Granot‐Hershkovitz, Einat; Tarraf, Wassim; Kurniansyah, Nuzulul; Daviglus, Martha; Isasi, Carmen R; Kaplan, Robert; Lamar, Melissa; Perreira, Krista M; Wassertheil‐Smoller, Sylvia; Stickel, Ariana; Thyagarajan, Bharat; Zeng, Donglin; Fornage, Myriam; DeCarli, Charles S; González, Hector M; Sofer, Tamar

doi:10.1002/alz.12205

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APOE alleles’ association with cognitive function differs across Hispanic/Latino groups and genetic ancestry in the study of Latinos‐investigation of neurocognitive aging (HCHS/SOL)

2021

Published Web Location

https://doi.org/10.1002/alz.12205

Abstract

Introduction

Apolipoprotein E (APOE) alleles are associated with cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease in Whites, but have weaker and inconsistent effects reported in Latinos. We hypothesized that this heterogeneity is due to ancestry-specific genetic effects.

Methods

We investigated the associations of the APOE alleles with significant cognitive decline and MCI in 4183 Latinos, stratified by six Latino backgrounds, and explored whether the proportion of continental genetic ancestry (European, African, and Amerindian) modifies these associations.

Results

APOE ε4 was associated with an increased risk of significant cognitive decline (odds ratio [OR] = 1.15, P-value = 0.03), with the strongest association in Cubans (OR = 1.46, P-value = 0.007). APOE-ε2 was associated with decreased risk of MCI (OR = 0.37, P-value = 0.04) in Puerto Ricans. Amerindian genetic ancestry was found to protect from the risk conferred by APOE ε4 on significant cognitive decline.

Discussion

Results suggest that APOE alleles' effects on cognitive outcomes differ across six Latino backgrounds and are modified by continental genetic ancestry.

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