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Carotid plaques and intima media thickness (IMT) were measured at baseline (1991\u20131994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), \u03b2\u2010amyloid<jats:sub>42<\/jats:sub> and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009\u20132015).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During 20\u2009years of follow\u2010up, 462 individuals developed dementia (mean age at baseline = 57.5\u2009\u00b1\u20095.9\u2009years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all\u2010cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03\u20131.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10\u20131.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77\u20131.17]). Carotid plaques were associated with vascular dementia when assessed as a 3\u2010graded score (adjusted HR = 1.90 [95% CI = 1.07\u20133.38]). In the cognitively unimpaired subcohort (53.8\u2009\u00b1\u20094.6\u2009years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05\u20132.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87\u20131.90] for A\u03b2<jats:sub>42<\/jats:sub> and 1.35 [95% CI = 0.86\u20132.13] for A\u03b2<jats:sub>42<\/jats:sub>\/p\u2010tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2020;87:52\u201362<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25645","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T06:35:47Z","timestamp":1573626947000},"page":"52-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-7388","authenticated-orcid":false,"given":"Anna\u2010M\u00e4rta","family":"Gustavsson","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6 Lund University  Malm\u00f6"},{"name":"Memory Clinic Sk\u00e5ne University Hospital  Malm\u00f6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-9874","authenticated-orcid":false,"given":"Danielle","family":"van Westen","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, Department of Clinical Sciences Lund Lund University  Lund"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stomrud","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6 Lund University  Malm\u00f6"},{"name":"Memory Clinic Sk\u00e5ne University Hospital  Malm\u00f6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Cardiovascular Epidemiology, Department of Clinical Sciences Malm\u00f6 Lund University  Malm\u00f6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"N\u00e4gga","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6 Lund University  Malm\u00f6"},{"name":"Department of Acute Internal Medicine and Geriatrics Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-7286","authenticated-orcid":false,"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6 Lund University  Malm\u00f6"},{"name":"Memory Clinic Sk\u00e5ne University Hospital  Malm\u00f6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67889-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-137-3-200208060-00006"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-091663"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.3090"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004749"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.0244"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0295-9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2014.04.003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/35025203"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.628875"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.160"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21073"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53360.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.672527"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.10.002"},{"key":"e_1_2_8_17_1","first-page":"45","article-title":"The Malmo Diet and Cancer Study","volume":"233","author":"Berglund G","year":"1993","journal-title":"Design and feasibility. 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