Weight Loss Comes Before a Cognitive Fall

ROCHESTER, Minn., Aug. 20 -- A decade before women develop dementia, they may begin to have an unexplained loss of weight, according to investigators here.
Women who went on to develop dementia weighed an average of 12 pounds less at the time of diagnosis than non-demented age-matched controls, reported David Knopman, M.D., of the Mayo Clinic, and colleagues, in a retrospective case-control study.
Weight loss did not predict dementia in men, however, the authors reported in the Aug. 21 issue of Neurology.
"One explanation for the weight loss is that, in the very early stages of dementia, people develop apathy, a loss of initiative, and also losses in the sense of smell," Dr. Knopman said. "When you can't smell your food, it won't have much taste, and you might be less inclined to eat it. And apathy and loss of initiative may make women less likely to prepare meals and more likely to skip meals."
In contrast, men are more likely to have their meals prepared for them, "which would lessen the effect of the apathy, loss of initiative and loss of sense of smell," Dr. Knopman added.
The authors identified patients who were diagnosed with dementia from 1990 through 1994, using records linked through the Rochester Epidemiology Project. They defined dementia according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria.
Each case was matched by gender and age to a patient from the same population. Controls were free of dementia in the year of dementia diagnosis of their matched cases. The weights of cases and controls were drawn from medical records.
The investigators identified a total of 481 patients who had been diagnosed with primary dementia of presumed vascular or degenerative origin during the study period and who had suitable matches. Information on weight for matched pairs was available for 295 female pairs and 76 male pairs.
The authors found that although there were no significant differences in weight between cases and controls from 21 to 30 years before the onset, women who developed dementia weighed significantly less than controls starting 11 to 20 years before the index year (the year of dementia onset), and that prior to the index year, and that this difference increased over time.
"We found a trend of increasing risk of dementia with decreasing weight in women both at the index year (test for linear trend, P<0.001) and nine to 10 years before the index year (test for linear trend, P<0.001)," they wrote.
Among men, however, there were no significant differences in weight at any time point, including the index year.
The authors suggested that the association between weight loss and dementia only in women may be attributable to hormonal factors.
"Women with lesser amounts of adipose tissue may have lower circulating levels of estrogen because the adipose tissue participates in the conversion of endogenous steroids to estrogen," they wrote. "Lower levels of estrogen in early menopause may increase the risk of neurodegenerative or vascular brain lesions. Similarly, the lack of association between weight loss and risk of dementia in men may be related to hormonal factors such as testosterone levels; however, a social explanation seems equally plausible."
Weight loss that precedes dementia might also be caused by dementia-related changes in limbic and hypothalamic function, alterations in insulin sensitivity, or age-related changes in metabolic function, they added.
The authors acknowledged that the study was limited by the retrospective case-control design, difficulties in diagnosing dementia in its early stages, and missing weight data for many of the cases.
The study was supported by grants from the National Institute on Aging and by the Rochester Epidemiology Project. Dr. Knopman has been a consultant to GE HealthCare, GlaxoSmithKline, and Myriad Pharmaceuticals, served on a Data Safety monitoring board for Neurochem Pharmaceuticals and Sanofi-Aventis, and was an investigator for in a trial sponsored by Elan Pharmaceuticals. Co-author Ronald C. Petersen M.D., Ph.D., has been a consultant to GE HealthCare, Servier, and Elan Pharmaceuticals. The remaining authors reported no conflicts of interest.Primary source: NeurologySource reference: Knopman DS et al. "Incident dementia in women is preceded by weight loss by at least a decade." Neurology 2007;69:739-746.