New and Noteworthy Information—February 2016

Herpes zoster is associated with a short-term increased risk of stroke, and preventing infection may prevent this increased risk, according to a study published online ahead of print December 9, 2015, in Mayo Clinic Proceedings. In a community cohort study, researchers compared the risk of stroke and myocardial infarction at four time points in 4,862 adults with and without herpes zoster. People with herpes zoster had more risk or confounding factors for myocardial infarction and stroke, suggesting that they had worse health status overall. People with herpes zoster were at increased risk for stroke at three months after infection, compared with those without a history of herpes zoster. Herpes zoster was not associated with an increased risk of stroke or myocardial infarction at any point beyond three months.

Supplementation with 10,400 IU of vitamin D3 daily is safe and well-tolerated in patients with multiple sclerosis (MS), according to a study published online ahead of print December 30, 2015, in Neurology. Supplementation also may mitigate patients’ hyperactive immune response. In a double-blind, single-center study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU of vitamin D3 daily for six months. Blood tests were performed at baseline and three and six months. In the high-dose group, researchers found a reduction in the proportion of interleukin-17+CD4+ T cells, CD161+CD4+ T cells, and effector memory CD4+ T cells, with a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. These effects were not observed in the low-dose group.

Weight loss is associated with rapid progression of Parkinson’s disease, according to a study published online ahead of print January 11 in JAMA Neurology. Researchers analyzed data for 1,673 participants in the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1. Of this cohort, 158 people lost weight, whereas 233 gained weight. After adjusting for covariates, researchers found that mean motor score increased by 1.48 more points per visit among people who lost weight than among people whose weight was stable. Mean motor score decreased by 0.51 points per visit for people who gained weight, relative to participants with stable weight. The observed difference in survival between the three BMI groups was not a significant outcome after data were adjusted for covariates.

Distal flow status is associated with risk for subsequent stroke in patients with symptomatic atherosclerotic vertebrobasilar occlusive disease, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. Researchers conducted a prospective, blinded, longitudinal cohort study of 82 patients with recent vertebrobasilar transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Distal flow status was low in 18 of the 72 participants included in the analysis and was significantly associated with risk for a subsequent vertebrobasilar stroke. The 12- and 24-month event-free survival rates were 78% and 70%, respectively, in the low-flow group, compared with 96% and 87%, respectively, in the normal-flow group. Hazard ratio for stroke was 11.55 among people with low distal flow.

The FDA has approved incobotulinumtoxinA for the treatment of upper limb spasticity in adult patients. The approval is based on the results of a randomized, multicenter, placebo-controlled trial. Treatment with incobotulinumtoxinA for adult upper limb spasticity resulted in statistically and clinically significant improvements in muscle tone. The product’s safety and efficacy were evaluated in multiple phase III clinical studies that included more than 400 patients. The safety profile for this indication is similar to that observed for other indications. FDA first approved incobotulinumtoxinA in August 2010 for the treatment of adults with cervical dystonia and blepharospasm. The most common adverse reactions include seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection. Merz Pharma Group, headquartered in Raleigh, North Carolina, markets the product under the name Xeomin.

Cannabidiol may reduce seizure frequency and have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy, according to a study published online ahead of print December 23, 2015, in Lancet Neurology. Patients received 2 to 5 mg/kg/day of oral cannabidiol, and the dose was increased until intolerance or to a maximum dose of 25 mg/kg/day or 50 mg/kg/day. Adverse events included somnolence, decreased appetite, diarrhea, fatigue, and convulsion. Five patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 patients, including one death regarded as unrelated to the study drug. Twenty patients had severe adverse events possibly related to cannabidiol use, the most common being status epilepticus. The median reduction in monthly motor seizures was 36.5%.

For every hour of reperfusion delay, the benefit of intra-arterial treatment for ischemic stroke decreases and the absolute risk difference for a good outcome is reduced by 6%, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) compared intra-arterial treatment with no intra-arterial treatment in 500 patients. The median time to treatment was 260 minutes. Median time from treatment to reperfusion was 340 minutes. The researchers found an interaction between time from treatment to reperfusion and treatment effect, but not between time to treatment and treatment effect. The adjusted risk difference was 25.9% when reperfusion was achieved at three hours, 18.8% at four hours, and 6.7% at six hours.

