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Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes

Circulation, Ahead of Print. BACKGROUND:Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) and dementia. We examined whether an increased genetic risk for CAD is associated with long-term risk of developing all-cause, Alzheimer’s, or vascular dementia, and investigated whether differences in potentially modifiable lifestyle factors in the mid- to late-life period may attenuate this risk.METHODS:A prospective cohort study of 365 782 participants free from dementia for at least 5 years after baseline assessment was conducted within the UK Biobank cohort. Genetic risk was assessed using a genomewide polygenic risk score (PRS) for CAD and lifestyle risk using a modified version of the American Heart Association’s Life’s Essential 8 Lifestyle Risk Score (LRS). Higher values for both scores were deemed to represent increased risk. Primary outcomes were incident all-cause, Alzheimer’s, and vascular dementia diagnoses obtained from electronic health records. Secondary outcomes were neuroimaging phenotypes measured in 32 028 participants recalled for magnetic resonance imaging. Sensitivity analyses were conducted to test the extent by which biological and behavioral risk factors contributed to observed associations.RESULTS:A total of 8870 cases of all-cause dementia were observed over a median 13.9-year follow-up. Both genetic (PRS) and lifestyle (LRS) risk scores for CAD were associated with a modestly elevated risk of all-cause dementia (subhazard ratio per SD increase, 1.10 [1.08, 1.12],P

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