Loss of Body Mass Linked to Alzheimer’s

Researchers at the Rush Alzheimer’s Disease Center have found that the 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.

The findings, published in the September 27 issue of Neurology, are the first to report an association between decline in body mass index (BMI) with the eventual onset of AD. Principal investigator Aron S. Buchman, M.D., suggests that the loss of body mass reflects disease processes that may contribute to the eventual development of AD

Along with Buchman, Dr. David A. Bennett, director of the Rush Alzheimer’s Disease Center, and colleagues at Rush University Medical Center, conducted the research as part of the Religious Orders Study (ROS). The ROS 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), 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.

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.

Buchman found a similar relationship between changes in BMI and cognitive function, which is the clinical hallmark of AD. “Even when controlling for 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.”

Bennett says 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 one 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, “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 may reflect the disease process itself.”

“Our understanding of Alzheimer’s disease is changing as we get more and more information, particularly as we look at the pathology of the disease,” adds Buchman, “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 even if your cognition is intact.”

Based on the these 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 a thousand-dollar 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 researchers note that the ROS 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.

From Rush Medical Center



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