Anticholinergic drugs are not associated with impaired cognitive performance among patients with Parkinson’s disease, according to a study published October 2, 2015, in Journal of Parkinson’s Disease. Using data from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation—Parkinson’s Disease study, the researchers studied 195 patients with Parkinson’s disease and 84 controls. Patients’ detailed medication history, including over-the-counter drugs, was evaluated using the Anticholinergic Drug Scale (ADS). Each drug’s anticholinergic activity was classified on a scale from 0 to 3. Follow-up lasted 18 months. The investigators found no differences in global cognition, attention, memory, or executive function between patients with Parkinson’s disease who used anticholinergic drugs and those who did not. The proportion of patients with mild cognitive impairment was similar in both groups.

Anxiety symptoms are associated with an increased risk of dementia, according to a study published online ahead of print November 6, 2015, in Alzheimer’s & Dementia. The study included 1,082 fraternal and identical twins without dementia. Participants completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. The twins also completed in-person tests every three years, answered questionnaires, and were screened for dementia throughout the study. Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up. There was a 48% increased risk of dementia for people who had experienced high anxiety at any time, compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic, compared with monozygotic twins.

Common variants of MS4A6A and ABCA7 are associated with atrophy in cortical and hippocampal regions of the brain, according to a study published online ahead of print November 5, 2015, in Neurobiology of Aging. Researchers studied the relationship between the top 10 genetic variants associated with Alzheimer’s disease risk, excluding APOE, with cortical and hippocampal atrophy. They performed 1.5-T MRI to measure brain size and conducted genetic analyses for 50 cognitively normal participants and 98 participants with mild cognitive impairment. After explicit matching of cortical and hippocampal morphology, investigators computed in 3D the cortical thickness and hippocampal radial distance measures for each participant. MS4A6A rs610932 and ABCA7 rs3764650 had significant associations with cortical and hippocampal atrophy. The study may be the first to report the effect of these variants on neurodegeneration.

Anemia is associated with an increased risk of mild cognitive impairment (MCI), independent of traditional cardiovascular risk factors, according to a study published November 21, 2015, in Journal of Alzheimer’s Disease. Researchers examined 4,033 participants in a cohort study with available hemoglobin data and complete cognitive assessments. Participants’ age ranged between 50 and 80, and they were assessed between 2000 and 2003. Participants with anemia (ie, hemoglobin level less than 13 g/dl in men and less than 12 g/dl in women) had poorer cognitive performance in verbal memory and executive function, compared with people without anemia. The fully adjusted odds ratios for MCI, amnestic MCI, and nonamnestic MCI in anemic versus nonanemic participants were 1.92, 1.96, and 1.88, respectively.

By manipulating the WNT pathway, researchers efficiently differentiated human pluripotent stem cells to cells resembling central serotonin neurons, according to a study published in the January issue of Nature Biotechnology. For their investigation, the researchers used stem cells derived from embryos and stem cells derived from adult cells. The resulting serotonin neurons resembled those located in the rhombomeric segments 2-3 of the rostral raphe. They expressed a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2. The cells also exhibited typical electrophysiologic properties and released serotonin in an activity-dependent manner. When treated with tramadol and escitalopram oxalate, the serotonin neurons released or took up serotonin in a dose- and time-dependent manner. These cells may help researchers to evaluate drug candidates, according to the investigators.

Vascular and Lewy body pathologies and vascular risk factors modify the risk of psychosis in Alzheimer’s disease, according to a study published November 30, 2015, in Journal of Alzheimer’s Disease. Researchers reviewed a group of patients with clinically diagnosed Alzheimer’s disease who had neuropathology data, as well as a group of neuropathologically definite cases of Alzheimer’s disease. They investigated the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. In all, 1,073 participants were included in this study. A total of 34% of clinically diagnosed patients and 37% of neuropathologically definite cases had psychotic symptoms during their illness. Overall, Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis.

