- A study published in JAMA Neurology indicated that low-dose oral lithium could slow memory decline in older adults with mild cognitive impairment (MCI).
- This neuroprotective effect was especially apparent in those who tested positive for amyloid-beta, a hallmark of Alzheimer’s.
- While lithium offers the potential to slow the clock, evidence does not indicate it is a cure for restoring memory.
- Experts agree that lifestyle changes offer broader and more robust benefits not only for brain health but also for cardiovascular and metabolic health.
Could a decades-old treatment for bipolar disorder be the key to slowing memory loss that comes with age? Researchers from the University of Pittsburgh think so.
Led by Ariel Gildengers, professor of psychiatry at Pitt and a geriatric psychiatrist at UPMC, the researchers launched a 2-year exploratory clinical trial to investigate the effects of low-dose oral lithium on older adults (ages 60+) with mild cognitive impairment (MCI).
Lithium is a mood stabilizer and gold-standard long-term treatment for bipolar disorder that helps manage episodes of acute mania and depression, and reduces suicide risk.
The doses used in this study, however, were very small doses — much lower than those used for bipolar disorder.
Among 80 participants, those who received a daily low-dose lithium carbonate showed a slower rate of decline in verbal memory, the ability to remember and recall words and sentences, compared to those who were on a placebo.
The fact that such low doses of lithium were safe and well-tolerated makes these findings encouraging — smaller doses may confer cognitive benefits with fewer side effects.
Lithium also showed a stronger neuroprotective effect in participants who tested positive for amyloid-beta. Although there is no definitive cause of Alzheimer’s,
The findings were published in
It is important to note that this pilot trial is a “proof-of-concept”, meaning larger clinical trials will be needed before experts start recommending lithium for brain health.
Lithium also requires medical supervision and regular blood monitoring to ensure safety.
It’s not yet clear exactly which types of cognitive decline — for example, Alzheimer’s versus vascular dementia — lithium may treat most effectively.
And although lithium showed a protective effect over 2 years, the study cannot prove whether this effect is sustained in the long term.
The study also cannot determine what the “sweet spot” is when it comes to dosage, both in terms of brain benefits and also with minimal risk to kidney or thyroid health, so more research will be needed.
Medical News Today spoke to Dung Trinh, MD, internist at MemorialCare Medical Group and Chief Medical Officer of Healthy Brain Clinic in Irvine, CA, and Ramon Velazquez, PhD, assistant professor at the Arizona State University (ASU) School of Life Sciences and member of the ASU-Banner Neurodegenerative Disease Research Center to discuss key takeaways for brain health, the yet-unknowns about lithium, and other lifestyle changes people can take to protect their aging brain.
When asked how lithium achieves this effect, Velazquez explained:
“Lithium appears to affect multiple pathways that have to do with the health of the brain. One way it might work is by inhibiting GSK-3, an enzyme that plays a role in tau phosphorylation, which in Alzheimer’s disease is associated with neuronal dysfunction and degeneration. The compound has also been shown to influence pathways involving brain-derived neurotrophic factor, or BDNF, which is important for brain cell survival and plasticity.”
He added that both animal and lab tests have shown that lithium reduces some of the toxic effects associated with amyloid proteins.
Meanwhile, Trinh said the “mood stabilizing” effect of lithium may also play a role.
“It’s possible that better mood stability, sleep, and reduced stress reactivity could indirectly support cognition—especially in people with MCI, where depression/anxiety can worsen performance,” he said.
“But lithium also has direct neurobiology that’s separate from mood: it affects intracellular signaling pathways and has been linked in preclinical and translational work to neurotrophic and anti-inflammatory effects and reduced tau-related pathology. So, it’s likely not ‘mood or neuroprotection’—it may be both, and future trials can separate those effects by tracking mood and biomarkers in parallel,” he explained.
There is currently no definitive evidence about what the optimal dose of lithium is for it to confer brain protection. It is also important to emphasize that lithium is not a cure for restoring lost memory.
“While this study shows that doses in the 150 to 300 milligram range were generally well tolerated in many older adults under medical supervision, it was a pilot trial and none of its primary outcomes met the prespecified threshold for statistical significance. It wasn’t designed to establish the best dose for slowing cognitive decline,” Velazquez said.
“[S]howing an effect at that level does not prove that there will be a clear clinical benefit in humans,” he added.
“‘Optimal’ isn’t a single number yet—it’s a dose window that balances biologic engagement with minimal risk. In the LATTICE pilot, most participants ended up around 195 mg/day on average, with mean blood levels [of approximately] 0.17 mEq/L [milliequivalents per liter] — well below typical psychiatric targets—and the study was designed to estimate effect sizes and feasibility, not to lock in the best dose,” Trinh explained.
He said the next step in research would be a larger trial to determine which serum range best correlates with cognitive or biomarker changes while still being safe for kidney and thyroid health.
“No. ‘Safe and well-tolerated’ means safe under the study’s conditions—with screening, exclusion criteria, controlled dosing, and lab monitoring,” Trinh said.
Velazquez stressed that this study should not give people the impetus to try lithium on their own.
“In a clinical trial, participants are screened beforehand and monitored. Clinicians check lithium levels in the blood regularly to make sure they stay within a therapeutic range and to monitor kidney and thyroid function. People should never start lithium without medical supervision. In evaluating safety, a clinician would need to know the dose, personal health history, and ensure appropriate monitoring,” he said.
As with all medications and supplements, there may be unwanted side effects, as is the case with lithium.
“Lithium is [a] good example where context matters: risk rises with kidney disease, dehydration, interacting meds (like NSAIDs/diuretics), and older age physiology, and toxicity can occur even with ‘normal’ levels. So, this is not a ‘try it at home’ medication—any use should be clinician-supervised with renal/thyroid monitoring,” Trinh said.
Trinh reminded that lithium, if it works in humans, would likely be an adjunct therapy in reducing dementia risk.
“Lifestyle interventions are the highest-confidence, broadest-benefit strategy we have for brain health because they improve not just cognition, but also cardiovascular risk, function, and overall mortality risk. We now have large, randomized trials showing that multidomain lifestyle programs can improve or protect cognition over 2 years in at-risk older adults—like the FINGER trial and the U.S. POINTER trial,” he said.
Velazquez reiterated that low dose lithium was still being studied, but that evidence so far on lifestyle changes and habits to reduce dementia risk was stronger and more consistent.
“Physical activity, sleep, cardiovascular fitness, cognitive activity, metabolic health — all support brain function through numerous biological pathways simultaneously, including effects on inflammation, blood flow, and neural plasticity,” he explained.
“Even if a drug ultimately proves beneficial, it would likely be in addition to these lifestyle factors. Living a Healthy lifestyle remains the first line of defense when it comes to protecting your brain,” he added.
