Published online Jan 15, 2021. doi: 10.4239/wjd.v12.i1.69
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
In spite of an increase in the incidence and prevalence of diabetes mellitus (DM) and Alzheimer’s disease (AD) in the aging population worldwide, limited attention has been paid to their potential association.
To investigate the association of DM and cardiometabolic syndrome (CMS, a precursor to DM) with risk of incident AD among postmenopausal women.
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 participant-reported history of doctor-diagnosis of incident AD in the WHIOS. DM was defined by participant-report or treated because of diabetes or serum glucose concentrations ≥ 126 mg/dL. 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.
During a median follow-up of 20 years (range: 3.36 to 23.36 years), of 63117 participants, 8340 developed 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 indicated that women with DM or CMS had a 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 diminished with age and became non-significant in the oldest age group.
During a median follow-up of 20 years, DM and CMS were significantly associated with the risk of AD among postmenopausal women. More specifically, women aged 50-69 with DM or CMS vs those without these conditions had significantly higher relative risks of AD than the relative risks of AD in those aged 70-79 with DM or CMS vs those without DM or CMS.
Core Tip: Data from population-based studies on the association of diabetes and cardiometabolic syndrome (CMS) with risk of Alzheimer’s disease (AD) was limited. This study, using data from one of the largest population-based cohort studies in the United States women aged 50-79 at baseline to test a hypothesis that diabetes and CMS are significantly associated with the risk of AD. This analysis is one of the first studies to prospectively test this hypothesis using a large-scale longitudinal cohort data. Findings from the study add new evidence to the body of research literature and provide new insights into the prevention of AD through control of diabetes and CMS.