New and Noteworthy Information—November 2013

In early December 2013, the FDA will formally recommend to the US Department of Health and Human Services (HHS) that hydrocodone combination products be reclassified as Schedule II drugs. The proposed change would tighten the controls on these products, which now are classified as Schedule III. The recommendation follows the US Drug Enforcement Administration’s (DEA) 2009 request for guidance from HHS regarding hydrocodone combination products such as Vicodin. The FDA’s determination is the result of an analysis of the scientific literature, a review of hundreds of public comments on the issue, and several public meetings, according to a statement by Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research. The recommendation will influence the DEA’s final decision on the appropriate scheduling of these products.

Influenza vaccination may reduce patients’ risk of major adverse cardiovascular events, including stroke, according to a meta-analysis published October 23 in JAMA. Researchers conducted a systematic review of randomized clinical trials listed in MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials that compared influenza vaccine with placebo or control in patients at high risk of cardiovascular disease. Six trials encompassing 6,735 patients were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%) in published trials. A treatment interaction was detected between patients with and without recent acute coronary syndrome. The greatest treatment effect was observed among the highest-risk patients with more active coronary disease, and a larger trial is warranted to assess these findings, said the researchers.

Short sleep duration and poor sleep quality may be associated with greater β-amyloid burden among community-dwelling older adults, according to research published online ahead of print October 21 in JAMA Neurology. Investigators performed a cross-sectional study of 70 adult participants (mean age, 76) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. The study’s main outcome measure was β-amyloid burden, measured by carbon 11-labeled Pittsburgh compound B PET distribution volume ratios. After adjustment for potential confounders, the researchers found an association between reports of shorter sleep duration and greater β-amyloid burden, measured by mean cortical distribution volume ratio and precuneus distribution volume ratio. Reports of lower sleep quality were associated with greater β-amyloid burden, measured by precuneus distribution volume ratio.

High blood glucose levels may adversely affect cognition, even among patients without type 2 diabetes or impaired glucose tolerance, researchers reported online ahead of print October 23 in Neurology. The effect may be mediated by structural changes in learning-relevant brain areas, the authors noted. The group tested memory in 141 individuals using the Rey Auditory Verbal Learning Test and acquired peripheral levels of fasting HbA1c, glucose, and insulin. Clinicians performed 3-T MRI scans to assess hippocampal volume and microstructure. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Mediation analyses indicated that beneficial effects of lower HbA1c on memory are partly mediated by hippocampal volume and microstructure.

Among older adults, arterial stiffness may be associated with b-amyloid plaque deposition in the brain, independent of blood pressure and APOE ε4 allele, according to a study published online ahead of print October 16 in Neurology. Investigators studied 91 dementia-free participants between ages 83 and 96. Participants underwent brain MRI and PET imaging with Pittsburgh compound B. The researchers measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed vascular beds. A total of 44 subjects were β-amyloid positive on PET scan. The investigators found that β-amyloid deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in brachial ankle PWV resulted in a twofold increase in the odds of being β-amyloid positive.

The FDA has approved Vizamyl (flutemetamol F 18 injection), a radioactive diagnostic drug, for use with PET imaging of the brain in adults being evaluated for Alzheimer’s disease and dementia. Vizamyl attaches to β-amyloid and produces a PET image that is used to evaluate the presence of β-amyloid. The drug’s effectiveness was established in two clinical studies of 384 participants with a range of cognitive function. All participants were injected with Vizamyl and scanned. The images were interpreted by five independent readers masked to all clinical information. A portion of scan results was also confirmed by autopsy. Following the approval of Amyvid (Florbetapir F 18 injection) in 2012, Vizamyl, manufactured by Medi-Physics (Arlington Heights, Illinois), becomes the second diagnostic drug available for visualizing β-amyloid on a PET scan of the brain.

Clostridium perfringens type B, an epsilon toxin-secreting bacillus, may trigger multiple sclerosis (MS), according to research published October 16 in PLOS One. After detecting C. perfringens type B in a woman with MS, investigators tested blood and CSF from patients with MS and controls for antibody reactivity to the epsilon toxin. Levels of epsilon toxin antibodies were 10 times higher in patients with MS, compared with controls. After examining stool samples, the study authors found the human commensal C. perfringens type A in approximately 50% of healthy controls, compared with 23% of patients with MS. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation because these lesions are characterized by blood–brain barrier permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate, said the researchers.

