Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline

We examined longitudinal associations between the apolipoprotein E ε4 allele (ApoE4⁺ status) and several cognitive outcomes and tested effect modification by sex. Data on 644 non-Hispanic Caucasian adults, from the Baltimore Longitudinal Study of Aging (BLSA) were used. Dementia onset, cognitive impairment and decline were assessed longitudinally. After 27.5 years median follow-up, 113 participants developed dementia. ApoE4⁺ predicted dementia significantly (hazard ratio [HR] = 2.89; 95% confidence interval [CI], 1.93-4.33), with nonsignificant sex differences. Taking all time points for predicting cognition, women had significantly stronger positive associations than men between ApoE4⁺ status and impairment or decline on the California Verbal Learning Test (CVLT; delayed recall and List A total recall) and on Verbal Fluency Test-Categories. This ApoE4 × sex interaction remained significant with Bonferroni correction only for CVLT-delayed recall. Taking time points prior to dementia for cognitive predictions, the positive association between impairment in CVLT-delayed recall and ApoE4⁺ status remained stronger among women, though only before Bonferroni correction. While ApoE4+ status appears to be a sex neutral risk factor for dementia, its association with verbal memory and learning decline and impairment was stronger among women.