Fat Hormone May Protect Against Alzheimer's

High levels of leptin associated with lower dementia risk, research finds

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By Ed Edelson
HealthDay Reporter

TUESDAY, Dec. 15 (HealthDay News) -- High blood levels of leptin, a hormone that regulates appetite, may guard against Alzheimer's disease, new research suggests.

"Hopefully, in 10 or 15 years this may be one of many agents that we use to reduce the risk of Alzheimer's disease," said senior study author Dr. Sudha Seshadri, an associate professor of neurology at Boston University School of Medicine. "Or it may be one of many markers that we measure in combination to predict risk."

But many more studies of different population groups are needed to determine whether leptin can play such a pivotal role in predicting the risk of Alzheimer's, Seshadri said.

The research, which was reported in the Dec. 16 issue of the Journal of the American Medical Association, was done because "there has been some data relating body weight to the risk of Alzheimer's disease," Seshadri said. "When we looked at animal studies, we found some data to indicate that leptin not only produces a feeling of satiety but also has a beneficial effect on the hippocampus. It was important to see if that was true in humans."

The hippocampus is a portion of the brain that plays a role in important aspects of memory.

Some human studies have shown that people with Alzheimer's disease have lower levels of leptin, but those studies didn't show which came first, the lower leptin levels or the decline in mental function, Seshadri said. So she and her colleagues turned to the Framingham Heart Study, which has followed residents of a Massachusetts community for decades.

Leptin levels had been measured in 785 Framingham participants in the early 1990s. For the new study, 198 of them had MRI scans that measured brain volume an average of 7.7 years after leptin was measured. The study authors also kept track of new Alzheimer's diagnoses among the study participants.

The researchers found that higher leptin levels were associated with a lower incidence of Alzheimer's and all other forms of dementia. The 25 percent of participants with the lowest leptin levels had a 25 percent risk of developing Alzheimer's over a 12-year period; the incidence was only 6 percent for those with the highest leptin levels. And lower leptin levels were associated with a greater decrease in total brain size.

It's not now possible to say what leptin might be doing to help the aging brain, and "we're not recommending that anyone get leptin or increase leptin levels," Seshadri said. For starters, animal studies are needed to better determine possible risks as well as benefits, she said.

"Other cohort studies are needed to substantiate our findings," Seshadri said. Because the Framingham population is overwhelming white, "we need to look at people who are non-Caucasian," she said. "We also need to look at younger people, in their 50s or 60s."

Another report in the same issue of the journal described disappointing results in a trial of a once-promising drug to prevent Alzheimer's disease.

The drug, tarenflurbil, was designed to reduce production of amyloid, a protein that forms plaques in the brains of people with Alzheimer's disease. The study of 1,684 people who began taking the drug in the early stages of Alzheimer's disease showed no benefit, the report said.

But the anti-amyloid strategy is far from dead, said Dr. Lon S. Schneider, a professor of psychiatry, neurology and gerontology at the University of Southern California, and a co-author of the journal report.

"This was one of the early anti-amyloid approaches," Schneider said. "It was a definitive trial showing definitely that there was nothing here. But it doesn't mean that anti-amyloid strategies will fail, just that this drug isn't effective."

A number of other therapies that target amyloid are now in human trials, Schneider said. They include monoclonal antibodies that bind to the protein and drugs that inhibit the production of the amyloid fragments that are believed to be toxic to the brain.

Those trials are still recruiting participants, and results are not expected for a few years, Schneider said. Even if the results are negative, the anti-amyloid strategy can live on, although with a different approach, in which the drugs are given earlier in life, he said.