Sex differences in associations betweenAPOE ε2and longitudinal cognitive decline

INTRODUCTION We examined whether sex modifies the association between APOE ε 2 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 (ε 2 or ε 4 carrier vs. ε 3/ ε 3 ) 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 ε 2 and cognitive decline in NHW participants. Specifically, relative to APOE ε 3/ ε 3, APOE ε 2 protected against cognitive decline in men but not women. Among APOE ε 2 carriers, men had slower decline than women. Among APOE ε 3/ ε 3 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 ε 2 may selectively protect men against cognitive decline.