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ST. LOUIS, Sept. 11 -- An early warning sign for Alzheimer's disease could be accelerated weight loss, researchers here suggested.

Among more than 400 healthy older adults ages 65 to 95, followed as part of a longitudinal study of Alzheimer's, those who had a sudden doubling of the rate of weight loss developed dementia about a year later, found David K. Johnson, Ph.D., of Washington University, and colleagues.

"Specific factors contributing to weight loss are unknown, but these data suggest they operate before the development of dementia of Alzheimer's type," the authors reported in the Sept. 11 issue of Archives of Neurology. "Hence, weight loss may be a preclinical indicator of Alzheimer disease."

Other studies have shown that weight loss is associated with development of dementia and with nursing home placement, but the timing and rate of the weight loss in relationship to the first signs of dementia are unknown, the authors noted.

They looked at rates of weight change in 449 volunteers (192 men, 257 women), who were cognitively healthy at baseline. The volunteers were controls in a longitudinal study of memory and aging.

Participants were weighed at study outset and at annual visits. The investigators created piecewise linear regression and random effects models to test longitudinal rates of weight change between the demented and non-demented groups.

In all, 125 of the original cohort went on to develop Alzheimer's-type dementia, and 324 remained cognitively healthy.

The investigators found that participants without dementia lost 0.65 (standard error, 0.13) pounds per year over the entire study period (January 1991 to March 2005).

Weight loss in the group that went on to develop dementia was similar (0.68 lbs per year, SE 0.27) until one year before the diagnosis of dementia. At that time, "there was a sharp acceleration such that the slope roughly doubled in magnitude."

In the year before the diagnosis, these participants lost 1.2 pounds, double the rate of the non-demented patients.

They also found that participants in the dementia group weighed an average of 8.2 lbs less at baseline than the participants whose mental faculties remained intact at study end.

The association between accelerated weight loss and dementia held up even when the investigators controlled for other factors potentially associated with weight loss, such as age, gender, health status, hypertension, and history of stroke.

The weight loss among patients with dementia was greatest when other health factors such as cardiovascular symptoms, male gender, and poor health were present, but these risks did not mediate the doubling of weight loss, the authors wrote.

"Other health risks investigated (depressive symptoms, marital status, use of potentially anorectic medications, APOE-4 expression, diabetes mellitus, and appetite change) were not related to weight loss and dementia progression," they added.

The findings from this and other epidemiologic studies suggest that Alzheimer's disease may be preceded by two phases of weight loss, the authors wrote.

"At midlife, participants who will eventually have dementia weigh as much as their peers without dementia," they wrote. "At late midlife or early late life, these individuals begin to lose weight at faster rates, and by six years before dementia detection, participants who will eventually develop dementia are six to eight pounds lighter on average."

"The present study shows that at least one year before dementia detection, the rate of weight loss again increases. Thus, weight loss associated with dementia of the Alzheimer's type probably begins very early in the course of the disease and then accelerates in the one to two years before the onset of cognitive symptoms," they wrote.

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