4.7 Article

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

Journal

ALZHEIMERS & DEMENTIA
Volume 17, Issue 8, Pages 1287-1296

Publisher

WILEY
DOI: 10.1002/alz.12295

Keywords

cognitive aging; cohort studies; genetics; memory

Funding

  1. Alzheimer's Association [AARFD-18-562691]
  2. NIA [RF1AG022018, P30AG010161, R0AG15819, R01AG017917, K01 AG051718]
  3. Zinfandel Pharmaceuticals

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The study investigated the effects of APOE-TOMM40-'523 haplotypes on cognitive decline in non-demented non-Hispanic Blacks (NHB) and compared these effects to non-Hispanic Whites (NHW). Results showed that the '523-S/S haplotype had different effects on cognitive decline in NHB depending on APOE allele, and that differences in the effect of epsilon 4-'523-S in NHB may explain previous mixed findings on epsilon 4 and decline in this population.
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 epsilon 3/epsilon 3 (N = 294), '523-S/S was associated with faster decline in global cognition (beta = -0.048, P = 0.017), episodic memory (beta = -0.05, P = 0.031), and visuospatial ability (beta = -0.037, P = 0.034) relative to those without '523-S. For NHB epsilon 4+ (N = 182), '523-S/S had slower decline in global cognition (beta = 0.047, P = 0.042) and visuospatial ability (beta = 0.07, P = 0.0005) relative to '523-S non-carriers. NHB epsilon 4+ with '523-S also had a slower rate of decline than NHWs epsilon 4+ 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 epsilon 4-'523-S in NHB may explain prior mixed findings on epsilon 4 and decline in this population.

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