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Incident dementia in women is preceded by weight loss by at least a decade

From the Department of Neurology (D.S.K., R.C.P., W.A.R.) and the Divisions of Epidemiology (W.A.R.) and Biostatistics (R.H.C.), Department of Health Sciences Research, Mayo Clinic College of Medicine, and Mayo Clinic Alzheimer Disease Center (D.S.K., R.H.C., R.C.P., W.A.R.), Rochester, MN; and Division of Biostatistics, Department of Family and Preventative Medicine (S.D.E.), University of California–San Diego.

Address correspondence and reprint requests to Dr Knopman, Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 knopman{at}mayo.edu

Background: Although several studies reported weight loss preceding the onset of dementia, other studies suggested that obesity in midlife or even later in life may be a risk factor for dementia.

Methods: The authors used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, MN, for the 5-year period 1990 to 1994. The authors defined dementia using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Each case was individually matched by age (±1 year) and sex to a person drawn randomly from the same population, and free from dementia in the index year (year of onset of dementia in the matched case). Weights were abstracted from the medical records in the system.

Results: There were no differences in weight between cases and controls 21 to 30 years prior to the onset of dementia. However, women with dementia had lower weight than controls starting at 11 to 20 years prior to the index year, and the difference increased over time through the index year. 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 9 to 10 years before the index year (test for linear trend; p = 0.001).

Conclusions: Even accounting for delays in diagnosis, weight loss precedes the diagnosis of dementia in women but not in men by several years. This loss may relate to predementia apathy, loss of initiative, and reduced olfactory function.

Supported by NIA grants U01 AG06786 and P50 AG16574, and made possible by the Rochester Epidemiology Project (R01 AR30582).

Disclosure: Dr. Knopman has been a consultant to GE HealthCare, GlaxoSmithKline, and Myriad Pharmaceuticals and has served on a Data Safety monitoring board for Neurochem Pharmaceuticals and Sanofi-Aventis. The latter involves the drug rimonabont and its effects on cardiovascular disease; one of its actions is weight loss. He is also an investigator in a clinical trial sponsored by Elan Pharmaceuticals. Dr. Petersen has been a consultant to GE HealthCare, Servier, and Elan Pharmaceuticals. The remaining authors report no conflicts of interest.

Received November 9, 2006. Accepted in final form March 23, 2007.

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