{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:09:32Z","timestamp":1784304572995,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["F30NS124136"],"award-info":[{"award-number":["F30NS124136"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R35AG071916"],"award-info":[{"award-number":["R35AG071916"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG082730"],"award-info":[{"award-number":["R01AG082730"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's & Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Lower blood pressure (BP) is linked to reduced dementia risk, though it is uncertain whether this benefit stems solely from mitigating vascular brain injury (VBI) or also extends to directly influencing Alzheimer's disease (AD) pathology. We leveraged Mendelian randomization (MR) to assess whether lifelong lower BP is causally associated with neuropathological correlates of VBI and AD.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We identified genetic proxies for systolic and diastolic BP (\n n\u00a0<\/jats:italic>\n =\u00a01,028,980) and applied them in MR analyses of post mortem neuropathological measures of VBI and AD (\n n\u00a0=\u00a0<\/jats:italic>\n 6363\u20137786).\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Genetically proxied lower systolic BP associated with reduced risk of all VBI measures, including atherosclerosis, arteriolosclerosis, gross infarcts, and microinfarcts. There was no evidence for associations between systolic BP and AD pathology, including measures of amyloid and tau pathology. Diastolic BP analyses yielded similar results.<\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n These findings suggest that BP\u2010lowering protects against dementia by mitigating VBI rather than by directly affecting AD pathology.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n It is uncertain whether blood pressure impacts dementia risk solely through its effects on blood vessel health, or whether it also impacts Alzheimer's disease (AD) pathology.<\/jats:p>\n <\/jats:list-item>\n \n We performed a Mendelian randomization study using genetic predictors of blood pressure applied to a unique autopsy study of neuropathological correlates of both vascular brain injury and AD pathology.<\/jats:p>\n <\/jats:list-item>\n \n We found evidence that genetically lowered blood pressure solely impacts vascular brain injury, with no effects on AD pathology.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70515","type":"journal-article","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T03:34:18Z","timestamp":1752982458000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically proxied blood pressure, vascular brain injury, and Alzheimer's disease pathology"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-0641","authenticated-orcid":false,"given":"Iyas","family":"Daghlas","sequence":"first","affiliation":[{"name":"Department of Neurology University of California San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle R.","family":"Caunca","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lincoln M. P.","family":"Shade","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Nassan","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer's Disease Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yaffe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of California San Francisco San Francisco California USA"},{"name":"Department of Epidemiology and Biostatistics University of California San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Fardo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipender","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Imperial College London London 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