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Steady Weight Loss May Indicate Alzheimer’s Onset
for Senior Citizens
Sept. 26, 2005 – The latest theory on predicting
Alzheimer’s disease is that a steady loss of weight - body mass - over
time appears to be strongly linked to older adults' risk of developing
the disease. And, the researchers say, the greater the loss the greater
the chance of a person developing Alzheimer’s. They theorize that the
loss of body mass reflects disease processes and that change in BMI
might be a clinical predictor of the development of AD.
The research, reported in the September 27, 2005,
issue of Neurology, was conducted by Aron S. Buchman, M.D., David A.
Bennett, M.D., and colleagues at Rush University Medical Center in
Chicago, IL, as part of the Religious Orders Study.
The Religious Orders Study is a comprehensive,
long-term look at aging and AD among Catholic nuns, priests, and
brothers nationwide that has been funded by the National Institute on
Aging (NIA), a component of the National Institutes of Health, U.S.
Department of Health and Human Services, since 1993. Rush University
Medical Center is one of more than 30 Alzheimer's Disease Centers
supported by the NIA.
"People with Alzheimer's disease are known to lose
weight and body mass after they have the disease," says Dallas W.
Anderson, Ph.D., program director for population studies in the
Dementias of Aging Branch of NIA's Neuroscience and Neuropsychology of
Aging Program.
"This study is significant in that it looks at body
mass changes in the years preceding dementia and cognitive decline.
Other studies have looked at BMI at only one point in time or studied
body mass loss in people who already have AD," he says.
Each of the 820 study participants took part in
yearly clinical evaluations that included a medical history, neurologic
examination, and extensive cognitive function testing. The participants'
weights and heights were also measured to determine their BMI, a widely
used measure of body composition that is calculated by dividing weight
in kilograms by height in meters squared. (To use our BMI calculator,
click here.)
They completed an average of 6.6 annual
evaluations, with a 95 percent follow-up rate. All of the participants
were older than 65 years, and the vast majority of them were white and
of European ancestry.
When the study began, none of the participants had
dementia, and their average BMI was 27.4. During the follow-up period,
151 of the participants (18.4 percent) developed AD. Both baseline BMI
and the annual rate of change in BMI were linked to the risk of
developing AD.
People who lost approximately one unit of BMI per
year had a 35 percent greater risk of developing AD than that of people
with no change in BMI over the course of the study. Those with no change
in BMI had a 20 percent greater risk of developing the disease than that
of people who gained six-tenths of a unit of BMI per year.
The findings held true even after adjusting for
factors such as chronic health problems, age, sex, and education. They
also held true when those who developed AD in the first 4 years of
follow-up--and might have had mild, undiagnosed AD early in the
study--were excluded from the analysis.
The investigators found a similar relationship
between changes in BMI and rate of cognitive decline, which is the
clinical hallmark of AD. Even when controlling for baseline cognitive
function, baseline BMI, age, sex, and education, the rate of cognitive
decline among people losing approximately one unit of BMI per year was
more than 35 percent higher than that of people with no change in BMI
and 80 percent higher than that of people who gained six-tenths of a
unit of BMI per year.
Further analyses showed that depressive symptoms,
participants' physical activity levels, and female participants' use of
estrogen replacement did not explain the link between BMI loss and
development of AD.
In addition, when the researchers looked at changes
in weight rather than BMI, they found that a loss of 1 pound per year
was associated with a 5 percent increase in the risk of AD.
"These findings suggest that subtle, unexplained
body mass and weight loss in an older person may be an early sign of AD
and can precede the development of obvious memory problems," explains
Bennett, who directs the Rush Alzheimer's Disease Center. "The most
likely explanation is that there is something about these individuals or
about this disease that affects BMI before the clinical syndrome becomes
apparent--that loss of BMI reflects the disease process itself."
"Our understanding of Alzheimer's disease is
changing as we get more information, particularly as we look at the
pathology of the disease," adds Buchman, the lead investigator for the
study. "It turns out that Alzheimer's disease not only results in
cognitive dysfunction, but also may have a variety of other symptoms,
depending on which brain regions are affected. If the disease pathology
affects a region of the brain that controls weight, your body mass may
decline prior to loss of cognition."
Based on the Religious Orders Study findings and
other evidence, the researchers suggest that loss of body mass could be
added to the "relatively short list" of signs doctors can use to predict
a person's risk of developing AD.
"There are actually very few predictors of
Alzheimer's disease," Bennett explains. "This study makes us think about
the spectrum of clinical signs of AD beyond changes in memory and
behavior and motor skills. Changes in BMI are easy to measure in a
doctor's office without an expensive scan," he says.
Bennett and colleagues acknowledge that the study
participants were limited to Catholic clergy living in communal settings
and recommend replication of the research with more diverse groups of
people. They also note that the group's homogeneity strengthened their
research because they knew that all of the participants had access to
ample, nutritious food. The authors are indebted to the altruism and
support of the participants in the Religious Orders Study.
The findings are the first to associate decline in
body mass index (BMI) with the eventual onset of AD, say the
researchers. They note, however, that the Religious Orders Study
research complements recently published findings of the Honolulu-Asia
Aging Study, a 32-year population-based study funded jointly by NIA and
the National Heart, Lung, and Blood Institute, NIH.
Those findings, released in the January 2005
Archives of Neurology, show that dementia-associated weight loss in
Japanese-American men begins before the onset of dementia and
accelerates by the time of diagnosis.
For more information on participation in an AD
clinical trial, visit
http://www.clinicaltrials.gov/ (search for "Alzheimer's disease
trials") or the Alzheimer's Disease Education and Referral (ADEAR)
Center website at
http://www.alzheimers.org. ADEAR may also be contacted toll free at
1-800-438-4380. The ADEAR Center is sponsored by the NIA to provide
information to the public and health professionals about AD and
age-related cognitive change and may be contacted at the website and
phone number above for a variety of publications and fact sheets, as
well as information on clinical trials.
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