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 approximately 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 cognitive function score at each visit, between-visit change in global cognitive function score, MCI diagnosis, and presence of significant cognitive decline at visit 2 (V2). There were significant associations between greater acceleration for all clocks and lower global cognitive function at each visit. The strongest associations were observed for GrimAge and DunedinPACE. Similar results were observed for domain-specific cognitive function at each visit and MCI diagnosis at V2. There was a significant association of decline in global cognitive function with increase in age acceleration between the two visits for PhenoAge and GrimAge. Between-visit increase in age acceleration for these two clocks was also associated with a greater risk of MCI diagnosis and presence of significant cognitive decline 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.