{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:37:16Z","timestamp":1790116636802,"version":"4.0.1"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171197"],"award-info":[{"award-number":["82171197"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021177","name":"Shenzhen Bay Laboratory","doi-asserted-by":"publisher","award":["S241101004\u20101"],"award-info":[{"award-number":["S241101004\u20101"]}],"id":[{"id":"10.13039\/501100021177","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":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) patients with higher educational attainment (EA) often exhibit better cognitive function. However, the relationship among EA status, AD pathology, structural brain reserve, and cognitive decline requires further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We compared cognitive performance across different amyloid beta (A\u03b2) positron emission tomography (A\u00a0\u00b1) statuses and EA levels (High EA\/Low EA). We examined the effects of A\u03b2 plaques, tau tangles, and gray matter volume (GMV) on the relationship between EA and domain\u2010specific cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>A+\/High\u2010EA individuals exhibited slower cognitive decline in global cognition and language domains than A+\/Low\u2010EA individuals. This cognitive benefit was independently and synergistically explained by reduced AD pathology, including lower A\u03b2 and tau burdens, as well as preserved GMV. Additionally, High\u2010EA individuals experienced a median delay of 1.9 years in the onset of significant brain atrophy among A+ individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings highlight the independent and synergistic contributions of EA\u2010associated AD pathology and GMV alterations to longitudinal cognitive decline.<\/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>Alzheimer's disease (AD) individuals with high educational attainment (EA) show slower declines in global cognition and language.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>EA\u2010related slower cognitive decline is linked to reduced tau and greater gray matter volume in AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>AD individuals with high EA show a median 1.9 year delayed onset of brain atrophy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14400","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T04:29:20Z","timestamp":1737692960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Educational attainment, A\u03b2, tau, and structural brain reserve in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Yue","family":"Cai","sequence":"first","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"},{"name":"Division of Life Science The Hong Kong University of Science and Technology  HKSAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"},{"name":"Department of Neurology Xuanwu Hospital of Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"},{"name":"School of Biomedical Engineering Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbo","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"},{"name":"School of Life Science and Technology Harbin Institute of Technology  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2956-8521","authenticated-orcid":false,"given":"Qingyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Shenzhen Guangming District People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-0865","authenticated-orcid":false,"given":"Tengfei","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Neurological and Psychiatric Disorders Shenzhen Bay Laboratory  Shenzhen China"},{"name":"Institute of Biomedical Engineering Shenzhen Bay Laboratory  Shenzhen China"},{"name":"Institute of Biomedical Engineering Peking University Shenzhen Graduate School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13439"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afae005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007036"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.05.013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000665\u20108"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24995"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.11.1509"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005303"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70191\u20106"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038268"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101551"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2009.10.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu035"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/aft150"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.10.013"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2005.072306"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617706060206"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12679"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0164027506294245"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010024\u201001458\u2010z"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181cb3e25"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.01.001"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2020.03.003"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.021"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209205"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010024\u201006835\u20102"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010023\u201001178\u2010w"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009216"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.803"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.06.029"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.05.017"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102702.2012.04178.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010191332"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afw107"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/geronb\/gbz053"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000341782.71418.6c"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910\u2010004\u20100084\u20107"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320311"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617711001044"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010171168"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201073911\u20106"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/1529100620920576"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30029\u20102"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.6669"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010314"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.01.023"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208053"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010019\u201004342\u20103"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/psyg.12552"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010190370"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.06.053"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140945"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.09.023"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00006.2019"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0296"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2668\u201018.2019"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101644118"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.14400","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:37:07Z","timestamp":1789558627000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/alz.14400"],"URL":"https:\/\/doi.org\/10.1002\/alz.14400","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,24]]},"assertion":[{"value":"2024-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14400"}}