Lithium, a treatment long used for bipolar disorder, may offer neuroprotective effects that extend beyond mood stabilisation. An exploratory clinical trial conducted by the University of Pittsburgh suggests that low-dose oral lithium could help slow the decline of verbal memory—the ability to remember and recall words and sentences—in older adults with mild cognitive impairment. The potential benefit appeared most pronounced among individuals with evidence of amyloid beta, a key biomarker associated with Alzheimer’s disease.
The study, published in JAMA Neurology on 2 March, was designed to address an important early-stage question: whether lithium shows enough promise to justify a larger clinical trial focused on slowing cognitive decline linked to Alzheimer’s disease. While lithium has been studied for decades in psychiatric contexts, its possible role in neurodegeneration remains an area of active investigation.
The research was led by Dr Ariel Gildengers, a professor of psychiatry at the University of Pittsburgh and a geriatric psychiatrist at UPMC. His previous work found that older adults with bipolar disorder who used lithium over long periods tended to show signs of better brain integrity. These earlier findings provided the scientific basis for testing whether lithium’s apparent protective effects on the brain might also apply beyond mood disorders.
To explore this question, the research team designed a two-year clinical trial involving adults aged 60 and above who had mild cognitive impairment. Participants were randomly assigned to receive either a low dose of lithium or a placebo. Over the course of the study, which concluded in August 2024, participants underwent annual evaluations that included detailed cognitive assessments, high-resolution brain imaging, and analysis of biological markers associated with Alzheimer’s disease.
The results indicated that those receiving lithium experienced a slower rate of decline in verbal memory, a cognitive function that is often affected early in Alzheimer’s disease. Although the findings were not definitive, they were considered encouraging, particularly in this domain. Brain imaging revealed that the hippocampus, a region essential for memory, decreased in size over time in both groups. However, exploratory analyses suggested that participants with amyloid beta showed potentially greater benefit from lithium, hinting at a biological effect that warrants further study. Importantly, the treatment was found to be safe and well-tolerated when carefully monitored.
One limitation of the study was that participants were selected based on clinical symptoms rather than confirmed amyloid status, as blood-based diagnostic tools were not widely available when the trial began. This may have reduced the ability to detect stronger effects. Future research aims to address this by using modern biomarker testing to enrol participants more precisely. Researchers are now seeking support for a larger trial that could determine whether lithium can meaningfully delay cognitive decline and neurodegeneration. While the current findings are preliminary, they suggest that further investigation is both feasible and justified.
More information: Ariel Gildengers et al, Low-Dose Lithium for Mild Cognitive Impairment A Pilot Randomized Clinical Trial, JAMA Neurology. DOI: 10.1001/jamaneurol.2026.0072
Journal information: JAMA Neurology Provided by University of Pittsburgh
