Racial disparities in epigenetic and cognitive aging

Abstract

AbstractBackgroundRacial disparities in cognitive health are persistent and pervasive among older Americans. Black Americans have higher rates of cognitive impairment and dementia than their White counterparts and a significantly higher gap between epigenetic age and chronological age. Epigenetic aging measured by DNA methylation (DNAm) has been linked to cognitive outcomes in previous research, but these studies lacked racial diversity or did not account for important confounders. Rigorous evaluation of DNAm‐age’s contribution to cognitive health disparities is needed. We hypothesize that DNAm‐age gap, measured by two epigenetic clocks GrimAge and Dunedin Pace of Aging methylation (DPoAm), is associated with cognitive performance and decline and mediates significant portions of the Black‐White disparities in these outcomes.MethodWe performed retrospective analyses among 3278 non‐Hispanic participants (80.3% White, 19.7% Black) in the Health and Retirement Study whose 2016 epigenetic age is linked to survey responses and cognitive data. DNAm‐age gap is defined as the residual after regressing epigenetic age on chronological age. Cognitive outcomes are Telephone Interview for Cognitive Status (TICS) score in 2016 and change in TICS score from 2016 to 2018. We include age, gender, and measures of socioeconomic status, health status, and health behaviors as confounders. We implement multiple linear regression models to evaluate associations between DNAm‐age gap and cognitive outcomes and mediation models to evaluate the extent to which DNAm‐age gap mediates the relationship between race and cognitive outcomes.ResultWe found that although both GrimAge and DPoAm age gaps are associated with baseline cognitive performance and longitudinal decline in minimally adjusted models, only GrimAge remained a significant predictor after adjusting for confounders. Similarly, both GrimAge and DPoAm mediate a small but significant portion (∼6‐10%) of the racial disparities in cognitive performance and decline before adjusting for confounding variables. Socioeconomic status (education, wealth, and income) has the greatest attenuating effect.ConclusionAccelerated epigenetic aging for Black compared to White Americans may play a role in racial cognitive aging disparities. Follow‐up work is ongoing to determine the role of chronic psychosocial stressors and other important determinants of cognitive health in DNAm aging and racial disparities.