Lithium and Alzheimer’s Disease

Edited and Approved by Stephen C. Rose, PhD, MS

Could an overlooked trace element help explain why memory fails with age? A 2025 Nature paper places lithium at the center of that question. Its findings deserve attention, but the practical issue is more demanding: would giving lithium to people preserve their memory? [1]

What the Nature study found

Aron and colleagues found reduced lithium in the prefrontal cortex of people with mild cognitive impairment or Alzheimer’s disease. Average blood levels did not show the same difference. Amyloid plaques, deposits of an Alzheimer’s-associated protein, concentrated lithium, potentially reducing its availability elsewhere. [1]

In mice, dietary lithium depletion lowered available cortical lithium by about half and worsened memory and brain pathology. GSK3β, an enzyme involved in cellular signaling, contributed to the effects. Lithium orotate reduced pathology and preserved memory in mouse experiments. This combination supports a biological hypothesis, not proof that supplements prevent human Alzheimer’s disease. [1]

What would count as convincing evidence

There is a useful way to read a study like this. First ask what was measured. A tissue concentration is a measurement of location and amount. It is not automatically a diagnosis or a treatment target. Then ask what was changed experimentally. Deliberately changing an exposure can strengthen a causal explanation, but the conclusion still belongs to the organism and conditions studied. Finally, ask whether the proposed treatment improved an outcome people care about.

For a reader worried about dementia, that outcome is likely to be maintaining memory, independence, and everyday function. A laboratory mechanism can explain why a treatment is worth testing without telling us whether it will deliver those benefits. This distinction also protects promising research from unrealistic expectations. A finding can be scientifically valuable while remaining several unanswered questions away from routine care.

It also helps to distinguish treatment from prevention. Improving a test score in someone with existing memory difficulties would not, by itself, show that healthy adults should take the same substance for decades. Each claim needs evidence from a suitable population, an appropriate comparison group, and enough follow-up to answer the question being asked.

An earlier human trial offered encouragement

Lithium had been studied for cognitive impairment before the Nature report. In a randomized trial published in 2019, 61 older adults with amnestic mild cognitive impairment received lithium carbonate or placebo. Amnestic means that memory was the main difficulty. The study included two years of double-blind treatment, followed by two additional years of follow-up with a different blinding arrangement. Participants were physically healthy older adults living in the community. [2]

The lithium group remained relatively stable on cognitive and functional measures over two years, while the placebo group declined. Researchers also reported advantages on memory and attention testing and a change in a spinal-fluid amyloid biomarker. These were encouraging clinical signals from a small, selected population. They did not establish that lithium prevents dementia in the general population, and the treatment was lithium carbonate, not lithium orotate. [2]

The newer trial makes the picture less certain

A 2026 pilot trial provides a more cautious result. Researchers randomized 83 adults aged 60 or older with mild cognitive impairment; 80 began treatment. Participants received low-dose lithium carbonate or placebo for two years. The study examined cognition, brain imaging, and a blood growth-factor measure through six prespecified primary outcomes. None met the study’s threshold for statistical significance. [3]

One verbal-memory measure declined more slowly with lithium, producing a potentially interesting signal. But it did not satisfy the prespecified significance requirement. Brain-volume changes also showed no significant treatment-by-time differences. The fair reading is that this pilot supports further investigation while leaving efficacy unproven. It does not demonstrate that lithium prevents Alzheimer’s disease. [3]

Why emphasize the primary outcomes? Researchers specify these before examining the results to reduce the temptation to highlight whichever finding looks favorable afterward. A suggestive result can guide the next experiment. It cannot simply replace the test a study originally set out to pass. Conversely, a small trial that misses its targets does not prove that every formulation, dose, or patient group would fail.

