Introduction: The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline. Methods: We analyzed Framingham Heart Study Offspring Cohort data (n=2,296; 46% male; baseline age M=62, SD=9, range=25-101y). We measured cognitive decline across two decades of neuropsychological-testing follow-up. We measured pace of aging using the DunedinPACE epigenetic clock. Analysis tested if participants with faster DunedinPACE values experienced more rapid preclinical cognitive decline as compared to 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.

Disclosures: AC, TEM, KS, and DWB are inventors of the Duke University and University of Otago Invention DunedinPACE, which is licensed to TruDiagnostic.

Acknowledgments: DWB is a fellow of the CIFAR CBD Network. Sources of Funding: This project was supported by US National Institutes on Aging grants R01AG073402, R01AG073207. MJS is supported by a Diversity Supplement from the National Institute on Aging R01AG073402-0251. DWB is a fellow of the CIFAR CBD Network.

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The study used only openly available human data that were originally located at Framingham Heart Study

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