Low-Dose Lithium May Slow Verbal Memory Decline in Older Adults with Mild Cognitive Impairment
An exploratory clinical trial conducted by the University of Pittsburgh indicates that low-dose oral lithium may contribute to slowing the decline of verbal memory in older adults diagnosed with mild cognitive impairment. This effect was particularly observed in individuals presenting with amyloid beta, a recognized biomarker for Alzheimer's disease. The study findings were published in JAMA Neurology.
Study Overview and Background
The two-year trial, which concluded in August 2024, aimed to determine if lithium showed sufficient promise to warrant further investigation in larger clinical trials for slowing Alzheimer's-related cognitive decline. The research was led by Dr. Ariel Gildengers, a professor of psychiatry at the University of Pittsburgh. Lithium is an established treatment for bipolar disorder, and prior research by Dr. Gildengers had indicated a correlation between long-term lithium use in older adults with bipolar disorder and improved brain integrity.
Participants in the trial included adults aged 60 and above who had been diagnosed with mild cognitive impairment. They were randomly assigned to receive either a low dose of lithium or a placebo. Throughout the study, participants underwent annual follow-ups that included detailed cognitive testing, high-resolution brain imaging, and biomarker assessments.
Key Findings
Over the two-year period, participants who received lithium exhibited a slower rate of decline on a sensitive test of verbal memory, a cognitive function that typically declines early in Alzheimer's disease.
Brain imaging analyses revealed that the hippocampus, a brain region important for memory, experienced shrinkage in both the lithium and placebo groups. The overall difference in hippocampal shrinkage between the groups was not statistically significant. However, exploratory analyses identified potentially greater protective effects among participants who tested positive for amyloid beta, a key biomarker for Alzheimer's disease.
The study also confirmed that low-dose lithium was safe and well tolerated in older adults under careful monitoring. Dr. Gildengers noted that lithium's observed effect is to slow deterioration, rather than to restore lost memory.
Limitations and Future Directions
A limitation of the initial study was that blood-based tests for Alzheimer's pathology were not available when the trial commenced. Consequently, participants were enrolled based on clinical symptoms alone, and only a portion were later found to be amyloid-positive. This factor may have limited the study's capacity to detect more pronounced effects across the entire participant group.
Dr. Gildengers and his team are now pursuing funding for a larger, more definitive clinical trial. This subsequent trial would utilize blood-based biomarkers to identify individuals most likely to benefit and aims to enroll sufficient participants to ascertain if lithium can significantly delay cognitive and neurodegenerative changes linked to Alzheimer's disease.