added, “and we found evidence that this DNA is enriched for sequences from nucleosomes.”
The FDA has approved two new dosage strengths for Stalevo (carbidopa, levodopa, and entacapone) tablets: 75 (18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg entacapone) and 125 (31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone). The new dosage strengths are in addition to the already existing Stalevo 50, 100, 150, and 200 tablets. Stalevo is indicated for patients with Parkinson’s disease who experience end-of-dose “wearing off.” It combines levodopa with the enzyme inhibitors carbidopa and entacapone to provide greater and more sustained levels of levodopa in the blood and improve bodily movement control. The most common side effects include dyskinesia, hypokinesia, hyperkinesia, nausea, diarrhea, discoloration of urine, sweat, and/or saliva, abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Stalevo was originally approved by the FDA in June 2003 and is marketed by Novartis Pharmaceuticals Corporation in East Hanover, New Jersey.
Vitamin D deficiency may have a role in Parkinson’s disease, reported researchers in the October Archives of Neurology. Patients with Parkinson’s disease were matched by age to healthy controls and patients with Alzheimer’s disease. More patients with Parkinson’s disease (55%) had insufficient vitamin D, compared with controls (36%) and patients with Alzheimer’s disease (41%). The Parkinson’s disease subjects also had significantly lower mean plasma 25-hydroxyvitamin D concentration than the Alzheimer’s disease and control cohorts (31.9 vs 34.8 and 37.0 ng/mL, respectively). “Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of Parkinson’s disease,” suggested the investigators.
Treatment with valproic acid was associated with improved memory and reduced brain lesions in a mouse model, reported researchers in the October 27 online Journal of Experimental Medicine. Valproic acid decreased β-amyloid protein production by inhibiting glycogen synthase kinase 3β–mediated γ-secretase cleavage of β-amyloid precursor protein in vitro and in vivo. “Valproic acid treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic Alzheimer’s disease model mice,” observed the investigators. In addition, treatment with valproic acid in the early stages of Alzheimer’s disease alleviated memory deficits in the mice.
Education and occupation may reduce the severity and delay the clinical expression of Alzheimer’s disease, according to a study in the October 21 Neurology. The researchers assessed 242 patients with probable Alzheimer’s disease for the impact of education and occupation on brain glucose metabolism (rCMRglc) in patients with amnestic mild cognitive impairment (aMCI). A significant association was shown between higher education and occupation and lower rCMRglc in the posterior temporoparietal cortex and precuneus in those with probable Alzheimer’s disease and aMCI converters; no such correlation was found in aMCI nonconverters or the control group. “This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer’s disease pathology,” the researchers concluded.
A high level of physical activity is associated with less severe first stroke and improved long-term outcome, according to a report in the October 21 Neurology. Researchers compiled data on 265 subjects (mean age, 68) who represented a subset of patients with first-ever stroke enrolled in the ExStroke Pilot Trial. Prestroke level of physical activity was measured retrospectively using the Physical Activity Scale for the Elderly questionnaire. Stroke severity was measured with the Scandinavian Stroke Scale, and long-term outcome was assessed after two years with the modified Rankin Scale. Patients in the lowest quartile of physical activity had the poorest outcome, as well as a more severe stroke. Higher physical activity was associated with a less severe stroke (odds ratio [OR], 2.54) and a decreased likelihood of poor long-term outcome (OR, 0.46).
Multiplex ligation-dependent probe amplification (MLPA) is an efficient and inexpensive tool for screening chromosomal abnormalities present in autism spectrum disorders, researchers reported in the October BMC Medical Genomics. A screening of 279 unrelated subjects showed duplications of the 15q11-q13 region in two subjects, as well as duplications of the 22q11 region in two subjects. In an additional two patients, smaller de novo duplications were identified. Genes in these novel duplications included GABRB3 and ATP10A in one case and MKRN3, MAGEL2, and NDN in the other. These duplications likely exacerbate symptoms and/or increase liability for autism spectrum disorders. The researchers also found a partial duplication of the ASMT gene in 6% to 7% of cases, compared with 2% of controls, indicating that further study is needed to determine its potential impact on autism spectrum disorders. “MLPA proves to be an efficient method to screen for chromosomal abnormalities,” they stated.
Brain microbleeds are more prevalent in black patients than in white patients, according to a report in the October 7 Neurology. A total of 87 subjects (42 black, 45 white) with intracerebral hemorrhage (ICH) were analyzed. Black subjects were younger and had a greater rate of hypertension but did not have other vascular risk factors. Seventy-four percent of black patients had one or more microbleeds, compared with 42% of white patients. “The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%),” the researchers observed. Race remained an independent predictor of microbleeds (odds ratio, 3.3), after adjusting for age, hypertension, and alcohol use. “Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression,” the investigators concluded.
