{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:14:30Z","timestamp":1784740470636,"version":"3.55.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K99AG071742"],"award-info":[{"award-number":["K99AG071742"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P50 AG005134"],"award-info":[{"award-number":["P50 AG005134"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["201110DFS-277667-DRB-217413"],"award-info":[{"award-number":["201110DFS-277667-DRB-217413"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health","doi-asserted-by":"crossref","award":["R56 ES017876"],"award-info":[{"award-number":["R56 ES017876"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["N01-AG-1-2100"],"award-info":[{"award-number":["N01-AG-1-2100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN27120120022C"],"award-info":[{"award-number":["HHSN27120120022C"]}],"id":[{"id":"10.13039\/100000002","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"}]},{"name":"the Icelandic Parliament"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Epidemiol"],"published-print":{"date-parts":[[2022,6]]},"DOI":"10.1007\/s10654-022-00864-7","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T06:02:53Z","timestamp":1650952973000},"page":"591-601","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["APOE \u03b54 and late-life cognition: mediation by structural brain imaging markers"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0207-3620","authenticated-orcid":false,"given":"Yuan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Sajeev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J.","family":"VanderWeele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Viswanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigurdur","family":"Sigurdsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudny","family":"Eiriksdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor","family":"Aspelund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Betensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francine","family":"Grodstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Hofman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilmundur","family":"Gudnason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenore","family":"Launer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6107-7376","authenticated-orcid":false,"given":"Deborah","family":"Blacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"issue":"16","key":"864_CR1","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","volume":"278","author":"LA Farrer","year":"1997","unstructured":"Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis APOE and Alzheimer Disease Meta Analysis Consortium. JAMA\u202f: J Am Med Assoc. 1997;278(16):1349\u201356.","journal-title":"JAMA : J Am Med Assoc"},{"issue":"9","key":"864_CR2","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41582-019-0228-7","volume":"15","author":"Y Yamazaki","year":"2019","unstructured":"Yamazaki Y, Zhao N, Caulfield TR, Liu C-C, Bu G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol. 2019;15(9):501\u201318. https:\/\/doi.org\/10.1038\/s41582-019-0228-7.","journal-title":"Nat Rev Neurol"},{"issue":"7399","key":"864_CR3","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nature11087","volume":"485","author":"RD Bell","year":"2012","unstructured":"Bell RD, Winkler EA, Singh I, et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature. 2012;485(7399):512\u20136. https:\/\/doi.org\/10.1038\/nature11087.","journal-title":"Nature"},{"issue":"2","key":"864_CR4","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1093\/ije\/dyt034","volume":"42","author":"TA Khan","year":"2013","unstructured":"Khan TA, Shah T, Prieto D, et al. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of primary biomarker data from up to 60,883 individuals. Int J Epidemiol. 2013;42(2):475\u201392. https:\/\/doi.org\/10.1093\/ije\/dyt034.","journal-title":"Int J Epidemiol"},{"issue":"3","key":"864_CR5","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1212\/wnl.0b013e31829bfda4","volume":"81","author":"S Schilling","year":"2013","unstructured":"Schilling S, Destefano AL, Sachdev PS, et al. APOE genotype and MRI markers of cerebrovascular disease: systematic review and meta-analysis. Neurology. 