—Kimberly Williams

Herpes zoster is associated with a short-term increased risk of stroke, and preventing infection may prevent this increased risk, according to a study published online ahead of print December 9, 2015, in Mayo Clinic Proceedings. In a community cohort study, researchers compared the risk of stroke and myocardial infarction at four time points in 4,862 adults with and without herpes zoster. People with herpes zoster had more risk or confounding factors for myocardial infarction and stroke, suggesting that they had worse health status overall. People with herpes zoster were at increased risk for stroke at three months after infection, compared with those without a history of herpes zoster. Herpes zoster was not associated with an increased risk of stroke or myocardial infarction at any point beyond three months.

Supplementation with 10,400 IU of vitamin D3 daily is safe and well-tolerated in patients with multiple sclerosis (MS), according to a study published online ahead of print December 30, 2015, in Neurology. Supplementation also may mitigate patients’ hyperactive immune response. In a double-blind, single-center study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU of vitamin D3 daily for six months. Blood tests were performed at baseline and three and six months. In the high-dose group, researchers found a reduction in the proportion of interleukin-17+CD4+ T cells, CD161+CD4+ T cells, and effector memory CD4+ T cells, with a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. These effects were not observed in the low-dose group.

Weight loss is associated with rapid progression of Parkinson’s disease, according to a study published online ahead of print January 11 in JAMA Neurology. Researchers analyzed data for 1,673 participants in the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1. Of this cohort, 158 people lost weight, whereas 233 gained weight. After adjusting for covariates, researchers found that mean motor score increased by 1.48 more points per visit among people who lost weight than among people whose weight was stable. Mean motor score decreased by 0.51 points per visit for people who gained weight, relative to participants with stable weight. The observed difference in survival between the three BMI groups was not a significant outcome after data were adjusted for covariates.

Distal flow status is associated with risk for subsequent stroke in patients with symptomatic atherosclerotic vertebrobasilar occlusive disease, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. Researchers conducted a prospective, blinded, longitudinal cohort study of 82 patients with recent vertebrobasilar transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Distal flow status was low in 18 of the 72 participants included in the analysis and was significantly associated with risk for a subsequent vertebrobasilar stroke. The 12- and 24-month event-free survival rates were 78% and 70%, respectively, in the low-flow group, compared with 96% and 87%, respectively, in the normal-flow group. Hazard ratio for stroke was 11.55 among people with low distal flow.

The FDA has approved incobotulinumtoxinA for the treatment of upper limb spasticity in adult patients. The approval is based on the results of a randomized, multicenter, placebo-controlled trial. Treatment with incobotulinumtoxinA for adult upper limb spasticity resulted in statistically and clinically significant improvements in muscle tone. The product’s safety and efficacy were evaluated in multiple phase III clinical studies that included more than 400 patients. The safety profile for this indication is similar to that observed for other indications. FDA first approved incobotulinumtoxinA in August 2010 for the treatment of adults with cervical dystonia and blepharospasm. The most common adverse reactions include seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection. Merz Pharma Group, headquartered in Raleigh, North Carolina, markets the product under the name Xeomin.

Cannabidiol may reduce seizure frequency and have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy, according to a study published online ahead of print December 23, 2015, in Lancet Neurology. Patients received 2 to 5 mg/kg/day of oral cannabidiol, and the dose was increased until intolerance or to a maximum dose of 25 mg/kg/day or 50 mg/kg/day. Adverse events included somnolence, decreased appetite, diarrhea, fatigue, and convulsion. Five patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 patients, including one death regarded as unrelated to the study drug. Twenty patients had severe adverse events possibly related to cannabidiol use, the most common being status epilepticus. The median reduction in monthly motor seizures was 36.5%.

For every hour of reperfusion delay, the benefit of intra-arterial treatment for ischemic stroke decreases and the absolute risk difference for a good outcome is reduced by 6%, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) compared intra-arterial treatment with no intra-arterial treatment in 500 patients. The median time to treatment was 260 minutes. Median time from treatment to reperfusion was 340 minutes. The researchers found an interaction between time from treatment to reperfusion and treatment effect, but not between time to treatment and treatment effect. The adjusted risk difference was 25.9% when reperfusion was achieved at three hours, 18.8% at four hours, and 6.7% at six hours.

