{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:50:20Z","timestamp":1784857820196,"version":"3.55.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95159"],"award-info":[{"award-number":["N01-HC-95159"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95160"],"award-info":[{"award-number":["N01-HC-95160"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95161"],"award-info":[{"award-number":["N01-HC-95161"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95162"],"award-info":[{"award-number":["N01-HC-95162"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95163"],"award-info":[{"award-number":["N01-HC-95163"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95164"],"award-info":[{"award-number":["N01-HC-95164"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95165"],"award-info":[{"award-number":["N01-HC-95165"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95166"],"award-info":[{"award-number":["N01-HC-95166"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95167"],"award-info":[{"award-number":["N01-HC-95167"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95168"],"award-info":[{"award-number":["N01-HC-95168"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["N01-HC-95169"],"award-info":[{"award-number":["N01-HC-95169"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1-TR-000040"],"award-info":[{"award-number":["UL1-TR-000040"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1-TR-001079"],"award-info":[{"award-number":["UL1-TR-001079"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["P30AG021334"],"award-info":[{"award-number":["P30AG021334"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Our understanding of the specific aspects of vascular contributions to dementia remains unclear.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>We aim to identify the correlates of incident dementia in a multi-ethnic cardiovascular cohort.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A total of 6806 participants with follow-up data for incident dementia were included. Probable dementia diagnoses were identified using hospitalization discharge diagnoses according to the International Classification of Diseases Codes (ICD). We used Random Forest analyses to identify the correlates of incident dementia and cognitive function from among 198 variables collected at the baseline MESA exam entailing demographic risk factors, medical history, anthropometry, lab biomarkers, electrocardiograms, cardiovascular magnetic resonance imaging, carotid ultrasonography, coronary artery calcium and liver fat content. Death and stroke were considered competing events.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Over 14 years of follow-up, 326 dementia events were identified. Beyond age, the top correlates of dementia included coronary artery calcification, high sensitivity troponin, common carotid artery intima to media thickness, NT-proBNP, physical activity, pulse pressure, tumor necrosis factor-\u03b1, history of cancer, and liver to spleen attenuation ratio from computed tomography. Correlates of cognitive function included income and physical activity, body size, serum glucose, glomerular filtration rate, measures of carotid artery stiffness, alcohol use, and inflammation indexed as IL-2 and TNF soluble receptors and plasmin-antiplasmin complex.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In a deeply phenotyped cardiovascular cohort we identified the key correlates of dementia beyond age as subclinical atherosclerosis and myocyte damage, vascular function, inflammation, physical activity, hepatic steatosis, and history of cancer.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0298952","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T18:08:27Z","timestamp":1713463707000},"page":"e0298952","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deep phenotyping of dementia in a multi-ethnic cardiovascular cohort: The Multi-Ethnic Study of Atherosclerosis (MESA)"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3175-3606","authenticated-orcid":true,"given":"Mohammad R.","family":"Ostovaneh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin O.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn L.","family":"McClelland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Casanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bluemke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P.","family":"Tracy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Shea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Heckbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o A. C.","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2330-2373","authenticated-orcid":true,"given":"Bharath","family":"Ambale-Venkatesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"issue":"4","key":"pone.0298952.ref001","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1161\/CIRCRESAHA.118.314338","article-title":"Implementing the National Heart, Lung, and Blood Institute\u2019s Strategic Vision in the Division of Cardiovascular Sciences","volume":"124","author":"DC Goff","year":"2019","journal-title":"Circulation research"},{"issue":"23","key":"pone.0298952.ref002","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1212\/WNL.0000000000004717","article-title":"Alzheimer\u2019s Disease-Related Dementias Summit 2016: National research priorities","volume":"89","author":"RA Corriveau","year":"2017","journal-title":"Neurology"},{"issue":"3","key":"pone.0298952.ref003","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1161\/CIRCRESAHA.116.308426","article-title":"Vascular Cognitive Impairment","volume":"120","author":"M Dichgans","year":"2017","journal-title":"Circulation research"},{"issue":"14","key":"pone.0298952.ref004","first-page":"1326","article-title":"Langa KMJNEJoM","volume":"368","author":"MD Hurd","year":"2013","journal-title":"Monetary costs of dementia in the United States"},{"issue":"2","key":"pone.0298952.ref005","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1474-4422(03)00305-3","article-title":"Vascular cognitive impairment","volume":"2","author":"JT O\u2019Brien","year":"2003","journal-title":"The Lancet Neurology"},{"issue":"11","key":"pone.0298952.ref006","first-page":"3137","volume":"43","author":"M Dichgans","year":"2012","journal-title":"Prevention of Vascular Cognitive Impairment"},{"key":"pone.0298952.ref007","unstructured":"National Heart L, and Blood Institute. Charting the Future Together. The NHLBI Strategic Vision."