Alzheimer's, Dementia & Mental Health
Higher Levels of Protein Hormone Leptin May Lower
Risk of Dementia, Alzheimer Disease
Leptin levels in older adults may serve as one of
several biomarkers for healthy brain aging; may open new
preventive and therapeutic intervention
Dec. 15, 2009 Senior citizens with higher levels
of leptin, a protein hormone produced by fat cells and involved in the
regulation of appetite, appear to be less likely to have Alzheimer
disease or dementia, according to a study in the December 16 issue of
the Journal of the American Medical Association (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.
Wolfgang Lieb, M.D., of the Framingham Heart Study,
Framingham, Mass., and colleagues examined the relationship between
measurements of plasma leptin concentrations and incidence of dementia
and Alzheimer disease (AD).
For this study, plasma leptin concentrations were
measured in 785 persons without dementia (average age, 79 years; 62
percent female), who were in the original Framingham study group at the
22nd examination cycle (1990-1994).
A subsample of 198 dementia-free survivors
underwent volumetric brain magnetic resonance imaging (MRI) between 1999
and 2005, approximately 7.7 years after leptin was measured. Two
measures of brain aging were assessed: total cerebral brain volume and
temporal horn (a region of the brain) volume, both of which are markers
of early AD pathology and subsequent dementia risk.
The researchers conducted follow-up for new cases
of dementia and AD until Dec. 2007. During a median (midpoint) follow-up
of 8.3 years, 111 participants developed dementia; 89 of them were
diagnosed with AD.
The researchers found that higher leptin levels
were associated with a lower incidence of all-cause 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.
Higher leptin levels were also associated with
higher total cerebral brain volume. Lower temporal horn volume was not
significantly related to leptin levels.
"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."
Did not predict those that developed dementia not caused by
Alzheimer's disease