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

Abstract

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). 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. 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. '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.