},{"issue":"6","key":"pone.0298952.ref008","first-page":"523","article-title":"Incidence of dementia over three decades in the Framingham Heart Study","volume":"374","author":"CL Satizabal","year":"2016","journal-title":"JNEJo"},{"issue":"6","key":"pone.0298952.ref009","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1001\/jama.2019.10551","article-title":"Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions","volume":"322","author":"Group TSMIftSR","year":"2019","journal-title":"JAMA"},{"issue":"6","key":"pone.0298952.ref010","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1001\/jama.2018.21442","article-title":"Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial","volume":"321","author":"Group TSMIftSR","year":"2019","journal-title":"JAMA"},{"issue":"3","key":"pone.0298952.ref011","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1161\/HYPERTENSIONAHA.117.10289","article-title":"Left Ventricular Hypertrophy and Remodeling and Risk of Cognitive Impairment and Dementia: MESA (Multi-Ethnic Study of Atherosclerosis)","volume":"71","author":"K Moazzami","year":"2018","journal-title":"Hypertension (Dallas, Tex: 1979)"},{"issue":"2","key":"pone.0298952.ref012","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1161\/HYPERTENSIONAHA.119.13952","article-title":"Change in NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Level and Risk of Dementia in Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"75","author":"MR Ostovaneh","year":"2020","journal-title":"Hypertension (Dallas, Tex: 1979)"},{"key":"pone.0298952.ref013","article-title":"Cardiovascular event prediction by machine learning: the Multi-Ethnic Study of Atherosclerosis","author":"B Ambale-Venkatesh","year":"2017","journal-title":"Circulation research"},{"issue":"3","key":"pone.0298952.ref014","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1214\/ss\/1009213726","article-title":"Statistical modeling: The two cultures (with comments and a rejoinder by the author)","volume":"16","author":"L. Breiman","year":"2001","journal-title":"Statistical science"},{"issue":"3","key":"pone.0298952.ref015","first-page":"841","article-title":"Random survival forests","volume":"2","author":"H Ishwaran","year":"2008","journal-title":"JTaoas"},{"issue":"9","key":"pone.0298952.ref016","first-page":"871","volume":"156","author":"DE Bild","year":"2002","journal-title":"Multi-ethnic study of atherosclerosis: objectives and design"},{"issue":"5","key":"pone.0298952.ref017","first-page":"e005349","volume":"10","author":"A Fujiyoshi","year":"2017","journal-title":"Coronary artery calcium and risk of dementia in MESA (Multi-Ethnic Study of Atherosclerosis)"},{"issue":"2","key":"pone.0298952.ref018","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/WAD.0000000000000164","article-title":"Validity of Death Certificate and Hospital Discharge ICD Codes for Dementia Diagnosis: The Multi-Ethnic Study of Atherosclerosis","volume":"31","author":"A Fujiyoshi","year":"2017","journal-title":"Alzheimer disease and associated disorders"},{"key":"pone.0298952.ref019","first-page":"1141","article-title":"A class of K-sample tests for comparing the cumulative incidence of a competing risk","author":"RJ Gray","year":"1988","journal-title":"JTAos"},{"issue":"3","key":"pone.0298952.ref020","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/WAD.0000000000000388","article-title":"Expanded Demographic Norms for Version 3 of the Alzheimer Disease Centers\u2019 Neuropsychological Test Battery in the Uniform Data Set","volume":"34","author":"BC Sachs","year":"2020","journal-title":"Alzheimer disease and associated disorders"},{"issue":"4","key":"pone.0298952.ref021","first-page":"558","article-title":"Standard errors and confidence intervals for variable importance in random forest regression, classification, and survival","volume":"38","author":"H Ishwaran","year":"2019","journal-title":"Sim"},{"key":"pone.0298952.ref022","first-page":"519","article-title":"Variable importance in binary regression trees and forests","volume":"1","author":"HJ Ishwaran","year":"2007","journal-title":"EJoS"},{"issue":"13","key":"pone.0298952.ref023","first-page":"2173","article-title":"Estimating a time\u2010dependent concordance index for survival prediction models with covariate dependent censoring","volume":"32","author":"TA Gerds","year":"2013","journal-title":"SiM"},{"issue":"6","key":"pone.0298952.ref024","first-page":"1029","article-title":"Consistent estimation of the expected Brier score in general survival models with right\u2010censored event times","volume":"48","author":"TA Gerds","year":"2006","journal-title":"BJ"},{"issue":"7874","key":"pone.0298952.ref025","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0140-6736(74)91496-2","article-title":"Multi-infarct dementia. A cause of mental deterioration in the elderly","volume":"2","author":"VC Hachinski","year":"1974","journal-title":"Lancet (London, England)"},{"issue":"20","key":"pone.0298952.ref026","first-page":"2025","volume":"79","author":"M Duering","year":"2012","journal-title":"Incident subcortical infarcts induce focal thinning in connected cortical regions"},{"issue":"16","key":"pone.0298952.ref027","first-page":"1685","volume":"84","author":"M