Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts

Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by n

Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 7 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 7 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community.

Background-Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD). Methods and Results-We prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (FHS). Using a common nonsynonomous single nucleotide polymorphism (SNP) in the BDNF gene (rs6265), we then performed a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis) consortium (> 22 000 coronary artery disease [CAD] cases, > 60 000 controls) to investigate whether SNP rs6265 was associated with CAD in CARDIoGRAM and, if so, whether the effect estimate differed from that predicted based on FHS data. On follow-up (median 8.9 years), 467 individuals (261 women) in FHS experienced a CVD event, and 835 (430 women) died. In multivariable-adjusted Cox regression, serum BDNF was associated inversely with CVD risk (hazard ratio [HR] per 1-SD increase 0.88, 95% CI 0.80 to 0.97, P=0.01) and with mortality (HR 0.87, 95% CI 0.80 to 0.93, P=0.0002). SNP rs6265 was associated with BDNF concentrations (0.772 ng/mL increase per minor allele copy) in FHS. In CARDIoGRAM, SNP rs6265 was associated with CAD (odds ratio 0.957, 95% CI 0.923 to 0.992), a magnitude consistent with the predicted effect (HR per minor allele copy 0.99, 95% CI 0.98 to 1.0; P=0.06 for difference between predicted and observed effect). Conclusion-Higher serum BDNF is associated with a decreased risk of CVD and mortality. Mendelian randomization suggests a causal protective role of BDNF in the pathogenesis of CVD

No advantage of Aβ 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies

10.1212/01.wnl.0000313933.17796.f6Neurology70242291-2298NEUR

Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage

Discussion: Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.Paroxysmal Cerebral Disorder

The association between blood pressure variability (BPV) with dementia and cognitive function: a systematic review and meta-analysis protocol

BACKGROUND:A body of empirical work demonstrates that wide fluctuations in a person's blood pressure across consecutive measures, known as blood pressure variability (BPV), hold prognostic value to predict stroke and transient ischemic attack. However, the magnitude of association between BPV and other neurological outcomes remains less clear. This systematic review aims to pool together data regarding BPV with respect to incident dementia, cognitive impairment, and cognitive function. METHODS:Electronic databases (MEDLINE, EMBASE, and SCOPUS) will be searched for the key words blood pressure variability and outcomes of dementia, cognitive impairment, and cognitive function. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows: population-adult humans (over 18 years but with no upper age limit) without dementia at baseline, with or without elevated blood pressure, or from hypertensive populations (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or use of antihypertensive drug for hypertension) and from primary care, community cohort, electronic database registry, or randomized controlled trial (RCT); exposure-any metric of BPV (systolic, diastolic or both) over any duration; comparison-persons without dementia who do not have elevated BPV; and outcome-dementia, cognitive impairment, cognitive function at follow-up from standardized neurological assessment, or cognitive testing. Article screening will be undertaken by two independent reviewers with disagreements resolved through discussion. Data extraction will include original data specified as hazard ratios, odds ratios, correlations, regression coefficients, and original cell data if available. Risk of bias assessment will be undertaken by two independent reviewers. Meta-analytic methods will be used to synthesize the data collected relating to the neurological outcomes with Comprehensive Meta-Analysis Version 2.0 (Biostat Inc., Engelwood, NJ). DISCUSSION:This systematic review aims to clarify whether BPV is associated with elevated risk for dementia, cognitive impairment, and cognitive function. An evaluation of the etiological links between BPV with incident dementia might inform evidence-based clinical practice and policy concerning blood pressure measurement and hypertension management. The review will identify sources of heterogeneity and may inform decisions on whether it is feasible and desirable to proceed with an individual participant data meta-analysis. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42017081977.Phillip J. Tully, Deborah A. Turnbull ... Nicholas R. Burns, Suzanne Cosh ... Diana Dorstyn ... Rajiv Mahajan ... Kristy Giles ... Phoebe Drioli-Phillips, Umama Aaimir, Frank Connolly ... et al. (VARIABLE BRAIN consortium

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

The association between blood pressure variability (BPV) with dementia and cognitive function: a systematic review and meta-analysis protocol

Background: A body of empirical work demonstrates that wide fluctuations in a person's blood pressure across consecutive measures, known as blood pressure variability (BPV), hold prognostic value to predict stroke and transient ischemic attack. However, the magnitude of association between BPV and other neurological outcomes remains less clear. This systematic review aims to pool together data regarding BPV with respect to incident dementia, cognitive impairment, and cognitive function. Methods: Electronic databases (MEDLINE, EMBASE, and SCOPUS) will be searched for the key words blood pressure variability and outcomes of dementia, cognitive impairment, and cognitive function. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows: population - adult humans (over 18 years but with no upper age limit) without dementia at baseline, with or without elevated blood pressure, or from hypertensive populations (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or use of antihypertensive drug for hypertension) and from primary care, community cohort, electronic database registry, or randomized controlled trial (RCT); exposure - any metric of BPV (systolic, diastolic or both) over any duration; comparison - persons without dementia who do not have elevated BPV; and outcome - dementia, cognitive impairment, cognitive function at follow-up from standardized neurological assessment, or cognitive testing. Article screening will be undertaken by two independent reviewers with disagreements resolved through discussion. Data extraction will include original data specified as hazard ratios, odds ratios, correlations, regression coefficients, and original cell data if available. Risk of bias assessment will be undertaken by two independent reviewers. Meta-analytic methods will be used to synthesize the data collected relating to the neurological outcomes with Comprehensive Meta-Analysis Version 2.0 (Biostat Inc., Engelwood, NJ). Discussion: This systematic review aims to clarify whether BPV is associated with elevated risk for dementia, cognitive impairment, and cognitive function. An evaluation of the etiological links between BPV with incident dementia might inform evidence-based clinical practice and policy concerning blood pressure measurement and hypertension management. The review will identify sources of heterogeneity and may inform decisions on whether it is feasible and desirable to proceed with an individual participant data meta-analysis