An unexplained and persistent loss of body mass in an older person may be the first sign of Alzheimer’s disease, say researchers from Rush University Medical Center here.

“It has long been known that people with Alzheimer’s disease lose body mass and become cachectic,” said neurologist David Bennett, M.D., of the university’s Alzheimer’s Research Center.

But a new study, reported in the Sept. 27 edition of the journal Neurology, shows that the decline in body mass begins long before the first clinical signs of cognitive impairment can be seen, Dr. Bennett said.

An unexplained drop in body mass index (BMI), defined as weight (kilograms) divided by the square of height (meters), he said, may be “predictive” of Alzheimer’s.

The researchers studied 820 Catholic clergy, both male and female, who were taking part in the long-term Religious Orders Study, financed by the National Institute on Aging (NIA). All of the participants were older than 65 when they started the study; the majority were of European descent and their median BMI at the beginning was 27.4.

The researchers measured the BMI of participants every year, during clinical evaluations that included medical history, neurological examination, and cognitive function testing. During the mean 5.5 years of follow-up, 151 of the participants developed Alzheimer’s, although none was demented at the beginning.

People who lost one unit of BMI a year over five years had a 35% increase in the risk of Alzheimer’s disease, Dr. Bennett and colleagues found. (The hazard ratio was 0.730, with a 95% confidence interval ranging from 0.625 to 0.852.)

Because BMI is a function of both weight and height, it varies from person to person. For a woman who is five feet tall and weighs 120 pounds, one unit of BMI is about 5 pounds.

The BMI-Alzheimer’s association, Dr. Bennett said, is related to a clinical diagnosis of the disease; the researchers will also be able later to see how BMI is linked to the pathology of Alzheimer’s because the participants have agreed to autopsy.

He added that it’s not clear why the link exists; one possibility is that the Alzheimer’s pathology, usually thought to affect mainly the memory pathways of the brain, may also affect the parts that govern appetite or feelings of satiety.

“Unexplained weight loss in the elderly -  usually triggers an investigation (by the person’s physician),” Dr. Bennett said; the two main causes are cancer or an occult infection.

“Here’s another reason why people might be inexplicably losing weight,” he said.

In the future, said epidemiologist David Anderson, Ph.D., of the NIA, having an early sign of Alzheimer’s might be valuable as treatments become available. “The earlier the better,” said Dr. Anderson, who is program director for population studies in the Dementias of Aging Branch of NIA’s neuroscience and neuropsychology of aging program.

Dr. Anderson said the Rush study is valuable because it has “great data” acquired during regular and repeated clinical examinations. “Many longitudinal studies don’t do it so often,” he said.

The Rush finding is similar to that of a study earlier this year in which researchers found that a diagnosis of Alzheimer’s disease in Japanese-American men was often preceded by a sudden weight loss a few years earlier, Dr. Anderson noted.

The Rush study found that those who developed Alzheimer’s were significantly older - 80.2 years versus 74 on average - and had a lower BMI and cognitive function at the start of the study.

To eliminate the possibility that mild, undiagnosed disease would skew the results, the researchers repeated the analysis four times, each time excluding people who developed Alzheimer’s in each of the first four years of the study.

With each calculation, the BMI-Alzheimer’s association didn’t change substantially, the researchers found.

Source reference:
Buchman AS et al. Change in body mass index and risk of incident Alzheimer disease. Neurology 2005;65:892-897