Sex differences in the association of APOE E4 allele and cognitive decline in a biracial population sample

Abstract

AbstractBackgroundPrior studies of sex differences on the association of Apolipoprotein E4 allele and cognitive decline have reported conflicting results and have been done in predominantly White populations. In this study, we tested whether the association of the APOE E4 allele and cognitive decline differs between men and women in a biracial population‐based sample of older adults.MethodParticipants (N = 5,807, 63% females and 60% Black) underwent brief cognitive assessments at 3‐year intervals from 1993 to 2012. Using linear mixed effects models, adjusted for age, education and race, we examined the rate of cognitive decline among women and men with and without the APOE E4 allele.ResultThe presence of the APOE E4 allele did not vary between women and men (32% vs. 34%). Among participants without the APOE E4 allele, the rate of annual decline in global cognition was higher in women compared to men (0.048 standard deviation units [SDU] vs. 0.033 SDU per year, p = 0.0002). Among participants with APOE E4 allele, the rate of decline in global cognitive function and episodic memory was about twice as high among White women compared to white men (0.097 SDU vs. 0.057 SDU per year, p < 0.0001; 0.077 SDU vs. 0.031 SDU per year, p < 0.0001) respectively. Black men and women with APOE E4 did not differ in rates of global cognitive decline (0.078 vs. 0.073 per year, p = 0.58), or in any domains.ConclusionThe rates of global cognitive decline, especially in APOE E4 carriers differed significantly between White women and men, but was similar between Black women and men. Additionally, the APOE E4 genotype was associated with a faster rate of decline in global cognitive function and episodic memory in women compared to men. The reason for sex differences among Black and White participants and especially among White women needs further attention.