Lithium Shows Early Promise in Treating Alzheimer’s

When Yankner’s team evaluated human brain tissue and experimented with mice, they found that declining lithium levels were linked to memory loss. Lithium deficiency was also associated with the buildup of amyloid plaques as well as tau tangles, a second hallmark of Alzheimer’s.

Yankner’s team tested mice by severely reducing lithium in their diets so their levels in the brain dropped by about half. The mice with less lithium had worse memory. When mice with low levels were given lithium orotate, the memory problems reversed.

When the team took mice that were engineered to have genes that gave them Alzheimer’s symptoms and gave them a low lithium diet, “the pathology dramatically increased,” Yankner says. Also, the mice were less able to clear amyloid plaques, he says.

Yankner’s human data came from an existing trial that evaluated participants who were either cognitively normal, had MCI or had Alzheimer’s. The participants had agreed to regular testing and consented to let researchers examine their brain tissue after they died.

The researchers looked at levels of 27 metals in the brain tissue and blood. Of all the metals, lithium was the only one with low levels in the prefrontal cortex of people with MCI and Alzheimer’s — an area of the brain important for reasoning, planning and language.

Along with those who had Alzheimer’s, people with MCI — early on, even before amyloid began to form the telltale plaques — had lower lithium uptake, which could be due to genetic and environmental factors, Yankner says. People also may have less lithium because amyloid plaques sequester the metal in the brain.

As amyloid plaques start to accumulate in the brain, they trap lithium as the disease progresses, Yankner explains. Lithium carbonate, used for bipolar disorder, got snared by the plaques. Lithium orotate was less likely to get grabbed, and it restored the mice’s memory. 

Next steps for studying lithium

 “This was a pilot trial, and its main goal was to determine if a study of low-dose lithium in older adults with MCI was feasible and safe,” says Dr. Manisha Parulekar, codirector of the Center for Memory Loss and Brain Health at the Hackensack Meridian Neuroscience Institute at Hackensack University Medical Center. She reviewed both studies.

“The researchers successfully demonstrated this, confirming the treatment’s tolerability and providing the essential data needed to design a larger, more definitive clinical trial,” Parulekar says.

Scientists need to do more studies on humans, Parulekar says. Any treatments must be shown to be effective and safe in large studies of people before they can be recommended.

Lithium has several forms. Lithium orotate as well as lithium aspartate are available on the market as supplements. Lithium carbonate and lithium citrate are prescription-only, according to ConsumerLabs.com, an independent tester of health and nutrition products.

Lithium can be toxic to humans at certain levels, so no one should take it without a doctor’s care, Parulekar says. Patients who are taking lithium by prescription for bipolar disorder should have their blood levels checked regularly, she adds.

Gildengers strongly cautions against over-the-counter lithium supplements. “Lithium is a powerful medication that requires careful dosing and close monitoring of kidney and thyroid function,” he says. “Larger, well-designed clinical trials are still needed before lithium could be considered a viable option for people concerned about dementia.”

Yankner agrees, noting that lithium supplements are not regulated by the Food and Drug Administration. “You can never be sure what’s in them,” he says. 

“We need to wait for the clinical trials to really know what is the best dose for a person and to be assured that there won’t be toxicity,” he adds.