{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:18:56Z","timestamp":1785417536508,"version":"3.56.0"},"reference-count":0,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"unspecified","delay-in-days":159,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Spectr."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cognitive impairment is a major determinant of disability in bipolar disorder (BD) and a defining feature of both mild cognitive impairment (MCI) and Alzheimer\u2019s disease (AD). Lithium, a first-line maintenance treatment for BD, is implicated in neuroprotective mechanisms including glycogen synthase kinase-3\u03b2 inhibition, amyloid and tau modulation, and neurogenesis promotion. The overarching aim of this systematic review is to evaluate the long-term effects of lithium on cognition across BD, MCI, and early-to-moderate AD using randomized controlled trial (RCT) evidence. Online databases were searched from inception through May 2025 for RCTs reporting lithium\u2019s effect on cognitive outcomes in BD, MCI, or early-to-moderate AD with \u22658\u00a0weeks of follow-up. Risk of bias was assessed using the Cochrane RoB 2 tool. Eight RCTs met the inclusion criteria, ranging from 10\u00a0weeks to 3\u00a0years in duration. Across four BD trials, lithium did not exhibit consistent improvement or worsening on composite cognitive scores. Three of four MCI\/AD trials reported attenuated global cognitive deterioration with low-dose lithium, especially when exposure was \u226512\u00a0months. Methodological limitations included small sample sizes, exploratory endpoints, and variable measures for cognitive function as well as lithium strategies. Lithium demonstrates preliminary signals of slower cognitive decline in MCI\/AD. Available evidence suggests lithium has neutral effects on cognitive impairment in BD. Future adequately powered RCTs with cognition as a primary endpoint, functional measures, and biomarker outcomes are warranted to clarify lithium\u2019s role as a maintenance treatment in psychiatric disorders and its potential neuroprotective effects in neurodegenerative diseases.<\/jats:p>","DOI":"10.1017\/s1092852926100996","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:54:55Z","timestamp":1780998895000},"source":"Crossref","is-referenced-by-count":0,"title":["Lithium and long-term cognitive outcomes in bipolar disorder and early dementia: a systematic review"],"prefix":"10.1017","volume":"31","author":[{"given":"Rosalyn","family":"Deng","sequence":"first","affiliation":[{"name":"Queen\u2019s University Faculty of Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Shargorodsky","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-6563","authenticated-orcid":false,"given":"Kayla","family":"Teopiz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto Institute of Medical Science"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Dri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Wong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042xt5161","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network"},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gia Han","family":"Le","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto Institute of Medical Science"},{"id":[{"id":"https:\/\/ror.org\/042xt5161","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3238-696X","authenticated-orcid":false,"given":"Yang Jing","family":"Zheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto Institute of Medical Science"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4733-2523","authenticated-orcid":false,"given":"Roger S.","family":"McIntyre","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto"},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2026,6,9]]},"container-title":["CNS Spectrums"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1092852926100996","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T08:05:50Z","timestamp":1782720350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1092852926100996\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026]]}},"alternative-id":["S1092852926100996"],"URL":"https:\/\/doi.org\/10.1017\/s1092852926100996","relation":{},"ISSN":["1092-8529","2165-6509"],"issn-type":[{"value":"1092-8529","type":"print"},{"value":"2165-6509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"e18"}}