Sex differences in associations between APOE ε2 and longitudinal cognitive decline

INTRODUCTIONWe examined whether sex modifies the association between APOE {varepsilon}2 and cognitive decline across two independent samples. METHODSWe 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 ({varepsilon}2 or {varepsilon}4 carrier vs. {varepsilon}3/{varepsilon}3) and sex on cognitive decline in NHW and NHB participants separately. RESULTSIn both Sample 1 (N=9,766) and Sample 2 (N=915), sex modified the association between APOE {varepsilon}2 and cognitive decline in NHW participants. Specifically, relative to APOE {varepsilon}3/{varepsilon}3, APOE {varepsilon}2 protected against cognitive decline in men but not women. Among APOE {varepsilon}2 carriers, men had slower decline than women. Among APOE {varepsilon}3/{varepsilon}3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE {varepsilon}2 with cognitive decline in NHB participants (N=2,010). DISCUSSIONIn NHW adults, APOE {varepsilon}2 may selectively protect men against cognitive decline.