Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2021; 12(1): 69-83
Published online Jan 15, 2021. doi: 10.4239/wjd.v12.i1.69
Impact of diabetes mellitus and cardiometabolic syndrome on the risk of Alzheimer’s disease among postmenopausal women
Longjian Liu, Edward J Gracely, Xiaoyan Yin, Howard J Eisen
Longjian Liu, Edward J Gracely, Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, United States
Edward J Gracely, Department of Family, Community and Preventive Medicine, Drexel University College of Medicine, Philadelphia, PA 19129, United States
Xiaoyan Yin, Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
Howard J Eisen, Heart and Vascular Institute, Pennsylvania State University, Hershey, PA 17033, United States
Author contributions: Liu L formulated the research questions and analysis designs, performed data analysis and drafted the manuscript; Gracely EJ critically reviewed and carefully edited this manuscript; Yin X and Eisen HJ critically reviewed and gave comments; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by Drexel University Institutional Review Board (Approval No. 1910007425).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors report no potential conflicts of interest relevant to this article.
Data sharing statement: Researchers who are interested in using the data should directly apply to the U.S. National Heart, Lung and Blood Institute through a standard application process. The authors are unable to share with the data.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Longjian Liu, MD, MSc, PhD, Doctor, Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Office 515, Nesbitt Hall, 3215 Market Street, Philadelphia, PA 19104, United States. longjian.liu@drexel.edu
Received: May 18, 2020
Peer-review started: May 18, 2020
First decision: September 24, 2020
Revised: November 13, 2020
Accepted: December 22, 2020
Article in press: December 22, 2020
Published online: January 15, 2021
Research background

In spite of an increase in the incidence and prevalence of diabetes mellitus (DM) and Alzheimer’s disease (AD) in the aging population, limited attention has been paid to investigate their associations.

Research motivation

To investigate the association of DM and cardiometabolic syndrome with risk of AD among the United States older adults.

Research objectives

To examine the association of DM and cardiometabolic syndrome (CMS, a precursor to DM) with risk of incident AD among postmenopausal women.

Research methods

Postmenopausal women aged 50-79 (n = 63117) who participated in the U.S. Women’s Health Initiative Observational Study (WHIOS), recruited in 1993-1998 without baseline AD and followed up through March 1, 2019 were analyzed. AD was classified by participants-reported history of doctor-diagnosis of first-listed AD. DM was defined by participant-report or serum glucose concentrations or those anti-diabetic medication use. CMS was defined as having ≥ 3 of five CMS components: large waist circumference, high blood pressure, elevated triglycerides, elevated glucose, and low high-density lipoprotein cholesterol. The associations of DM and CMS with AD were analyzed using Cox’s proportional hazards regression analysis.

Research results

Within a median follow-up of 20 years (range: 3.36 to 23.36 years), of 63117 participants, 8340 had incident AD. Women with DM had significantly higher incidence of AD [8.5, 95% confidence interval (CI): 8.0-9.0 per 1000 person-years (PY)] than those without DM (7.1, 95%CI: 6.9-7.2 per 1000 PY). Multivariate Cox’s regression analysis indicates that women with DM or CMS had significantly higher risk of AD than those without DM or CMS. The corresponding hazard ratios [HR (95%CI)] were 1.22 (1.13-1.31, P < 0.001) in subjects with DM, and 1.18 (1.09-1.27, P < 0.001) in subjects with CMS. The HRs of AD in those with DM or MS vs those without DM or CMS diminished with age and became non-significant in the oldest age group.

Research conclusions

Diabetes and cardiometabolic syndrome were significantly associated with risk of Alzheimer's disease.

Research perspectives

Further studies are needed to investigate the mechanisms by which DM and CMS may cause the development of AD.