Patients with acute ischemic stroke who require aggressive measures to lower blood pressure should not be excluded from receiving intravenous t-PA therapy, according to a study in the September Archives of Neurology. Medical records of 178 patients with acute ischemic stroke who were treated with t-PA therapy were reviewed. Fifty patients required blood pressure–lowering treatment before receiving t-PA therapy; of these, 24 patients received nicardipine as first-line therapy or after receiving labetalol. There were no significant differences in adverse events between those treated with nicardipine or labetalol and those who did not receive blood pressure–lowering treatment. “Data suggest that patients with acute ischemic stroke requiring aggressive treatment to lower blood pressure should not be excluded from receiving t-PA therapy,” the authors concluded, noting that a prospective study is needed.
News Roundup: New and Noteworthy Information
Low levels of vitamin B12 may cause brain atrophy and, subsequently, cognitive impairment in the elderly, according to the a study in the September 9 Neurology. The prospective five-year study included 107 community-dwelling volunteers ages 61 to 87 who did not have cognitive impairment at baseline. Patients with lower vitamin B12 and holotranscobalamin (holoTC) levels and higher plasma total homocysteine (tHcy) and methylmalonic acid levels at baseline had a greater decrease in brain volume. Associations between vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, apolipoprotein E ε4 status, tHcy, and serum folate. The increased rate of brain volume loss was associated with the bottom tertile of vitamin B12 (Heavy alcoholic consumption is associated with increased mortality from total stroke and total cardiovascular disease for men and with increased mortality from coronary heart disease for women; however, light to moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes, according to a report in the November Stroke. Of the 34,776 men and 48,906 women from Japan who completed a self-administered questionnaire, 1,628 died from stroke and 736 died from coronary heart disease in the 14.2-year follow-up period. Among men, heavy drinking (≥ 46 g of ethanol per day) was associated with increased total mortality (hazard ratio [HR], 1.48) and mortality from hemorrhagic and ischemic strokes (HRs, 1.67 and 1.35, respectively). Light to moderate drinking was associated with reduced mortality from total cardiovascular disease (HR, 0.88) in this group, compared with not drinking. Women who drank heavily had increased mortality from coronary heart disease (HR, 4.10), while those who drank moderate amounts of alcohol (0.1 to 22.9 g of ethanol/day) had a reduced mortality from total cardiovascular disease (HR, 0.75), compared with nondrinkers.
The FDA has approved Xenazine (tetrabenazine) for the treatment of chorea associated with Huntington’s disease. Tetrabenazine is the first and only FDA-approved treatment for any symptom of Huntington’s disease and is expected to be available later this year. The approval was based on a double-blind placebo-controlled study that found that tetrabenazine significantly reduced patients’ chorea burden, improved global outcome scores, and was generally safe and well tolerated. Side effects included depression and suicidal thoughts and actions. Other common side effects included insomnia, drowsiness, restlessness, and nausea. The drug will be marketed under the Risk Evaluation and Mitigation Strategy, which includes educational materials to help decrease these risks. Xenazine is manufactured by Prestwick Pharmaceuticals.
Migraineurs do not have an increased risk for atherosclerosis but may have a higher risk for venous thromboembolism, reported researchers in the September 16 Neurology. A total of 574 participants ages 55 to 94 underwent neurologic and laboratory examinations. “Prevalence, severity, and five-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs,” the investigators stated. There was also a tendency for atherosclerosis to be less pronounced and for the intima-media thickness to be lower among patients with migraine. However, migraineurs had a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs), after adjustment for age and gender.
Keppra XR (levetiracetam extended-release tablets) has been approved by the FDA as an add-on to other antiepileptic treatments for patients 16 and older with partial-onset seizures. “We found in the clinical trial that Keppra XR provided significant partial-onset seizure control in once-daily dosing when added to other antiepileptic drugs and that it was well tolerated,” said lead investigator Jukka Peltola, MD. The most common adverse reactions were somnolence and irritability. Adverse reactions to the extended-release form of levetiracetam are expected to be similar to those seen in patients taking the immediate-release form. Levetiracetam extended-release should be gradually withdrawn to minimize the potential for increased seizure frequency. For patients with end-stage renal disease who are on dialysis, the immediate-release form of levetiracetam is recommended over the extended-release form. Keppra XR is marketed by UCB.
Warfarin use is associated with larger initial intracerebral hemorrhage (ICH) volume and therefore greater mortality risk, according to a retrospective study in the September 30 Neurology. ICH volumes of hospitalized patients in the Cincinnati region throughout 2005 were measured using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine the influence of the international normalized ratio (INR) on ICH, after adjusting for age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Of 258 patients, 51 were taking warfarin. “In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category,” the researchers said. “This effect was only observed for INR values greater than 3.0.” These findings may partially account for the higher mortality rate in this group.
Elevated levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM-2) in CSF may inhibit anti-inflammatory function of membrane-bound receptor cells and promote phagocytosis in microglial cells, according to a study in the September 12 online Brain. These findings suggest that sTREM-2 may be a possible target for future multiple sclerosis (MS) therapies. sTREM-2 levels were compared among subjects with various forms of MS and other inflammatory neurologic diseases, as well as noninflammatory neurologic diseases. Although levels of sTREM-2 in the bloodstream did not differ among groups, higher levels were found in the CSF of patients with relapsing-remitting MS, primary-progressive MS, and other inflammatory neurologic diseases.
