The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2025
Efficacy and Safety of Lithium for Behavioral and Cognitive Symptoms in Alzheimer's Disease Dementia: A Systematic Review With Frequentist and Bayesian Meta-Analysis.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод в очереди
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Pereira da Silva Anderson Matheus, de Deus Ocilio, Ribeiro Filipe Virgilio, Tudella Gabriel Caruso Novaes, Cabeça Lucas Silva, Silva Levi Leal, Han Mariana Lee, Franco Julia Oliveira, Costa João Gabriel Pereira, Santos do Nascimento Maria da Vitória, Andrade Fernandes João Vitor, Franco Eryvelton de Souza, de Sousa Maia Maria Bernadete
Аннотация
BACKGROUND: Alzheimer's disease (AD) dementia is the leading cause of cognitive decline in late life, yet treatment options remain limited. Lithium, widely used in bipolar disorder, has been suggested to exert neuroprotective effects through inhibition of GSK-3β and modulation of amyloid and tau pathology. We aimed to evaluate the efficacy and safety of lithium in AD dementia.
METHODS: This systematic review and meta-analysis was prospectively registered in PROSPERO and conducted following PRISMA guidelines. We searched PubMed, Embase, and Cochrane Library through April 2025 for randomized controlled trials (RCTs) comparing lithium with placebo or standard therapy in patients with AD dementia or amnestic mild cognitive impairment. Outcomes included cognition (MMSE, ADAS-Cog, memory tasks), function (CDR-SB, conversion to AD), neuropsychiatric symptoms (NPI), CSF biomarkers, and safety (adverse events [AEs], serious AEs [SAEs]). Random-effects meta-analyses were complemented by Bayesian methods and trial sequential analyses.
RESULTS: Six RCTs involving 394 participants (196 lithium, 198 placebo) met inclusion criteria. Lithium did not significantly improve global cognition (MMSE: MD -1.61, 95% CI -4.11 to 0.88; ADAS-Cog: MD -1.82, -3.05 to -0.60; both with high heterogeneity). Memory outcomes were mixed, with possible benefit for figure recall but not delayed verbal recall. No consistent benefits were observed for episodic memory, functional outcomes (CDR-SB), neuropsychiatric symptoms, or CSF biomarkers. Safety analyses showed no increased risk of SAEs; drug-related AEs were more frequent but heterogeneous across trials.
CONCLUSIONS: Lithium demonstrated an acceptable safety profile within the dosing regimens studied. However, current evidence does not support consistent cognitive or functional benefits in AD dementia. Larger, well-designed RCTs are warranted to clarify its potential therapeutic role.
METHODS: This systematic review and meta-analysis was prospectively registered in PROSPERO and conducted following PRISMA guidelines. We searched PubMed, Embase, and Cochrane Library through April 2025 for randomized controlled trials (RCTs) comparing lithium with placebo or standard therapy in patients with AD dementia or amnestic mild cognitive impairment. Outcomes included cognition (MMSE, ADAS-Cog, memory tasks), function (CDR-SB, conversion to AD), neuropsychiatric symptoms (NPI), CSF biomarkers, and safety (adverse events [AEs], serious AEs [SAEs]). Random-effects meta-analyses were complemented by Bayesian methods and trial sequential analyses.
RESULTS: Six RCTs involving 394 participants (196 lithium, 198 placebo) met inclusion criteria. Lithium did not significantly improve global cognition (MMSE: MD -1.61, 95% CI -4.11 to 0.88; ADAS-Cog: MD -1.82, -3.05 to -0.60; both with high heterogeneity). Memory outcomes were mixed, with possible benefit for figure recall but not delayed verbal recall. No consistent benefits were observed for episodic memory, functional outcomes (CDR-SB), neuropsychiatric symptoms, or CSF biomarkers. Safety analyses showed no increased risk of SAEs; drug-related AEs were more frequent but heterogeneous across trials.
CONCLUSIONS: Lithium demonstrated an acceptable safety profile within the dosing regimens studied. However, current evidence does not support consistent cognitive or functional benefits in AD dementia. Larger, well-designed RCTs are warranted to clarify its potential therapeutic role.