APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.

Abstract	We aimed to examine the relationship between Apolipoprotein E ε4 (APOE4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE4 allele. Vascular risk factors were related to an increased effect of APOE4 on memory decline in younger women, but a weaker effect of APOE4 on general cognitive decline in older men. The relationship between APOE4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.
Authors	Steve R Makkar, Darren M Lipnicki, John D Crawford, Nicole A Kochan, Erico Castro-Costa, Maria Fernanda Lima-Costa, Breno Satler Diniz, Carol Brayne, Blossom Stephan, Fiona Matthews, Juan J Llibre-Rodriguez, Jorge J Llibre-Guerra, Adolfo J Valhuerdi-Cepero, Richard B Lipton, Mindy J Katz, Cuiling Wang, Karen Ritchie, Sophie Carles, Isabelle Carriere, Nikolaos Scarmeas, Mary Yannakoulia, Mary Kosmidis, Linda Lam, Wai Chi Chan, Ada Fung, Antonio Guaita, Roberta Vaccaro, Annalisa Davin, Ki Woong Kim, Ji Won Han, Seung Wan Suh, Steffi G Riedel-Heller, Susanne Roehr, Alexander Pabst, Mary Ganguli, Tiffany F Hughes, Beth Snitz, Kaarin J Anstey, Nicolas Cherbuin, Simon Easteal, Mary N Haan, Allison E Aiello, Kristina Dang, Tze Pin Ng, Qi Gao, Ma Shwe Zin Nyunt, Henry Brodaty, Julian N Trollor, Yvonne Leung, Jessica W Lo, Perminder Sachdev
Journal	The journals of gerontology. Series A, Biological sciences and medical sciences (J Gerontol A Biol Sci Med Sci) Vol. 75 Issue 10 Pg. 1863-1873 (09 25 2020) ISSN: 1758-535X [Electronic] United States
PMID	32396611 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright	© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected].
Chemical References	Apolipoprotein E4
Topics	Age Factors Aged Aged, 80 and over Aging (genetics) Alleles Apolipoprotein E4 (genetics) Cognitive Dysfunction (ethnology, genetics) Female Genotype Humans Longitudinal Studies Male Middle Aged Risk Factors Sex Factors

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