Pittsburgh, PA – A recent pilot clinical trial conducted at the University of Pittsburgh School of Medicine has offered cautious insights into the potential of low-dose lithium carbonate in slowing cognitive decline associated with mild cognitive impairment (MCI). While the study, published in JAMA Neurology on March 2, 2026, did not meet pre-specified statistical significance thresholds, researchers found encouraging signals suggesting a possible benefit, particularly among individuals with evidence of amyloid beta, a biomarker linked to Alzheimer’s disease. The findings are prompting further investigation into whether this readily available and inexpensive medication could offer a new avenue for protecting cognitive function in at-risk populations.
The study, formally known as the Lithium as a Treatment to Prevent Impairment of Cognition in Elders (LATTICE) trial, involved 80 participants aged 60 and older diagnosed with MCI. Participants were randomly assigned to receive either a low dose of lithium carbonate or a placebo for two years. The average daily dose of lithium carbonate administered was 195 mg, resulting in an average blood lithium level of 0.17 mmol/l. Researchers meticulously monitored participants for safety and cognitive changes, utilizing advanced brain imaging and Alzheimer’s biomarkers to assess the drug’s impact.
Exploring Lithium’s Neuroprotective Potential
The rationale behind investigating lithium stems from prior research suggesting neuroprotective effects beyond its established role in treating bipolar disorder. Ariel Gildengers, professor of psychiatry at the University of Pittsburgh School of Medicine and a geriatric psychiatrist at UPMC, explained that previous studies had shown a correlation between long-term lithium use in older adults with bipolar disorder and better brain integrity. This observation fueled the hypothesis that lithium might possess properties capable of safeguarding cognitive function even in individuals without mood disorders.
“In a prior study, we observed that older adults with bipolar disorder who accept lithium long-term tend to show markers of better brain integrity,” Gildengers said. “The new question was whether those apparent neuroprotective effects might extend beyond mood disorders—and whether we could test that rigorously in a prospective clinical trial.”
The LATTICE study was designed as a pilot-feasibility trial, meaning it wasn’t powered to definitively prove lithium’s efficacy. Instead, its primary goals were to assess the safety and tolerability of low-dose lithium in older adults with MCI and to gather preliminary data to inform the design of larger, more conclusive trials. The research team, comprised of experts in brain imaging, Alzheimer’s biomarkers, and psychiatry, focused on six pre-specified outcomes, including cognitive performance, hippocampal volume, cortical gray matter volume, and levels of brain-derived neurotrophic factor.
Study Results: A Promising, Though Inconclusive, Trend
While none of the six primary outcomes reached the pre-defined statistical significance threshold, the study revealed a noteworthy trend. Verbal memory decline was approximately half the rate in the lithium group compared to the placebo group. Specifically, the study, as detailed in JAMA Neurology, showed that mean CVLT-II baseline scores were 7.95 (3.4) for the lithium group and 7.90 (3.9) for the placebo group; scores declined 1.42 points annually in the placebo group versus 0.73 points in the lithium group (difference, 0.69 points per year; 95% CI, 0.01-1.37; P = .05). This difference, while not statistically significant, suggests a potential slowing of verbal memory decline with lithium treatment.
Importantly, the study confirmed that low-dose lithium was safe and well-tolerated by the participants. This is a crucial finding, as concerns about potential side effects often limit the use of lithium, even in established clinical settings. Researchers emphasized that the trial generated valuable methodological insights and effect size estimates that will be instrumental in designing a larger, adequately powered confirmatory trial.
Understanding Mild Cognitive Impairment and Alzheimer’s Disease
Mild cognitive impairment (MCI) represents a stage between normal age-related cognitive decline and dementia. Individuals with MCI may experience noticeable problems with memory, thinking, or reasoning skills, but these difficulties are generally not severe enough to interfere significantly with daily life. However, MCI increases the risk of developing Alzheimer’s disease, a progressive neurodegenerative disorder that is the most common cause of dementia.
Alzheimer’s disease is characterized by the accumulation of amyloid plaques and tau tangles in the brain, leading to neuronal damage and cognitive decline. Amyloid beta is a protein fragment that clumps together to form plaques, while tau is a protein that forms tangles inside neurons. The presence of these biomarkers is often used to identify individuals at higher risk of developing Alzheimer’s disease. The LATTICE study specifically focused on individuals with evidence of amyloid beta, recognizing that lithium’s potential benefits might be more pronounced in this subgroup.
Future Directions and Implications
The researchers believe that future trials should focus on enrolling participants with confirmed Alzheimer’s pathology using blood-based biomarkers. This targeted approach could increase the likelihood of detecting a statistically significant effect of lithium. The team is currently planning a larger, multi-center clinical trial to further investigate the potential of low-dose lithium as a preventative strategy for Alzheimer’s disease.
The findings from the LATTICE study add to a growing body of evidence suggesting that lithium may have protective effects against dementia. A growing body of evidence suggests that lithium may protect against dementia, but no randomized clinical trial had yet combined cognitive assessment, neuroimaging, and plasma biomarkers to test this rigorously in humans, as noted in a publication from the University of Pittsburgh Psychiatry department. If confirmed in larger trials, low-dose lithium could offer a relatively inexpensive and accessible option for delaying cognitive decline and improving the quality of life for individuals at risk of Alzheimer’s disease.
The study, conducted between February 2018 and August 2024, with data analyzed through December 2025, represents a significant step forward in understanding the potential of repurposing existing medications for neurodegenerative diseases. The University of Pittsburgh School of Medicine continues to be at the forefront of Alzheimer’s research, seeking innovative approaches to prevent and treat this devastating condition.
Key Takeaways
- A pilot study suggests low-dose lithium may slow verbal memory decline in individuals with mild cognitive impairment.
- The study confirmed the safety and tolerability of low-dose lithium in older adults.
- Larger clinical trials are needed to confirm these findings and determine the optimal dose and duration of treatment.
- The research highlights the potential of repurposing existing medications for neurodegenerative diseases.
Researchers will continue to analyze data from the LATTICE trial and refine their research protocols. The next steps involve securing funding for a larger, multi-center trial and recruiting a more diverse participant population. Readers interested in learning more about Alzheimer’s disease and clinical trials can visit the Alzheimer’s Association website. We encourage you to share this article with anyone who may be interested in this important research and to leave your comments and questions below.
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