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Whether vascular and Alzheimer disease\u2010associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants in the Atherosclerosis Risk in Communities\u2013Positron Emission Tomography study were followed from 1987\u20131989 (45\u201364\u2009years old) through 2016\u20132017 (74\u201394\u2009years old), with repeat cognitive assessment and dementia adjudication. In 2011\u20132013, dementia\u2010free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (A\u03b2) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated A\u03b2 standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 298 individuals, 36 developed dementia (median follow\u2010up\u00a0=\u00a04.9\u2009years). Midlife hypertension and A\u03b2 each independently predicted dementia risk (hypertension: hazard ratio [HR] =\u20092.57, 95% confidence interval [CI] =\u20091.16\u20135.67; A\u03b2 SUVR [per standard deviation (SD)]: HR\u00a0=\u00a02.57, 95% CI\u00a0=\u00a01.72\u20133.84), but did not interact significantly, whereas late life diabetes (HR\u00a0=\u00a02.50, 95% CI\u00a0=\u00a01.18\u20135.28) and A\u03b2 independently predicted dementia risk. WMHs (per SD: HR\u00a0=\u00a01.51, 95% CI\u00a0=\u00a01.03\u20132.20) and A\u03b2 SUVR (HR\u00a0=\u00a02.52, 95% CI\u00a0=\u00a01.83\u20133.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of A\u03b2 and MVRFs (HR\u00a0=\u00a02.18, 95% CI\u00a0=\u00a01.18\u20134.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Midlife hypertension and late life A\u03b2 are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607\u2013619<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26447","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T22:50:01Z","timestamp":1655938201000},"page":"607-619","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Associations of Vascular Risk and Amyloid Burden with Subsequent Dementia"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9504-1256","authenticated-orcid":false,"given":"Rebecca F.","family":"Gottesman","sequence":"first","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke Intramural Program  National Institutes of Health, Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aozhou","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-066X","authenticated-orcid":false,"given":"David S.","family":"Knopman","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Clifford R.","family":"Jack","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Rahmim","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Physics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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