TOMM40‐APOE haplotypes are associated with cognitive decline in non‐demented Blacks

• Published in: Alzheimer's & dementia Vol. 17; no. 8; pp. 1287 - 1296
• Main Authors: Deters, Kacie D., Mormino, Elizabeth C., Yu, Lei, Lutz, Michael W., Bennett, David A., Barnes, Lisa L.
• Format: Journal Article
• Language: English
• Published: United States 01-08-2021
• Subjects: African Americans - genetics; African Americans - statistics & numerical data; Aged; Alleles; Apolipoproteins E - genetics; Cognition - physiology; cognitive aging; Cognitive Dysfunction - genetics; cohort studies; Female; genetics; Genotype; Haplotypes - genetics; Humans; Male; Membrane Transport Proteins - genetics; memory; Memory, Episodic; Mitochondrial Precursor Protein Import Complex Proteins; Poly T; cohort studies; genetics; memory; cognitive aging
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.12295

Introduction
The goal was to investigate effects of APOE‐TOMM40‐‘523 haplotypes on cognitive decline in non‐demented non‐Hispanic Blacks (NHB), and determine whether effects differ from non‐Hispanic Whites (NHW).
Methods
The impact of zero to two copies of the ’523‐Short variant (S; poly‐T alleles < 20) within apolipoprotein E (APOE) genotype on a composite measure of global cognition and five domains was examined.
Results
In NHB with ε3/ε3 (N = 294), ‘523‐S/S was associated with faster decline in global cognition (β = –0.048, P = 0.017), episodic memory (β = –0.05, P = 0.031), and visuospatial ability (β = ‐0.037, P = 0.034) relative to those without ‘523‐S. For NHB ε4+ (N = 182), ‘523‐S/S had slower decline in global cognition (β = 0.047, P = 0.042) and visuospatial ability (β = 0.07, P = 0.0005) relative to ‘523‐S non‐carriers. NHB ε4+ with ‘523‐S also had a slower rate of decline than NHWs ε4+ with ‘523‐S.
Discussion
‘523‐S/S has a different effect on cognitive decline among NHB dependent on APOE allele. Differences in the effect of ε4‐‘523‐S in NHB may explain prior mixed findings on ε4 and decline in this population.