Pain is a nonmotor feature of Parkinson’s disease that begins with the onset of the disease, according to a report in the September Archives of Neurology. A total of 402 patients with Parkinson’s disease were compared with 317 age-matched controls using logistic regression models that took into account the type of pain, time between pain and onset of Parkinson’s disease, and possible confounders. Overall pain frequency was substantially greater for those with Parkinson’s disease than for controls (69.9% vs 62.8%). Patients with Parkinson’s disease also had a higher frequency of cramping and central neuropathic pain. Nondystonic pain frequency was similar between both groups. “Nevertheless, we observed a significant association between Parkinson’s disease and nondystonic pain, beginning after the onset of parkinsonian symptoms,” the researchers stated. Approximately one-quarter of the subjects reported onset of pain before beginning antiparkinsonian therapy.
Intravenous alteplase treatment for acute ischemic stroke is safe and effective up to 4.5 hours after onset, according to a study in the September 25 New England Journal of Medicine. A total of 821 patients were randomly assigned to an alteplase group (418) or a placebo group (403) in a double-blind study. The alteplase group was treated a median of three hours and 59 minutes after stroke onset. Disability at 90 days was determined as the primary end point. Subjects treated with alteplase had a favorable outcome of 0 or 1 on the modified Rankin scale, compared with the placebo group (52.4% vs 45.2%) and also faired better in global analysis measured by neurologic and disability scores. Other differences, including mortality, were not significant between groups.
The ketogenic diet should be the first-line therapy for epileptic infants, as it causes fewer side effects and relapses than adrenocorticotropic hormone (ACTH), according to a report in the September Epilepsia. A retrospective chart review of infants started on the ketogenic diet or high-dose ACTH was conducted. Researchers found that eight of 13 infants treated with the ketogenic diet were spasm-free within one month, compared with 18 of 20 treated with ACTH. EEG normalization was achieved within two to five months in the eight infants who became spasm-free with the ketogenic diet. Of the five patients in whom the ketogenic diet was unsuccessful, four became spasm-free after ACTH or topiramate was administered. The ketogenic diet was associated with fewer side effects and relapses than ACTH, the researchers concluded.
Microvascular changes caused by vitamin B deficiency may lead to hyperhomocysteinemia and vascular cognitive impairment, according to a study in the August 26 Proceedings of the National Academy of Sciences. Researchers fed male mice a vitamin B–deficient diet for 10 weeks. This induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. “Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies, and with plasma total homocysteine,” the investigators reported. A methionine-rich diet was associated with similar but less pronounced effects. The research suggests that “cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration,” the study authors noted. “Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.”
Low levels of vitamin B12 may cause brain atrophy and, subsequently, cognitive impairment in the elderly, according to the a study in the September 9 Neurology. The prospective five-year study included 107 community-dwelling volunteers ages 61 to 87 who did not have cognitive impairment at baseline. Patients with lower vitamin B12 and holotranscobalamin (holoTC) levels and higher plasma total homocysteine (tHcy) and methylmalonic acid levels at baseline had a greater decrease in brain volume. Associations between vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, apolipoprotein E ε4 status, tHcy, and serum folate. The increased rate of brain volume loss was associated with the bottom tertile of vitamin B12 (Heavy alcoholic consumption is associated with increased mortality from total stroke and total cardiovascular disease for men and with increased mortality from coronary heart disease for women; however, light to moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes, according to a report in the November Stroke. Of the 34,776 men and 48,906 women from Japan who completed a self-administered questionnaire, 1,628 died from stroke and 736 died from coronary heart disease in the 14.2-year follow-up period. Among men, heavy drinking (≥ 46 g of ethanol per day) was associated with increased total mortality (hazard ratio [HR], 1.48) and mortality from hemorrhagic and ischemic strokes (HRs, 1.67 and 1.35, respectively). Light to moderate drinking was associated with reduced mortality from total cardiovascular disease (HR, 0.88) in this group, compared with not drinking. Women who drank heavily had increased mortality from coronary heart disease (HR, 4.10), while those who drank moderate amounts of alcohol (0.1 to 22.9 g of ethanol/day) had a reduced mortality from total cardiovascular disease (HR, 0.75), compared with nondrinkers.
The FDA has approved Xenazine (tetrabenazine) for the treatment of chorea associated with Huntington’s disease. Tetrabenazine is the first and only FDA-approved treatment for any symptom of Huntington’s disease and is expected to be available later this year. The approval was based on a double-blind placebo-controlled study that found that tetrabenazine significantly reduced patients’ chorea burden, improved global outcome scores, and was generally safe and well tolerated. Side effects included depression and suicidal thoughts and actions. Other common side effects included insomnia, drowsiness, restlessness, and nausea. The drug will be marketed under the Risk Evaluation and Mitigation Strategy, which includes educational materials to help decrease these risks. Xenazine is manufactured by Prestwick Pharmaceuticals.
