Brain agingHumans

Novel APOE profile links to cognitive decline in Latinos

In Hispanic and Latino adults, a newly identified APOE cluster raised the odds of significant cognitive decline with an odds ratio of 1.47 over the main cluster.

Alzheimer's & Dementia4 Oct 2026, 08:39 BST

In a study of Hispanic and Latino adults, researchers identified a novel genetic profile in the APOE region that associates more strongly with cognitive decline than the conventional APOE ε4 allele. The ε4 variant has previously shown weaker associations with Alzheimer's disease and related dementias in Hispanic and Latino individuals compared to non-Hispanic White and East Asian populations.

To explore alternative genetic signals, the researchers analyzed whole-genome sequencing data from 13,025 Hispanic and Latino adults, using short DNA sequences at the APOE gene region to infer three population clusters. They tested whether these clusters were associated with mild cognitive impairment and age-adjusted significant cognitive decline in 5,334 participants from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). Relative to the largest cluster, Cluster 1, individuals in Cluster 3 showed higher odds of significant cognitive decline, yielding an odds ratio of 1.47.

Why it matters

The findings show that regional genetic variation around APOE may influence brain aging differently across ancestral groups. This provides a clearer genetic picture of age-related cognitive decline in populations where standard risk alleles show weaker effects.

Caveats

The findings are based on observational data from the SOL-INCA cohort, and functional studies are needed to determine the exact mechanisms driving this risk profile.