Sex variation in the relationship between APOE ε4, cognitive decline, and dementia

We examine if the relationship between apolipoprotein E (APOE) ε4 and cognitive decline and dementia onset differs by sex in non-Hispanic White and Black respondents from the Health and Retirement Study.

We used race-stratified linear mixed models to estimate cognitive decline and Cox proportional hazards models to estimate time to dementia onset. Sex differences were estimated using interaction terms.

APOE ε4 was associated with cognitive decline (b = -0.4) and dementia onset (hazard ratio [HR] = 1.48) in White adults, and cognitive decline (b = -0.5) in Black adults. The relationship between APOE ε4 and cognitive decline or dementia onset did not differ by sex in either group.

Our findings question a key hypothesis in the field-that female APOE ε4 carriers experience faster cognitive decline and earlier dementia onset than their male counterparts-and highlight the importance of using probability samples to reduce survivor and participation bias commonly found in genetics research.

White apolipoprotein E ε4 allele (APOE ε4) carriers had faster cognitive decline and earlier dementia onset.Black APOE ε4 carriers had faster cognitive decline.These patterns did not vary by sex for either Black or White adults.