{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:24:44Z","timestamp":1793413484934,"version":"4.5.0"},"reference-count":54,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG072177"],"award-info":[{"award-number":["U01AG072177"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Ministry of Science, ICT, and Future Planning, Republic of Korea","award":["NRF-2014M3C7A1046042"],"award-info":[{"award-number":["NRF-2014M3C7A1046042"]}]},{"name":"the Ministry of Science, ICT, and Future Planning, Republic of Korea","award":["NRF-2020R1G1A1099652"],"award-info":[{"award-number":["NRF-2020R1G1A1099652"]}]},{"name":"the Ministry of Science, ICT, and Future Planning, Republic of Korea","award":["RS-2022-00165636"],"award-info":[{"award-number":["RS-2022-00165636"]}]},{"name":"the Ministry of Health & Welfare, Republic of Korea","award":["HI18C0630"],"award-info":[{"award-number":["HI18C0630"]}]},{"name":"the Ministry of Health & Welfare, Republic of Korea","award":["HI19C0149"],"award-info":[{"award-number":["HI19C0149"]}]},{"name":"the Ministry of Health & Welfare, Republic of Korea","award":["HU23C0140"],"award-info":[{"award-number":["HU23C0140"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Metformin has been proposed to have neuroprotective benefits, but its effects on AD-related brain changes remain unclear and may be influenced by apolipoprotein E \u03b54 (\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      ) genotype, a major genetic risk factor for AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To examine the association between metformin use and in vivo AD pathologies and to evaluate whether\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      status moderates these associations in older adults with type 2 diabetes mellitus (T2DM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This cross-sectional study used baseline data from 76 non-demented older adults with T2DM (aged 55\u201390 years), who were enrolled in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment and multimodal neuroimaging, including global amyloid- \u03b2 (A\u03b2) retention ([\n                      <jats:sup>11<\/jats:sup>\n                      C] PiB-PET), inferior temporal tau deposition ([\n                      <jats:sup>18<\/jats:sup>\n                      F] AV-1451 PET), AD-signature cortical thickness (AD-CT), and white matter hyperintensity (WMH) volume. Global cognition was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 76 participants, 55 (72%) were metformin users and 21 (28%) were non-users. Metformin use was significantly associated with greater AD-CT, but not with A\u03b2, tau, or WMH volume. A significant interaction between metformin use and\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      status was observed with respect to AD-CT. In\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      -stratified analyses, metformin use was significantly associated with greater AD-CT and better global cognition among\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      non-carriers, but not among carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that metformin use is associated with greater AD-CT\u2014independently of amyloid or tau pathology\u2014particularly among\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      non-carriers, and this structural preservation is accompanied by better cognitive outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261418688","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T06:59:46Z","timestamp":1772261986000},"page":"937-947","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>APOE4<\/i>\n                    -dependent association between metformin use and Alzheimer's disease\u2013related cortical thickness in older adults with type 2 diabetes"],"prefix":"10.1177","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-7397","authenticated-orcid":false,"given":"Minjae","family":"Kim","sequence":"first","affiliation":[{"name":"Soonchunhyang University Hospital"}],"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":"Seoul National University Hospital"},{"name":"Seoul National University College of Medicine"}],"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, Jongno-gu, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6613-4680","authenticated-orcid":false,"given":"Hyejin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Seoul National University College of Humanities"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5952-3373","authenticated-orcid":false,"given":"Gijung","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Jongno-gu, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1669-6113","authenticated-orcid":false,"given":"Joon Hyung","family":"Jung","sequence":"additional","affiliation":[{"name":"Chungbuk National University Hospital"}],"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":"Inje University, Sanggye Paik Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4325-5156","authenticated-orcid":false,"given":"Kyungtae","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-3963","authenticated-orcid":false,"given":"Hyeji","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0083-6134","authenticated-orcid":false,"given":"Jeongmin","family":"Choi","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-3124","authenticated-orcid":false,"given":"Jun-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"SMG-SNU Boramae Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9643-2008","authenticated-orcid":false,"given":"Koung Mi","family":"Kang","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0039-5746","authenticated-orcid":false,"given":"Chul-Ho","family":"Sohn","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-2090","authenticated-orcid":false,"given":"Yun-Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"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":"SMG-SNU Boramae Medical Center"}],"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":"Seoul National University Hospital"},{"name":"Seoul National University College of Medicine"},{"name":"Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Jongno-gu, Seoul, Republic of Korea"},{"name":"Seoul National University College of Humanities"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the KBASE Research Group *","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.5.661"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0048-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.06.010"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052687"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4349-5"},{"key":"e_1_3_3_7_2","article-title":"Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records","volume":"12","author":"William D","year":"2024","unstructured":"William D, Louis T, Rutendo M, et al. Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records. BMJ Open Diabetes Res Care 2024; 12: e003548.","journal-title":"BMJ Open Diabetes Res Care"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad366"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2022-003036"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2020.108496"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5014"},{"key":"e_1_3_3_12_2","article-title":"Metformin and risk of Alzheimer\u2019s disease among community-dwelling people with diabetes: a national case-control study","volume":"105","author":"Sluggett JK","year":"2019","unstructured":"Sluggett JK, Koponen M, Bell JS, et al. Metformin and risk of Alzheimer\u2019s disease among community-dwelling people with diabetes: a national case-control study. J Clin Endocrinol Metab 2019; 105: e963\u2013e972.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.622262"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tria.2024.100365"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-023-00469-1"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114613"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.03.016"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab131"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.09.008"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00761-9"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807991106"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-151200"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111890"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-0892"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-022-00568-6"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e7ca05"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.10"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.773797"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000202"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150493"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12161"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.4306\/pi.2017.14.6.851"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/geronb\/57.1.P47"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617704101094"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000130531.90205.EF"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000167607.63000.38"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92823-K"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy347"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0978"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900345106"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24546"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4409-12.2013"},{"key":"e_1_3_3_44_2","first-page":"1512","article-title":"Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people","volume":"70","author":"Wirth M","year":"2013","unstructured":"Wirth M, Villeneuve S, Haase CM, et al. Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people. JAMA Neurol 2013; 70: 1512\u20131519.","journal-title":"JAMA Neurol"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12983"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104011"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120538"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70188-0"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173290"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.12.009"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-017-2199-y"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1159\/000514431"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.003"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23974"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104795"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261418688","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877261418688","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261418688","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T10:21:04Z","timestamp":1778667664000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877261418688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":54,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1177\/13872877261418688"],"URL":"https:\/\/doi.org\/10.1177\/13872877261418688","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}