{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:48:54Z","timestamp":1787312934347,"version":"build-2736575974"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R13 AG030995"],"award-info":[{"award-number":["R13 AG030995"]}],"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":["T32AG000247"],"award-info":[{"award-number":["T32AG000247"]}],"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":["K99AG065501"],"award-info":[{"award-number":["K99AG065501"]}],"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":["R01AG072475"],"award-info":[{"award-number":["R01AG072475"]}],"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":["R01AG059727"],"award-info":[{"award-number":["R01AG059727"]}],"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":["P30AG066546"],"award-info":[{"award-number":["P30AG066546"]}],"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":["P30AG010161"],"award-info":[{"award-number":["P30AG010161"]}],"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":["P30AG072975"],"award-info":[{"award-number":["P30AG072975"]}],"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":["R01AG015819"],"award-info":[{"award-number":["R01AG015819"]}],"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":["R01AG17917"],"award-info":[{"award-number":["R01AG17917"]}],"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":["R01AG022018"],"award-info":[{"award-number":["R01AG022018"]}],"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":["RF1AG054617"],"award-info":[{"award-number":["RF1AG054617"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UF1NS125513"],"award-info":[{"award-number":["UF1NS125513"]}],"id":[{"id":"10.13039\/100000002","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":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late\u2010life cognition through Alzheimer's disease (AD) and non\u2010AD neuropathologies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS\/MAP\/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (A\u03b2), neurofibrillary tangles), vascular (athero\/arteriolo\u2010sclerosis, micro\u2010infarcts\/macro\u2010infarcts), and non\u2010AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP\u201043], Lewy bodies, amyloid angiopathy, hippocampal sclerosis).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The detrimental effect of\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 on cognition was mediated by summary measures of AD and non\u2010AD neurodegenerative neuropathologies but not vascular neuropathologies; effects were strongest in individuals with dementia. The protective effect of APOE \u03b52 was partly mediated by AD neuropathology and stronger in women than in men.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype influences cognition and dementia through multiple neuropathological pathways, with implications for different therapeutic strategies targeting people at increased risk for dementia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Both apolipoprotein E (\n                            <jats:italic>APOE<\/jats:italic>\n                            ) \u03b52 and\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b54 effects on late\u2010life cognition are mediated by AD neuropathology.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The estimated mediated effects of most measures of AD neuropathology were similar.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Non\u2013Alzheimer's disease (AD) neurodegenerative pathologies mediate the effect of \u03b54 independently from AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Non\u2010AD vascular pathologies did not mediate the effect of the\n                            <jats:italic>APOE<\/jats:italic>\n                            genotype on cognition.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The protective effect of\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b52 on cognition was stronger in women.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.12885","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T12:00:01Z","timestamp":1671019201000},"page":"2508-2519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["AD and non\u2010AD mediators of the pathway between the\n                    <i>APOE<\/i>\n                    genotype and cognition"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-3872","authenticated-orcid":false,"given":"Emma","family":"Nichols","sequence":"first","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin B.","family":"Casaletto","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Dams\u2010O'Connor","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Human Performance Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences University of California Davis School of Medicine  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj G.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Human Performance Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Palta","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Epidemiology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Rabin","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre University of Toronto  Toronto Canada"},{"name":"Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program Sunnybrook Research Institute  Toronto Ontario Canada"},{"name":"Rehabilitation Sciences Institute University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L.","family":"Satizabal","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Biggs Institute for Alzheimer's and Neurodegenerative Diseases UT Health San Antonio  San Antonio Texas USA"},{"name":"Department of Neurology Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Schneider","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center  Chicago Illinois USA"},{"name":"Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Pa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"La Joie","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000149643.91367.8A"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1977"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000128091.92139.0F"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.026"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010016\u20100361\u20104"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24369"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws127"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.054445"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010150252"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307023"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt034"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.8.1.1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.14.9.1412"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1999.0273"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306923200"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.155"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30251\u20105"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glaa247"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010021\u201000458\u20103"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318190a855"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2730"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010publhealth\u2010032315\u2010021402"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12173"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.09.010"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000431"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2018.06.004"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glaa116"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.0821"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.237"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197\u20104580(97)00057\u20102"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.7275\/4vng\u20105608"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102012\u2010303898"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2002.tb04797.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010179939"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1214\/09-SS057"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199203000-00013"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102009\u20101158"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010160365"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102288\u201012\u201021"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000126908"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31829a25b9"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540340047031"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072\u2010199702000\u201000007"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.1123"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt188"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010021\u201000503\u2010x"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201019786\u20107"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1385\/jmn:17:2:225"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24388"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010008\u20100366\u20102"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694\u2010180"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24135"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.12156"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.12.004"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.2188"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.08.002"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.04.011"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002939"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12050"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12213"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1159\/000511506"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883\u2010014\u20100169\u20100"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.48"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12242"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(09)70299\u20106"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010021\u201000855\u2010y"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617722000030"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12885","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.12885","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12885","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:54:06Z","timestamp":1759971246000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/alz.12885"],"URL":"https:\/\/doi.org\/10.1002\/alz.12885","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]},"assertion":[{"value":"2022-08-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}