Loss of body mass over time appears to be strongly linked to olderadults' risk of developing Alzheimer's disease (AD), and the greaterthe loss the greater the chance of a person developing the disease, newresearch has found. The findings are the first to associate decline inbody mass index (BMI) with the eventual onset of AD. The researcherssuggest that the loss of body mass reflects disease processes and thatchange in BMI might be a clinical predictor of the development of AD.
The research, reported in the September 27, 2005, issue ofNeurology, 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 acomprehensive, long-term look at aging and AD among Catholic nuns,priests, and brothers nationwide that has been funded by the NationalInstitute on Aging (NIA), a component of the National Institutes ofHealth, U.S. Department of Health and Human Services, since 1993. RushUniversity Medical Center is one of more than 30 Alzheimer's DiseaseCenters supported by the NIA.
"People with Alzheimer's disease are known to lose weight and body massafter they have the disease," says Dallas W. Anderson, Ph.D., programdirector for population studies in the Dementias of Aging Branch ofNIA's Neuroscience and Neuropsychology of Aging Program. "This study issignificant in that it looks at body mass changes in the yearspreceding dementia and cognitive decline. Other studies have looked atBMI at only one point in time or studied body mass loss in people whoalready have AD."
Each of the 820 study participants took part in yearly clinicalevaluations that included a medical history, neurologic examination,and extensive cognitive function testing. The participants' weights andheights were also measured to determine their BMI, a widely usedmeasure of body composition that is calculated by dividing weight inkilograms by height in meters squared. They completed an average of 6.6annual evaluations, with a 95 percent follow-up rate. All of theparticipants were older than 65 years, and the vast majority of themwere white and of European ancestry.
When the study began, none of the participants had dementia, and theiraverage BMI was 27.4. During the follow-up period, 151 of theparticipants (18.4 percent) developed AD. Both baseline BMI and theannual 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 percentgreater risk of developing AD than that of people with no change in BMIover the course of the study. Those with no change in BMI had a 20percent greater risk of developing the disease than that of people whogained six-tenths of a unit of BMI per year.
The findings held true even after adjusting for factors such as chronichealth problems, age, sex, and education. They also held true whenthose who developed AD in the first 4 years of follow-up--and mighthave had mild, undiagnosed AD early in the study--were excluded fromthe analysis.
The investigators found a similar relationship between changes in BMIand 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 peoplelosing approximately one unit of BMI per year was more than 35 percenthigher than that of people with no change in BMI and 80 percent higherthan 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 estrogenreplacement did not explain the link between BMI loss and developmentof AD.
In addition, when the researchers looked at changes in weight ratherthan BMI, they found that a loss of 1 pound per year was associatedwith a 5 percent increase in the risk of AD.
"These findings suggest that subtle, unexplained body mass and weightloss in an older person may be an early sign of AD and can precede thedevelopment of obvious memory problems," explains Bennett, who directsthe Rush Alzheimer's Disease Center. "The most likely explanation isthat there is something about these individuals or about this diseasethat affects BMI before the clinical syndrome becomes apparent--thatloss of BMI reflects the disease process itself."
"Our understanding of Alzheimer's disease is changing as we get moreinformation, particularly as we look at the pathology of the disease,"adds Buchman, the lead investigator for the study. "It turns out thatAlzheimer's disease not only results in cognitive dysfunction, but alsomay have a variety of other symptoms, depending on which brain regionsare affected. If the disease pathology affects a region of the brainthat controls weight, your body mass may decline prior to loss ofcognition."
Based on the Religious Orders Study findings and other evidence, theresearchers suggest that loss of body mass could be added to the"relatively short list" of signs doctors can use to predict a person'srisk of developing AD.
"There are actually very few predictors of Alzheimer's disease,"Bennett explains. "This study makes us think about the spectrum ofclinical signs of AD beyond changes in memory and behavior and motorskills. Changes in BMI are easy to measure in a doctor's office withoutan expensive scan," he says.
Bennett and colleagues acknowledge that the study participants werelimited to Catholic clergy living in communal settings and recommendreplication of the research with more diverse groups of people. Theyalso note that the group's homogeneity strengthened their researchbecause they knew that all of the participants had access to ample,nutritious food. The authors are indebted to the altruism and supportof the participants in the Religious Orders Study.
The researchers note that the Religious Orders Study researchcomplements recently published findings of the Honolulu-Asia AgingStudy, a 32-year population-based study funded jointly by NIA and theNational Heart, Lung, and Blood Institute, NIH. Those findings,released in the January 2005 Archives of Neurology, show thatdementia-associated weight loss in Japanese-American men begins beforethe 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 ADEARCenter is sponsored by the NIA to provide information to the public andhealth professionals about AD and age-related cognitive change and maybe contacted at the website and phone number above for a variety ofpublications and fact sheets, as well as information on clinicaltrials.
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