APOE Ε4 Carrier Status and Sex Differentiate Rates of Cognitive Decline in Early‐ and Late‐onset Alzheimer's Disease

Background: We studied the effect of apolipoprotein E (APOE) epsilon 4 status and sex on rates of cognitive decline in early- (EO) and late- (LO) onset Alzheimer's disease (AD). Method: We ran mixed-effects models with longitudinal cognitive measures as dependent variables, and sex, APOE epsilon 4 carrier status, and interaction terms as predictor variables in 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center. Results: APOE epsilon 4 carriers showed accelerated cognitive decline relative to non-carriers in both EOAD and LOAD, although the patterns of specific cognitive domains that were affected differed. Female participants showed accelerated cognitive decline relative to male participants in EOAD only. The effect of APOE epsilon 4 was greater in EOAD for executive functioning (p < 0.0001) and greater in LOAD for language (p < 0.0001). Conclusion: We found APOE epsilon 4 effects on cognitive decline in both EOAD and LOAD and female sex in EOAD only. The specific patterns and magnitude of decline are distinct between the two disease variants.