{
  "abstract": "Cognitive impairment is a major determinant of disability in bipolar disorder (BD) and a defining feature of both mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Lithium, a first-line maintenance treatment for BD, is implicated in neuroprotective mechanisms including glycogen synthase kinase-3β 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’s effect on cognitive outcomes in BD, MCI, or early-to-moderate AD with ≥8 weeks of follow-up. Risk of bias was assessed using the Cochrane RoB 2 tool. Eight RCTs met the inclusion criteria, ranging from 10 weeks to 3 years 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 ≥12 months. 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’s role as a maintenance treatment in psychiatric disorders and its potential neuroprotective effects in neurodegenerative diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Queen’s University Faculty of Health Sciences, Canada",
    "Brain and Cognition Discovery Foundation, Canada",
    "Department of Human Biology, University of Toronto, Canada",
    "University of Toronto Institute of Medical Science, Canada",
    "Poul Hansen Family Centre for Depression, University Health Network, Canada",
    "Department of Pharmacology, University of Toronto, Canada",
    "Department of Psychiatry, University of Toronto, Canada"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Rosalyn Deng"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Alisa Shargorodsky"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Kayla Teopiz",
      "orcid": "0000-0001-8429-6563"
    },
    {
      "affs": [
        1
      ],
      "name": "Christine E. Dri"
    },
    {
      "affs": [
        4,
        5,
        1
      ],
      "name": "Sabrina Wong"
    },
    {
      "affs": [
        3,
        4,
        1
      ],
      "name": "Gia Han Le"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Yang Jing Zheng",
      "orcid": "0009-0001-3238-696X"
    },
    {
      "affs": [
        6,
        5
      ],
      "name": "Roger S. McIntyre",
      "orcid": "0000-0003-4733-2523"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/erge1qe4qhxyy.bib",
  "cited_by": 0,
  "doi": "10.1017/s1092852926100996",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732605/",
  "id": "erge1qe4qhxyy",
  "issns": [
    "1092-8529",
    "2165-6509"
  ],
  "landing_url": "https://doi.org/10.1017/s1092852926100996",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2738|Bipolar Disorder and Treatment"
    ]
  ],
  "openalex": "W7164051323",
  "pdf_url": "https://www.cambridge.org/core/services/aop-cambridge-core/content/view/5167B2A6DE3276122027C53296B8FF16/S1092852926100996a.pdf/div-class-title-lithium-and-long-term-cognitive-outcomes-in-bipolar-disorder-and-early-dementia-a-systematic-review-div.pdf",
  "pmcid": "PMC13732605",
  "pmid": "42261768",
  "published": "2026-06-09",
  "publisher": "Cambridge University Press",
  "ris": "https://research.draconitic.com/paper/erge1qe4qhxyy.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:34Z",
      "native_id": "PMC13732605",
      "source": "pmc",
      "url": "https://doi.org/10.1017/s1092852926100996"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Bipolar Disorder and Treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Lithium and long-term cognitive outcomes in bipolar disorder and early dementia: a systematic review",
  "title_text": "Lithium and long-term cognitive outcomes in bipolar disorder and early dementia: a systematic review",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:34Z",
  "url": "https://research.draconitic.com/paper/erge1qe4qhxyy",
  "venue": "CNS Spectrums",
  "versions": []
}