A new study published in Nature reveals that low lithium levels in the brains of people with Alzheimer’s disease and mild cognitive impairment could point to a new approach for treating the neurodegenerative condition.
The research, led by Bruce Yankner, MD, PhD, at Harvard Medical School, also found that a form of lithium, lithium orotate, reversed memory loss in mice with Alzheimer’s-like symptoms.
Analyzing postmortem brain tissue from hundreds of older adults, Yankner’s team discovered that lithium was the only trace metal significantly depleted in the brains of those with Alzheimer’s and mild cognitive impairment compared to healthy controls. The study noted lithium accumulation in amyloid plaques, a hallmark of Alzheimer’s, suggesting these plaques disrupt the brain’s lithium balance, potentially contributing to memory loss.
“The idea that lithium deficiency could be a cause of Alzheimer’s disease is new and suggests a different therapeutic approach,” Yankner said in a press release. “You have to be careful about extrapolating from mouse models, and you never know until you try it in a controlled human clinical trial, but so far the results are very encouraging.”
In mouse models, a lithium-deficient diet accelerated cognitive decline and plaque buildup, while low doses of lithium orotate in drinking water prevented plaque and tau protein accumulation, reversing memory loss without the kidney and thyroid toxicity associated with lithium carbonate, used for bipolar disorder.
“My hope is that lithium will do something more fundamental than anti-amyloid or anti-tau therapies, not just lessening but reversing cognitive decline and improving patients’ lives,” Yankner said.
“For years, the fight against Alzheimer’s has been dominated by a single-target approach, focusing almost exclusively on clearing amyloid plaques,” said Manisha Parulekar, MD, director of geriatrics at Hackensack University Medical Center, who was not involved in the study, Medical News Today reported. “This study suggests a depletion of a natural element, and how restoring that balance could potentially impact all the major hallmarks of the disease — the plaques, the tangles, and cognitive function itself.”
Peter Gliebus, MD, a neurologist at Marcus Neuroscience Institute, called the findings promising but urged caution.
“The study underscores the potential of lithium replacement therapy as a preventive or therapeutic intervention,” he said, per MNT. “These findings have the potential to contribute to the early detection and treatment of Alzheimer’s disease in the future.”
Ashley Bush, a psychiatrist at the Florey Institute, described the paper as a “thorough and pioneering exploration” of lithium’s role in cognitive decline, offering “some of the most compelling data yet” that the mineral plays a key role in brain function, per Science magazine.
However, Puja Agarwal, a nutritional epidemiologist at Rush University, and Perminder Sachdev, a neuropsychiatrist at the University of New South Wales, cautioned that lithium orotate, an unregulated supplement in the U.S., needs further testing to confirm safety and efficacy in humans.
Researchers emphasized that while the results in mice are promising, human trials are still needed before lithium can be considered a safe or effective treatment for Alzheimer’s.