Study suggests lithium may help prevent dementia, but practical use remains uncertain

Lithium may play a role in the early development of Alzheimer’s disease, according to research discussed by former cardiologist Hsieh An-min. But the findings do not yet support widespread use of lithium to prevent or treat dementia.

The Harvard Medical School research team examined molecular changes linked to early Alzheimer’s disease and studied how lithium ions affected those changes. The work, published online in Nature in 2025, used postmortem human brains from cognitively healthy people, people with mild cognitive impairment and Alzheimer’s patients. Researchers assessed 27 metals and found that lithium was the only one present at clearly lower concentrations in the brains of people with cognitive impairment, particularly those with Alzheimer’s disease.

The researchers also reported that amyloid plaques bind and trap lithium, leaving less of the mineral available elsewhere in the brain. In mice fed a lithium-deficient diet, cortical lithium levels fell below 5% of their original level. The animals then developed more amyloid deposition and phosphorylated tau, activation of inflammatory microglia, loss of synapses, axons and myelin, and faster cognitive decline. The changes resembled features associated with Alzheimer’s disease in humans.

Lithium carbonate has been used for years to treat bipolar disorder, but high doses can be toxic and poorly tolerated. The team tested 16 lithium salts and reported that lithium orotate performed better than the others in lithium-deficient animals. It appeared to bind less readily to beta-amyloid, restore lithium availability in the brain, and improve pathological changes and memory loss in Alzheimer’s mouse models and aging normal mice.

Hsieh described the Harvard report as potentially groundbreaking, but noted that another lithium treatment study under review found a statistically significant difference at only one of six tested endpoints. More research is needed, including evidence on the effectiveness and safety of lithium orotate, before it can be broadly used for Alzheimer’s disease.