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This study used genome\u2010wide association study (GWAS) summary data, Mendelian randomization (MR), and colocalization analyzes to prioritize blood metabolites and candidate therapeutic targets associated with VaD. Key analyzes included metabolic pathway enrichment, a descriptive Phenome\u2010Wide Association Study (PheWAS) of the broader curated association profiles of prioritized genes, mediation analysis, and in\u2010silico compound prioritization with molecular docking. Twenty\u2010four metabolites were associated with VaD, with taurocholate and glutaroyl carnitine prioritized as tier 1 metabolite\u2013gene pairs. Pathway analysis implicated aminoacyl\u2010tRNA and branched\u2010chain amino acid biosynthesis pathways. Apolipoprotein E (APOE) and glutaryl\u2010CoA dehydrogenase (GCDH) were prioritized candidate genes. The PheWAS recapitulated APOE's curated associations with Alzheimer's disease and lipid traits, whereas GCDH had a more restricted curated association profile dominated by glutaric acidemia type I; these patterns provide pleiotropic context but do not establish safety. Single\u2010cell RNA\u2010sequencing analysis localized APOE predominantly to microglia and astrocytes and GCDH predominantly to oligodendrocytes, providing cell\u2010type\u2010specific context. Mediation analysis identified a statistically supported indirect pathway involving alpha\u20102\u2010macroglobulin receptor\u2010associated protein for taurocholate. Aflatoxin B1 was highly ranked in an in\u2010silico query but, because of its established toxicity, is not a therapeutic candidate. This study prioritizes metabolic and genetic candidates for experimental and clinical follow\u2010up rather than establishing therapeutic targets.<\/jats:p>","DOI":"10.1002\/gepi.70056","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:20:07Z","timestamp":1790688007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Determinants of Vascular Dementia: Blood Metabolite Associations and Candidate Therapeutic Target Prioritization"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-5387","authenticated-orcid":false,"given":"Chengwei","family":"Chen","sequence":"first","affiliation":[{"name":"Neurosurgery Center, Department of Cerebrovascular Surgery, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Zhujiang Hospital Southern Medical University Guangzhou 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