Anticholinergic drugs are not associated with impaired cognitive performance among patients with Parkinson’s disease, according to a study published October 2, 2015, in Journal of Parkinson’s Disease. Using data from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation—Parkinson’s Disease study, the researchers studied 195 patients with Parkinson’s disease and 84 controls. Patients’ detailed medication history, including over-the-counter drugs, was evaluated using the Anticholinergic Drug Scale (ADS). Each drug’s anticholinergic activity was classified on a scale from 0 to 3. Follow-up lasted 18 months. The investigators found no differences in global cognition, attention, memory, or executive function between patients with Parkinson’s disease who used anticholinergic drugs and those who did not. The proportion of patients with mild cognitive impairment was similar in both groups.

Anxiety symptoms are associated with an increased risk of dementia, according to a study published online ahead of print November 6, 2015, in Alzheimer’s & Dementia. The study included 1,082 fraternal and identical twins without dementia. Participants completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. The twins also completed in-person tests every three years, answered questionnaires, and were screened for dementia throughout the study. Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up. There was a 48% increased risk of dementia for people who had experienced high anxiety at any time, compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic, compared with monozygotic twins.

Common variants of MS4A6A and ABCA7 are associated with atrophy in cortical and hippocampal regions of the brain, according to a study published online ahead of print November 5, 2015, in Neurobiology of Aging. Researchers studied the relationship between the top 10 genetic variants associated with Alzheimer’s disease risk, excluding APOE, with cortical and hippocampal atrophy. They performed 1.5-T MRI to measure brain size and conducted genetic analyses for 50 cognitively normal participants and 98 participants with mild cognitive impairment. After explicit matching of cortical and hippocampal morphology, investigators computed in 3D the cortical thickness and hippocampal radial distance measures for each participant. MS4A6A rs610932 and ABCA7 rs3764650 had significant associations with cortical and hippocampal atrophy. The study may be the first to report the effect of these variants on neurodegeneration.

Anemia is associated with an increased risk of mild cognitive impairment (MCI), independent of traditional cardiovascular risk factors, according to a study published November 21, 2015, in Journal of Alzheimer’s Disease. Researchers examined 4,033 participants in a cohort study with available hemoglobin data and complete cognitive assessments. Participants’ age ranged between 50 and 80, and they were assessed between 2000 and 2003. Participants with anemia (ie, hemoglobin level less than 13 g/dl in men and less than 12 g/dl in women) had poorer cognitive performance in verbal memory and executive function, compared with people without anemia. The fully adjusted odds ratios for MCI, amnestic MCI, and nonamnestic MCI in anemic versus nonanemic participants were 1.92, 1.96, and 1.88, respectively.

By manipulating the WNT pathway, researchers efficiently differentiated human pluripotent stem cells to cells resembling central serotonin neurons, according to a study published in the January issue of Nature Biotechnology. For their investigation, the researchers used stem cells derived from embryos and stem cells derived from adult cells. The resulting serotonin neurons resembled those located in the rhombomeric segments 2-3 of the rostral raphe. They expressed a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2. The cells also exhibited typical electrophysiologic properties and released serotonin in an activity-dependent manner. When treated with tramadol and escitalopram oxalate, the serotonin neurons released or took up serotonin in a dose- and time-dependent manner. These cells may help researchers to evaluate drug candidates, according to the investigators.

Vascular and Lewy body pathologies and vascular risk factors modify the risk of psychosis in Alzheimer’s disease, according to a study published November 30, 2015, in Journal of Alzheimer’s Disease. Researchers reviewed a group of patients with clinically diagnosed Alzheimer’s disease who had neuropathology data, as well as a group of neuropathologically definite cases of Alzheimer’s disease. They investigated the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. In all, 1,073 participants were included in this study. A total of 34% of clinically diagnosed patients and 37% of neuropathologically definite cases had psychotic symptoms during their illness. Overall, Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis.

