A Verdict on Low-Dose Lithium for Cognitive Preservation?
A pilot trial called LATTICE tested low-dose lithium carbonate in 79 adults aged 60+ with mild cognitive impairment (MCI) but failed to meet its six primary endpoints for cognition, brain volume, or biomarkers, though verbal memory decline was half as fast in the lithium group compared to placebo. Researchers, including lead investigator Ariel Gildengers from the University of Pittsburgh, called the results encouraging but not definitive, noting lithium may slow deterioration under certain conditions without improving memory or reversing impairment.
A pilot study called the Lithium as a Treatment to Prevent Impairment of Cognition in Elders (LATTICE) trial examined whether low-dose lithium carbonate could slow cognitive decline in older adults with mild cognitive impairment (MCI). The trial, led by Ariel Gildengers, MD, professor of psychiatry at the University of Pittsburgh School of Medicine, randomized 41 participants to lithium (mean age 72.9) and 39 to placebo (mean age 71.2). Over two years, participants received about 195 mg of lithium daily, roughly one-fifth the standard psychiatric dose, with serum levels around 0.17 mEq/L. None of the six primary endpoints—measuring cognition, brain volume, or plasma biomarkers—showed meaningful differences between groups. However, verbal memory scores on the California Verbal Learning Test-II declined 1.42 points per year in the placebo group versus 0.73 points in the lithium group, though this result did not meet the study’s prespecified significance threshold (*P* = .05). Hippocampal volume also trended favorably (*P* = .09) but was not statistically significant. Researchers confirmed low-dose lithium was safe and well-tolerated, with serious adverse events reported in 29% of the lithium group and 23% of the placebo group. Gildengers emphasized the findings do not prove lithium improves memory or reverses cognitive impairment, but they suggest it may slow decline under specific conditions. The study builds on decades of observational and epidemiological research linking lithium to lower dementia rates, including a 2025 *Nature* paper proposing Alzheimer’s disease might involve a lithium deficiency in the brain. Earlier observational work by Gildengers also showed better brain health in older bipolar patients on long-term lithium, raising questions about broader neuroprotective effects. While the results were mixed, experts say they could inform future trials. Some question whether the observed signal holds up, leaving the field with more questions than answers. Gildengers described the findings as encouraging but not definitive, calling for further investigation into lithium’s potential role in cognitive preservation.
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