Race, APOE genotypes, and cognitive decline among middle-aged urban adults

Abstract

Background Associations of Apolipoprotein (APOE) ε₂ or ε₄ (APOE₂ or APOE₄) dosages with cognitive change may differ across racial groups.

Methods Longitudinal data on 1770 middle-aged White and African American adults was compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS 2004-2013) study. APOE₂ and APOE₄ dosages were the two main exposures, while v₁ and annual rate of change in cognitive performance (between v₁ and v₂) on 11 test scores were the main outcomes of interest (v1: 2004–2009 and v2: 2009–2013). Mixed-effects linear regression models were conducted adjusting for socio-demographic, lifestyle, and health-related potential confounders. Race (African American vs. White) and sex within racial groups were main effect modifiers.

Results Upon adjustment for multiple testing and potential confounders, APOE₄ allelic dosage was associated with faster decline on a test of verbal memory among Whites only (CVLT-List A: γ₁₂ = − 0.363 ± 0.137, p = 0.008), but not among African Americans. In contrast, among African American women, APOE₄ dosage was linked to slower decline on a test of attention (BTA: γ₁₂ = + 0.106 ± 0.035, p = 0.002), while no association was detected among African American men. APOE₂ and APOE₄ dosages showed inconsistent results in other domains of cognition overall and across racial groups that did not survive correction for multiple testing.

Conclusions In conclusion, APOE₄ dosage was associated with faster decline on a test of verbal memory among Whites only, while exhibiting a potential protective effect among African American women in the domain of attention. Further longitudinal studies are needed to replicate our race and sex-specific findings.