{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T15:32:09Z","timestamp":1793892729376,"version":"4.8.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T00:00:00Z","timestamp":1239580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-55015"],"award-info":[{"award-number":["N01-HC-55015"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-55016"],"award-info":[{"award-number":["N01-HC-55016"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-55018"],"award-info":[{"award-number":["N01-HC-55018"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-55019"],"award-info":[{"award-number":["N01-HC-55019"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-55020"],"award-info":[{"award-number":["N01-HC-55020"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-55021"],"award-info":[{"award-number":["N01-HC-55021"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-55022"],"award-info":[{"award-number":["N01-HC-55022"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Strokes, vascular risk factors, and <jats:italic>apolipoprotein E<\/jats:italic> (<jats:italic>APOE<\/jats:italic>) genotype are associated with cognitive decline in the elderly, but definitive evidence that these affect cognition as early as middle age is limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We describe the relationships of <jats:italic>APOE<\/jats:italic> genotype, stroke, and vascular risk factors with cognitive change over a 14\u2010year follow\u2010up in the Atherosclerosis Risk in Communities (ARIC) Study cohort recruited while in middle age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants included a subset of the ARIC Study who underwent assessments of cognitive function and vascular risk factors. Four cognitive assessments were performed between 1990\u20131992 and 2004\u20132006. Cognitive assessments included the Delayed Word Recall (DWR) Test, the Digit Symbol Substitution (DSS) Test, and the Word Fluency (WF) Test. Vascular risk factors were assessed during the baseline visit in 1990\u20131992. Incident stroke was recorded over the 14 years of follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 1130 participants (mean age, 59 \u00b1 4.3 [SD] years; 62% women; 52% African\u2010American) with longitudinal data. In multivariate, random\u2010effects linear models adjusted for age, education, gender, and race, the risk factors diabetes and <jats:italic>APOE<\/jats:italic> \u025b4 genotype were independently associated with a decline in performance on the DSS test (both <jats:italic>P<\/jats:italic> &lt; .005), whereas hypertension and stroke were not. For DWR, stroke and <jats:italic>APOE<\/jats:italic> \u025b4 genotype were independent predictors of decline (both <jats:italic>P<\/jats:italic> &lt; .001). For the WF test, metabolic syndrome, hypertension, and stroke were independently associated with decline (all <jats:italic>P<\/jats:italic> &lt; .005). No evidence of differential effects of risk factors on cognitive decline by race, gender, or interactions between risk factors was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The vascular risk factors diabetes and hypertension, a history of stroke itself, and <jats:italic>APOE<\/jats:italic> \u025b4 genotype independently contribute to cognitive decline in late middle age and early elderly years.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2009.01.027","type":"journal-article","created":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T02:05:57Z","timestamp":1239588357000},"page":"207-214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":204,"title":["Fourteen\u2010year longitudinal study of vascular risk factors, <i>APOE<\/i> genotype, and cognition: The ARIC MRI Study"],"prefix":"10.1002","volume":"5","author":[{"given":"David S.","family":"Knopman","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Mosley","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center Jackson MS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane J.","family":"Catellier","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of North Carolina Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura H.","family":"Coker","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences Wake Forest University School of Medicine Winston-Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Atherosclerosis Risk in Communities Study Brain MRI Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00096-8"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000149519.47454.F2"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.6.1580"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530230032026"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000021991"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.1.42"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000149643.91367.8A"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a115184"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000176074.09733.a8"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000165985.97397.88"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.30.4.736"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009019"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.19.2486"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.23.8.1062"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1989.00520380041011"},{"key":"e_1_2_6_17_2","volume-title":"Wechsler adult intelligence scale-revised","author":"Wechsler D","year":"1981"},{"key":"e_1_2_6_18_2","volume-title":"Neuropsychological assessment","author":"Lezak MD","year":"1995"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-3797(18)30622-6"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.6.808"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.45.5.957"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1997.tb03091.x"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1159\/000067109"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.8.1427"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38446.466238.E0"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.12.1683"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199802193380804"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03520400044042"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000042478.08543.F7"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1994.00540240033012"},{"key":"e_1_2_6_32_2","unstructured":"DSKnopman RORoberts YEGeda BFBoeve VSPankratz RHCha et al.Association of prior stroke with cognitive function and cognitive impairment: a population-based study. Arch Neurol (in press)."},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200002)47:2<145::AID-ANA3>3.0.CO;2-P"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh553"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.10.1545"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.8.1066"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.1.40"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.7.1154"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00223-8"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.4.571"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1997.00550210044011"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00106-8"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.4.1256"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.11.1300"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526009000302?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526009000302?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.jalz.2009.01.027","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2009.01.027","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.jalz.2009.01.027","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2009.01.027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:32:30Z","timestamp":1759951950000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.jalz.2009.01.027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,13]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,5]]}},"alternative-id":["10.1016\/j.jalz.2009.01.027"],"URL":"https:\/\/doi.org\/10.1016\/j.jalz.2009.01.027","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,13]]},"assertion":[{"value":"2009-04-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}