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Original Investigation
April 2016

Decline in Weight and Incident Mild Cognitive ImpairmentMayo Clinic Study of Aging

Author Affiliations
  • 1Mayo Clinic Graduate School of Medicine, Rochester, Minnesota
  • 2Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 3Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 4Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 5Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
  • 6Departments of Psychiatry and Psychology and of Neurology, Mayo Clinic, Scottsdale, Arizona
JAMA Neurol. 2016;73(4):439-446. doi:10.1001/jamaneurol.2015.4756

Importance  Unintentional weight loss has been associated with risk of dementia. Because mild cognitive impairment (MCI) is a prodromal stage for dementia, we sought to evaluate whether changes in weight and body mass index (BMI) may predict incident MCI.

Objective  To investigate the association of change in weight and BMI with risk of MCI.

Design, Setting, and Participants  A population-based, prospective study of participants 70 years of age or older from the Mayo Clinic Study of Aging, which was initiated on October 1, 2004. Maximum weight and height in midlife (40-65 years of age) were retrospectively ascertained from the medical records of participants using a medical records–linkage system. The statistical analyses were performed between January and November 2015.

Main Outcomes and Measures  Participants were evaluated for cognitive outcomes of normal cognition, MCI, or dementia at baseline and prospectively assessed for incident events at each 15-month evaluation. The association of rate of change in weight and BMI with risk of MCI was investigated using proportional hazards models.

Results  Over a mean follow-up of 4.4 years, 524 of 1895 cognitively normal participants developed incident MCI (50.3% were men; mean age, 78.5 years). The mean (SD) rate of weight change per decade from midlife to study entry was greater for participants who developed incident MCI vs those who remained cognitively normal (−2.0 [5.1] vs −1.2 [4.9] kg; P = .006). A greater decline in weight per decade was associated with an increased risk of incident MCI (hazard ratio [HR], 1.04 [95% CI, 1.02-1.06]; P < .001) after adjusting for sex, education, and apolipoprotein E (APOE) ε4 allele. A weight loss of 5 kg per decade corresponds to a 24% increase in risk of MCI (HR, 1.24). A higher decrease in BMI per decade was also associated with incident MCI (HR, 1.08 [95% CI, 1.03-1.13]; P = .003).

Conclusions and Relevance  These findings suggest that increasing weight loss per decade from midlife to late life is a marker for MCI and may help identify persons at increased risk for MCI.