Chronic cerebrospinal venous insufficiency (CCSVI), which has been proposed as a contributor to multiple sclerosis (MS), occurs rarely in patients with MS and in controls, according to a study published online ahead of print October 8 in Lancet. Researchers performed an assessor-blinded, case-control, multicenter study of 79 people with MS, 55 unaffected siblings, and 43 unrelated healthy volunteers. Catheter venography criteria for CCSVI were positive for 2% of people with MS, 2% of siblings, and 3% of unrelated controls. Greater than 50% narrowing of any major vein was present in 74% of people with MS, 66% of siblings, and 70% of unrelated controls. The Zamboni ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography, and the significance of venous narrowing to MS remains unknown, said the investigators.

Measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with Parkinson’s disease, according to research published online ahead of print October 2 in Neurology. Investigators examined 20 patients with Parkinson’s disease and 14 age- and sex-matched control subjects. The researchers performed autonomic testing and skin biopsies at the distal leg, distal thigh, and proximal thigh for all participants. Deposition of α-synuclein and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. The investigators normalized α-synuclein deposition to nerve fiber density. Patients with Parkinson’s disease had greater α-synuclein deposition and higher α-synuclein ratios than controls within pilomotor nerves and sudomotor nerves, but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores, sympathetic adrenergic function, and parasympathetic function.

Depression may be an independent risk factor for Parkinson’s disease, according to research published October 22 in Neurology. Investigators conducted a retrospective study of 4,634 patients with depression and 18,544 matched controls who were selected from a national health insurance database. Patients were observed for a maximum of 10 years to determine the rates of new-onset Parkinson’s disease. Cox regression was used to identify the predictors of the disease. During the follow-up period, 66 patients with depression and 97 controls were diagnosed with Parkinson’s disease. After adjusting for age and sex, the researchers found that patients with depression were 3.24 times more likely to develop Parkinson’s disease, compared with the control patients. The investigators observed that age and difficult-to-treat depression are independent risk factors for Parkinson’s disease in patients with depression.

The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in red blood cells may have no association with age-associated cognitive decline, researchers reported in the October 22 issue of Neurology. The investigators conducted a retrospective cohort study of 2,157 women with normal cognition who were followed with annual cognitive testing for a median of 5.9 years. End points were composite cognitive function and performance in seven cognitive domains. After adjustment for demographic, clinical, and behavioral characteristics, the investigators found no significant cross-sectional cognitive differences between women in the high and low DHA and EPA tertiles at the first annual cognitive battery. In addition, no significant differences were found between the high and low DHA and EPA tertiles in the rate of cognitive change over time.

Common psychosocial stressors (eg, divorce, widowhood, work problems, and illness in a relative) may have severe and long-standing physiologic and psychologic consequences such as dementia, according to research published September 30 in BMJ Open. In a prospective longitudinal population study, clinicians performed psychiatric examinations for 800 women born in 1914, 1918, 1922, and 1930. Baseline examinations took place in 1968, and follow-up occurred in 1974, 1980, 1992, 2000, and 2005. During follow-up, 153 women developed dementia. The number of psychosocial stressors in 1968 was associated with higher incidence of dementia and Alzheimer’s disease (AD) between 1968 and 2005 in multivariate Cox regressions. The number of psychosocial stressors in 1968 was also associated with distress in 1968, 1974, 1980, 2000, and 2005 in multivariate logistic regressions.

Aggressive medical management may provide more benefit than percutaneous transluminal angioplasty and stenting (PTAS) for high-risk patients with atherosclerotic intracranial arterial stenosis, according to a study published online ahead of print October 26 in Lancet. Investigators randomized 451 patients with recent transient ischemic attack or stroke to aggressive medical management or aggressive medical management plus stenting with the Wingspan stent. The cumulative probability of stroke or death was smaller in the medical group vs the PTAS group. Beyond 30 days, 10% of patients in the medical group and 10% of patients in the stenting group had a primary end point. The absolute differences in the primary end point rates between the two groups were 7.1% at year 1, 6.5% at year 2 and 9.0% at year 3.