Migraineurs do not have an increased risk for atherosclerosis but may have a higher risk for venous thromboembolism, reported researchers in the September 16 Neurology. A total of 574 participants ages 55 to 94 underwent neurologic and laboratory examinations. “Prevalence, severity, and five-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs,” the investigators stated. There was also a tendency for atherosclerosis to be less pronounced and for the intima-media thickness to be lower among patients with migraine. However, migraineurs had a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs), after adjustment for age and gender.
Keppra XR (levetiracetam extended-release tablets) has been approved by the FDA as an add-on to other antiepileptic treatments for patients 16 and older with partial-onset seizures. “We found in the clinical trial that Keppra XR provided significant partial-onset seizure control in once-daily dosing when added to other antiepileptic drugs and that it was well tolerated,” said lead investigator Jukka Peltola, MD. The most common adverse reactions were somnolence and irritability. Adverse reactions to the extended-release form of levetiracetam are expected to be similar to those seen in patients taking the immediate-release form. Levetiracetam extended-release should be gradually withdrawn to minimize the potential for increased seizure frequency. For patients with end-stage renal disease who are on dialysis, the immediate-release form of levetiracetam is recommended over the extended-release form. Keppra XR is marketed by UCB.
Warfarin use is associated with larger initial intracerebral hemorrhage (ICH) volume and therefore greater mortality risk, according to a retrospective study in the September 30 Neurology. ICH volumes of hospitalized patients in the Cincinnati region throughout 2005 were measured using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine the influence of the international normalized ratio (INR) on ICH, after adjusting for age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Of 258 patients, 51 were taking warfarin. “In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category,” the researchers said. “This effect was only observed for INR values greater than 3.0.” These findings may partially account for the higher mortality rate in this group.
Elevated levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM-2) in CSF may inhibit anti-inflammatory function of membrane-bound receptor cells and promote phagocytosis in microglial cells, according to a study in the September 12 online Brain. These findings suggest that sTREM-2 may be a possible target for future multiple sclerosis (MS) therapies. sTREM-2 levels were compared among subjects with various forms of MS and other inflammatory neurologic diseases, as well as noninflammatory neurologic diseases. Although levels of sTREM-2 in the bloodstream did not differ among groups, higher levels were found in the CSF of patients with relapsing-remitting MS, primary-progressive MS, and other inflammatory neurologic diseases.
Pain is a nonmotor feature of Parkinson’s disease that begins with the onset of the disease, according to a report in the September Archives of Neurology. A total of 402 patients with Parkinson’s disease were compared with 317 age-matched controls using logistic regression models that took into account the type of pain, time between pain and onset of Parkinson’s disease, and possible confounders. Overall pain frequency was substantially greater for those with Parkinson’s disease than for controls (69.9% vs 62.8%). Patients with Parkinson’s disease also had a higher frequency of cramping and central neuropathic pain. Nondystonic pain frequency was similar between both groups. “Nevertheless, we observed a significant association between Parkinson’s disease and nondystonic pain, beginning after the onset of parkinsonian symptoms,” the researchers stated. Approximately one-quarter of the subjects reported onset of pain before beginning antiparkinsonian therapy.
Intravenous alteplase treatment for acute ischemic stroke is safe and effective up to 4.5 hours after onset, according to a study in the September 25 New England Journal of Medicine. A total of 821 patients were randomly assigned to an alteplase group (418) or a placebo group (403) in a double-blind study. The alteplase group was treated a median of three hours and 59 minutes after stroke onset. Disability at 90 days was determined as the primary end point. Subjects treated with alteplase had a favorable outcome of 0 or 1 on the modified Rankin scale, compared with the placebo group (52.4% vs 45.2%) and also faired better in global analysis measured by neurologic and disability scores. Other differences, including mortality, were not significant between groups.
The ketogenic diet should be the first-line therapy for epileptic infants, as it causes fewer side effects and relapses than adrenocorticotropic hormone (ACTH), according to a report in the September Epilepsia. A retrospective chart review of infants started on the ketogenic diet or high-dose ACTH was conducted. Researchers found that eight of 13 infants treated with the ketogenic diet were spasm-free within one month, compared with 18 of 20 treated with ACTH. EEG normalization was achieved within two to five months in the eight infants who became spasm-free with the ketogenic diet. Of the five patients in whom the ketogenic diet was unsuccessful, four became spasm-free after ACTH or topiramate was administered. The ketogenic diet was associated with fewer side effects and relapses than ACTH, the researchers concluded.
Microvascular changes caused by vitamin B deficiency may lead to hyperhomocysteinemia and vascular cognitive impairment, according to a study in the August 26 Proceedings of the National Academy of Sciences. Researchers fed male mice a vitamin B–deficient diet for 10 weeks. This induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. “Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies, and with plasma total homocysteine,” the investigators reported. A methionine-rich diet was associated with similar but less pronounced effects. The research suggests that “cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration,” the study authors noted. “Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.”
