{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:12:52Z","timestamp":1789560772227,"version":"build-2803163510"},"reference-count":29,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T00:00:00Z","timestamp":1558915200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2019,6,18]]},"abstract":"\n Background:<\/jats:title>\n The efficacy and safety of glycogen synthase kinase 3 (GSK-3) inhibitors in patients with Alzheimer\u2019s disease (AD) is unknown.<\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n A systematic review and meta-analysis of randomized controlled trials (RCTs) to test GSK-3 inhibitors on AD patients.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n We included RCTs of GSK-3 inhibitors in AD patients and subjects with mild cognitive impairment (MCI), using cognitive function scores as a primary measure.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Five RCTs (three RCTs using lithium and two RCTs using tideglusib) with 568 patients were included. There was no significant difference in cognitive function scores between the GSK-3 inhibitors and placebo groups [standardized mean difference (SMD)\u200a=\u200a\u20130.25, p\u200a=\u200a0.11, I\n 2<\/jats:sup>\n \u200a=\u200a55% ]. However, significant heterogeneity remained. A sensitivity analysis revealed that the lithium subgroup was more effective on cognitive function scores than placebo for AD and MCI (lithium subgroup: SMD\u200a=\u200a\u20130.41, p\u200a=\u200a0.04; tideglusib subgroup: SMD\u200a=\u200a\u20130.02, p\u200a=\u200a0.89). Moreover, a meta-regression analysis showed that the effect size of GSK-3 inhibitors on cognitive function scores was associated with study duration (coefficient, \u20130.0116). For safety outcomes, tideglusib was associated with a higher incidence of increased aspartate aminotransferase than placebo. There were no significant differences in other secondary outcomes between treatments.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Our results suggested that GSK-3 inhibitors were ineffective in treating AD and MCI; however, several studies included in the present meta-analysis were small, and future studies using a larger sample size are needed.<\/jats:p>\n <\/jats:sec>","DOI":"10.3233\/jad-190256","type":"journal-article","created":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T12:22:31Z","timestamp":1559046151000},"page":"1031-1039","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":51,"title":["Efficacy and Safety of Glycogen Synthase Kinase 3 Inhibitors for Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis"],"prefix":"10.1177","volume":"69","author":[{"given":"Shinji","family":"Matsunaga","sequence":"first","affiliation":[{"name":"Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, Kutsukake, Toyoake, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshige","family":"Fujishiro","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Kawasaki Memorial Hospital, Miyamae, Kawasaki, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Takechi","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, Kutsukake, Toyoake, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,5,27]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00062-4"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01124-1"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033118"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.11.103"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.10.018"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.1.27"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05194.x"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.08.130"},{"key":"ref009","first-page":"533","volume":"11","author":"Medina M","year":"2008","journal-title":"Curr Opin Drug Discov Devel"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.08m04606"},{"key":"ref011","first-page":"104","volume":"10","author":"Nunes MA","year":"2013","journal-title":"Curr Alzheimer Res"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.110.080044"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-120805"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141959"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150437"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.141.11.1356"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.12.2308"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1992.00530360051017"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyx012"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610217002344"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.306472"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1004-07.2007"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00297"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61516-X"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2015.2014"},{"key":"ref029","first-page":"MR000033","volume":"2","author":"Lundh A","year":"2017","journal-title":"Cochrane Database Syst Rev"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190256","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-190256","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:09:48Z","timestamp":1777370988000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-190256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,27]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,6,18]]}},"alternative-id":["10.3233\/JAD-190256"],"URL":"https:\/\/doi.org\/10.3233\/jad-190256","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,27]]}}}