Novel genetic profile linked to cognitive decline in Hispanics/Latinos.

Hrytsenko Y, Purushotham Y, Li Z, Isasi CR, Tarraf W, Ramos AR, et al. Novel genetic profile linked to cognitive decline in Hispanics/Latinos.. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2026;22(10):e71855.

Abstract

BACKGROUND: The APOE ε4 allele has weaker association with ADRD outcomes in Hispanic/Latino populations compared to non-Hispanic White and East Asian populations.

METHODS: We used whole-genome sequencing data from 13,025 Hispanic/Latino adults to infer population groups (clusters) from short DNA sequences at the APOE gene region. We estimated the associations between these clusters and mild cognitive impairment (MCI) and age-adjusted significant cognitive decline assessed via the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) study (n = 5334). We compared these associations to those of the conventional APOE alleles.

RESULTS: We identified three clusters of individuals. Relative to the largest Cluster 1, being in Cluster 3 had higher likelihood of having significant cognitive decline, with odds ratio (OR) = 1.47, 95% confidence interval (CI) [1.18, 1.84], p < 0.001. The association with having prevalent MCI at the SOL-INCA exam was not statistically significant, with OR = 1.33, 95% CI [0.97, 1.83], p = 0.08. Associations of the ε4 allele with these traits were not statistically significant.

DISCUSSION: The new APOE profile has stronger risk association with age-adjusted significant cognitive decline in SOL-INCA Hispanics/Latinos compared to the ε4 allele.

Last updated on 10/08/2026
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