—Erik Greb
Senior Associate Editor

In early December 2013, the FDA will formally recommend to the US Department of Health and Human Services (HHS) that hydrocodone combination products be reclassified as Schedule II drugs. The proposed change would tighten the controls on these products, which now are classified as Schedule III. The recommendation follows the US Drug Enforcement Administration’s (DEA) 2009 request for guidance from HHS regarding hydrocodone combination products such as Vicodin. The FDA’s determination is the result of an analysis of the scientific literature, a review of hundreds of public comments on the issue, and several public meetings, according to a statement by Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research. The recommendation will influence the DEA’s final decision on the appropriate scheduling of these products.

Influenza vaccination may reduce patients’ risk of major adverse cardiovascular events, including stroke, according to a meta-analysis published October 23 in JAMA. Researchers conducted a systematic review of randomized clinical trials listed in MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials that compared influenza vaccine with placebo or control in patients at high risk of cardiovascular disease. Six trials encompassing 6,735 patients were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%) in published trials. A treatment interaction was detected between patients with and without recent acute coronary syndrome. The greatest treatment effect was observed among the highest-risk patients with more active coronary disease, and a larger trial is warranted to assess these findings, said the researchers.

Short sleep duration and poor sleep quality may be associated with greater β-amyloid burden among community-dwelling older adults, according to research published online ahead of print October 21 in JAMA Neurology. Investigators performed a cross-sectional study of 70 adult participants (mean age, 76) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. The study’s main outcome measure was β-amyloid burden, measured by carbon 11-labeled Pittsburgh compound B PET distribution volume ratios. After adjustment for potential confounders, the researchers found an association between reports of shorter sleep duration and greater β-amyloid burden, measured by mean cortical distribution volume ratio and precuneus distribution volume ratio. Reports of lower sleep quality were associated with greater β-amyloid burden, measured by precuneus distribution volume ratio.

High blood glucose levels may adversely affect cognition, even among patients without type 2 diabetes or impaired glucose tolerance, researchers reported online ahead of print October 23 in Neurology. The effect may be mediated by structural changes in learning-relevant brain areas, the authors noted. The group tested memory in 141 individuals using the Rey Auditory Verbal Learning Test and acquired peripheral levels of fasting HbA1c, glucose, and insulin. Clinicians performed 3-T MRI scans to assess hippocampal volume and microstructure. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Mediation analyses indicated that beneficial effects of lower HbA1c on memory are partly mediated by hippocampal volume and microstructure.

Among older adults, arterial stiffness may be associated with b-amyloid plaque deposition in the brain, independent of blood pressure and APOE ε4 allele, according to a study published online ahead of print October 16 in Neurology. Investigators studied 91 dementia-free participants between ages 83 and 96. Participants underwent brain MRI and PET imaging with Pittsburgh compound B. The researchers measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed vascular beds. A total of 44 subjects were β-amyloid positive on PET scan. The investigators found that β-amyloid deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in brachial ankle PWV resulted in a twofold increase in the odds of being β-amyloid positive.

The FDA has approved Vizamyl (flutemetamol F 18 injection), a radioactive diagnostic drug, for use with PET imaging of the brain in adults being evaluated for Alzheimer’s disease and dementia. Vizamyl attaches to β-amyloid and produces a PET image that is used to evaluate the presence of β-amyloid. The drug’s effectiveness was established in two clinical studies of 384 participants with a range of cognitive function. All participants were injected with Vizamyl and scanned. The images were interpreted by five independent readers masked to all clinical information. A portion of scan results was also confirmed by autopsy. Following the approval of Amyvid (Florbetapir F 18 injection) in 2012, Vizamyl, manufactured by Medi-Physics (Arlington Heights, Illinois), becomes the second diagnostic drug available for visualizing β-amyloid on a PET scan of the brain.

Clostridium perfringens type B, an epsilon toxin-secreting bacillus, may trigger multiple sclerosis (MS), according to research published October 16 in PLOS One. After detecting C. perfringens type B in a woman with MS, investigators tested blood and CSF from patients with MS and controls for antibody reactivity to the epsilon toxin. Levels of epsilon toxin antibodies were 10 times higher in patients with MS, compared with controls. After examining stool samples, the study authors found the human commensal C. perfringens type A in approximately 50% of healthy controls, compared with 23% of patients with MS. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation because these lesions are characterized by blood–brain barrier permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate, said the researchers.

