{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:31:37Z","timestamp":1787164297190,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K10690"],"award-info":[{"award-number":["24K10690"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP15km0908001"],"award-info":[{"award-number":["JP15km0908001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21dk0207056"],"award-info":[{"award-number":["JP21dk0207056"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Despite the clinical importance and significant social burden of neuropsychiatric symptoms (NPS) in dementia, the underlying neurobiological mechanism remains poorly understood. Recently, neuroimaging\u2010derived brain\u2010age estimation by machine\u2010learning analysis has shown promise as an individual\u2010level biomarker. We investigated the relationship between NPS and brain\u2010age in amnestic mild cognitive impairment (MCI) and early dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this cross\u2010sectional study, clinical data, including neuropsychiatric inventory (NPI), and structural brain MRI of 499 individuals with clinical diagnoses of amnestic MCI (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u2009185), early Alzheimer's disease (AD) (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u2009258) or dementia with Lewy bodies (DLB) (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200956) were analyzed. We established a brain\u2010age prediction model using 694 healthy brain MRIs and a support vector regression model and applied it to the participants' data. Finally, the brain\u2010predicted age difference (brain\u2010PAD: predicted age minus chronological age) was calculated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All groups showed significantly increased brain\u2010PAD, and the median (IQR) brain\u2010PAD was 4.3 (5.4) years in MCI, 6.3 (6.2) years in AD, and 5.0 (6.5) years in DLB. The NPI scores were subdivided into the following four categories: (i) Agitation and Irritability, (ii) Depression and Apathy, (iii) Delusions and Hallucinations, and (iv) Euphoria and Disinhibition. We found a significantly positive correlation between brain\u2010PAD and the depression\/apathy factor (Spearman's rs\u2009=\u20090.156, FDR\u2010corrected\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002), whereas no significance was shown for the other NPS factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Higher brain\u2010age may be associated with depression and apathy symptoms presented in MCI to early dementia stages, and brain\u2010age analysis may be useful as a novel biomarker for the assessment or monitoring of NPS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pcn.13777","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T03:55:10Z","timestamp":1737086110000},"page":"158-164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neuropsychiatric symptoms and neuroimaging\u2010based brain age in mild cognitive impairment and early dementia: A multicenter study"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9617-706X","authenticated-orcid":false,"given":"Daichi","family":"Sone","sequence":"first","affiliation":[{"name":"Department of Psychiatry Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Beheshti","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Tagai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kameyama","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Takasaki","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Kashibayashi","sequence":"additional","affiliation":[{"name":"Nishi\u2010Harima Dementia\u2010Related Disease Medical Center Hyogo Prefectural Rehabilitation Hospital at Nishi\u2010Harima  Tatsuno Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Nishi\u2010Harima Dementia\u2010Related Disease Medical Center Hyogo Prefectural Rehabilitation Hospital at Nishi\u2010Harima  Tatsuno Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunari","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Radiology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3662-1469","authenticated-orcid":false,"given":"Hideki","family":"Kanemoto","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Osaka University Graduate School of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Osaka University Graduate School of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Shigeta","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-6141","authenticated-orcid":false,"given":"Shunichiro","family":"Shinagawa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kazui","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Kochi Medical School Kochi University  Kochi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000137689"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-1016"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2015.06.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2017.07.001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac133"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.01.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13076"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610221000934"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12154"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01576-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00789"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12111850"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067346"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.11.005"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.4470"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.5_Suppl_6.10S"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2004.01380.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.5.1113"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12189"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1109\/RBME.2021.3107372"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.102063"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1020"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2019.0617"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.08.020"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.12.001"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2011_181"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.13436"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1237"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/JGP.0b013e3181e898d0"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.12.1475"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1532-5415.2001.49282.x"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.JGP.0000235689.42910.0d"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2021.06.016"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610222001089"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.10.008"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/00048674221114597"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01793-5"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.03.014"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-017-1491-2"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.04.007"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.4037"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2734"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.006"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.3904"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giae049"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1749"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610205002930"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1194917"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.1133"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2023.120815"}],"container-title":["Psychiatry and Clinical Neurosciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcn.13777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:52:22Z","timestamp":1743727942000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcn.13777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/pcn.13777"],"URL":"https:\/\/doi.org\/10.1111\/pcn.13777","archive":["Portico"],"relation":{},"ISSN":["1323-1316","1440-1819"],"issn-type":[{"value":"1323-1316","type":"print"},{"value":"1440-1819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]},"assertion":[{"value":"2024-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}