Low levels of vitamin B12 may cause brain atrophy and, subsequently, cognitive impairment in the elderly, according to the a study in the September 9 Neurology. The prospective five-year study included 107 community-dwelling volunteers ages 61 to 87 who did not have cognitive impairment at baseline. Patients with lower vitamin B12 and holotranscobalamin (holoTC) levels and higher plasma total homocysteine (tHcy) and methylmalonic acid levels at baseline had a greater decrease in brain volume. Associations between vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, apolipoprotein E ε4 status, tHcy, and serum folate. The increased rate of brain volume loss was associated with the bottom tertile of vitamin B12 (Heavy alcoholic consumption is associated with increased mortality from total stroke and total cardiovascular disease for men and with increased mortality from coronary heart disease for women; however, light to moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes, according to a report in the November Stroke. Of the 34,776 men and 48,906 women from Japan who completed a self-administered questionnaire, 1,628 died from stroke and 736 died from coronary heart disease in the 14.2-year follow-up period. Among men, heavy drinking (≥ 46 g of ethanol per day) was associated with increased total mortality (hazard ratio [HR], 1.48) and mortality from hemorrhagic and ischemic strokes (HRs, 1.67 and 1.35, respectively). Light to moderate drinking was associated with reduced mortality from total cardiovascular disease (HR, 0.88) in this group, compared with not drinking. Women who drank heavily had increased mortality from coronary heart disease (HR, 4.10), while those who drank moderate amounts of alcohol (0.1 to 22.9 g of ethanol/day) had a reduced mortality from total cardiovascular disease (HR, 0.75), compared with nondrinkers.
The FDA has approved Xenazine (tetrabenazine) for the treatment of chorea associated with Huntington’s disease. Tetrabenazine is the first and only FDA-approved treatment for any symptom of Huntington’s disease and is expected to be available later this year. The approval was based on a double-blind placebo-controlled study that found that tetrabenazine significantly reduced patients’ chorea burden, improved global outcome scores, and was generally safe and well tolerated. Side effects included depression and suicidal thoughts and actions. Other common side effects included insomnia, drowsiness, restlessness, and nausea. The drug will be marketed under the Risk Evaluation and Mitigation Strategy, which includes educational materials to help decrease these risks. Xenazine is manufactured by Prestwick Pharmaceuticals.
Migraineurs do not have an increased risk for atherosclerosis but may have a higher risk for venous thromboembolism, reported researchers in the September 16 Neurology. A total of 574 participants ages 55 to 94 underwent neurologic and laboratory examinations. “Prevalence, severity, and five-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs,” the investigators stated. There was also a tendency for atherosclerosis to be less pronounced and for the intima-media thickness to be lower among patients with migraine. However, migraineurs had a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs), after adjustment for age and gender.
Keppra XR (levetiracetam extended-release tablets) has been approved by the FDA as an add-on to other antiepileptic treatments for patients 16 and older with partial-onset seizures. “We found in the clinical trial that Keppra XR provided significant partial-onset seizure control in once-daily dosing when added to other antiepileptic drugs and that it was well tolerated,” said lead investigator Jukka Peltola, MD. The most common adverse reactions were somnolence and irritability. Adverse reactions to the extended-release form of levetiracetam are expected to be similar to those seen in patients taking the immediate-release form. Levetiracetam extended-release should be gradually withdrawn to minimize the potential for increased seizure frequency. For patients with end-stage renal disease who are on dialysis, the immediate-release form of levetiracetam is recommended over the extended-release form. Keppra XR is marketed by UCB.
Warfarin use is associated with larger initial intracerebral hemorrhage (ICH) volume and therefore greater mortality risk, according to a retrospective study in the September 30 Neurology. ICH volumes of hospitalized patients in the Cincinnati region throughout 2005 were measured using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine the influence of the international normalized ratio (INR) on ICH, after adjusting for age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Of 258 patients, 51 were taking warfarin. “In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category,” the researchers said. “This effect was only observed for INR values greater than 3.0.” These findings may partially account for the higher mortality rate in this group.
Elevated levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM-2) in CSF may inhibit anti-inflammatory function of membrane-bound receptor cells and promote phagocytosis in microglial cells, according to a study in the September 12 online Brain. These findings suggest that sTREM-2 may be a possible target for future multiple sclerosis (MS) therapies. sTREM-2 levels were compared among subjects with various forms of MS and other inflammatory neurologic diseases, as well as noninflammatory neurologic diseases. Although levels of sTREM-2 in the bloodstream did not differ among groups, higher levels were found in the CSF of patients with relapsing-remitting MS, primary-progressive MS, and other inflammatory neurologic diseases.
