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

May A. Beydoun(National Institute on Aging), Jordan Weiss(University of California, Berkeley), Hind A. Beydoun(Alexander T. Augusta Military Medical Center), Sharmin Hossain(National Institute on Aging), Ana I. Maldonado(National Institute on Aging), Botong Shen(National Institute on Aging), Michele K. Evans(National Institute on Aging), Alan B. Zonderman(National Institute on Aging)
Alzheimer s Research & Therapy
June 30, 2021
Cited by 52Open Access
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Abstract

Abstract Background Associations of Apolipoprotein ( APOE ) ε 2 or ε 4 ( APOE 2 or APOE 4) 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. APOE 2 and APOE 4 dosages were the two main exposures, while v 1 and annual rate of change in cognitive performance (between v 1 and v 2 ) 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, APOE 4 allelic dosage was associated with faster decline on a test of verbal memory among Whites only (CVLT-List A: γ 12 = − 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: γ 12 = + 0.106 ± 0.035, p = 0.002), while no association was detected among African American men. APOE 2 and APOE 4 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, APOE 4 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.


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