Dataset Information

Genetic architecture of age-related cognitive decline in African Americans.

ABSTRACT: OBJECTIVE:To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). METHODS:We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. RESULTS:We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. CONCLUSIONS:The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.

SUBMITTER: Raj T

PROVIDER: S-EPMC5206965 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Genetic architecture of age-related cognitive decline in African Americans.

Raj Towfique T Chibnik Lori B LB McCabe Cristin C Wong Andus A Replogle Joseph M JM Yu Lei L Gao Sujuan S Unverzagt Frederick W FW Stranger Barbara B Murrell Jill J Barnes Lisa L Hendrie Hugh C HC Foroud Tatiana T Krichevsky Anna A Bennett David A DA Hall Kathleen S KS Evans Denis A DA De Jager Philip L PL

Neurology. Genetics 20161221 1

<h4>Objective</h4>To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs).<h4>Methods</h4>We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS.<h4 ...[more]

PMID: 28078323

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Project description:Preclinical studies demonstrate that generalized endothelial cell dysfunction and microvascular impairment are potentially reversible causes of age-related vascular cognitive impairment and dementia (VCID). The present study was designed to test the hypothesis that severity of age-related macro- and microvascular dysfunction measured in the peripheral circulation is an independent predictor of cognitive performance in older adults. In this study, we enrolled 63 healthy individuals into young (< 45 years old) and aged (> 65 years old) groups. We used principal component analysis (PCA) to construct a comprehensive peripheral vascular health index (VHI) encompassing peripheral microvascular reactivity, arterial endothelial function, and vascular stiffness, as a marker of aging-induced generalized vascular dysfunction. Peripheral macrovascular and microvascular endothelial function were assessed using flow-mediated dilation (FMD) and laser speckle contrast imaging tests. Pulse waveform analysis was used to evaluate the augmentation index (AIx), a measure of arterial stiffness. Cognitive function was measured using a panel of CANTAB cognitive tests, and PCA was then applied to generate a cognitive impairment index (CII) for each participant. Aged subjects exhibited significantly impaired macrovascular endothelial function (FMD, 5.6 ± 0.7% vs. 8.3 ± 0.6% in young, p = 0.0061), increased arterial stiffness (AIx 29.3 ± 1.8% vs 4.5 ± 2.6% in young, p < 0.0001), and microvascular dysfunction (2.8 ± 0.2 vs 3.4 ± 0.1-fold change of perfusion in young, p = 0.032). VHI showed a significant negative correlation with age (r = - 0.54, p < 0.0001) and CII significantly correlated with age (r = 0.79, p < 0.0001). VHI significantly correlated with the CII (r = - 0.46, p = 0.0003). A decline in peripheral vascular health may reflect generalized vascular dysfunction and predict cognitive impairment in older adults.

Dataset Information

Genetic architecture of age-related cognitive decline in African Americans.

Publications

Genetic architecture of age-related cognitive decline in African Americans.

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