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

TitleThe PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.
Publication TypeJournal Article
Year of Publication2018
AuthorsWest NA, Tingle JV, Simino J, Selvin E, Bressler J
Secondary AuthorsMosley TH
JournalAlzheimer Dis Assoc Disord
Volume32
Issue2
Pagination131-136
Date Published2018 Apr-Jun
ISSN1546-4156
KeywordsAfrican Americans, Alleles, Cognitive Aging, Cognitive Dysfunction, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genotype, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Polymorphism, Genetic, PPAR gamma, Prospective Studies, Sex Factors
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.

DOI10.1097/WAD.0000000000000217
Alternate JournalAlzheimer Dis Assoc Disord
PubMed ID29116943
PubMed Central IDPMC5938164
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
K24 DK106414 / DK / NIDDK NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States