Scientists estimate that there are about 32 million people globally living with a type of dementia known as Alzheimer’s disease.
Researchers also believe the amount of people worldwide living with Alzheimer’s disease and related dementias will hit 152 million by 2050.
There is currently no cure for Alzheimer’s disease. While there are some medications available, they are only used in the earliest stages to help slow cognitive decline or at more advanced stages to treat common symptoms of the condition.
“Alzheimer’s disease and other dementias are devastating conditions for individuals, families, and society at large,” Husseini K Manji, MD, FRCPC, professor at both Oxford University in the United Kingdom and at Yale University in the United States, co-chair of the U.K. Government Mental Health Goals Program (formerly MH Mission), told Medical News Today.
“Despite recent advances in monoclonal antibodies, Alzheimer’s disease and other dementias remain a massive and growing global public health crisis. Current therapies largely focus on single pathologies, such as removing amyloid plaques, but Alzheimer’s is incredibly complex and involves a progressive cascade of cellular vulnerabilities, including mitochondrial decay, oxidative stress, and loss of synaptic connections,” Manji explained.
He is the lead author of a new study published in the journal JAMA Psychiatry making the case for treating Alzheimer’s disease with low-dose lithium — a medication used to treat bipolar disorder — as the drug helps to counter neuroprogression and provides neuroprotective benefits.
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Over the last 25 years, Manji explained, a convergence of molecular, imaging, and epidemiological data from research conducted in his lab and others, has shown that lithium is much more than just a psychiatric drug — it possesses major neurotrophic and neuroprotective properties.
“However, traditional psychiatric doses of lithium carbonate are often poorly tolerated by older individuals due to a high adverse effect burden, particularly risks to kidney and thyroid function,” he continued.
“My lab, therefore, did a number of studies with low-dose lithium to show that many of the neurotrophic and neuroprotective properties are seen at considerably lower doses/levels than those traditionally used in bipolar disorder,” Manji told us.
“These findings have been replicated by other independent laboratories,” he noted. “Thus, low-dose lithium may exert neurotrophic effects but have considerably fewer side effects.”
In this study, Manji and his team explain that low-dose lithium is not only a mood stabilizer, but also helps to counter brain changes known as neuroprogression.
“In bipolar disorder, neuroprogression refers to the way repeated mood episodes cause cumulative, structural damage, and shrinkage in key brain areas over time,” he detailed.
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“Lithium is unique because it can actually preserve or even reverse this brain shrinkage. We believe low-dose lithium can counter a similar progressive decline in Alzheimer’s disease. Lithium exerts effects on major neurotrophic cascades — especially BDNF, bcl-2, and GSK-3 — which would be postulated to attenuate disease progression; these findings have been replicated numerous times by independent labs.”
– Husseini K Manji, MD, FRCPC
“Additionally, in humans, lithium treatment has been shown to reverse illness-related neurotrophic deficits in bipolar disorder,” Manji added. “Although the diseases are distinct, lithium affects very fundamental cellular neurotrophic processes, which would be applicable to Alzheimer’s disease as well.”
The study also reports that low-dose lithium may provide neuroprotective benefits.
Manji explained that rather than just trying to clean up a single toxic protein, low-dose lithium acts like a master switch that upgrades the brain’s overall cellular defense system by turning up the production of BDNF, blocking the activity of deleterious enzymes, and improving brain energetics.
In short, he said, lithium is helping vulnerable brain cells survive and stay healthy despite the toxic environment of Alzheimer’s.
“Seventy-five years after transforming psychiatric care, lithium is at the forefront of a new frontier as a powerful, multi-targeted intervention capable of slowing progression in early dementia,” Manji added.
“By shifting our focus to low-dose strategies, we can harness its robust neuroprotective capabilities safely, opening the door to an accessible, low-cost weapon in the global fight against Alzheimer’s disease,” he told us.
MNT had the opportunity to speak with Laura Nisenbaum, PhD, executive director of drug development for the Alzheimer’s Drug Discovery Foundation (ADDF) — who was not involved in this research — about this study.
Nisenbaum said her first reaction to the study was one of genuine interest, and what makes this review compelling is that so many independent lines of evidence are pointing in the same direction.
“The field has been asking questions about lithium for years, and this review synthesizes more than 2 decades of research and presents a case for further exploration of lithium to determine if it’s a potential disease-modifying therapy, rather than simply a repurposed psychiatric medication,” she explained.
“The breadth of biological rationale is also intriguing. Lithium appears to act on several biological processes central to Alzheimer’s, including protein clearance, mitochondrial function, and tau pathology. That multi-target profile is significant because Alzheimer’s is not a single-pathway disease,” Nisenbaum detailed.
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Nisenbaum stressed it was it is important for researchers to continue to find new potential treatment options for Alzheimer’s disease and other types of dementia.
“The treatments available today offer meaningful progress, but they leave a lot on the table,” she explained. “There is a real opportunity to bring new treatments forward, whether in combination with existing therapies or through a precision medicine approach, the way we now treat cancer, matching the right therapy to the right patient at the right time.”
“Repurposed drugs like lithium are worth taking seriously in that context,” Nisenbaum continued. “Lithium has a long clinical history, a well-understood safety profile at low doses, and a cost and accessibility profile that could make it viable at scale globally.“
“Identifying established therapies that target the underlying biology of Alzheimer’s and can realistically reach broad populations is an important avenue for the field to explore,” she said.
Finally, MNT also spoke to Dung Trinh, MD, internist for the MemorialCare Medical Group and chief medical officer of the Healthy Brain Clinic in Irvine, CA, about this study.
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Trinh, who was not involved in the research, commented that his first reaction was one of cautious optimism.
“This review raises an intriguing possibility that low-dose lithium could affect several biological pathways involved in neurodegeneration, including neuronal survival, inflammation, oxidative stress, mitochondrial function, and tau biology,” he, explained.
“That said, this is not yet a practice-changing finding,” he cautioned. “As a clinician, I would not recommend that patients start lithium on their own, especially because lithium can affect kidney and thyroid function and may interact with other medications.”
“The study is best viewed as a strong rationale for rigorous clinical trials, not as proof that lithium should be used routinely for Alzheimer’s prevention or treatment,” Trinh told us.
According to him:
“The next step should be a well-designed randomized, placebo-controlled clinical trial in people with biomarker-confirmed mild cognitive impairment or early Alzheimer’s disease. Researchers should clearly define the lithium formulation, dose, duration, blood-level targets, and safety-monitoring plan, especially for kidney and thyroid function. I would also like to see outcomes that go beyond memory testing, including biomarkers of amyloid, tau, neurodegeneration, MRI changes, daily function, caregiver-reported outcomes, and quality of life. The key question is whether low-dose lithium can provide meaningful brain benefits while remaining safe enough for older adults over time.”
