The findings are the first to associate decline in body mass index (BMI) with the eventual onset of AD. The loss of body mass may reflect disease processes at work, the researchers suggest, and the change in BMI might be a clinical predictor of the development of AD.

Aron S. Buchman, MD, David A. Bennett, MD, and colleagues at Rush University Medical Center in Chicago conducted the research as part of the nationwide Religious Orders Study, a comprehensive, long-term look at aging and AD among Catholic nuns, priests and brothers that began in 1993. Funding has been provided by the National Institute on Aging (NIA), a component of the National Institutes of Health, US Department of Health and Human Services. Rush University Medical Center is one of more than 30 Alzheimer's Disease Centers supported by the NIA.

Changes Preceding Dementia

"People with Alzheimer's disease are known to lose weight and body mass after they have the disease," says Dallas W. Anderson, PhD, 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," Anderson notes. "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 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.

Findings Held After Adjusting for Other Factors

Over the course of the study, people who lost approximately one unit of BMI per year had a 35 percent greater risk of developing AD compared to people with no change in BMI. Those with no change in BMI had a 20 percent greater risk of developing the disease than did people who gained six-tenths of a unit of BMI per year.

The findings held true even after adjusting for such factors as chronic health problems, age, sex and education. They also held true when those who developed AD in the first four 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.

Short List of AD Signs

"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," he suggests.

"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," he points out.

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, say the researchers.

"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.

Information on participation in AD clinical trials is available at ClinicalTrials.gov (search for "Alzheimer's disease trials") or at the Alzheimer's Disease Education and Referral (ADEAR) Center. ADEAR also may be contacted toll free at 1-800-438-4380.