Duering","year":"2015","journal-title":"Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts"},{"issue":"7","key":"pone.0298952.ref028","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S1474-4422(02)00190-4","article-title":"Subcortical ischaemic vascular dementia","volume":"1","author":"GC Rom\u00e1n","year":"2002","journal-title":"The Lancet Neurology"},{"issue":"9","key":"pone.0298952.ref029","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1001\/archinte.166.9.1003","article-title":"Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study","volume":"166","author":"C Qiu","year":"2006","journal-title":"Archives of internal medicine"},{"issue":"23","key":"pone.0298952.ref030","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1212\/WNL.0b013e318295d71a","article-title":"Severe carotid stenosis and impaired cerebral hemodynamics can influence cognitive deterioration","volume":"80","author":"S Balestrini","year":"2013","journal-title":"Neurology"},{"issue":"3","key":"pone.0298952.ref031","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S1474-4422(11)70307-6","article-title":"Cerebral microinfarcts: the invisible lesions","volume":"11","author":"EE Smith","year":"2012","journal-title":"The Lancet Neurology"},{"issue":"1","key":"pone.0298952.ref032","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1148\/radiol.13130743","article-title":"Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging","volume":"270","author":"S van Rooden","year":"2014","journal-title":"Radiology"},{"issue":"4","key":"pone.0298952.ref033","first-page":"513","article-title":"A priori collaboration in population imaging: The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement consortium","volume":"1","author":"HH Adams","year":"2015","journal-title":"Alzheimer\u2019s & dementia (Amsterdam, Netherlands)"},{"issue":"8","key":"pone.0298952.ref034","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration","volume":"12","author":"JM Wardlaw","year":"2013","journal-title":"The Lancet Neurology"},{"issue":"3","key":"pone.0298952.ref035","doi-asserted-by":"crossref","first-page":"e007241","DOI":"10.1161\/CIRCIMAGING.117.007241","article-title":"Association of Liver Fibrosis With Cardiovascular Diseases in the General Population: The Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"11","author":"MR Ostovaneh","year":"2018","journal-title":"Circulation Cardiovascular imaging"},{"issue":"4","key":"pone.0298952.ref036","article-title":"Forbes SJCdosr","volume":"2015","author":"D Forbes","journal-title":"Exercise programs for people with dementia"},{"issue":"2","key":"pone.0298952.ref037","first-page":"106","volume":"74","author":"CM Roe","year":"2010","journal-title":"Cancer linked to Alzheimer disease but not vascular dementia"},{"issue":"2","key":"pone.0298952.ref038","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.neurobiolaging.2012.04.019","article-title":"Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy","volume":"34","author":"N Zieren","year":"2013","journal-title":"Neurobiology of aging"},{"issue":"6","key":"pone.0298952.ref039","first-page":"887","volume":"59","author":"T Anttila","year":"2002","journal-title":"Midlife income, occupation, APOE status, and dementia: a population-based study"},{"issue":"6","key":"pone.0298952.ref040","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1176\/appi.ajp.160.6.1157","article-title":"Does cognitive recovery after treatment of poststroke depression last? A 2-year follow-up of cognitive function associated with poststroke depression","volume":"160","author":"K Narushima","year":"2003","journal-title":"The American journal of psychiatry"},{"issue":"2","key":"pone.0298952.ref041","first-page":"209","article-title":"Heart failure and cognitive impairment: challenges and opportunities","volume":"2","author":"GA Heckman","year":"2007","journal-title":"Clinical interventions in aging"},{"issue":"10","key":"pone.0298952.ref042","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1177\/0004867413483593","article-title":"Primary cerebral lupus as a cause of reversible cognitive impairment","volume":"47","author":"D Singh","year":"2013","journal-title":"The Australian and New Zealand journal of psychiatry"},{"issue":"489","key":"pone.0298952.ref043","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1198\/jasa.2009.tm08622","article-title":"High-dimensional variable selection for survival data","volume":"105","author":"H Ishwaran","year":"2010","journal-title":"Journal of the American Statistical Association"},{"key":"pone.0298952.ref044","first-page":"1","article-title":"Machine learning methods for predicting progression from mild cognitive impairment to Alzheimer\u2019s disease dementia: a systematic review","volume":"13","author":"S Grueso","year":"2021","journal-title":"JAsr therapy"},{"issue":"Preprint","key":"pone.0298952.ref045","first-page":"1","volume":"2023","author":"H Ding","journal-title":"Multimodal Machine Learning for 10-Year Dementia Risk Prediction: The Framingham Heart Study"},{"issue":"1","key":"pone.0298952.ref046","first-page":"168","article-title":"Dementia prediction in the general population using clinically accessible variables: a proof-of-concept study using machine learning","volume":"23","author":"EL Twait","year":"2023","journal-title":"The AGES-Reykjavik study JBmi"},{"issue":"1","key":"pone.0298952.ref047","first-page":"9480","volume":"13","author":"S Mostafaei","year":"2023","journal-title":"Machine learning algorithms for identifying predictive variables of mortality risk following dementia diagnosis: a longitudinal cohort study"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T18:08:56Z","timestamp":1713463736000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298952"}},"subtitle":[],"editor":[{"given":"Tomoki","family":"Nakamizo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0298952","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,18]]}}}