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Repurposing drugs for known risk factors could have clinical impact. Using Mendelian randomization, we proxied 46 lipid-lowering, antihypertensive and anti-inflammatory drug effects across five VaD outcomes: clinical diagnosis (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20097,009 cases,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009899,672 non-cases\/controls) and neuroimaging features (max\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200950,559), white matter hyperintensity volume, fractional anisotropy, mean diffusivity and lacunar stroke diagnosis. Beta-1 adrenergic receptor indicated potential benefit (clinical diagnosis: odds ratio (OR)\u2009=\u20090.90, 95% confidence interval (CI)\u2009=\u20090.80\u20131.01; white matter hyperintensity volume: estimated causal effect\u2009=\u2009\u22120.03, 95% CI\u2009=\u2009\u22120.07\u20130.00; mean diffusivity: estimated causal effect =\u2009\u22120.18, 95% CI\u2009=\u2009\u22120.37\u20130.00; lacunar stroke: OR\u2009=\u20090.91, 95% CI\u2009=\u20090.80\u20131.03). Angiotensin-converting enzyme inhibition suggested increased VaD risk (OR\u2009=\u20091.12, 95% CI\u2009=\u20091.01\u20131.24). Findings remained largely null after multiple-testing correction. Here we show that although little evidence supported repurposing most lipid-lowering, antihypertensive and anti-inflammatory drugs for VaD prevention or treatment, beta-1 adrenergic receptor antagonism could be a promising repurposing candidate, but replication is needed as further data becomes available. Pharmacovigilance studies should examine angiotensin-converting enzyme inhibitors\u2019 potential to increase risk.\n                  <\/jats:p>","DOI":"10.1038\/s43587-026-01106-1","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:03:28Z","timestamp":1776675808000},"page":"905-915","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Repurposing drugs for the prevention of vascular dementia using evidence from drug target Mendelian randomization"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-862X","authenticated-orcid":false,"given":"Victoria","family":"Taylor-Bateman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8685-5979","authenticated-orcid":false,"given":"Phazha","family":"Bothongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5064-446X","authenticated-orcid":false,"given":"Venexia","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7542-1139","authenticated-orcid":false,"given":"Patrick G.","family":"Kehoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5490-0034","authenticated-orcid":false,"given":"Liv Tybj\u00e6rg","family":"Nordestgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Ben-Shlomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2460-0508","authenticated-orcid":false,"given":"Neil M.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-2487","authenticated-orcid":false,"given":"Dylan M.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"1106_CR1","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S0140-6736(00)03589-3","volume":"357","author":"Neuropathology Group. 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