Phenotypic and Genetic Associations Between Cardiovascular Disease Subtypes and Alzheimer's Disease

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

We examined associations between AD and 11 CVD subtypes using logistic regression models in two 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 colocalization of significant single nucleotide polymorphisms (SNPs) (p < 5×10^-8) using genome-wide association study (GWAS) data.

Most CVD subtypes were significantly associated with AD in both cohorts. Hypotension had the strongest and most consistent association, followed by hypertension and cerebral infarction. Acute myocardial infarction was the only subtype 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.

This study identifies subtype-specific CVD associations with AD across two 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.