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Original Investigation |

Decline in Weight and Incident Mild Cognitive Impairment Mayo Clinic Study of Aging

Rabe E. Alhurani, MBBS1,2; Maria Vassilaki, MD, PhD3; Jeremiah A. Aakre, MPH4; Michelle M. Mielke, PhD2,3; Walter K. Kremers, PhD4; Mary M. Machulda, PhD5; Yonas E. Geda, MD, MSc3,6; David S. Knopman, MD2; Ronald C. Peterson, MD, PhD2,3; Rosebud O. Roberts, MB, ChB2,3
[+] 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.
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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.

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Hazard Ratios for Midlife Weight Quartiles by the Rate of Weight Change per Decade

The estimates are based on a model adjusted for sex, years of education, APOE*E4, and weight at study entry, with age as the time scale. The mean (SD) maximum weight measurements in midlife were 62.0 (5.1) kg for the first quartile (Q1), 75.9 (3.6) kg for the second quartile (Q2), 86.8 (2.9) kg for the third quartile (Q3), and 103.7 (11.8) kg for the fourth quartile (Q4). The observed median (fifth and 95th percentile) rates of weight change from midlife to study entry for the 4 weight quartiles were −0.4 (−6.5 to 5.2) kg per decade for Q1, −1.0 (−8.2 to 5.2) kg per decade for Q2, −1.7 (−9.4 to 6.0) kg per decade for Q3, and −2.3 (−14.4 to 7.7) kg per decade for Q4. We provided the fifth and 95th percentiles to give a broader sense of the distribution of weight change for each midlife weight quartile.

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