{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:21:03Z","timestamp":1783297263470,"version":"3.54.6"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T00:00:00Z","timestamp":1537228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["N01-AG-12100"],"award-info":[{"award-number":["N01-AG-12100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["ZIAEY000401"],"award-info":[{"award-number":["ZIAEY000401"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013258","name":"Hjartavernd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013258","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":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>We sought to examine the genetic overlap between vascular pathologies and Alzheimer's disease (AD) dementia, and the potential mediating role of vascular pathologies between AD\u2010related genetic variants and late\u2010life cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For 2907 stroke\u2010free older individuals, we examined the association of polygenic risk scores for AD dementia (ADPRSs) with vascular pathologies and with cognition. Mediation analyses addressed whether association between ADPRSs and cognition was mediated by a vascular pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ADPRSs were associated with lobar cerebral microbleeds, white matter lesion load, and coronary artery calcification, mostly explained by single nucleotide polymorphisms in the 19q13 region. The effect of ADPRSs on cognition was partially but significantly mediated by cerebral microbleeds, white matter lesions, and coronary artery calcification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings provide evidence for genetic overlap, mostly due to apolipoprotein E (<jats:italic>APOE<\/jats:italic>) gene, between vascular pathologies and AD dementia. The association between AD polygenic risk and late\u2010life cognition is mediated in part via effects on vascular pathologies.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2018.08.002","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T21:52:10Z","timestamp":1537393930000},"page":"65-75","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Genetic overlap between vascular pathologies and Alzheimer's dementia and potential causal mechanisms"],"prefix":"10.1002","volume":"15","author":[{"given":"Yen\u2010Feng","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Psychiatry Taipei City Psychiatric Center Taipei City Hospital Taipei Taiwan"},{"name":"Department of Epidemiology Harvard T. H. Chan School of Public Health Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert Vernon","family":"Smith","sequence":"additional","affiliation":[{"name":"Icelandic Heart Association Kopavogur Iceland"},{"name":"Faculty of Medicine University of Iceland Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor","family":"Aspelund","sequence":"additional","affiliation":[{"name":"Icelandic Heart Association Kopavogur Iceland"},{"name":"Faculty of Medicine University of Iceland Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Betensky","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T. H. Chan School of Public Health Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan W.","family":"Smoller","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T. H. Chan School of Public Health Boston MA USA"},{"name":"Psychiatric and Neurodevelopmental Genetics Unit Center for Genomic Medicine Massachusetts General Hospital Boston MA USA"},{"name":"Department of Psychiatry Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilmundur","family":"Gudnason","sequence":"additional","affiliation":[{"name":"Icelandic Heart Association Kopavogur Iceland"},{"name":"Faculty of Medicine University of Iceland Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenore J.","family":"Launer","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences National Institute of Ageing National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Blacker","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T. H. Chan School of Public Health Boston MA USA"},{"name":"Department of Psychiatry Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Gerontology Research Unit Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,18]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt188"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.598326"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000307750.41970.d9"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.558197"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182020349"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70013-4"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq321"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2011.03490.x"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.10.1531"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c3666"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31820e7baa"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh688"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e31829344ed"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2010.04.002"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.308018"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21073"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.672527"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.01.008"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.08.038"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.579581"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.06.015"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31829bfda4"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.11.1300"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt034"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.121913"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-0996-2"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.015489"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24621"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.10.084"},{"key":"e_1_2_7_31_2","volume-title":"Mediation Analysis in Understanding Mechanism of Alzheimer's Disease Risk","author":"Sajeev G","year":"2015"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwk115"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.801"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-publhealth-032315-021402"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199203000-00013"},{"key":"e_1_2_7_36_2","volume-title":"PARAMED: Stata Module to Perform Causal Mediation Analysis Using Parametric Regression Models","author":"Emsley R","year":"2013"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182452928"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.06.024"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00205"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.579078"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007020200068"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12221"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.11.1629"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf077"},{"key":"e_1_2_7_45_2","first-page":"668","article-title":"Current understanding of coronary artery calcification","volume":"12","author":"Liu W","year":"2015","journal-title":"J Geriatr Cardiol."},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1547-z"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.08.025"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.006"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.02.003"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002922"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.07.018"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526018334939?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526018334939?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.2018.08.002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2018.08.002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.jalz.2018.08.002","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2018.08.002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T14:51:13Z","timestamp":1759848673000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.jalz.2018.08.002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,18]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1016\/j.jalz.2018.08.002"],"URL":"https:\/\/doi.org\/10.1016\/j.jalz.2018.08.002","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,18]]},"assertion":[{"value":"2018-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}