2013;81(3):292\u2013300. https:\/\/doi.org\/10.1212\/wnl.0b013e31829bfda4.","journal-title":"Neurology"},{"issue":"5","key":"864_CR6","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1161\/01.STR.0000160747.27470.2a","volume":"36","author":"JA Schneider","year":"2005","unstructured":"Schneider JA, Bienias JL, Wilson RS, Berry-Kravis E, Evans DA, Bennett DA. The apolipoprotein E epsilon4 allele increases the odds of chronic cerebral infarction [corrected] detected at autopsy in older persons. Stroke; J Cereb Circ. 2005;36(5):954\u20139. https:\/\/doi.org\/10.1161\/01.STR.0000160747.27470.2a.","journal-title":"Stroke; J Cereb Circ"},{"issue":"2","key":"864_CR7","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1136\/jnnp-2011-301308","volume":"83","author":"A Charidimou","year":"2012","unstructured":"Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry. 2012;83(2):124\u201337. https:\/\/doi.org\/10.1136\/jnnp-2011-301308.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"6","key":"864_CR8","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1002\/ana.22516","volume":"70","author":"A Viswanathan","year":"2011","unstructured":"Viswanathan A, Greenberg SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol. 2011;70(6):871\u201380. https:\/\/doi.org\/10.1002\/ana.22516.","journal-title":"Ann Neurol"},{"issue":"4","key":"864_CR9","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1002\/ana.23654","volume":"72","author":"DA Bennett","year":"2012","unstructured":"Bennett DA, Wilson RS, Boyle PA, Buchman AS, Schneider JA. Relation of neuropathology to cognition in persons without cognitive impairment. Ann Neurol. 2012;72(4):599\u2013609. https:\/\/doi.org\/10.1002\/ana.23654.","journal-title":"Ann Neurol"},{"issue":"24","key":"864_CR10","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1212\/01.wnl.0000271090.28148.24","volume":"69","author":"JA Schneider","year":"2007","unstructured":"Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197\u2013204. https:\/\/doi.org\/10.1212\/01.wnl.0000271090.28148.24.","journal-title":"Neurology"},{"issue":"Pt 9","key":"864_CR11","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.1093\/brain\/awt188","volume":"136","author":"JB Toledo","year":"2013","unstructured":"Toledo JB, Arnold SE, Raible K, et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer\u2019s Coordinating Centre. Brain. 2013;136(Pt 9):2697\u2013706. https:\/\/doi.org\/10.1093\/brain\/awt188.","journal-title":"Brain"},{"issue":"4","key":"864_CR12","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1177\/0891988705281872","volume":"18","author":"L White","year":"2005","unstructured":"White L, Small BJ, Petrovitch H, et al. Recent clinical-pathologic research on the causes of dementia in late life: update from the Honolulu-Asia Aging Study. J Geriatr Psychiatry Neurol. 2005;18(4):224\u20137. https:\/\/doi.org\/10.1177\/0891988705281872.","journal-title":"J Geriatr Psychiatry Neurol"},{"issue":"5","key":"864_CR13","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/S1474-4422(17)30086-8","volume":"16","author":"LN The","year":"2017","unstructured":"The LN. Vascular disease and neurodegeneration: advancing together. Lancet Neurol. 2017;16(5):333. https:\/\/doi.org\/10.1016\/S1474-4422(17)30086-8.","journal-title":"Lancet Neurol"},{"issue":"6","key":"864_CR14","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.jalz.2014.10.008","volume":"11","author":"HM Snyder","year":"2015","unstructured":"Snyder HM, Corriveau RA, Craft S, et al. Vascular contributions to cognitive impairment and dementia including Alzheimer\u2019s disease. Alzheimers Dement. 2015;11(6):710\u20137. https:\/\/doi.org\/10.1016\/j.jalz.2014.10.008.","journal-title":"Alzheimers Dement"},{"issue":"9","key":"864_CR15","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1136\/jnnp.2004.054445","volume":"76","author":"DA Bennett","year":"2005","unstructured":"Bennett DA, Schneider JA, Wilson RS, Bienias JL, Berry-Kravis E, Arnold SE. Amyloid mediates the association of apolipoprotein E e4 allele to cognitive function in older people. J Neurol Neurosurg Psychiatry. 2005;76(9):1194\u20139. https:\/\/doi.org\/10.1136\/jnnp.2004.054445.