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High Leptin Levels May Protect Against Dementia
by Pauline Anderson for Medscape
December 15, 2009

--dementia prevalence is increasing
--new evidence found that leptin may protect against Alzheimer’s disease
--new study suggests that high leptin-->lower dementia incidence incl AD
--participants with highest leptin had a 6% risk of developing AD during 12 years
--lowest leptin levels-->25% risk in 12 years
--leptin is produced in subcutaneous and visceral adipose tissue
((it is my recollection that more is made by subcu and less by visceral fat))
--leptin appears to promote weight loss
--leptin influences caloric intake and fat store utilization via the hypothalamus
--emerging animal research indicates leptin may function in the hippocampus too
--hippocampus key in memory
--this is the first time leptin has been implicated in memory
--lead author Sudha Seshadri, MD, assoc prof of neurology, Boston U. School of Medicine in MA
--AD research so far has concentrated on beta-amyloid plaques and the tau protein
--study published in December 15 2009 issue of JAMA
--n = 785 in Framingham Heart study, long term study
--baseline plasma leptin levels measured between 1990 and 1994
-->then followed up for dementia until December 31, 2007
--average age at baseline was 79 years, 62% of them were female
--subset n = 198 underwent volumetric brain MRIs between 1999 and 2005 while dementia free
-->a single measurement of total cerebral brain volume and temporal horn volume
--temporal horn volume is inversely related to hippocampal volume
--both measurements are markers of early AD
--median follow-up of 8.3 years: 111 participants developed dementia (incl 89 with AD)
--strong inverse relationship between baseline leptin levels and the risk for dementia
--relationship remained significant after adjusting for age, sex, waist to hip ratio, changes to waist to hip ratio, and other vascular and dementia risk factors (what other factors?)
--waist to hip ratio was used as the measure of body fat content because correlates more strongly with plasma leptin levels and AD risk than BMI
--incidence of dementia decreased across increasing sex-specific leptin quartiles
--a pt with baseline leptin in lowest quartile had a 25% risk of developing AD after 12 years
--pt in top quartile for leptin levels had 6% chance of developing AD in 12 yrs
--*higher leptin levels also assoc w/ larger brain parenchymal and smaller ventricular volumes

--pts in study all older and of European ancestry
--leptin not measured in CSF
--correlation between plasma and CSF leptin is strong
--study did not include measures of physical activity

--a previous study found that leptin-deficient mice have:
1) lower brain weight
2) an immature expression pattern of synaptic and glial proteins
3) disrupted projection pathways within the hypothalamus
--SO: leptin is necessary for normal brain development

--another study demonstrated that leptin increases apolipoprotein E (APOE)
--has something to do with beta-amyloid uptake into cells
--anOther study shows that long-term leptin tx improved memory performance in animals

--leptin clearly has a role in energy metabolism
--leptin seems to have a beneficial effect on some aspects of the brain

--the association of high leptin levels with a lower incidence of dementia was only significant among patients who were not obese
--obese people may have high levels of leptin, but they may be resistant to it

--relationship between beta-amyloid and leptin remains unclear
--some animal studies suggest that leptin interacts with APOE
--APOE = a chaperone protein that helps clear beta-amyloid
--leptin may be part of future AD tx
--leptin mb a biomarker by which physicians can predict risk
--JAMA. 2009;302:2565-2572.




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