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

Abstract

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.

FIGURE 1

Kaplan-Meier survival curve of incident dementia by apolipoprotein E epsilon 4 allele status by sex Abbreviations: ApoE4=Apolipoprotein E ε4 allele carrier status; CI=Confidence Interval; HR=Hazard Ratio. Notes: Failure is defined as first incidence of dementia at or after age 50. HR is adjusted for sex, first-visit age, education, first-visit smoking status, first-visit self-reported type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease and measured body mass index. *p<0.05 for null hypothesis that Loge(HR)=0. N=6,515 observations representing 631 participants (371 men and 260 women) n=107 failures after age 50 (64 men and 43 women).

FIGURE 1

Kaplan-Meier survival curve of incident dementia by apolipoprotein E epsilon 4 allele status by sex Abbreviations: ApoE4=Apolipoprotein E ε4 allele carrier status; CI=Confidence Interval; HR=Hazard Ratio. Notes: Failure is defined as first incidence of dementia at or after age 50. HR is adjusted for sex, first-visit age, education, first-visit smoking status, first-visit self-reported type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease and measured body mass index. *p<0.05 for null hypothesis that Loge(HR)=0. N=6,515 observations representing 631 participants (371 men and 260 women) n=107 failures after age 50 (64 men and 43 women).

FIGURE 1

Kaplan-Meier survival curve of incident dementia by apolipoprotein E epsilon 4 allele status by sex Abbreviations: ApoE4=Apolipoprotein E ε4 allele carrier status; CI=Confidence Interval; HR=Hazard Ratio. Notes: Failure is defined as first incidence of dementia at or after age 50. HR is adjusted for sex, first-visit age, education, first-visit smoking status, first-visit self-reported type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease and measured body mass index. *p<0.05 for null hypothesis that Loge(HR)=0. N=6,515 observations representing 631 participants (371 men and 260 women) n=107 failures after age 50 (64 men and 43 women).