Wood, Madeline E; Xiong, Lisa Y; Wong, Yuen Yan; Buckley, Rachel F; Swardfager, Walter; Masellis, Mario; Lim, Andrew SP; Nichols, Emma; La Joie, Renaud; Casaletto, Kaitlin B; Kumar, Raj G; Dams‐O'Connor, Kristen; Palta, Priya; George, Kristen M; Satizabal, Claudia L; Barnes, Lisa L; Schneider, Julie A; Binet, Alexa Pichette; Villeneuve, Sylvia; Pa, Judy; Brickman, Adam M; Black, Sandra E; Rabin, Jennifer S; Groups, for the ADNI and Prevent‐AD Research

doi:10.1002/alz.13036

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Sex differences in associations between APOE ε2 and longitudinal cognitive decline

Published Web Location

https://doi.org/10.1002/alz.13036

Abstract

Introduction

We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.

Methods

We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.

Results

In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010).

Discussion

In NHW adults, APOE ε2 may protect men but not women against cognitive decline.

Highlights

We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

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