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Overall vascular risk factor burden was calculated using the Framingham Stroke Risk Profile (FSRP). Mid\u2010life FSRP was measured at 50 to 60\u00a0years of age. Following death, brains were autopsied and semi\u2010quantitatively assessed by board\u2010certified neuropathologists for cerebrovascular outcomes (cortical infarcts, subcortical infarcts, atherosclerosis, arteriosclerosis) and Alzheimer\u2019s disease pathology (Braak stage, cerebral amyloid angiopathy, and neuritic plaque score). We estimated adjusted odds ratios between vascular risk burden (at mid\u2010life and before death) and neuropathological outcomes using logistic and proportional\u2010odds logistic models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median time interval between FSRP and death was 33.4\u00a0years for mid\u2010life FSRP and 4.4\u00a0years for final FSRP measurement before death. Higher mid\u2010life vascular risk burden was associated with increased odds of all cerebrovascular pathology, even with adjustment for vascular risk burden before death. Late\u2010life vascular risk burden was associated with increased odds of cortical infarcts (OR [95% CI]: 1.04 [1.00, 1.08]) and arteriosclerosis stage (OR [95% CI]: 1.03 [1.00, 1.05]). Mid\u2010life vascular risk burden was not associated with Alzheimer\u2019s disease pathology, though late\u2010life vascular risk burden was associated with increased odds of higher Braak stage (OR [95% CI]: 1.03 [1.01, 1.05]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Mid\u2010life vascular risk burden was predictive of cerebrovascular but not Alzheimer\u2019s disease neuropathology, even after adjustment for vascular risk factors before death.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50936","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T06:14:46Z","timestamp":1573020886000},"page":"2403-2412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mid\u2010life and late\u2010life vascular risk factor burden and neuropathology in old age"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0929-9948","authenticated-orcid":false,"given":"Sarah C.","family":"Conner","sequence":"first","affiliation":[{"name":"Framingham Heart Study Framingham Massachusetts"},{"name":"Department of Biostatistics Boston University School of Public Health Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Pase","sequence":"additional","affiliation":[{"name":"Framingham Heart Study Framingham Massachusetts"},{"name":"Melbourne Dementia Research Centre The Florey Institute for Neuroscience and Mental Health Melbourne Australia"},{"name":"Centre for Human Psychopharmacology Swinburne University of Technology Melbourne Australia"},{"name":"Faculty of Medicine Dentistry and Health Sciences The University of Melbourne Melbourne 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