Is lithium orotate a better option

The choice of lithium salt has become a scientific debate. A salt combines lithium with another chemical component; carbonate and orotate are different examples. In a 2026 analysis, Hajek and colleagues challenged the assumption that lithium orotate remains a distinct complex after ingestion. They argued that stomach chemistry should favor its breakdown and noted the lack of demonstrated stable lithium-orotate complexes in physiological fluids. [4]

This is a mechanistic critique, not a clinical comparison proving one product superior. Its relevance is straightforward: a proposed advantage in an experimental system needs to be shown under the conditions in which a person actually takes a treatment. The authors call for more chemical and biological evidence before concentrating future trials on orotate. That leaves the best formulation an open research question, not a settled reason to choose a supplement. [4]

What about lithium in drinking water

Environmental studies are another part of the story. A Danish investigation compared 73,731 people with dementia with 733,653 controls, estimating long-term lithium exposure from drinking water and residential information. The association was not a simple pattern of more lithium and less dementia. The highest exposure category had lower dementia incidence than the reference category, while an intermediate category had higher incidence. [5]

Because nobody was randomly assigned a water supply, other differences between communities could contribute to the findings. Estimated exposure also differs from measuring what each person actually consumed. The researchers acknowledged possible confounding by factors related to place of residence. This study is useful for generating hypotheses about long-term environmental exposure; it cannot determine an individual’s supplement dose or show that changing drinking water will prevent dementia. [5]

Why self-treatment is not the next step

Lithium is also an established prescription medicine for bipolar disorder, with effects that require medical monitoring. MedlinePlus advises patients to keep laboratory appointments and report kidney, heart, or thyroid conditions. Diuretics and common nonprescription anti-inflammatory drugs, including ibuprofen and naproxen, may interact with lithium. Fever, heavy sweating, or severe diarrhea can also require medical attention during treatment. [6]

These cautions concern prescription use; they do not establish the exact risk of every low-dose supplement. They do explain why a familiar mineral name is not sufficient evidence of safety. Anyone considering lithium for memory should discuss the specific product and their medications with a clinician. People already prescribed lithium should not change or stop it because of an Alzheimer’s headline. [6]

Protecting brain health while the research develops

There are useful steps that do not depend on resolving the lithium question. The National Institute on Aging emphasizes managing cardiovascular health, staying physically active, eating a balanced diet, and keeping mentally engaged. Blood-pressure management has evidence relevant to cognitive health, including trial findings for reduced mild cognitive impairment. Exercise has broad health benefits, although its precise role in preventing dementia remains under investigation. [7]

These measures are not guarantees against Alzheimer’s disease. They are practical ways to support health while more specific treatments are tested. A new memory concern also deserves assessment rather than an assumption that a nutrient is missing. The most useful question to bring to a clinical visit is what could explain the change and what evaluation is appropriate, not which experimental supplement to start. [7]

The lithium story is worth following because it offers a testable idea. Progress will mean independent replication, clearer information about how formulations behave in the body, and adequately powered trials that assess lasting clinical benefit. Until then, curiosity and restraint belong together. Taking the science seriously includes taking its unanswered questions seriously.

References

[1] Aron L, Ngian ZK, Qiu C, et al. Lithium deficiency and the onset of Alzheimer’s disease. Nature. 2025;645:712–721. doi:10.1038/s41586-025-09335-x.

[2] Forlenza OV, Radanovic M, Talib LL, Gattaz WF. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. British Journal of Psychiatry. 2019;215:668–674. doi:10.1192/bjp.2019.76.

[3] Gildengers AG, Ibrahim TS, Anderson SJ, et al. Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. JAMA Neurology. 2026;83:310–319. doi:10.1001/jamaneurol.2026.0072.

[4] Hajek T, Munthe S, Licht RW. Lithium orotate: distinct compound or simply Li+ after administration? British Journal of Psychiatry. Published online June 18, 2026. doi:10.1192/bjp.2026.10699.

[5] Kessing LV, Gerds TA, Knudsen NN, et al. Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry. 2017;74:1005–1010. doi:10.1001/jamapsychiatry.2017.2362.

[6] MedlinePlus. Lithium. Drug information. Accessed September 12, 2026.

[7] National Institute on Aging. Cognitive Health and Older Adults. Accessed September 12, 2026.