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"2","key":"864_CR16","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1212\/01.WNL.0000042478.08543.F7","volume":"60","author":"DA Bennett","year":"2003","unstructured":"Bennett DA, Wilson RS, Schneider JA, et al. Apolipoprotein E epsilon4 allele, AD pathology, and the clinical expression of Alzheimer\u2019s disease. Neurology. 2003;60(2):246\u201352.","journal-title":"Neurology"},{"issue":"2","key":"864_CR17","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1097\/WAD.0b013e318190a855","volume":"23","author":"JA Mortimer","year":"2009","unstructured":"Mortimer JA, Snowdon DA, Markesbery WR. The effect of APOE-epsilon4 on dementia is mediated by Alzheimer neuropathology. Alzheimer Dis Assoc Disord. 2009;23(2):152\u20137.","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"4","key":"864_CR18","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1037\/a0031642","volume":"28","author":"L Yu","year":"2013","unstructured":"Yu L, Boyle P, Schneider JA, et al. APOE epsilon4, Alzheimer\u2019s disease pathology, cerebrovascular disease, and cognitive change over the years prior to death. Psychol Aging. 2013;28(4):1015\u201323. https:\/\/doi.org\/10.1037\/a0031642.","journal-title":"Psychol Aging"},{"issue":"9","key":"864_CR19","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1093\/aje\/kwk115","volume":"165","author":"TB Harris","year":"2007","unstructured":"Harris TB, Launer LJ, Eiriksdottir G, et al. Age, gene\/environment susceptibility-Reykjavik study: multidisciplinary applied phenomics. Am J Epidemiol. 2007;165(9):1076\u201387. https:\/\/doi.org\/10.1093\/aje\/kwk115.","journal-title":"Am J Epidemiol"},{"issue":"4","key":"864_CR20","doi-asserted-by":"publisher","first-page":"3862","DOI":"10.1016\/j.neuroimage.2011.11.024","volume":"59","author":"S Sigurdsson","year":"2012","unstructured":"Sigurdsson S, Aspelund T, Forsberg L, et al. Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study. Neuroimage. 2012;59(4):3862\u201370. https:\/\/doi.org\/10.1016\/j.neuroimage.2011.11.024.","journal-title":"Neuroimage"},{"issue":"22","key":"864_CR21","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1212\/wnl.0000000000003983","volume":"88","author":"J Ding","year":"2017","unstructured":"Ding J, Sigur\u00f0sson S, J\u00f3nsson PV, et al. Space and location of cerebral microbleeds, cognitive decline, and dementia in the community. Neurology. 2017;88(22):2089\u201397. https:\/\/doi.org\/10.1212\/wnl.0000000000003983.","journal-title":"Neurology"},{"issue":"6","key":"864_CR22","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1001\/jamaneurol.2015.0174","volume":"72","author":"J Ding","year":"2015","unstructured":"Ding J, Sigurdsson S, Garcia M, et al. Risk factors associated with incident cerebral microbleeds according to location in older people. JAMA Neurol. 2015;72(6):682. https:\/\/doi.org\/10.1001\/jamaneurol.2015.0174.","journal-title":"JAMA Neurol"},{"issue":"24","key":"864_CR23","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1212\/wnl.0b013e3182020349","volume":"75","author":"C Qiu","year":"2010","unstructured":"Qiu C, Cotch MF, Sigurdsson S, et al. Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology. 2010;75(24):2221\u20138. https:\/\/doi.org\/10.1212\/wnl.0b013e3182020349.","journal-title":"Neurology"},{"key":"864_CR24","doi-asserted-by":"crossref","unstructured":"Delis D, Kramer J, Kaplan E, Ober B. The California Verbal Learning Test: Research Edition, Adult Version. 1987, San Antonio, TX. The Psychological Corporation. 1987","DOI":"10.1037\/t15072-000"},{"key":"864_CR25","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1037\/0012-1649.27.5.763","volume":"27","author":"T Salthouse","year":"1991","unstructured":"Salthouse T, Babcock R. Decomposing adult age differences in executive function. Dev Psychol. 1991;27:763\u201376.","journal-title":"Dev Psychol"},{"issue":"6","key":"864_CR26","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1037\/h0054651","volume":"18","author":"JR Stroop","year":"1935","unstructured":"Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol. 1935;18(6):643.","journal-title":"J Exp Psychol"},{"key":"864_CR27","unstructured":"Wechsler D. Wechsler adult intelligence scale. Archives of Clinical Neuropsychology. 