Chronic cerebrospinal venous insufficiency (CCSVI), which has been proposed as a contributor to multiple sclerosis (MS), occurs rarely in patients with MS and in controls, according to a study published online ahead of print October 8 in Lancet. Researchers performed an assessor-blinded, case-control, multicenter study of 79 people with MS, 55 unaffected siblings, and 43 unrelated healthy volunteers. Catheter venography criteria for CCSVI were positive for 2% of people with MS, 2% of siblings, and 3% of unrelated controls. Greater than 50% narrowing of any major vein was present in 74% of people with MS, 66% of siblings, and 70% of unrelated controls. The Zamboni ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography, and the significance of venous narrowing to MS remains unknown, said the investigators.

Measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with Parkinson’s disease, according to research published online ahead of print October 2 in Neurology. Investigators examined 20 patients with Parkinson’s disease and 14 age- and sex-matched control subjects. The researchers performed autonomic testing and skin biopsies at the distal leg, distal thigh, and proximal thigh for all participants. Deposition of α-synuclein and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. The investigators normalized α-synuclein deposition to nerve fiber density. Patients with Parkinson’s disease had greater α-synuclein deposition and higher α-synuclein ratios than controls within pilomotor nerves and sudomotor nerves, but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores, sympathetic adrenergic function, and parasympathetic function.

Depression may be an independent risk factor for Parkinson’s disease, according to research published October 22 in Neurology. Investigators conducted a retrospective study of 4,634 patients with depression and 18,544 matched controls who were selected from a national health insurance database. Patients were observed for a maximum of 10 years to determine the rates of new-onset Parkinson’s disease. Cox regression was used to identify the predictors of the disease. During the follow-up period, 66 patients with depression and 97 controls were diagnosed with Parkinson’s disease. After adjusting for age and sex, the researchers found that patients with depression were 3.24 times more likely to develop Parkinson’s disease, compared with the control patients. The investigators observed that age and difficult-to-treat depression are independent risk factors for Parkinson’s disease in patients with depression.

The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in red blood cells may have no association with age-associated cognitive decline, researchers reported in the October 22 issue of Neurology. The investigators conducted a retrospective cohort study of 2,157 women with normal cognition who were followed with annual cognitive testing for a median of 5.9 years. End points were composite cognitive function and performance in seven cognitive domains. After adjustment for demographic, clinical, and behavioral characteristics, the investigators found no significant cross-sectional cognitive differences between women in the high and low DHA and EPA tertiles at the first annual cognitive battery. In addition, no significant differences were found between the high and low DHA and EPA tertiles in the rate of cognitive change over time.

Common psychosocial stressors (eg, divorce, widowhood, work problems, and illness in a relative) may have severe and long-standing physiologic and psychologic consequences such as dementia, according to research published September 30 in BMJ Open. In a prospective longitudinal population study, clinicians performed psychiatric examinations for 800 women born in 1914, 1918, 1922, and 1930. Baseline examinations took place in 1968, and follow-up occurred in 1974, 1980, 1992, 2000, and 2005. During follow-up, 153 women developed dementia. The number of psychosocial stressors in 1968 was associated with higher incidence of dementia and Alzheimer’s disease (AD) between 1968 and 2005 in multivariate Cox regressions. The number of psychosocial stressors in 1968 was also associated with distress in 1968, 1974, 1980, 2000, and 2005 in multivariate logistic regressions.

Aggressive medical management may provide more benefit than percutaneous transluminal angioplasty and stenting (PTAS) for high-risk patients with atherosclerotic intracranial arterial stenosis, according to a study published online ahead of print October 26 in Lancet. Investigators randomized 451 patients with recent transient ischemic attack or stroke to aggressive medical management or aggressive medical management plus stenting with the Wingspan stent. The cumulative probability of stroke or death was smaller in the medical group vs the PTAS group. Beyond 30 days, 10% of patients in the medical group and 10% of patients in the stenting group had a primary end point. The absolute differences in the primary end point rates between the two groups were 7.1% at year 1, 6.5% at year 2 and 9.0% at year 3.

