Persons with higher levels of leptin, a protein hormone produced by fat cells and involved in the regulation of appetite, may have an associated reduced incidence of Alzheimer disease and dementia, according to a study in the December 16 issue of JAMA.

Previous studies have shown that overweight and obesity in mid-life are associated with poorer cognitive function in the general population and an increased risk of dementia. There has been evidence that leptin exerts additional functions on the brain outside the hypothalamus (a region of the brain that controls body temperature, hunger, and thirst), according to background information in the article.

The researchers found that higher leptin levels were associated with a lower incidence of  dementia and AD. The incidence of dementia decreased gradually across increasing levels of leptin: a person with a baseline leptin level in the lowest quartile group had a 25 percent risk of developing AD after 12 years of follow-up, whereas the corresponding risk for a person in the top quartile group was only 6 percent.

“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. Due to the exploratory character of the present analyses, we did not adjust for multiple comparisons and acknowledge that our findings require confirmation in independent samples,” the authors write.

“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. 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 AD.”
(JAMA 2009;302[23]:2565-2572. )