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Observational Study
. 2025 May 13;104(9):e213534.
doi: 10.1212/WNL.0000000000213534. Epub 2025 Apr 11.

Association of Body Mass Index in Late Life, and Change from Midlife to Late Life, With Incident Dementia in the ARIC Study Participants

Affiliations
Observational Study

Association of Body Mass Index in Late Life, and Change from Midlife to Late Life, With Incident Dementia in the ARIC Study Participants

Ethan J Cannon et al. Neurology. .

Abstract

Background and objectives: Midlife obesity is a risk factor of dementia, but late-life obesity has been associated with lower dementia risk. We investigated this paradox by exploring the relationship between late-life body mass index (BMI) category and dementia, with and without considering midlife to late-life BMI change.

Methods: This observational cohort study included participants of the community-based Atherosclerosis Risk in Communities (ARIC) study who were dementia-free at visit 5 (2011-2013). Dementia was ascertained by expert-adjudicated, algorithmic classification from an in-person neuropsychological battery, as well as telephone interviews and International Classification of Diseases codes from medical records. We first assessed the association of incident dementia with visit 5 BMI categories (normal weight, overweight, obese). Next, we used a cross-classification of visit 5 BMI categories with visit 4-visit 5 BMI change (decrease [loss of ≥2 kg/m2], increase [gain of ≥2 kg/m2], or stable [loss or gain of <2 kg/m2]) occurring during the 15 years before baseline. Cox regression was used.

Results: A total of 5,129 participants were included in the study (59% female; 22% identified as Black; mean (standard deviation) age at visit 5 of 75 (5) years). Over 8 years of follow-up, 20% of the sample developed dementia (n = 1,026). After covariate adjustment, participants with high late-life BMI had a lower risk of dementia; the hazard ratio (95% CI) was 0.86 (0.73-1.00) for overweight and 0.81 (0.68-0.96) for obesity. In stratified models, elevated dementia risk was observed only for participants of each late-life BMI category whose BMI had decreased from midlife to late life. Compared with normal-weight individuals who had maintained BMI from midlife to late life, the hazard ratio (95% CI) for those with BMI loss was 2.08 (1.62-2.67) for normal-weight individuals, 1.62 (1.25-2.10) for those with overweight, and 1.36 (1.00-1.85) for those with obesity.

Discussion: Our results provide insight into the dementia obesity paradox at older ages, tempering a causal interpretation of high late-life BMI as protective against dementia. Instead, they highlight the importance of considering weight loss from midlife to late life in conjunction with late-life BMI in dementia risk stratification.

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Conflict of interest statement

E.J. Cannon, B.G. Windham, M. Griswold, and P. Palta report no disclosures relevant to this manuscript. D.S. Knopman reports no conflicts with respect to the current work; serves on a data safety monitoring board for the Dominantly Inherited Alzheimer Network Treatment Unit study and a study of nicorandil for the treatment of hippocampal sclerosis of aging sponsored by the University of Kentucky; was a site investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California, and is currently a site investigator in a trial in frontotemporal degeneration with Alector; and he has served as a consultant for Roche, Biovie, Linus Health, and Alzeca Biosciences but receives no personal compensation. S. Sedaghat and P.L. Lutsey report no disclosures relevant to this manuscript. Go to Neurology.org/N for full disclosures.

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