{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:21:26Z","timestamp":1791976886090,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We investigated the moderating effects of midlife and late\u2010life cognitive activity (CA) on the relationship between tau pathology and both cognition and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Eighty\u2010nine non\u2010demented older adults from a Korean cohort underwent comprehensive evaluations, including CA assessments and tau neuroimaging at baseline, and Mini\u2010Mental State Examination (MMSE) at baseline and the 2\u2010year follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Greater midlife CA was associated with higher MMSE scores in a given amount of tau pathology, whereas higher levels of midlife CA were associated with faster tau\u2010related decline in MMSE scores, particularly in individuals with mild cognitive impairment. Late\u2010life CA did not exhibit any interaction with tau on either MMSE scores or their 2\u2010year change.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Greater midlife CA is generally associated with better cognitive performance despite the presence of tau pathology. However, paradoxically, increased midlife CA appears to be linked to a more rapid tau\u2010related cognitive decline in already cognitively impaired individuals.<\/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>Greater midlife cognitive activity (CA) was generally associated with better cognitive performance in a given amount of tau pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Paradoxically, higher levels of midlife CA were related to a more rapid tau\u2010related cognitive decline in already cognitively impaired individuals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Late\u2010life CA did not exhibit any moderation effect on the association between tau and cognitive performance or decline.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14606","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:09:51Z","timestamp":1741727391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Moderation of midlife cognitive activity on tau\u2010related cognitive impairment"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9457-3456","authenticated-orcid":false,"given":"Kang","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Psychiatry Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Psychiatry National Health Insurance Service Ilsan Hospital  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0860-0946","authenticated-orcid":false,"given":"Dahyun","family":"Yi","sequence":"additional","affiliation":[{"name":"Institute of Human Behavioral Medicine Medical Research Center Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3159-4510","authenticated-orcid":false,"given":"Min Soo","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Neuropsychiatry Seoul National University Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Hyung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Chungbuk National University Hospital  Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9095-1701","authenticated-orcid":false,"given":"Nayeong","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Keimyung University Dongsan Hospital  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5952-3373","authenticated-orcid":false,"given":"Gijung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Seoul National University Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyejin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Seoul National University Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0279-1880","authenticated-orcid":false,"given":"Yoon Young","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Inje University Sanggye Paik Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0855-8637","authenticated-orcid":false,"given":"Musung","family":"Keum","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Seoul National University Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-3124","authenticated-orcid":false,"given":"Jun\u2010Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Neuropsychiatry SMG\u2010SNU Boramae Medical Center  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-2090","authenticated-orcid":false,"given":"Yun\u2010Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Seoul National University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3282-822X","authenticated-orcid":false,"given":"Yu Kyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine SMG\u2010SNU Boramae Medical Center  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-8320","authenticated-orcid":false,"given":"Dong Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Human Behavioral Medicine Medical Research Center Seoul National University  Seoul Republic of Korea"},{"name":"Department of Neuropsychiatry Seoul National University Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the KBASE Research Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26417"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.13793"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617705050459"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.3822"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000271087.67782.cb"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007021"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.23690"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1941"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.2748"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.01.023"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910\u2010019\u20100917\u2010z"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70191\u20106"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200675"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005303"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu393"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.10.005"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13355"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4306\/pi.2017.14.6.851"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.11.2412-a"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JALZ.2011.03.008"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617704101094"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/geronb\/57.1.P47"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181523"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140\u20106736(91)92823\u2010K"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy347"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24546"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010006\u20100127\u2010z"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900345106"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.01.013"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000435556.21319.e4"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2015.03.001"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097\u20100258(20000615\/30)19:11\/12<1607::aid\u2010sim449>3.0.co;2\u2010o"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682\u2010016\u20109640\u20104"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.05.004"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010019\u201004342\u20103"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010017\u20100078\u20104"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.09.002"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007821"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.04.002"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1809"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(17)30077\u20107"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010022\u201000521\u20103"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.36510"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1076\/jcen.25.5.634.14572"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532\u20105415.1992.tb01992.x"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14606","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.14606","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14606","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:40:45Z","timestamp":1789558845000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/alz.14606"],"URL":"https:\/\/doi.org\/10.1002\/alz.14606","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14606"}}