medRxiv PreprintsInternational4 November 2026
PRISM-AD quantifies clinical and genetic contributions to cognitive risk prediction
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Background: Older adults with high inherited Alzheimer's disease (AD) susceptibility can still be cognitively normal (CN). An overall risk estimate alone does not show the cognitive and genetic contributions within a forecast. Objective: To quantify clinical and genetic contributions to cognitive prognosis. Methods: PRISM-AD combined nonlinear clinical functions and a polygenic risk score (PRS) term in 4,435 European-ancestry participants. Participant-level internal validation evaluated first recorded mild cognitive impairment (MCI) after CN in 908 participants and AD dementia after MCI in 714
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