Longitudinal associations of epigenetic aging with cognitive aging in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos

Due to the paucity of longitudinal DNA methylation data (DNAm), especially among Hispanic/Latino adults, the association between changes in epigenetic clocks over time and cognitive aging phenotypes has not been investigated. This longitudinal study included 2671 Hispanic/Latino adults (57 years; 66% women) with blood DNAm data and neurocognitive function assessed at two visits ~7 years apart. We evaluated the associations of 5 epigenetic clocks and their between-visit change with multiple measures of cognitive aging that included a global and domain-specific cognitive function score at each visit, between-visit change in global and domain-specific cognitive function score, and MCI diagnosis at visit 2 (V2). There were significant associations between greater acceleration of all clocks and lower cognitive function at each visit and MCI at V2. The strongest associations were observed for GrimAge and DunedinPACE. There were significant associations of between-visit increase in PhenoAge and GrimAge acceleration with decline in cognitive function and greater risk of MCI diagnosis at V2. Epigenetic aging is associated with lower global and domain-specific cognitive function, greater cognitive decline, and greater risk of MCI in Hispanic/Latino adults. Longitudinal assessment of change in age acceleration for second-generation clocks, GrimAge and PhenoAge may provide additional value in predicting cognitive aging beyond a single time point assessment.