Pain is a nonmotor feature of Parkinson’s disease that begins with the onset of the disease, according to a report in the September Archives of Neurology. A total of 402 patients with Parkinson’s disease were compared with 317 age-matched controls using logistic regression models that took into account the type of pain, time between pain and onset of Parkinson’s disease, and possible confounders. Overall pain frequency was substantially greater for those with Parkinson’s disease than for controls (69.9% vs 62.8%). Patients with Parkinson’s disease also had a higher frequency of cramping and central neuropathic pain. Nondystonic pain frequency was similar between both groups. “Nevertheless, we observed a significant association between Parkinson’s disease and nondystonic pain, beginning after the onset of parkinsonian symptoms,” the researchers stated. Approximately one-quarter of the subjects reported onset of pain before beginning antiparkinsonian therapy.
Intravenous alteplase treatment for acute ischemic stroke is safe and effective up to 4.5 hours after onset, according to a study in the September 25 New England Journal of Medicine. A total of 821 patients were randomly assigned to an alteplase group (418) or a placebo group (403) in a double-blind study. The alteplase group was treated a median of three hours and 59 minutes after stroke onset. Disability at 90 days was determined as the primary end point. Subjects treated with alteplase had a favorable outcome of 0 or 1 on the modified Rankin scale, compared with the placebo group (52.4% vs 45.2%) and also faired better in global analysis measured by neurologic and disability scores. Other differences, including mortality, were not significant between groups.
The ketogenic diet should be the first-line therapy for epileptic infants, as it causes fewer side effects and relapses than adrenocorticotropic hormone (ACTH), according to a report in the September Epilepsia. A retrospective chart review of infants started on the ketogenic diet or high-dose ACTH was conducted. Researchers found that eight of 13 infants treated with the ketogenic diet were spasm-free within one month, compared with 18 of 20 treated with ACTH. EEG normalization was achieved within two to five months in the eight infants who became spasm-free with the ketogenic diet. Of the five patients in whom the ketogenic diet was unsuccessful, four became spasm-free after ACTH or topiramate was administered. The ketogenic diet was associated with fewer side effects and relapses than ACTH, the researchers concluded.
Microvascular changes caused by vitamin B deficiency may lead to hyperhomocysteinemia and vascular cognitive impairment, according to a study in the August 26 Proceedings of the National Academy of Sciences. Researchers fed male mice a vitamin B–deficient diet for 10 weeks. This induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. “Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies, and with plasma total homocysteine,” the investigators reported. A methionine-rich diet was associated with similar but less pronounced effects. The research suggests that “cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration,” the study authors noted. “Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.”
News Roundup: New and Noteworthy Information
Modest consumption of fish with high omega-3 fatty acids, such as tuna, is associated with a lower risk for cognitive decline and stroke. According to a report in the August 5 Neurology, 3,660 participants 65 and older underwent MRI; five years later, 2,313 participants had repeat scanning. Dietary intake was assessed using food frequency questionnaires. The risk for having one or more prevalent subclinical infarcts was lower among subjects who consumed fish three or more times per week, compared with less than once per month (relative risk, 0.74). Fish consumption was also associated with trends toward lower incidence of subclinical infarcts. “Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy,” noted the researchers. These associations were not found for fried fish consumption.
High and low thyrotropin levels are associated with an increased risk for Alzheimer’s disease in women, according to a study in the July 28 Archives of Internal Medicine. A total of 1,864 cognitively intact, clinically euthyroid participants were studied (mean age, 71; 59% were women). Alzheimer’s disease was diagnosed in 209 participants (142 women) during the mean follow-up of 12.7 years. Women at the lowest ( 2.1 mIU/L) tertiles of serum thyrotropin concentration had adjusted hazard ratios of 2.39 and 2.15, respectively, compared with those in the middle tertile, the investigators observed. This relationship continued after exclusion of those receiving thyroid supplementation and when analyses were limited to participants with serum thyrotropin levels of 0.1 to 10.0 mIU/L, but not when analyses were limited to patients with serum thyrotropin levels of 0.5 to 5.0 mIU/L. The association between thyrotropin level and Alzheimer’s disease was not found in men.
PET scans involving use of carbon 11–labeled Pittsburgh Compound B ([(11)C]PiB) may help to assess β-amyloid deposition in the brain among patients with Alzheimer’s disease. In a study in the August 11 online Archives of Neurology, 10 patients underwent intraventricular pressure monitoring with a frontal cortical biopsy for suspected normal-pressure hydrocephalus. “In patients with β-amyloid aggregates in the frontal cortical biopsy specimen, PET imaging revealed higher [(11)C]PiB uptake in the frontal, parietal, and lateral temporal cortices and in the striatum as compared with the patients without frontal β-amyloid deposits,” stated the researchers. They concluded that studies are needed to determine whether [(11)C]PiB could be used as a diagnostic tool, particularly for early Alzheimer’s disease.
