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Genetic Risk of Cognitive Decline Varies Between Latino Populations, Study Finds

NEW YORK – The effect of APOE alleles on cognitive function differs across Latino groups, according to a new analysis.

More than 5.8 million people in the US have Alzheimer's disease or a related dementia, but the conditions occur at higher rates among Black and Latino populations. While the APOE-ε4 allele is a major genetic risk factor for Alzheimer's disease, its effect has largely been studied in populations of European ancestry.

As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), researchers from Brigham and Women's Hospital conducted an association study of the APOE allele and cognitive outcomes within a cohort of middle-aged and older Latinos. While they uncovered an association between the APOE-ε4 allele and risk of cognitive decline, the researchers noted that when they stratified their cohort further, the effect only remained among Cubans, as they reported on Friday in the journal Alzheimer's & Dementia.

At the same time, they found that the APOE-ε2 allele was linked to decreased risk of mild cognitive impairment among Puerto Ricans and that, across Latino groups, increased Amerindian ancestry was associated with a protective effect stemming from the APOE-ε4 allele.

"Historically, Latinx populations have been underrepresented in research, especially genetic research," first author Einat Granot-Hershkovitz from the Brigham said in a statement. "But our findings highlight how important it is to look beyond European ancestry and European genetic risk factors to understand in what ways genes may or may not contribute to their risk."

The researchers drew upon a subset of the HCHS/SOL cohort that had undergone cognitive testing a mean seven years apart as well as APOE genotyping. In all, their dataset included 4,183 individuals, 1,250 of whom had significant cognitive decline. Of those, 430 individuals had mild cognitive impairment and another 12 had only mild cognitive impairment.

The APOE-ε3 allele was the most common APOE allele across all Latino backgrounds. Individuals with one APOE-ε4 allele had an increased risk of cognitive decline, an odds ratio of 1.15 odds ratio, as compared to those without an APOE-ε4 allele.

But when the researchers stratified their cohort further by background group — Cuban, Dominican, Mexican, Puerto Rican, South American, and Central American — the link between the APOE-ε4 allele and cognitive decline only remained significant for Cubans, with an odds ratio of 1.46. This effect, the researchers noted, could be due to the higher proportion of European ancestry that is typically present among Cubans.

At the same time, the researchers found that the APOE-ε2 allele was nominally significant for protection against mild cognitive impairment among Puerto Ricans, a finding they said underscores the differential effects of APOE allele on various Latino backgrounds.

The researchers additionally stratified their cohort based on the individuals' proportions of continental genetic ancestry — European, African, and Amerindian. They uncovered an interaction between Amerindian ancestry and the effect of the APOE-ε4 allele on cognitive decline. In particular, Amerindian ancestry appeared to protect individuals against cognitive decline typically linked to the APOE-ε4 allele. 

This finding, the researchers noted, is in line with their other result that APOE-ε4 allele is linked to cognitive decline among Cubans, as Cubans also tend to have the lowest proportion of Amerindian ancestry, as compared to other Latino groups.

In a statement, first author Tamar Sofer from the Brigham noted that proportion of continental ancestry is a crude measure of genetics. 

"[B]ut there are probably specific genetic factors that may be specific to Amerindian ancestry that drive this difference in the effect of APOE," she said, adding that non-genetic factors such as nutrition, sleep, physical activity, or toxin exposure could also influence their findings.

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