Loss of body mass over time appears to be strongly linked to older adults’ risk of developing Alzheimer’s disease (AD), and the greater the loss the greater the chance of a person developing the disease, new research has found. The findings are the first to associate decline in body mass index (BMI) with the eventual onset of AD. The researchers suggest 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.”

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. 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 researchers note 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.

To contact Dr. Dallas Anderson: Call Susan Farrer or Vicky Cahan, NIA Office of Communications and Public Liaison, 301-496-1752.

To contact Dr. David Bennett or Dr. Aron Buchman: Call Mary Ann Schultz, Media Relations, Rush University Medical Center, 312-942-7816.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.