Dementia polygenic risk tracks disability and death
Compared to favorable profiles, poor dementia polygenic scores carried higher risk of dementia, disability, or death (HR 1.43, 95% CI 1.26–1.63).
medRxiv
In a prospective study of 14,333 U.S. adults from the Health and Retirement Study, researchers evaluated an integrated polygenic risk score for dementia. Participants had a median age of 55 years and were free of dementia and disability at baseline. Investigators categorized participants into favorable, intermediate, or poor polygenic profiles incorporating both neurodegenerative and vascular genetic components.
Compared with a favorable profile, a poor profile was associated with a higher risk of composite dementia, disability, or death (HR 1.43, 95% CI 1.26–1.63). Individually, poor profiles were associated with dementia (HR 1.58), disability (HR 1.43), and death (HR 1.33). Carrying an APOE ε4 allele alongside a poor polygenic score was associated with the highest dementia risk (HR 2.32).
Why it matters
Tracking combined vascular and neurodegenerative risk helps map how shared genetic susceptibility shapes disability-free survival across older age.
Caveats
This work is a preprint that has not undergone peer review. The authors also note limitations concerning genetic ancestry representation, generalizability, and direct clinical translation.
The paper
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Shufan Huo, Andrew Silberfeld, Tim D’Aoust, Stéphanie Debette, Adam de Havenon, Thomas M. Gill,Yale University
medRxiv · 11 Sep 2026 · Preprint, not peer-reviewed