—Erik Greb
Senior Associate Editor

In early December 2013, the FDA will formally recommend to the US Department of Health and Human Services (HHS) that hydrocodone combination products be reclassified as Schedule II drugs. The proposed change would tighten the controls on these products, which now are classified as Schedule III. The recommendation follows the US Drug Enforcement Administration’s (DEA) 2009 request for guidance from HHS regarding hydrocodone combination products such as Vicodin. The FDA’s determination is the result of an analysis of the scientific literature, a review of hundreds of public comments on the issue, and several public meetings, according to a statement by Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research. The recommendation will influence the DEA’s final decision on the appropriate scheduling of these products.

Influenza vaccination may reduce patients’ risk of major adverse cardiovascular events, including stroke, according to a meta-analysis published October 23 in JAMA. Researchers conducted a systematic review of randomized clinical trials listed in MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials that compared influenza vaccine with placebo or control in patients at high risk of cardiovascular disease. Six trials encompassing 6,735 patients were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%) in published trials. A treatment interaction was detected between patients with and without recent acute coronary syndrome. The greatest treatment effect was observed among the highest-risk patients with more active coronary disease, and a larger trial is warranted to assess these findings, said the researchers.

Short sleep duration and poor sleep quality may be associated with greater β-amyloid burden among community-dwelling older adults, according to research published online ahead of print October 21 in JAMA Neurology. Investigators performed a cross-sectional study of 70 adult participants (mean age, 76) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. The study’s main outcome measure was β-amyloid burden, measured by carbon 11-labeled Pittsburgh compound B PET distribution volume ratios. After adjustment for potential confounders, the researchers found an association between reports of shorter sleep duration and greater β-amyloid burden, measured by mean cortical distribution volume ratio and precuneus distribution volume ratio. Reports of lower sleep quality were associated with greater β-amyloid burden, measured by precuneus distribution volume ratio.

High blood glucose levels may adversely affect cognition, even among patients without type 2 diabetes or impaired glucose tolerance, researchers reported online ahead of print October 23 in Neurology. The effect may be mediated by structural changes in learning-relevant brain areas, the authors noted. The group tested memory in 141 individuals using the Rey Auditory Verbal Learning Test and acquired peripheral levels of fasting HbA1c, glucose, and insulin. Clinicians performed 3-T MRI scans to assess hippocampal volume and microstructure. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Mediation analyses indicated that beneficial effects of lower HbA1c on memory are partly mediated by hippocampal volume and microstructure.

Among older adults, arterial stiffness may be associated with b-amyloid plaque deposition in the brain, independent of blood pressure and APOE ε4 allele, according to a study published online ahead of print October 16 in Neurology. Investigators studied 91 dementia-free participants between ages 83 and 96. Participants underwent brain MRI and PET imaging with Pittsburgh compound B. The researchers measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed vascular beds. A total of 44 subjects were β-amyloid positive on PET scan. The investigators found that β-amyloid deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in brachial ankle PWV resulted in a twofold increase in the odds of being β-amyloid positive.

The FDA has approved Vizamyl (flutemetamol F 18 injection), a radioactive diagnostic drug, for use with PET imaging of the brain in adults being evaluated for Alzheimer’s disease and dementia. Vizamyl attaches to β-amyloid and produces a PET image that is used to evaluate the presence of β-amyloid. The drug’s effectiveness was established in two clinical studies of 384 participants with a range of cognitive function. All participants were injected with Vizamyl and scanned. The images were interpreted by five independent readers masked to all clinical information. A portion of scan results was also confirmed by autopsy. Following the approval of Amyvid (Florbetapir F 18 injection) in 2012, Vizamyl, manufactured by Medi-Physics (Arlington Heights, Illinois), becomes the second diagnostic drug available for visualizing β-amyloid on a PET scan of the brain.

Clostridium perfringens type B, an epsilon toxin-secreting bacillus, may trigger multiple sclerosis (MS), according to research published October 16 in PLOS One. After detecting C. perfringens type B in a woman with MS, investigators tested blood and CSF from patients with MS and controls for antibody reactivity to the epsilon toxin. Levels of epsilon toxin antibodies were 10 times higher in patients with MS, compared with controls. After examining stool samples, the study authors found the human commensal C. perfringens type A in approximately 50% of healthy controls, compared with 23% of patients with MS. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation because these lesions are characterized by blood–brain barrier permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate, said the researchers.

