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Alzheimer's risk linked to level of appetite hormone
High levels of a hormone that controls appetite appear to be linked to a reduced risk of developing Alzheimer's disease, US research suggests.
The 12-year-study of 200 volunteers found those with the lowest levels of leptin were more likely to develop the disease than those with the highest.
The JAMA study builds on work that links low leptin levels to the brain plaques found in Alzheimer's patients.
The hope is leptin could eventually be used as both a marker and a treatment.
The hormone leptin is produced by fat cells and tells the brain that the body is full and so reduces appetite. It has long been touted as a potential weapon in treating obesity.
But there is growing evidence that the hormone also benefits brain function.
Research on mice - conducted to establish why obese patients with diabetes often have long-term memory problems - found those who received doses of leptin were far more adept at negotiating their way through a maze.
The latest research, carried out at Boston University Medical Center, involved regular brain scans on 198 older volunteers over a 12-year period.
A quarter of those with the lowest levels of leptin went on to develop Alzheimer's disease, compared with 6% of those with the highest levels.
"If our findings our confirmed by others, leptin levels in older adults may serve as one of several possible biomarkers for healthy brain ageing and, more importantly, may open new pathways for possible preventive and therapeutic intervention."
Rebecca Wood, chief executive of the Alzheimer's Research Trust, said: "Previous studies have shown that obesity in mid-life is associated with an increased risk of dementia, but this new research suggests that leptin might have a role to play.
"There is evidence that leptin has functions in the brain - further studies in this area could lead to the possibility that this hormone plays a role in new treatments for Alzheimer's."
Susanne Sorensen, head of research at the Alzheimer's Society, described the research as "important".
She said: "Further investigation is now needed to understand this relationship.
"This could move us closer to understanding the causes of the disease and provide vital information for drug development."
There are currently 700,000 people in the UK living with dementia.
Association of Plasma Leptin Levels With Incident Alzheimer Disease and MRI Measures of Brain Aging
Wolfgang Lieb, MD; Alexa S. Beiser, PhD; Ramachandran S. Vasan, MD; Zaldy S. Tan, MD; Rhoda Au, PhD; Tamara B. Harris, MD; Ronenn Roubenoff, MD, MHS; Sanford Auerbach, MD; Charles DeCarli, MD; Philip A. Wolf, MD; Sudha Seshadri, MD
Context The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes β-amyloid clearance, and improves memory function in animal models of aging and Alzheimer disease (AD).
Objective To relate baseline circulating leptin concentrations in a community-based sample of individuals without dementia to incident dementia and AD during follow-up and magnetic resonance imaging (MRI) measures of brain aging in survivors.
Design, Setting, and Participants Prospective study of plasma leptin concentrations measured in 785 persons without dementia (mean [SD] age, 79  years; 62% female), who were in the Framingham original cohort at the 22nd examination cycle (1990-1994). A subsample of 198 dementia-free survivors 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.
Main Outcome Measure Incidence of dementia and AD during follow-up until December 31, 2007.
Results During a median follow-up of 8.3 years (range, 0-15.5 years), 111 participants developed incident dementia; 89 had AD. Higher leptin levels were associated with a lower risk of incident dementia and AD in multivariable models (hazard ratio per 1-SD increment in log leptin was 0.68 [95% confidence interval, 0.54-0.87] for all-cause dementia and 0.60 [95% confidence interval, 0.46-0.79] for AD). This corresponds to an absolute AD risk over a 12-year follow-up of 25% for persons in the lowest quartile (first quartile) vs 6% for persons in the fourth quartile of sex-specific leptin levels. In addition, a 1-SD elevation in plasma leptin level was associated with higher total cerebral brain volume and lower temporal horn volume, although the association of leptin level with temporal horn volume did not reach statistical significance.
Conclusion Circulating leptin was associated with a reduced incidence of dementia and AD and with cerebral brain volume in asymptomatic older adults.
Author Affiliations: Framingham Heart Study, Framingham, Massachusetts (Drs Lieb, Beiser, Vasan, Wolf, and Seshadri); Department of Biostatistics, School of Public Health (Dr Besier), Departments of Neurology (Drs Beiser, Au, Auerbach, Wolf, and Seshadri) and Preventive Medicine and Epidemiology (Dr Vasan), School of Medicine, Boston University, Boston, Massachusetts; Boston VA Healthcare System and Division of Aging, Brigham and Women's Hospital, Boston, Masschusetts (Dr Tan); Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland (Dr Harris); Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts (Dr Roubenoff); and Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento (Dr DeCarli).
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