Sex differences in associations betweenAPOE ε2and longitudinal cognitive decline

Abstract

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline across two independent samples. METHODS: We used observational data from non-Hispanic White (NHW) and non-Hispanic Black (NHB) cognitively unimpaired 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=9,766) 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 cognitive decline in NHB participants (N=2,010). DISCUSSION: In NHW adults, APOE ε2 may selectively protect men against cognitive decline.