1955."},{"issue":"5","key":"864_CR28","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1159\/000106735","volume":"5","author":"TW Robbins","year":"1994","unstructured":"Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L, Rabbitt P. Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. Dementia. 1994;5(5):266\u201381. https:\/\/doi.org\/10.1159\/000106735.","journal-title":"Dementia"},{"issue":"9","key":"864_CR29","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1093\/aje\/kwk115","volume":"165","author":"TB Harris","year":"2007","unstructured":"Harris TB, Launer LJ, Eiriksdottir G, et al. Age, gene\/environment susceptibility-Reykjavik study: multidisciplinary applied phenomics. Am J Epidemiol. 2007;165(9):1076\u201387. https:\/\/doi.org\/10.1093\/aje\/kwk115.","journal-title":"Am J Epidemiol"},{"issue":"1","key":"864_CR30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1146\/annurev-publhealth-032315-021402","volume":"37","author":"TJ VanderWeele","year":"2016","unstructured":"VanderWeele TJ. Mediation analysis: a practitioner\u2019s guide. Annu Rev Public Health. 2016;37(1):17\u201332. https:\/\/doi.org\/10.1146\/annurev-publhealth-032315-021402.","journal-title":"Annu Rev Public Health"},{"key":"864_CR31","doi-asserted-by":"crossref","unstructured":"VanderWeele T. Explanation in causal inference: methods for mediation and interaction: Oxford University Press; 2015.","DOI":"10.1093\/ije\/dyw277"},{"issue":"2","key":"864_CR32","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1037\/a0031034","volume":"18","author":"L Valeri","year":"2013","unstructured":"Valeri L, Vanderweele TJ. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. Psychol Methods. 2013;18(2):137\u201350. https:\/\/doi.org\/10.1037\/a0031034.","journal-title":"Psychol Methods"},{"issue":"1","key":"864_CR33","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1515\/em-2012-0010","volume":"2","author":"TJ VanderWeele","year":"2014","unstructured":"VanderWeele TJ, Vansteelandt S. Mediation Analysis with Multiple Mediators. Epidemiol Method. 2014;2(1):95\u2013115.","journal-title":"Epidemiol Method"},{"issue":"5","key":"864_CR34","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1097\/EDE.0000000000000121","volume":"25","author":"TJ VanderWeele","year":"2014","unstructured":"VanderWeele TJ. A unification of mediation and interaction: a 4-way decomposition. Epidemiology. 2014;25(5):749\u201361. https:\/\/doi.org\/10.1097\/EDE.0000000000000121.","journal-title":"Epidemiology"},{"issue":"4","key":"864_CR35","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1097\/EDE.0b013e3181df191c","volume":"21","author":"TJ VanderWeele","year":"2010","unstructured":"VanderWeele TJ. Bias formulas for sensitivity analysis for direct and indirect effects. Epidemiology. 2010;21(4):540\u201351. https:\/\/doi.org\/10.1097\/EDE.0b013e3181df191c.","journal-title":"Epidemiology"},{"issue":"4","key":"864_CR36","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1097\/EDE.0b013e318258f5e4","volume":"23","author":"TJ VanderWeele","year":"2012","unstructured":"VanderWeele TJ, Valeri L, Ogburn EL. The role of measurement error and misclassification in mediation analysis: mediation and measurement error. Epidemiology. 2012;23(4):561\u20134. https:\/\/doi.org\/10.1097\/EDE.0b013e318258f5e4.","journal-title":"Epidemiology"},{"issue":"7","key":"864_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041636","volume":"7","author":"CA Hawkes","year":"2012","unstructured":"Hawkes CA, Sullivan PM, Hands S, Weller RO, Nicoll JAR, Carare RO. Disruption of arterial perivascular drainage of amyloid-\u03b2 from the brains of mice expressing the human APOE \u03b54 Allele. PLoS ONE. 2012;7(7): e41636. https:\/\/doi.org\/10.1371\/journal.pone.0041636.","journal-title":"PLoS ONE"},{"issue":"2","key":"864_CR38","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/s0197-4580(00)00097-x","volume":"21","author":"K Horsburgh","year":"2000","unstructured":"Horsburgh K, McCarron MO, White F, Nicoll JAR. The role of apolipoprotein E in Alzheimer\u2019s disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models. Neurobiol Aging. 