Having low levels of leptin, a hormone that regulates appetite, is linked to an increased risk of Alzheimer’s disease in people who have memory problems, according to a new report. The findings confirm earlier reports that leptin, which like other hormones has widespread effects throughout the body, may play an important role in brain health.
The findings, presented at the Alzheimer’s Disease 28th International Conference in Taiwan, add to growing evidence that the hunger hormone may play a role in memory and dementia. Researchers hope that further exploration of the connection between leptin and Alzheimer’s may lead to better ways to diagnose or manage the disease.
Scientists have been studying leptin primarily for its effects on appetite and weight control, but there is growing interest in the effects of the hormone on healthy aging and the brain. In one eight-year study, older men and women with high levels of leptin had a reduced risk of developing Alzheimer's disease compared to those with low levels of the hormone. [See the alzinfo.org story, “Fat Hormone Leptin Linked to Alzheimer’s Disease,” at https://www.alzinfo.org/01/articles/diagnosis-and-causes-8 .]
People who develop Alzheimer’s disease often suffer from diminished appetite and weight loss in the years before the illness is diagnosed. Many tend to have low levels of leptin, which is made in fat cells. At the same time, people who are overweight in middle age are at increased risk for Alzheimer's with advancing age. One theory is that obesity at midlife may make the body, and the brain, less responsive to the beneficial effects of the hormone, though many factors are likely involved in obesity’s effects on the brain.
Studies have shown that giving leptin to animals who are bred to develop a disease resembling Alzheimer’s can reduce levels of beta-amyloid, a toxic protein that builds up in the brains of those with the disease. It also appears to boost cognitive abilities and may have particular benefits for the hippocampus, a part of the brain critical for memory and learning.
In the current study, researchers at the Queen Mary Hospital of the University of Hong Kong studied 232 older men and women, ages 55 to 93, with mild cognitive impairment, a serious form of memory loss that often leads to Alzheimer’s. All lived at home and could carry out day-to-day tasks, and none had full-blown dementia.
The researchers followed the participants for a year, administering tests of memory and thinking skills. During that time, some of the participants were diagnosed with Alzheimer’s disease. After controlling for age, sex and years of education, they found two factors that affected dementia risk: carrying the APOE-E4 gene, a well known risk factor for Alzheimer’s, and leptin levels.
Carrying the APOE-E4 gene was associated with a two- to three-fold risk in progressing to full-blown Alzheimer’s disease. Having higher blood levels of leptin, on the other hand, appeared to protect slightly against dementia. Those with higher leptin had a 7 percent reduced risk of progression to Alzheimer’s. Having other diseases like high blood pressure, heart disease, diabetes, a history of stroke or Parkinson’s disease was not associated with progression to Alzheimer’s disease, though other studies have linked some of these diseases with increased risk for developing Alzheimer’s.
Better understanding of the role of leptin levels in Alzheimer’s could lead to better ways to diagnose the disease. Tests that monitored leptin might, for example, signal the onset of Alzheimer’s at its earliest stages, a time when drugs may be most effective for protecting the brain against disease-induced damage.
Drugs that raise leptin levels might also prove effective as an Alzheimer’s treatment though at this time there is no evidence to support that. Larger and longer-term studies would be needed to determine whether giving leptin to people with mild cognitive impairment curbs progression to Alzheimer’s. Additional studies would also be needed to see if the hormone helps to prevent dementia in healthy seniors at risk for the disease, so it will likely be years before any kind of leptin therapy might be available, if at all.
Alzheimer's Disease International 28th International Conference. Abstract OC077. Presented April 20, 2013.