Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort

INTRODUCTION: The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline. METHODS: = 62, SD = 9, range = 25-101 y). We measured cognitive decline across two decades of neuropsychological-testing follow-up. We measured pace of aging using the DunedinPACE epigenetic clock(definition). Analysis tested if participants with faster DunedinPACE values experienced more rapid cognitive decline compared with those with slower DunedinPACE values. RESULTS: Participants with faster DunedinPACE had poorer cognitive functioning at baseline and experienced more rapid cognitive decline over follow-up. Results were robust to confounders and consistent across population strata. Findings were similar for the PhenoAge and GrimAge epigenetic clocks. DISCUSSION: Faster pace of aging is a risk factor for preclinical cognitive decline. Metrics of biological aging may inform risk stratification in clinical trials and prognosis in patient care. Highlights: Faster DunedinPACE is associated with preclinical cognitive aging.Higher baseline cognition was protective of DunedinPACE-associated cognitive decline.The DunedinPACE association with cognitive decline explained a fourth of dementia risk.