Background 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.

Methods 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.

Results 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.

Conclusions 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.

The authors have declared no competing interest.

This research has been conducted using the UK Biobank Resource under application number [61915]. It was in part supported by grants from the National Institutes of Health, USA (1R15HL172198 and 1R15HL173852), American Heart Association (25AIREA1377168) and a Michigan Technological University Undergraduate Research Internship Program.

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Data from the UK Biobank Resource and National Institutes of Health's All of Us Research Program are available online.

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This research has been conducted using the UK Biobank Resource under Application Number 61915.We also thank the National Institutes of Health?s All of Us Research Program for making available the participant data examined in this study. The computer source code for this study is available at https://github.com/MIILab-MTU/CVDSubtypesADCorrelation.