Cardiovascular Disease Subtypes and Alzheimer's Disease: Phenotypic and Genetic Associations in the UK Biobank and All of Us Research Program.

BACKGROUND

Cardiovascular disease (CVD) and Alzheimer's disease (AD) are major public health concerns that share overlapping risk factors and potential mechanistic pathways. Although vascular contributions to cognitive decline are well documented, the specific relationships between AD and different CVD subtypes remain poorly understood.

METHODS

In this cross-sectional study, we examined associations between AD and 11 CVD subtypes using logistic regression models in 2 large biobanks: the UK Biobank (n=502 133) and the All of Us Research Program (n=287 011). Models were adjusted for demographic, lifestyle, and clinical covariates. We also explored genetic overlap between AD and CVD traits through proximity-based analysis of significant single nucleotide variants (P<5 × 10-8) using genome-wide association study data.

RESULTS

Most CVD subtypes were significantly associated with AD in both cohorts. Hypotension had the strongest and most consistent association, although it has been comparatively understudied in AD research. Strong associations were also consistently observed between AD and hypertension and cerebral infarction. Notably, acute myocardial infarction was not significantly linked to AD. Genetic analyses revealed shared loci between AD- and CVD-related traits, particularly in regions near APOE, MAPT, and genes influencing myocardial structure and vascular function.

CONCLUSIONS

This study identifies subtype-specific CVD associations with AD across 2 diverse cohorts and highlights shared genetic architecture underlying heart-brain interactions. These findings underscore the importance of vascular health in AD risk and suggest that certain CVD subtypes, especially hypotension, may play underrecognized roles in cognitive decline.