—Kimberly Williams

Herpes zoster is associated with a short-term increased risk of stroke, and preventing infection may prevent this increased risk, according to a study published online ahead of print December 9, 2015, in Mayo Clinic Proceedings. In a community cohort study, researchers compared the risk of stroke and myocardial infarction at four time points in 4,862 adults with and without herpes zoster. People with herpes zoster had more risk or confounding factors for myocardial infarction and stroke, suggesting that they had worse health status overall. People with herpes zoster were at increased risk for stroke at three months after infection, compared with those without a history of herpes zoster. Herpes zoster was not associated with an increased risk of stroke or myocardial infarction at any point beyond three months.

Supplementation with 10,400 IU of vitamin D3 daily is safe and well-tolerated in patients with multiple sclerosis (MS), according to a study published online ahead of print December 30, 2015, in Neurology. Supplementation also may mitigate patients’ hyperactive immune response. In a double-blind, single-center study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU of vitamin D3 daily for six months. Blood tests were performed at baseline and three and six months. In the high-dose group, researchers found a reduction in the proportion of interleukin-17+CD4+ T cells, CD161+CD4+ T cells, and effector memory CD4+ T cells, with a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. These effects were not observed in the low-dose group.

Weight loss is associated with rapid progression of Parkinson’s disease, according to a study published online ahead of print January 11 in JAMA Neurology. Researchers analyzed data for 1,673 participants in the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1. Of this cohort, 158 people lost weight, whereas 233 gained weight. After adjusting for covariates, researchers found that mean motor score increased by 1.48 more points per visit among people who lost weight than among people whose weight was stable. Mean motor score decreased by 0.51 points per visit for people who gained weight, relative to participants with stable weight. The observed difference in survival between the three BMI groups was not a significant outcome after data were adjusted for covariates.

Distal flow status is associated with risk for subsequent stroke in patients with symptomatic atherosclerotic vertebrobasilar occlusive disease, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. Researchers conducted a prospective, blinded, longitudinal cohort study of 82 patients with recent vertebrobasilar transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Distal flow status was low in 18 of the 72 participants included in the analysis and was significantly associated with risk for a subsequent vertebrobasilar stroke. The 12- and 24-month event-free survival rates were 78% and 70%, respectively, in the low-flow group, compared with 96% and 87%, respectively, in the normal-flow group. Hazard ratio for stroke was 11.55 among people with low distal flow.

The FDA has approved incobotulinumtoxinA for the treatment of upper limb spasticity in adult patients. The approval is based on the results of a randomized, multicenter, placebo-controlled trial. Treatment with incobotulinumtoxinA for adult upper limb spasticity resulted in statistically and clinically significant improvements in muscle tone. The product’s safety and efficacy were evaluated in multiple phase III clinical studies that included more than 400 patients. The safety profile for this indication is similar to that observed for other indications. FDA first approved incobotulinumtoxinA in August 2010 for the treatment of adults with cervical dystonia and blepharospasm. The most common adverse reactions include seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection. Merz Pharma Group, headquartered in Raleigh, North Carolina, markets the product under the name Xeomin.

Cannabidiol may reduce seizure frequency and have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy, according to a study published online ahead of print December 23, 2015, in Lancet Neurology. Patients received 2 to 5 mg/kg/day of oral cannabidiol, and the dose was increased until intolerance or to a maximum dose of 25 mg/kg/day or 50 mg/kg/day. Adverse events included somnolence, decreased appetite, diarrhea, fatigue, and convulsion. Five patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 patients, including one death regarded as unrelated to the study drug. Twenty patients had severe adverse events possibly related to cannabidiol use, the most common being status epilepticus. The median reduction in monthly motor seizures was 36.5%.

For every hour of reperfusion delay, the benefit of intra-arterial treatment for ischemic stroke decreases and the absolute risk difference for a good outcome is reduced by 6%, according to a study published online ahead of print December 21, 2015, in JAMA Neurology. The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) compared intra-arterial treatment with no intra-arterial treatment in 500 patients. The median time to treatment was 260 minutes. Median time from treatment to reperfusion was 340 minutes. The researchers found an interaction between time from treatment to reperfusion and treatment effect, but not between time to treatment and treatment effect. The adjusted risk difference was 25.9% when reperfusion was achieved at three hours, 18.8% at four hours, and 6.7% at six hours.

