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High Levels of Leptin May Decrease Alzheimer's Disease Risk


A new study published in the December 16 issue of the in The Journal of the American Medical Association found a lower rate of Alzheimer’s disease (AD) associated with high levels of leptin, a hormone produced by fat cells which is important in regulating appetite and metabolism.

The prospective study involved a subset (198) of the original 785 dementia-free persons who had plasma leptin concentrations measured who were in the Framingham original cohort at the 22nd examination cycle (1990-1994). This subset underwent volumetric brain MRI between 1999 and 2005, approximately 7.7 years after leptin was assayed. Two measures of brain aging, total cerebral brain volume and temporal horn volume (which is inversely related to hippocampal volume) were assessed.

During a median follow-up of 8.3 years, 111 participants developed incident dementia. Of those 111, 89 were diagnosed with Alzheimer’s disease (AD). The researchers noted that those with the highest levels of leptin were least likely to develop dementia or AD.

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The association of high leptin levels with a lower incidence of all-cause dementia and AD remained significant after adjustment for traditional vascular risk factors and for waist-to-hip ratio. The waist-to-hip ratio was used as a measure of body fat content.

The association was not statistically significant in participants with higher waist-to-hip ratio and higher BMI, but the numbers of participants in those subgroups were limited.

"Our study raises a strong possibility that leptin may actually have a role in the various pathological processes that result in clinical Alzheimer's disease," senior researcher Sudha Seshadri, MD, of Boston University School of Medicine. "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 interventions."

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Association of Plasma Leptin Levels With Incident Alzheimer Disease and MRI Measures of Brain Aging; JAMA. 2009;302(23):2565-2572; Wolfgang Lieb; Alexa S. Beiser; Ramachandran S. Vasan; Zaldy S. Tan; Rhoda Au; Tamara B. Harris; Ronenn Roubenoff; Sanford Auerbach; Charles DeCarli; Philip A. Wolf; Sudha Seshadri