From the earliest stages of AD, many people tend to lose weight, despite the best efforts of caregivers to provide high-calorie, nutrient-rich meals and snacks, and to remind the person to eat regularly. Some people with AD also advance to a condition known as cachexia, a general wasting effect that involves unexplained weight loss, as well as fatigue, weakness, and significant loss of appetite.
The underlying cause or causes of weight loss and cachexia associated with AD remain unclear, however. Some scientists have suggested that abnormally high daily calorie use (from pacing, for example), combined with lower-than-normal daily calorie intake, results in the drop in body mass. Others hypothesize that weight loss results from loss of the initiative to eat; loss of the sense of smell; or atrophy or other changes in the brain that alter the person's metabolism, appetite, or behavior.
While decreased body mass is a well-accepted part of AD, recent studies funded by the NIA also suggest that unexplained weight loss actually precedes the measurable cognitive impairment and other signs of the disease often by years. For example:
- As part of the Honolulu-Asia Aging Study, NIA-funded researchers at the Pacific Health Research Institute in Hawaii looked at weight changes and the onset of dementia in 1,890 Japanese-American men ages 77 to 98 years over a 32-year time span. During the first 26 years, those with and without dementia did not differ with respect to baseline weight or change in weight. In the succeeding 6 years, though, those who were eventually diagnosed with AD or vascular dementia lost more weight yearly than did those who were not diagnosed with the disease. (Stewart et al., 2005)
- Investigators at the Rush Alzheimer's Disease Center in Chicago found an association between decreased body mass index (BMI) and the risk of AD within a group of older Catholic clergy participating in the Religious Orders Study. Those who lost approximately one unit of BMI per year had a 35 percent greater chance of developing AD than those with no change in BMI over the course of the study, and the greater the loss of BMI, the greater the chance of developing the disease. (Buchman et al., 2005)
- Using data from the Memory and Aging Project, researchers at the Washington University Alzheimer's Disease Research Center in St. Louis followed a group of 449 older adults over a 6-year period, during which 125 of the participants developed dementia. On average, those who did and did not develop dementia lost weight at the same rate for the first several years of the study. However, a year before the early signs of dementia appeared, those who eventually developed AD had lost twice as much weight as those who did not develop AD. (Johnson et al., 2006)
- In a retrospective review of medical records, scientists at the Mayo Clinic and the University of California San Diego compared the weights and heights of 481 people who were diagnosed with dementia with those of sex-matched controls without dementia. They found that by 11 to 20 years before the disease onset, women with primary dementia on average weighed nearly 6 pounds less than the female controls, and by the year of diagnosis weighed more than 13 pounds less than the controls. Among men, during the year of diagnosis, those with dementia weighed 5 pounds less than the controls, although the difference was not significant then or at earlier time points. (Knopman et al., 2006).
"Unexplained weight loss is well-recognized as part of the clinical constellation of Alzheimer's disease symptoms. Now, a growing body of evidence suggests that weight loss can actually begin before the signs of cognitive dysfunction appear," says Marcelle Morrison-Bogorad, PhD, director of the NIA's Neuroscience and Neuropsychology of Aging Program. "The jury is still out on whether weight loss is part of or a result of the Alzheimer's disease process, but these findings do suggest that even subtle decreases in weight might be a clinical predictor of AD."
Refernces:
Buchman, A.S. et al. (2005). Change in Body Mass Index and Risk of Incident Alzheimer Disease. Neurology, 65(6);892-7.
Johnson, D.K. et al. (2006). Accelerated Weight Loss May Precede Diagnosis in Alzheimer Disease. Archives of Neurology, 63(9):1312-7.
Knopman, D.S. et al. (2006). Incident Dementia in Women Preceded by Weight Loss by at Least a Decade (presented at the 10th International Conference on Alzheimer's Disease and Related Disorders; Abstract P1-207).
Stewart, R. et al. (2005). 32-Year Prospective Study of Change in Body Weight and Incident Dementia: The Honolulu-Asia Aging Study. Archives of Neurology, 62(1):55-60.
NIH 2007
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