JAMA Neurol

Pilot study finds modest memory effect of low-dose lithium in mild cognitive impairment

March 4, 2026

In a single-site, randomized, double-blind pilot trial (NCT03185208) of adults ≥60 years with mild cognitive impairment, low-dose lithium was feasible, safe, and well tolerated over two years. Although none of the six prespecified coprimary outcomes (encompassing cognitive performance, hippocampal volume, cortical gray matter volume, and brain-derived neurotrophic factor) met significance, lithium was associated with a smaller annual decline in California Verbal Learning Test-II (CVLT-II) delayed recall (0.73 vs. 1.42 points with placebo; difference 0.69 points/year; P=0.05). Neuroimaging outcomes showed similar rates of hippocampal and cortical atrophy across groups. Adverse events were common but comparable between arms, with no definitive lithium-related serious events.

Clinical takeaway: While not ready for clinical use, low-dose lithium’s modest cognitive signal supports larger, biomarker-enriched trials.

Source:

Gildengers AG, et al. (2026, March 2). JAMA Neurol. Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41770546/