Lithium is an effective mood stabilising medication used in the treatment of bipolar disorder and some forms of depression. New research, however, suggests that the much smaller amounts of lithium naturally present in the brain may also play a role in preserving memory and supporting brain health as people age.
A study published in the scientific journal Nature found reduced levels of available lithium in the brains of people with mild cognitive impairment and Alzheimer’s disease. Experiments in mice also suggested that lowering naturally occurring lithium may contribute to memory loss and several biological changes associated with Alzheimer’s disease.
Although the findings provide a promising direction for dementia research, they do not show that the lithium medication currently prescribed by psychiatrists can prevent or treat Alzheimer’s disease in human beings.
What Did the Study Examine?
The researchers measured 27 metals in the brain and blood samples from older adults who had:
- No cognitive impairment
- Mild cognitive impairment
- Alzheimer’s disease
Mild cognitive impairment involves perceptible changes in memory or thinking that are greater than what would be usually expected with ageing. Alzheimer’s disease is a more advanced version that inhibits a person from living independently. The researchers examined the prefrontal cortex, which is affected by Alzheimer’s disease, as well as the cerebellum which is generally less affected.
What Did the Researchers Find in Human Brain Tissue?
Lithium was the only one of the 27 metals found to be significantly reduced in the prefrontal cortex of people with mild cognitive impairment. The amount of lithium available to brain tissue was further reduced in people with Alzheimer’s disease. The same pattern was not identified in blood sample, suggesting that blood lithium levels may not necessarily reflect the amount naturally available within areas of the brain.
Researchers also found that lithium was concentrated within amyloid plaques in the brains of people with mild cognitive impairment and Alzheimer’s disease. Amyloid plaques are abnormal deposits of beta-amyloids proteins associated with Alzheimer’s disease. The researchers proposed that these plaques may trap lithium, leaving less available to surrounding brain cells. Lower levels of lithium outside the plaques were also associated with poorer scores on tests of memory and overall cognitive function. However, an association does not prove that reduced lithium caused the cognitive decline.
As the human part of the study examined tissues of the brain after death, it cannot establish whether lithium deficiency contributes to Alzheimer’s disease, occurs because of the disease, or is influenced by another underlying process.
What Happened When Lithium Was Reduced in Mice?
To explore whether reduced lithium might actively contribute to Alzheimer’s related changes, the researchers lowered dietary lithium in mouse models of Alzheimer’s disease and in aging mice without those genetic modifications.
Lithium deficiency was associated with
- Increased amyloid-beta accumulation
- Increased abnormal tau proteins
- Greater brain inflammation
- Damage to connections between brain cells
- Changes affecting myelin and several brain cell types
- Reduced ability of immune cells to clear amyloids
- Memory impairment.
The researchers found that lithium deficiency affected several biological pathways, including increased activity of an enzyme known as GSK-3β. The enzyme is involved in processes associated with tau proteins, inflammation and amyloid accumulation. The finding suggests that naturally occurring lithium may help regulate several processes involved in maintaining brain function. However, the findings in mice do not necessarily translate into safe or effective treatments for human beings.
Did Lithium Improve Memory in The Mice?
The researchers then tested lithium orotate (LiO), a form of lithium that demonstrated less binding to amyloid plaques than lithium carbonate. In the mouse models, low dose lithium orotate prevented or reversed several Alzheimer’s-like changes. It reduced neuroinflammation and abnormal protein accumulation and improved performance on memory tasks. Benefits were observed in both Alzheimer’s disease mouse models and ageing mice.
The dose was designed to restore lithium to the small amounts naturally present in the body rather than to the higher levels used for psychiatric treatment. Although these finding are promising, lithium orotate has not been showed by this study to safely prevent or treat Alzheimer’s in humans.
Is This the Same Lithium Prescribed for Bipolar Disorder?
No. The most promising findings involved lithium orotate, while the lithium commonly prescribed in Australia for Bipolar Disorder is lithium carbonate. The researchers found that lithium carbonate bound more readily to amyloid than lithium orotate. At the low dose examined, lithium carbonate also did not produce the same improvement in the mouse models.
The study therefore does not demonstrate that prescription lithium carbonate prevents Alzheimer’s disease. It also does not mean that the people taking lithium for Bipolar Disorder or depression should change their dose or medication.
Any changes to lithium treatment should only be made in consultation with the prescribing psychiatrist or doctor.
Should People Take Lithium Supplement for Brain Health?
There is currently insufficient evidence to recommend taking lithium or lithium containing supplements to prevent cognitive decline or dementia. The lithium orotate findings came from animal experimentation, not human clinical trials.
Researchers still need to establish:
- Whether the results can be replicated in people
- Which form of lithium should be tested
- What dose could be safe and effective
- Whether it would reach the necessary part of the brain in humans
- Whether long term usage would have any negative long-term effect
What Could the Findings Mean for Dementia Research?
Dementia is a significant and growing health concern in Australia. The Australian Institute of Health and Welfare (AIHW) estimate there are 439,000 Australians living with dementia in 2025. Dementia is also now the leading cause of death in Australia.
The new research suggests that disruption in naturally occurring lithium may be involved relatively early in the biological processes associated with Alzheimer’s’ disease. It also raises the possibility that safely restoring the safe amount of lithium naturally present in the brain could become an area for future treatment research.
For now, however, the findings should be viewed as an important scientific development rather than evidence of an available Alzheimer’s disease treatment. Carefully controlled human clinical trials will be required to determine whether the results can be translated into clinical care.
The psychiatrists at Eastern Suburbs Psychiatry provide assessment and treatment for a range of adult psychiatric conditions including old age psychiatry. To make an enquiry about an appointment to see a Sydney Psychiatrist for an individualised treatment plan, click here.
Source
https://www.nature.com/articles/s41586-025-09335-x