Abstract MP23: Cardiovascular Diseases and Risk of Dementia in the General Population: Observational and Genetic Studies

Importance: Cardiovascular diseases are associated with increased risk of subtypes of dementia. The causal nature is however unclear. Objective: To assess observational and genetic associations between a range of cardiovascular disease and risk of all-cause dementia and its major subtypes. Design, Settings, and Participants: We performed time-dependent Cox regression analyses in three prospective cohorts, the Copenhagen City Heart Study (N=10,373), the Copenhagen General Population Study (N=101,582), and the UK Biobank (N=377,706); median follow-up times were 15, 9, and 13 years, respectively. Estimates from each cohort were pooled in meta-analyses using fixed-effects models. Subsequently, we investigated genetic susceptibility for cardiovascular diseases and risk of all-cause dementia, Alzheimer’s disease, and vascular dementia, using individual-level data from the UK Biobank and summary statistics from the FinnGen study. Exposures: Ischemic heart disease, myocardial infarction, peripheral arterial disease, hypertensive heart disease, stroke, ischemic stroke, atrial fibrillation, heart failure, and the combination of all. Main Outcomes and Measures: Outcomes include all-cause dementia, Alzheimer’s disease, and vascular dementia. Measures are hazard ratios (HRs) and 95% confidence intervals (CIs) in observational studies and odds ratios (ORs) and 95% CIs in genetic studies. Results: Observationally, cardiovascular diseases were associated with high future risk of incident all-cause dementia, Alzheimer’s disease, and vascular dementia in meta-analyses, with HRs up to 7.49 (95% CI: 6.63, 8.46). Genetically, using individual level data from the UK Biobank, predisposition to ischemic stroke was associated with high risk of all-cause dementia, Alzheimer’s disease, and vascular dementia, with ORs of 1.64 (1.35, 1.98), 1.44 (1.10, 1.89), and 2.06 (1.41, 3.01), respectively, with similar estimates for ischemic stroke; genetic predisposition to ischemic heart disease was associated with high risk of vascular dementia, with an OR of 1.24 (1.03, 1.50). Genetic summary-level data from the FinnGen study confirmed the estimates for stroke and ischemic stroke. Conclusion and Relevance: Our study provides novel evidence that the association between stroke and all-cause dementia and its major subtypes may be of a causal nature. Further, we observe that genetic susceptibility for ischemic heart disease is associated with incident vascular dementia. These findings underscore the importance of integrating cardiovascular disease prevention into interventions to reduce dementia risk.