2000;21(2):245\u201355. https:\/\/doi.org\/10.1016\/s0197-4580(00)00097-x.","journal-title":"Neurobiol Aging"},{"issue":"7806","key":"864_CR39","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","volume":"581","author":"A Montagne","year":"2020","unstructured":"Montagne A, Nation DA, Sagare AP, et al. APOE4 leads to blood\u2013brain barrier dysfunction predicting cognitive decline. Nature. 2020;581(7806):71\u20136. https:\/\/doi.org\/10.1038\/s41586-020-2247-3.","journal-title":"Nature"},{"issue":"8","key":"864_CR40","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","volume":"12","author":"JM Wardlaw","year":"2013","unstructured":"Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822\u201338. https:\/\/doi.org\/10.1016\/S1474-4422(13)70124-8.","journal-title":"Lancet Neurol"},{"issue":"7","key":"864_CR41","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/s1474-4422(10)70104-6","volume":"9","author":"L Pantoni","year":"2010","unstructured":"Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9(7):689\u2013701. https:\/\/doi.org\/10.1016\/s1474-4422(10)70104-6.","journal-title":"Lancet Neurol"},{"issue":"Pt 2","key":"864_CR42","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/brain\/awq321","volume":"134","author":"C Cordonnier","year":"2011","unstructured":"Cordonnier C, van der Flier WM. Brain microbleeds and Alzheimer\u2019s disease: innocent observation or key player? Brain\u202f: a journal of neurology. 2011;134(Pt 2):335\u201344. https:\/\/doi.org\/10.1093\/brain\/awq321.","journal-title":"Brain : a journal of neurology"},{"issue":"3","key":"864_CR43","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/alzrt263","volume":"6","author":"S Martinez-Ramirez","year":"2014","unstructured":"Martinez-Ramirez S, Greenberg SM, Viswanathan A. Cerebral microbleeds: overview and implications in cognitive impairment. Alzheimer\u2019s research & therapy. 2014;6(3):33. https:\/\/doi.org\/10.1186\/alzrt263.","journal-title":"Alzheimer's research & therapy"},{"issue":"3","key":"864_CR44","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1161\/strokeaha.110.607184","volume":"42","author":"MM Poels","year":"2011","unstructured":"Poels MM, Ikram MA, van der Lugt A, et al. Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study. Stroke. 2011;42(3):656\u201361. https:\/\/doi.org\/10.1161\/strokeaha.110.607184.","journal-title":"Stroke"},{"issue":"3","key":"864_CR45","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1136\/jnnp-2013-306485","volume":"85","author":"K Rannikmae","year":"2014","unstructured":"Rannikmae K, Kalaria RN, Greenberg SM, et al. APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis. J Neurol Neurosurg Psychiatry. 2014;85(3):300\u20135. https:\/\/doi.org\/10.1136\/jnnp-2013-306485.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"7","key":"864_CR46","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1001\/jamaneurol.2014.681","volume":"71","author":"JM Ringman","year":"2014","unstructured":"Ringman JM, Sachs MC, Zhou Y, Monsell SE, Saver JL, Vinters HV. Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease. JAMA Neurol. 2014;71(7):878\u201383. https:\/\/doi.org\/10.1001\/jamaneurol.2014.681.","journal-title":"JAMA Neurol"},{"issue":"24","key":"864_CR47","doi-asserted-by":"publisher","first-page":"e3331","DOI":"10.1212\/wnl.0000000000010852","volume":"95","author":"MJ Knol","year":"2020","unstructured":"Knol MJ, Lu D, Traylor M, et al. Association of common genetic variants with brain microbleeds. Neurology. 2020;95(24):e3331\u201343. https:\/\/doi.org\/10.1212\/wnl.0000000000010852.","journal-title":"Neurology"},{"issue":"6","key":"864_CR48","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1002\/ana.24369","volume":"77","author":"A Serrano-Pozo","year":"2015","unstructured":"Serrano-Pozo A, Qian J, Monsell SE, Betensky RA, Hyman BT. APOEepsilon2 is associated with milder clinical and pathological Alzheimer disease. Ann Neurol. 2015;77(6):917\u201329. https:\/\/doi.org\/10.1002\/ana.24369.","journal-title":"Ann Neurol"},{"issue":"4","key":"864_CR49","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1161\/01.STR.0000259816.31370.44","volume":"38","author":"R Lemmens","year":"2007","unstructured":"Lemmens R, Gorner A, Schrooten M, Thijs V. Association of apolipoprotein E epsilon2 with white matter disease but not with microbleeds. Stroke; a journal of cerebral circulation. 