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