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. 2021 Jun 30;13(1):120.
doi: 10.1186/s13195-021-00855-y.

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

May A Beydoun #  1 , Jordan Weiss #  2 , Hind A Beydoun  3 , Sharmin Hossain  4 , Ana I Maldonado  4   5 , Botong Shen  4 , Michele K Evans  4 , Alan B Zonderman  4
Affiliations

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

May A Beydoun et al. Alzheimers Res Ther. .

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.

Keywords: Apolipoprotein E; Cognitive aging; Racial disparities.

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Conflict of interest statement

The authors declare no conflict of interest. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Fort Belvoir Community Hospital, the Defense Health Agency, Department of Defense, or U.S. Government. Reference to any commercial products within this publication does not create or imply any endorsement by Fort Belvoir Community Hospital, the Defense Health Agency, Department of Defense, or U.S. Government.

Figures

Fig. 1
Fig. 1
Participant flowchart. Abbreviations: APOE = Apolipoprotein E; HANDLS = Healthy Aging in Neighborhoods of Diversity across the Life Span
Fig. 2
Fig. 2
APOE4 allelic dosage vs. CVLT-List A trajectories among Whites and African Americans: predictive margins from mixed-effects linear regression modela. Abbreviations: APOE = Apolipoprotein E; CVLT-List A = California Verbal Learning Test, List A; HANDLS = Healthy Aging in Neighborhoods of Diversity across the Life Span. a Model 2B, Table 2, fully adjusted model, stratified by race. Figure shows predictive margins of CVLT-List A scores across time, highlighting the significant difference in slope across APOE4 dosage among Whites only. γ12 refers to the fixed effect of APOE4 dosage on the rate of change in CVLT-List A total score for each racial group. “b” is a standardized measure for the regression coefficient γ12 in model where CVLT-LIST A is entered as standardized z-scores within each racial group. It is interpreted as the SD of outcome change per year increase in follow-up time for each APOE4 dosage change. 1 SD of CVLT-LIST A corresponds to 7.71 change in score, overall
Fig. 3
Fig. 3
APOE4 allelic dosage vs. BTA trajectories among African American women and men: predictive margins from mixed-effects linear regression modela. Abbreviations: APOE = Apolipoprotein E; BTA = Brief Test of Attention; HANDLS = Healthy Aging in Neighborhoods of Diversity across the Life Span. a Model 2E, Table 2, fully adjusted model, stratified by race and sex. Figure shows predictive margins of BTA scores across time with their 95% CI, highlighting the significant difference in slope across APOE4 dosage among African American women only. γ12 refers to the fixed effect of APOE4 dosage on the rate of change in BTA total score for each sex group among African Americans. “b” is a standardized measure for the regression coefficient γ12 in model where BTA is entered as standardized z-scores within each racial/sex group. It is interpreted as the SD of outcome change per year increase in follow-up time for each APOE4 dosage change. 1 SD of BTA corresponds to 6.63 change in score, overall
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