Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial
Open accessAbstract
Background: Experimental studies indicate that lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of lithium to treat or prevent dementia. Aims: To determine the benefits of lithium treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease. Method: A total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25–0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale – cognitive subscale) and functional (Clinical Dementia Rating – Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0–48 months). Results: Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years. Lithium treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (Aβ 1−42 ) after 36 months. Conclusions: Long-term lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of lithium in the MCI–Alzheimer's disease continuum. Declaration of interest: None.
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Long-term lithium treatment at subtherapeutic doses attenuates cognitive and functional decline in amnestic MCI.
“Forlenza et al. reported that long-term lithium treatment at subtherapeutic doses attenuates cognitive and functional decline in amnestic MCI (ClinicalTrials.gov Identifier: NCT01055392) [214].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [214]
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A systematic analysis of neurobiological roles of lithium
Викторовна, Г. И., Громова, О. А., Torshin, I. Y., Гришина, Т. Р., & Пронин, А. В. (2022) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202212211117 · Cited by 7 · see citing works
- Authors
- Forlenza, O. V., Radanovic, M., Talib, L. L., & Gattaz, W. F.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Forlenza, Orestes V.
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2019-04-05
- Volume
- 215
- Issue
- 5
- Pages
- 668-674
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2932882403
- Cited by
- 171
- References
- 25
- Citations by year
- 2026: 30 · 2025: 22 · 2024: 24 · 2023: 20 · 2022: 33 · 2021: 21 · 2020: 10 · 2019: 10
- FWCI
- 14.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association (NIRG-08-90688)
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (554535/2005-0)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- lithium, amnestic mild cognitive impairment, Alzheimer's disease, dementia prevention, cognitive decline, functional decline, cerebrospinal fluid biomarkers, amyloid-beta 42, disease-modifying therapy, older adults, attention and memory
- MeSH terms
- Aged, Alzheimer Disease, Humans, Lithium, Neuropsychological Tests, Biomarkers, Amyloid beta-Peptides, Disease Progression, Cognitive Dysfunction
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