Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial

Area of Science:

• Neuroscience
• Gerontology
• Pharmacology

Background:

• Lithium deficiency is implicated in Alzheimer's disease pathogenesis.
• No prior randomized clinical trials have investigated lithium's impact on cognition, neuroimaging, and plasma biomarkers in mild cognitive impairment (MCI).

Purpose of the Study:

• To assess the feasibility, safety, and preliminary efficacy of lithium carbonate in delaying cognitive decline among older adults diagnosed with MCI.
• To establish effect size estimates for future research on low-dose lithium interventions for MCI.

Main Methods:

• A single-site, randomized, double-blind, placebo-controlled pilot feasibility trial involving 83 adults (aged 60+) with MCI.
• Participants received daily low-dose lithium carbonate or placebo for two years, with follow-up analyses using linear mixed-effects models.
• Six coprimary outcomes included cognitive performance (CVLT-II, BVMT-R, preclinical Alzheimer cognitive composite), hippocampal volume, cortical gray matter volume, and brain-derived neurotrophic factor.

Main Results:

• None of the six coprimary outcomes reached statistical significance.
• A trend suggested lithium may slow cognitive decline, with a 0.69 points/year difference in CVLT-II delayed recall compared to placebo (P=.05).
• Adverse events were similar between groups; no serious events were definitively treatment-related.

Conclusions:

• The pilot trial demonstrated that low-dose lithium carbonate is feasible, safe, and tolerable for individuals with MCI.
• While not statistically significant, the study provides valuable effect size estimates and suggests a potential benefit for lithium in slowing cognitive decline, warranting further investigation.