January 27, 2010
Older men and women with high levels of leptin, a hormone made by fat cells and linked to appetite regulation, may have a reduced risk of developing Alzheimer's disease compared to those with low levels of the hormone, a new study reports. More research is needed to explain the possible role of leptin in Alzheimer's disease, but the findings suggest that a complex web of factors, including hormones like leptin, may be important for healthy aging of the brain. The findings may open up new avenues of research into hormones, the brain and Alzheimer's disease.
Scientists have been studying leptin mainly because of its role in regulating appetite. Like all hormones, it also has wide-ranging effects throughout the body, including the brain. In animal studies, leptin has been shown to affect brain cell growth in the hippocampus, a part of the brain critical for memory and learning. The hormone also appears to stimulate clearance of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer's, and boost memory in animal studies.
The current findings, published in The Journal of the American Medical Association, come from the ongoing Framingham Heart Study, a large, decades-long analysis of men and women living in the town of Framingham, Mass. Researchers measured leptin levels in 785 older men and women; their average age was 79. None had Alzheimer's at the start of the study period.
During follow-up, about 8 years later, 111 of the study participants had developed Alzheimer's or other forms of dementia. The researchers found that higher leptin levels were associated with a lower incidence of Alzheimer's disease and other types of dementia. Those with the lowest leptin levels had a four fold greater chance of developing Alzheimer's after 12 years. The risk was independent of risk factors like blood vessel and heart disease. In contrast, those with the highest leptin levels had a lower risk. Higher leptin levels were also associated with higher total cerebral brain volume; decreased brain volume has been linked to Alzheimer's.
"These findings are consistent with recent experimental data indicating that leptin improves memory function in animals through direct effects on the hippocampus and strengthens the evidence that leptin is a hormone with a broad set of actions in the central nervous system," the authors wrote.
The role of weight and of hormones like leptin in the development of Alzheimer's disease requires further research and clarification. In some cases, weight loss in elderly people is an early warning sign of impending Alzheimer's.
At the same time, people who are overweight in middle age are at increased risk for Alzheimer's as they grow older, earlier research has shown. One hypothesis states that obesity at midlife may lead to leptin resistance, in which the body becomes less responsive to the effects of the hormone. As a result, the brain-protecting properties of the hormone may fail to take hold in later years, according to this hypothesis. However, it must be noted that obesity effects health in many ways. It is not yet known whether leptin is responsible for the increased risk of Alzheimer's in obese people.
The findings may also open up new avenues of research on Alzheimer's disease. Low blood leptin levels, for example, may emerge as a risk factor for Alzheimer's, the way high cholesterol may be a marker for heart disease. So far, there is no test for preclinical Alzheimer's, and the disease can be diagnosed with certainty only after death.
"If our findings are confirmed by others, leptin levels in older adults may serve as one of several possible biomarkers for healthy brain aging and, more importantly, may open new pathways for possible preventive and therapeutic intervention," the authors wrote. "Further exploration of the molecular and cellular basis for the observed association may expand our understanding of the pathophysiology underlying brain aging and the development of Alzheimer's disease."
Wolfgang Lieb, M.D.; Alexa S. Beiser, Ph.D.; Ramachandran S. Vasan, M.D.; et al: "Association of Plasma Leptin Levels With Incident Alzhemer Disease and MRI Measures of Brain Aging." Journal of the American Medical Association, Dec. 16, 2009, Vol. 302, No. 23, pages 2565-2572.