Research Paper Volume 13, Issue 13 pp 16974—16989

The risk of Alzheimer’s disease according to dynamic changes in metabolic health and obesity: a nationwide population-based cohort study

Yun Kyung Cho1, , Jiwoo Lee2, , Hwi Seung Kim2, , Joong-Yeol Park2, , Woo Je Lee2, , Ye-Jee Kim3, , Chang Hee Jung2, ,

  • 1 Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
  • 2 Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  • 3 Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Received: October 6, 2020       Accepted: June 18, 2021       Published: July 8, 2021
How to Cite

Copyright: © 2021 Cho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


We evaluated the association of metabolic health and obesity phenotypes with the risk of Alzheimer’s disease (AD).

This study enrolled 136,847 elderly participants aged 60 or above from the Korean National Health Insurance System. At baseline examinations in 2009 and 2010, subjects were categorized into four groups: the metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO) groups. Based on the phenotypic transition after 2 years, the subjects were further categorized into 16 subgroups. They were followed from 2009 to 2015 to monitor for AD development.

The MHO phenotype protected subjects from AD, relative to the MHNO phenotype (HR, 0.73; 95% CI, 0.65–0.81). Among subjects initially classified as MHO, 41.8% remained MHO, with a significantly lower risk of AD compared with the stable MHNO group (HR, 0.62; 95% CI, 0.50–0.77). Among MUO subjects at baseline, those who changed phenotype to MUNO were at higher risk of AD (HR, 1.47; 95% CI, 1.28–1.70), and the transition to the MHO phenotype protected subjects from AD (HR, 0.62; 95% CI, 0.50–0.78).

The MHO phenotype conferred a decreased risk of AD. Maintenance or recovery of metabolic health might mitigate AD risk among obese individuals.


AD: Alzheimer’s disease; BMI: body mass index; BP: blood pressure; FPG: fasting plasma glucose; HDL-C: high-density lipoprotein cholesterol; MHNO: metabolically healthy non-obese; MHO: metabolically healthy obese; MUNO: metabolically unhealthy non-obese; MUO: metabolically unhealthy obese; NHIS-HEALS: National Health Insurance Service-National Health Screening Cohort; TG: triglyceride.