Anticholinergic drugs are not associated with impaired cognitive performance among patients with Parkinson’s disease, according to a study published October 2, 2015, in Journal of Parkinson’s Disease. Using data from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation—Parkinson’s Disease study, the researchers studied 195 patients with Parkinson’s disease and 84 controls. Patients’ detailed medication history, including over-the-counter drugs, was evaluated using the Anticholinergic Drug Scale (ADS). Each drug’s anticholinergic activity was classified on a scale from 0 to 3. Follow-up lasted 18 months. The investigators found no differences in global cognition, attention, memory, or executive function between patients with Parkinson’s disease who used anticholinergic drugs and those who did not. The proportion of patients with mild cognitive impairment was similar in both groups.

Anxiety symptoms are associated with an increased risk of dementia, according to a study published online ahead of print November 6, 2015, in Alzheimer’s & Dementia. The study included 1,082 fraternal and identical twins without dementia. Participants completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. The twins also completed in-person tests every three years, answered questionnaires, and were screened for dementia throughout the study. Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up. There was a 48% increased risk of dementia for people who had experienced high anxiety at any time, compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic, compared with monozygotic twins.

Common variants of MS4A6A and ABCA7 are associated with atrophy in cortical and hippocampal regions of the brain, according to a study published online ahead of print November 5, 2015, in Neurobiology of Aging. Researchers studied the relationship between the top 10 genetic variants associated with Alzheimer’s disease risk, excluding APOE, with cortical and hippocampal atrophy. They performed 1.5-T MRI to measure brain size and conducted genetic analyses for 50 cognitively normal participants and 98 participants with mild cognitive impairment. After explicit matching of cortical and hippocampal morphology, investigators computed in 3D the cortical thickness and hippocampal radial distance measures for each participant. MS4A6A rs610932 and ABCA7 rs3764650 had significant associations with cortical and hippocampal atrophy. The study may be the first to report the effect of these variants on neurodegeneration.

Anemia is associated with an increased risk of mild cognitive impairment (MCI), independent of traditional cardiovascular risk factors, according to a study published November 21, 2015, in Journal of Alzheimer’s Disease. Researchers examined 4,033 participants in a cohort study with available hemoglobin data and complete cognitive assessments. Participants’ age ranged between 50 and 80, and they were assessed between 2000 and 2003. Participants with anemia (ie, hemoglobin level less than 13 g/dl in men and less than 12 g/dl in women) had poorer cognitive performance in verbal memory and executive function, compared with people without anemia. The fully adjusted odds ratios for MCI, amnestic MCI, and nonamnestic MCI in anemic versus nonanemic participants were 1.92, 1.96, and 1.88, respectively.

By manipulating the WNT pathway, researchers efficiently differentiated human pluripotent stem cells to cells resembling central serotonin neurons, according to a study published in the January issue of Nature Biotechnology. For their investigation, the researchers used stem cells derived from embryos and stem cells derived from adult cells. The resulting serotonin neurons resembled those located in the rhombomeric segments 2-3 of the rostral raphe. They expressed a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2. The cells also exhibited typical electrophysiologic properties and released serotonin in an activity-dependent manner. When treated with tramadol and escitalopram oxalate, the serotonin neurons released or took up serotonin in a dose- and time-dependent manner. These cells may help researchers to evaluate drug candidates, according to the investigators.

Vascular and Lewy body pathologies and vascular risk factors modify the risk of psychosis in Alzheimer’s disease, according to a study published November 30, 2015, in Journal of Alzheimer’s Disease. Researchers reviewed a group of patients with clinically diagnosed Alzheimer’s disease who had neuropathology data, as well as a group of neuropathologically definite cases of Alzheimer’s disease. They investigated the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. In all, 1,073 participants were included in this study. A total of 34% of clinically diagnosed patients and 37% of neuropathologically definite cases had psychotic symptoms during their illness. Overall, Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis.

—Kimberly Williams