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Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes. - The journals of gerontology. Series A, Biological sciences and medical sciences
Low vitamin D status is associated with poorer cognitive function in older adults, but little is known about the potential impact on cerebrospinal fluid (CSF) biomarkers and brain volumes. The objective of this study was to examine the relations between plasma 25-hydroxyvitamin D (25(OH)D) and cognitive impairment, CSF biomarkers of Alzheimer's disease (AD), and structural brain tissue volumes.A total of 75 patients (29 with subjective cognitive impairment, 28 with mild cognitive impairment, 18 with AD) referred to the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden were recruited. Plasma 25(OH)D, CSF levels of amyloid Î² (AÎ²(1-42)), total-tau, and phosphorylated tau, and brain tissue volumes have been measured.After adjustment for several potential confounders, the odds ratios (95% confidence interval) for cognitive impairment were as follows: 0.969 (0.948-0.990) per increase of 1 nmol/L of 25(OH)D and 4.19 (1.30-13.52) for 24(OH)D values less than 50 nmol/L compared with values greater than or equal to 50 nmol/L. Adjusting for CSF AÎ²(1-42) attenuated the 25(OH)D-cognition link. In a multiple linear regression analysis, higher 25(OH)D levels were related to higher concentrations of CSF AÎ²(1-42) and greater brain volumes (eg, white matter, structures belonging to medial temporal lobe). The associations between 25(OH)D and tau variables were not significant.This study suggests that vitamin D may be associated with cognitive status, CSF AÎ²(1-42) levels, and brain tissue volumes.Â© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: email@example.com.
Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. - Experimental gerontology
Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but Î±-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimer's disease.To investigate the association between serum levels of tocopherols and tocotrienols, markers of vitamin E oxidative/nitrosative damage (Î±-tocopherylquinone, 5-nitro-Î³-tocopherol) and incidence of cognitive impairment in a population-based study.A sample of 140 non-cognitively impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed-up for 8years to detect cognitive impairment, defined as development of mild cognitive impairment (MCI) or Alzheimer's dementia. The association between baseline serum vitamin E and cognitive impairment was analyzed with multiple logistic regression after adjusting for several confounders.The risk of cognitive impairment was lower in subjects in the middle tertile of the Î³-tocopherol/cholesterol ratio than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95% confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-Î³-tocopherol/Î³-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of Î³-tocopherol, Î²-tocotrienol, and total tocotrienols.Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans.Â© 2013.
Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study. - Brain : a journal of neurology
Elevated plasma total homocysteine is associated with increased risk of dementia/Alzheimer's disease, but underlying pathophysiological mechanisms are not fully understood. This study investigated possible links between baseline homocysteine, and post-mortem neuropathological and magnetic resonance imaging findings up to 10 years later in the Vantaa 85+ population including people aged â‰¥85 years. Two hundred and sixty-five individuals had homocysteine and autopsy data, of which 103 had post-mortem brain magnetic resonance imaging scans. Methenamine silver staining was used for amyloid-Î² and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, cerebral amyoloid angiopathy, and Î±-synuclein pathology. Magnetic resonance imaging was used for visual ratings of the degree of medial temporal lobe atrophy, and periventricular and deep white matter hyperintensities. Elevated baseline homocysteine was associated with increased neurofibrillary tangles count at the time of death: for the highest homocysteine quartile, odds ratio (95% confidence interval) was 2.60 (1.28-5.28). The association was observed particularly in people with dementia, in the presence of cerebral infarcts, and with longer time between the baseline homocysteine assessment and death. Also, elevated homocysteine tended to relate to amyloid-Î² accumulation, but this was seen only with longer baseline-death interval: odds ratio (95% confidence interval) was 2.52 (0.88-7.19) for the highest homocysteine quartile. On post-mortem magnetic resonance imaging, for the highest homocysteine quartile odds ratio (95% confidence interval) was 3.78 (1.12-12.79) for more severe medial temporal atrophy and 4.69 (1.14-19.33) for more severe periventricular white matter hyperintensities. All associations were independent of several potential confounders, including common vascular risk factors. No relationships between homocysteine and cerebral macro- or microinfarcts, cerebral amyoloid angiopathy or Î±-synuclein pathology were detected. These results suggest that elevated homocysteine in adults aged â‰¥85 years may contribute to increased Alzheimer-type pathology, particularly neurofibrillary tangles burden. This effect seems to be more pronounced in the presence of cerebrovascular pathology. Randomized controlled trials are needed to determine the impact of homocysteine-lowering treatments on dementia-related pathology.
Grey matter and cognitive patterns in cognitive impaired subjects using CSF biomarker cut-offs. - Journal of Alzheimer's disease : JAD
The aim of this study was to investigate brain tissue volumes, grey matter (GM) distribution, and cognitive performance for cognitively impaired subjects using cerebrospinal fluid (CSF) biomarker cut-offs as grouping criteria. 41 subjects attending the Memory Clinic, Karolinska University Hospital, Huddinge, Sweden, were divided into groups based on normal or abnormal CSF levels of AÎ²1-42, t-tau, and p-tau181. SIENAX algorithms were employed for brain tissue volumes estimation and voxel-based morphometry (VBM) for mapping the differences in GM patterns. VBM revealed significant lower GM volumes in temporo-parietal, occipital, and prefrontal cortices for those subjects belonging to abnormal CSF t-tau and p-tau181 groups. No differences were found between groups according to CSF AÎ²1-42 cut-offs. Patients with abnormal CSF p-tau181 showed lower cognitive performance compared to those with normal levels. Patients with abnormal levels of CSF tau (but not AÎ²1-42) showed an Alzheimer's disease-like pattern for both GM distribution and cognitive profile, compared to those with normal levels. These results support the hypothesis that CSF t-tau or p-tau181 levels may be of direct value for the evaluation of disease severity.
Association of Vitamin B12, Folate, and Sulfur Amino Acids With Brain Magnetic Resonance Imaging Measures in Older Adults: A Longitudinal Population-Based Study. - JAMA psychiatry
Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia.To investigate the association of circulating levels of vitamin B12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults.The magnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009.The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume.In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline vitamin B12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, Î² (SE) was 0.048 (0.013) for vitamin B12 (Pâ€‰<â€‰.001) and 0.040 (0.013) for holotranscobalamin (Pâ€‰=â€‰.002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (Î² [SE] per 1-SD increase, -0.035 [0.015]; Pâ€‰=â€‰.02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140 mm Hg (Î² [SE] per 1-SD increase, 0.000019 [0.00001]; Pâ€‰=â€‰.047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids.This study suggests that both vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B12 supplementation on slowing brain aging in older adults.
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