2007;38(4):1185\u20138. https:\/\/doi.org\/10.1161\/01.STR.0000259816.31370.44.","journal-title":"Stroke; a journal of cerebral circulation"},{"issue":"5","key":"864_CR50","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1212\/WNL.0b013e3182452928","volume":"78","author":"MM Poels","year":"2012","unstructured":"Poels MM, Ikram MA, van der Lugt A, et al. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology. 2012;78(5):326\u201333. https:\/\/doi.org\/10.1212\/WNL.0b013e3182452928.","journal-title":"Neurology"},{"issue":"1","key":"864_CR51","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1136\/jnnp.2009.176362","volume":"82","author":"M Schuur","year":"2011","unstructured":"Schuur M, van Swieten JC, Schol-Gelok S, et al. Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population. J Neurol Neurosurg Psychiatry. 2011;82(1):41\u20134. https:\/\/doi.org\/10.1136\/jnnp.2009.176362.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"8","key":"864_CR52","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1016\/j.neurobiolaging.2013.02.003","volume":"34","author":"J Barnes","year":"2013","unstructured":"Barnes J, Carmichael OT, Leung KK, et al. Vascular and Alzheimer\u2019s disease markers independently predict brain atrophy rate in Alzheimer\u2019s Disease Neuroimaging Initiative controls. Neurobiol Aging. 2013;34(8):1996\u20132002. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2013.02.003.","journal-title":"Neurobiol Aging"},{"issue":"3","key":"864_CR53","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1552-6569.2009.00370.x","volume":"20","author":"E Jouvent","year":"2010","unstructured":"Jouvent E, Viswanathan A, Chabriat H. Cerebral atrophy in cerebrovascular disorders. J Neuroimaging. 2010;20(3):213\u20138. https:\/\/doi.org\/10.1111\/j.1552-6569.2009.00370.x.","journal-title":"J Neuroimaging"},{"issue":"1","key":"864_CR54","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1002\/ana.25123","volume":"83","author":"PA Boyle","year":"2018","unstructured":"Boyle PA, Yu L, Wilson RS, Leurgans SE, Schneider JA, Bennett DA. Person-specific contribution of neuropathologies to cognitive loss in old age. Ann Neurol. 2018;83(1):74\u201383. https:\/\/doi.org\/10.1002\/ana.25123.","journal-title":"Ann Neurol"}],"container-title":["European Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-022-00864-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10654-022-00864-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-022-00864-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T22:02:38Z","timestamp":1658008958000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10654-022-00864-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,26]]},"references-count":54,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["864"],"URL":"https:\/\/doi.org\/10.1007\/s10654-022-00864-7","relation":{},"ISSN":["0393-2990","1573-7284"],"issn-type":[{"value":"0393-2990","type":"print"},{"value":"1573-7284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,26]]},"assertion":[{"value":"16 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No authors have any conflicts of interest relevant to this work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Data from the AGES study are available through collaboration under a Data Use Agreement with the Icelandic Heart Association (IHA) and an IRB approval in accordance with informed consent. For data access requests, interested researchers may contact: AGES_data_request@hjarta.is.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Code is available upon reasonable request from the corresponding author.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"All participants provided written consent for this study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics declarations"}},{"value":"The AGES-Reykjavik Study was approved by the Icelandic National Bioethics Committee (VSN: 00\u2013063), the Data Protection Authority and the institutional review board of the National Institute on Aging.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}