Reuters Health - Long-term consumption of tiny amounts of lithium may reduce the risk of Alzheimer’s disease and other forms of dementia, but only if the dose isn’t too small, according to a study that looked at levels of the element in drinking water throughout Denmark.

In fact, the wrong amount may actually increase dementia risk, researchers report in JAMA Psychiatry.

Lithium, used for years in drugs to treat depression and bipolar disorder, is a naturally-occurring element in drinking water in Denmark but levels vary by location. The team compared the estimated amount found in the water supplies of 275 municipalities to the rates of dementia, including Alzheimer’s, in those areas.

Residents who had been diagnosed with dementia from 1995 through 2013 tended to consume lower levels of lithium in their water than residents whose water had higher levels. However, there was a middle level of consumption where dementia risk was elevated or unchanged.

Compared to those whose water contained lithium concentrations of 2 to 5 micrograms of lithium per liter, which served as the baseline, the rate of dementia was 22 percent higher when the drinking water concentration was 5 to 10 micrograms.

Levels of 10.1 to 15 micrograms had no effect on the risk.

But at levels of 15.1 to 27 micrograms per liter, the dementia risk seemed to drop by 17 percent compared to places where the levels were 2 to 5 micrograms.

“It’s a really interesting study but you have to be careful about inferring cause and effect,” said Dr. Brent Forester, head of the geriatric division of McLean Hospital, a psychiatric hospital in Belmont, Massachusetts affiliated with Harvard Medical School, who wasn’t involved in the research.

In a telephone interview with Reuters Health, he called the fact that the effect didn’t strictly increase or decrease based on the lithium dose “a worrisome sign” and said the non-linear trend “could be a warning that there’s another confounding variable. It may not be the lithium itself but something about the mechanism of action might be protecting against developing dementia. The biology of lithium is worth exploring, for sure.”

The chief author of the study, Dr. Lars Vedel Kessing of the University of Copenhagen, did not respond to requests for an interview. But the researchers cautioned in their paper that “it cannot be excluded that other, unobserved environmental or social care factors related to individuals’ municipality of residence might have confounded the association between lithium exposure and dementia rate.”

The idea of a link between lithium and Alzheimer’s has been around for years, Forester said.

“Over a decade ago, a pathology study that looked at the brains of patients who had a lifelong history of bipolar disorder and were treated with lithium versus those with a lifelong history of bipolar disorder who were not on lithium showed that those exposed to lithium had about one sixth the rate of Alzheimer’s pathology,” he said. “It raised a lot of interesting questions and eyebrows about the mechanism.”

Other research has shown that low doses - but doses far higher than found in the drinking water in the Denmark trial - may reduce the odds of Alzheimer’s. But research has been limited because drug companies don’t stand to make a lot of money from lithium therapy.

Forester said he would not advise people to try using lithium to ward off Alzheimer’s because the drug can harm the kidneys, although the levels seen in the drinking water in Denmark are too low to pose a serious risk.

SOURCE: bit.ly/2voKL7m and bit.ly/2xsCHUN JAMA Psychiatry, online August 23, 2017.