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

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

METHODS: 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.

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

DISCUSSION: Our findings question a key hypothesis in the field-that female 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.

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