Physical frailty in old age is associated with Alzheimer’s disease pathology, reported researchers in the August 12 Neurology. Brain autopsies from 165 deceased participants from the Rush Memory and Aging Project were studied, and information was collected on physical frailty based on grip strength, time to walk 8 feet, body composition, and fatigue. “The level of Alzheimer’s disease pathology was associated with frailty proximate to death, accounting for 4% of the variance of physical frailty,” reported the investigators. Frailty had no association with cerebral infarcts or Lewy body disease pathology. The findings were unchanged after the researchers controlled for time interval between last clinical evaluation to autopsy. Other potential confounders such as the presence of dementia, physical activity, parkinsonian signs, pulmonary function, and history of chronic diseases did not change this association.
Individuals with a spouse who currently smokes may have an increased risk for stroke, researchers reported in the September American Journal of Preventive Medicine. The investigators followed 16,225 stroke-free participants 50 and older for an average of 9.1 years. Proxy and self-report of first stroke totaled 1,130 events. Having a spouse who currently smoked was associated with an increased risk for first stroke among both never smokers and former smokers (hazard ratio, 1.42 and 1.72, respectively). Former smokers married to current smokers had a stroke risk similar to current smokers. “The health benefits of quitting smoking likely extend to both the individual smoker and his or her spouse,” the study authors concluded.
Women with the MTHFR 677TT genotype who have migraine with aura have an increased risk for cardiovascular disease and stroke, according to a study in the August 12 Neurology. Of the 25,001 women studied, 4,577 (18.3%) reported a history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 625 cardiovascular disease events occurred. The TT genotype was associated with lower risk for migraine with aura (relative risk [RR], 0.79) and did not increase the risk for cardiovascular disease. However, migraine with aura doubled the risk for cardiovascular disease (RR, 2.06). The presence of migraine with aura and the TT genotype greatly increased that risk (RR, 3.66) and also increased the risk for ischemic stroke (RR, 4.19).
Modest consumption of fish with high omega-3 fatty acids, such as tuna, is associated with a lower risk for cognitive decline and stroke. According to a report in the August 5 Neurology, 3,660 participants 65 and older underwent MRI; five years later, 2,313 participants had repeat scanning. Dietary intake was assessed using food frequency questionnaires. The risk for having one or more prevalent subclinical infarcts was lower among subjects who consumed fish three or more times per week, compared with less than once per month (relative risk, 0.74). Fish consumption was also associated with trends toward lower incidence of subclinical infarcts. “Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy,” noted the researchers. These associations were not found for fried fish consumption.
High and low thyrotropin levels are associated with an increased risk for Alzheimer’s disease in women, according to a study in the July 28 Archives of Internal Medicine. A total of 1,864 cognitively intact, clinically euthyroid participants were studied (mean age, 71; 59% were women). Alzheimer’s disease was diagnosed in 209 participants (142 women) during the mean follow-up of 12.7 years. Women at the lowest ( 2.1 mIU/L) tertiles of serum thyrotropin concentration had adjusted hazard ratios of 2.39 and 2.15, respectively, compared with those in the middle tertile, the investigators observed. This relationship continued after exclusion of those receiving thyroid supplementation and when analyses were limited to participants with serum thyrotropin levels of 0.1 to 10.0 mIU/L, but not when analyses were limited to patients with serum thyrotropin levels of 0.5 to 5.0 mIU/L. The association between thyrotropin level and Alzheimer’s disease was not found in men.
PET scans involving use of carbon 11–labeled Pittsburgh Compound B ([(11)C]PiB) may help to assess β-amyloid deposition in the brain among patients with Alzheimer’s disease. In a study in the August 11 online Archives of Neurology, 10 patients underwent intraventricular pressure monitoring with a frontal cortical biopsy for suspected normal-pressure hydrocephalus. “In patients with β-amyloid aggregates in the frontal cortical biopsy specimen, PET imaging revealed higher [(11)C]PiB uptake in the frontal, parietal, and lateral temporal cortices and in the striatum as compared with the patients without frontal β-amyloid deposits,” stated the researchers. They concluded that studies are needed to determine whether [(11)C]PiB could be used as a diagnostic tool, particularly for early Alzheimer’s disease.
Physical frailty in old age is associated with Alzheimer’s disease pathology, reported researchers in the August 12 Neurology. Brain autopsies from 165 deceased participants from the Rush Memory and Aging Project were studied, and information was collected on physical frailty based on grip strength, time to walk 8 feet, body composition, and fatigue. “The level of Alzheimer’s disease pathology was associated with frailty proximate to death, accounting for 4% of the variance of physical frailty,” reported the investigators. Frailty had no association with cerebral infarcts or Lewy body disease pathology. The findings were unchanged after the researchers controlled for time interval between last clinical evaluation to autopsy. Other potential confounders such as the presence of dementia, physical activity, parkinsonian signs, pulmonary function, and history of chronic diseases did not change this association.
Individuals with a spouse who currently smokes may have an increased risk for stroke, researchers reported in the September American Journal of Preventive Medicine. The investigators followed 16,225 stroke-free participants 50 and older for an average of 9.1 years. Proxy and self-report of first stroke totaled 1,130 events. Having a spouse who currently smoked was associated with an increased risk for first stroke among both never smokers and former smokers (hazard ratio, 1.42 and 1.72, respectively). Former smokers married to current smokers had a stroke risk similar to current smokers. “The health benefits of quitting smoking likely extend to both the individual smoker and his or her spouse,” the study authors concluded.