Chronic cerebrospinal venous insufficiency (CCSVI), which has been proposed as a contributor to multiple sclerosis (MS), occurs rarely in patients with MS and in controls, according to a study published online ahead of print October 8 in Lancet. Researchers performed an assessor-blinded, case-control, multicenter study of 79 people with MS, 55 unaffected siblings, and 43 unrelated healthy volunteers. Catheter venography criteria for CCSVI were positive for 2% of people with MS, 2% of siblings, and 3% of unrelated controls. Greater than 50% narrowing of any major vein was present in 74% of people with MS, 66% of siblings, and 70% of unrelated controls. The Zamboni ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography, and the significance of venous narrowing to MS remains unknown, said the investigators.

Measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with Parkinson’s disease, according to research published online ahead of print October 2 in Neurology. Investigators examined 20 patients with Parkinson’s disease and 14 age- and sex-matched control subjects. The researchers performed autonomic testing and skin biopsies at the distal leg, distal thigh, and proximal thigh for all participants. Deposition of α-synuclein and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. The investigators normalized α-synuclein deposition to nerve fiber density. Patients with Parkinson’s disease had greater α-synuclein deposition and higher α-synuclein ratios than controls within pilomotor nerves and sudomotor nerves, but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores, sympathetic adrenergic function, and parasympathetic function.

Depression may be an independent risk factor for Parkinson’s disease, according to research published October 22 in Neurology. Investigators conducted a retrospective study of 4,634 patients with depression and 18,544 matched controls who were selected from a national health insurance database. Patients were observed for a maximum of 10 years to determine the rates of new-onset Parkinson’s disease. Cox regression was used to identify the predictors of the disease. During the follow-up period, 66 patients with depression and 97 controls were diagnosed with Parkinson’s disease. After adjusting for age and sex, the researchers found that patients with depression were 3.24 times more likely to develop Parkinson’s disease, compared with the control patients. The investigators observed that age and difficult-to-treat depression are independent risk factors for Parkinson’s disease in patients with depression.

The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in red blood cells may have no association with age-associated cognitive decline, researchers reported in the October 22 issue of Neurology. The investigators conducted a retrospective cohort study of 2,157 women with normal cognition who were followed with annual cognitive testing for a median of 5.9 years. End points were composite cognitive function and performance in seven cognitive domains. After adjustment for demographic, clinical, and behavioral characteristics, the investigators found no significant cross-sectional cognitive differences between women in the high and low DHA and EPA tertiles at the first annual cognitive battery. In addition, no significant differences were found between the high and low DHA and EPA tertiles in the rate of cognitive change over time.

Common psychosocial stressors (eg, divorce, widowhood, work problems, and illness in a relative) may have severe and long-standing physiologic and psychologic consequences such as dementia, according to research published September 30 in BMJ Open. In a prospective longitudinal population study, clinicians performed psychiatric examinations for 800 women born in 1914, 1918, 1922, and 1930. Baseline examinations took place in 1968, and follow-up occurred in 1974, 1980, 1992, 2000, and 2005. During follow-up, 153 women developed dementia. The number of psychosocial stressors in 1968 was associated with higher incidence of dementia and Alzheimer’s disease (AD) between 1968 and 2005 in multivariate Cox regressions. The number of psychosocial stressors in 1968 was also associated with distress in 1968, 1974, 1980, 2000, and 2005 in multivariate logistic regressions.

Aggressive medical management may provide more benefit than percutaneous transluminal angioplasty and stenting (PTAS) for high-risk patients with atherosclerotic intracranial arterial stenosis, according to a study published online ahead of print October 26 in Lancet. Investigators randomized 451 patients with recent transient ischemic attack or stroke to aggressive medical management or aggressive medical management plus stenting with the Wingspan stent. The cumulative probability of stroke or death was smaller in the medical group vs the PTAS group. Beyond 30 days, 10% of patients in the medical group and 10% of patients in the stenting group had a primary end point. The absolute differences in the primary end point rates between the two groups were 7.1% at year 1, 6.5% at year 2 and 9.0% at year 3.

—Erik Greb
Senior Associate Editor