Could a decades-old bipolar disorder treatment hold the key to slowing memory loss in Alzheimer's disease? It sounds like something out of a sci-fi novel, but a recent study suggests lithium, a drug long used for mood stabilization, might just do that.
Here’s the fascinating part: an exploratory clinical trial from the University of Pittsburgh (https://clinicaltrials.gov/study/NCT03185208) hints that low-dose lithium could slow the decline of verbal memory—the ability to remember and recall words and sentences—in older adults with mild cognitive impairment. But here's where it gets controversial: this effect seems particularly promising in individuals with amyloid beta, a hallmark biomarker of Alzheimer's disease. Does this mean lithium could be a game-changer for Alzheimer's prevention? Or is it too early to tell?
Published in JAMA Neurology (https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2026.0072?guestAccessKey=e2389e8c-2ab4-49e9-ac2e-d9fe54111a2a) on March 2, the study aimed to answer a critical question: Is lithium promising enough to warrant a larger trial focused on slowing Alzheimer's-related cognitive decline? Led by Dr. Ariel Gildengers (https://www.psychiatry.pitt.edu/about-us/our-people/faculty/ariel-g-gildengers-md), a geriatric psychiatrist renowned for his research on lithium's effects on the aging brain, the trial built on his earlier work. Gildengers had previously found that long-term lithium use in older adults with bipolar disorder was linked to better brain integrity—a discovery that inspired this latest investigation.
"We observed that older adults with bipolar disorder on long-term lithium treatment showed markers of healthier brains," Gildengers explained. "The question was whether these neuroprotective effects could extend beyond mood disorders—and if we could rigorously test this in a clinical trial."
To explore this, the research team assembled experts in advanced brain imaging (https://rf-research-facility.engineering.pitt.edu/) and cutting-edge Alzheimer's biomarkers. The two-year trial, completed in August 2024, enrolled adults aged 60 and older with mild cognitive impairment. Participants were randomly assigned to receive either low-dose lithium or a placebo. Researchers then tracked their progress annually through detailed cognitive tests, high-resolution brain imaging, and biomarker assessments.
And this is the part most people miss: while the results weren’t definitive, they showed particularly encouraging signs for verbal memory—a cognitive function that often declines early in Alzheimer's. Brain imaging revealed that the hippocampus, a brain region vital for memory, shrank over time in both groups. However, exploratory analyses suggested larger protective effects in participants with amyloid beta, hinting at a potential biological mechanism worth exploring further.
Crucially, the study confirmed that low-dose lithium is safe and well-tolerated in older adults when carefully monitored, addressing a major concern about using the drug in this population. "Lithium doesn’t restore lost memory," Gildengers emphasized. "What it seems to do—if the findings hold up—is slow its deterioration. That’s a critical distinction when designing and interpreting trials."
So, what’s next? When the trial began nearly a decade ago, blood-based tests for Alzheimer's pathology weren’t available. Participants were enrolled based solely on clinical symptoms, and only a subset turned out to be amyloid-positive—a limitation that may have weakened the study’s ability to detect stronger effects. "If we were designing this study today, we’d enroll participants based on amyloid status from the start," Gildengers said. "That’s exactly what we’re planning for the next phase."
Gildengers and his team are now seeking funding for a larger, more definitive trial informed by these pilot findings. The next phase would use blood-based biomarkers to identify individuals most likely to benefit and enroll enough participants to determine whether lithium can meaningfully delay cognitive and neurodegenerative changes associated with Alzheimer's.
"This study shows the approach is feasible, safe, and worth pursuing," Gildengers said. "But it also underscores why careful, well-powered trials are essential—especially when the stakes are this high."
Here’s a thought-provoking question for you: If lithium proves effective in slowing cognitive decline, could it revolutionize Alzheimer's prevention? Or are we placing too much hope in a single drug? Share your thoughts in the comments below.
Additional Resources:
- NCT03185208 | Lithium as a Treatment to Prevent Impairment of Cognition in Elders | ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT03185208)
- The LATTICE Study: Design of a pilot feasibility randomized controlled trial of lithium to delay cognitive decline in mild cognitive impairment (https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70112)
- Alzheimer's Disease Research Center | University of Pittsburgh (https://www.adrc.pitt.edu/)
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