Women with the MTHFR 677TT genotype who have migraine with aura have an increased risk for cardiovascular disease and stroke, according to a study in the August 12 Neurology. Of the 25,001 women studied, 4,577 (18.3%) reported a history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 625 cardiovascular disease events occurred. The TT genotype was associated with lower risk for migraine with aura (relative risk [RR], 0.79) and did not increase the risk for cardiovascular disease. However, migraine with aura doubled the risk for cardiovascular disease (RR, 2.06). The presence of migraine with aura and the TT genotype greatly increased that risk (RR, 3.66) and also increased the risk for ischemic stroke (RR, 4.19).
Modest consumption of fish with high omega-3 fatty acids, such as tuna, is associated with a lower risk for cognitive decline and stroke. According to a report in the August 5 Neurology, 3,660 participants 65 and older underwent MRI; five years later, 2,313 participants had repeat scanning. Dietary intake was assessed using food frequency questionnaires. The risk for having one or more prevalent subclinical infarcts was lower among subjects who consumed fish three or more times per week, compared with less than once per month (relative risk, 0.74). Fish consumption was also associated with trends toward lower incidence of subclinical infarcts. “Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy,” noted the researchers. These associations were not found for fried fish consumption.
High and low thyrotropin levels are associated with an increased risk for Alzheimer’s disease in women, according to a study in the July 28 Archives of Internal Medicine. A total of 1,864 cognitively intact, clinically euthyroid participants were studied (mean age, 71; 59% were women). Alzheimer’s disease was diagnosed in 209 participants (142 women) during the mean follow-up of 12.7 years. Women at the lowest ( 2.1 mIU/L) tertiles of serum thyrotropin concentration had adjusted hazard ratios of 2.39 and 2.15, respectively, compared with those in the middle tertile, the investigators observed. This relationship continued after exclusion of those receiving thyroid supplementation and when analyses were limited to participants with serum thyrotropin levels of 0.1 to 10.0 mIU/L, but not when analyses were limited to patients with serum thyrotropin levels of 0.5 to 5.0 mIU/L. The association between thyrotropin level and Alzheimer’s disease was not found in men.
PET scans involving use of carbon 11–labeled Pittsburgh Compound B ([(11)C]PiB) may help to assess β-amyloid deposition in the brain among patients with Alzheimer’s disease. In a study in the August 11 online Archives of Neurology, 10 patients underwent intraventricular pressure monitoring with a frontal cortical biopsy for suspected normal-pressure hydrocephalus. “In patients with β-amyloid aggregates in the frontal cortical biopsy specimen, PET imaging revealed higher [(11)C]PiB uptake in the frontal, parietal, and lateral temporal cortices and in the striatum as compared with the patients without frontal β-amyloid deposits,” stated the researchers. They concluded that studies are needed to determine whether [(11)C]PiB could be used as a diagnostic tool, particularly for early Alzheimer’s disease.
Physical frailty in old age is associated with Alzheimer’s disease pathology, reported researchers in the August 12 Neurology. Brain autopsies from 165 deceased participants from the Rush Memory and Aging Project were studied, and information was collected on physical frailty based on grip strength, time to walk 8 feet, body composition, and fatigue. “The level of Alzheimer’s disease pathology was associated with frailty proximate to death, accounting for 4% of the variance of physical frailty,” reported the investigators. Frailty had no association with cerebral infarcts or Lewy body disease pathology. The findings were unchanged after the researchers controlled for time interval between last clinical evaluation to autopsy. Other potential confounders such as the presence of dementia, physical activity, parkinsonian signs, pulmonary function, and history of chronic diseases did not change this association.
Individuals with a spouse who currently smokes may have an increased risk for stroke, researchers reported in the September American Journal of Preventive Medicine. The investigators followed 16,225 stroke-free participants 50 and older for an average of 9.1 years. Proxy and self-report of first stroke totaled 1,130 events. Having a spouse who currently smoked was associated with an increased risk for first stroke among both never smokers and former smokers (hazard ratio, 1.42 and 1.72, respectively). Former smokers married to current smokers had a stroke risk similar to current smokers. “The health benefits of quitting smoking likely extend to both the individual smoker and his or her spouse,” the study authors concluded.
Women with the MTHFR 677TT genotype who have migraine with aura have an increased risk for cardiovascular disease and stroke, according to a study in the August 12 Neurology. Of the 25,001 women studied, 4,577 (18.3%) reported a history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 625 cardiovascular disease events occurred. The TT genotype was associated with lower risk for migraine with aura (relative risk [RR], 0.79) and did not increase the risk for cardiovascular disease. However, migraine with aura doubled the risk for cardiovascular disease (RR, 2.06). The presence of migraine with aura and the TT genotype greatly increased that risk (RR, 3.66) and also increased the risk for ischemic stroke (RR, 4.19).