Dataset Information

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

ABSTRACT: Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Linear mixed models were used to estimate associations between the Ala12 allele and cognitive performance over 20 years of follow-up. Heterogeneity was present for rate of cognitive decline as measured by the global Z-score by race, sex, and Ala12 allele status (P=0.01 for 4-way interaction term: race×sex×time×Ala12 carrier status). Stratified analysis showed a significantly increased rate of global cognitive decline over the 20-year follow-up for carriers of the Ala12 allele compared with noncarriers among black male individuals (-0.92 SD decline vs. -0.57 SD; P=0.02) but not among black female, white male, or white female individuals. Decline in global cognitive function among black male Ala12 carriers was primarily driven by decline in verbal memory. Our data underscore the context-dependent association between the Pro12Ala polymorphism and cognitive decline, specifically race/ethnic background and sex.

SUBMITTER: West NA

PROVIDER: S-EPMC5938164 | biostudies-literature | 2018 Apr-Jun

REPOSITORIES: biostudies-literature

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The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

West Nancy A NA Tingle Jonathan V JV Simino Jeannette J Selvin Elizabeth E Bressler Jan J Mosley Thomas H TH

Alzheimer disease and associated disorders 20180401 2

Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Li ...[more]

PMID: 29116943

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Project description:Background:Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. Objective:To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Design:Longitudinal cohort study. Setting:Two ARIC (Atherosclerosis Risk in Communities) study sites with magnetic resonance imaging data (1993 to 1995) and up to 5 cognitive assessments over 20 years. Participants:Stroke-free participants aged 50 years or older. Measurements:Infarctions were categorized as none, smaller only, larger only (3 to 20 mm), or both smaller and larger. Global cognitive Z scores were derived from 3 cognitive tests administered up to 5 times. Mixed-effects models estimated adjusted associations between infarctions and cognitive decline. Results are the average difference in standardized cognitive decline associated with infarctions versus no infarctions. Results:Among 1884 participants (mean age, 62 years; 60% women; 50% black), 1611 (86%) had no infarctions, 50 (3%) had smaller infarctions only, 185 (10%) had larger infarctions only, and 35 (2%) had both. Participants with both smaller and larger infarctions had steeper cognitive decline by more than half an SD (difference, -0.57 SD [95% CI, -0.89 to -0.26 SD]) compared with those who had no infarctions. Amounts of cognitive decline associated with only smaller infarctions and only larger infarctions were similar and were not statistically different from that associated with no infarctions. Limitation:Few participants had only smaller infarctions or both smaller and larger infarctions, and the data lacked counts of smaller infarctions and volumes of white matter hyperintensities. Conclusion:The substantial cognitive decline from middle age associated with having both smaller and larger infarctions, but not larger infarctions alone, suggests that the combination of smaller and larger infarctions may escalate risk for cognitive decline later in life in stroke-free persons. Primary Funding Source:National Institutes of Health.

Dataset Information

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

Publications

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

Similar Datasets

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