Affiliations: Department of Medicine, Section of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health; William S. Middleton Memorial Veterans Hospital Geriatric Research, Education and Clinical Center (GRECC); Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA | Center for Alzheimer's Research, Banner Sun Health Research Institute, Sun City, AZ, USA
Correspondence:
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Correspondence to: Cynthia M. Carlsson, MD, MS, Assistant Professor of Medicine, Section of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health, Madison VA GRECC (D4211), 2500 Overlook Terrace, Madison, WI 53705, USA. Tel.: +1 608 280 7000; Fax: +1 608 280 7165; E-mail: cmc@medicine.wisc.edu.
Abstract: The prevalence of Alzheimer's disease (AD) is increasing rapidly, heightening the importance of finding effective preventive therapies for this devastating disease. Midlife vascular risk factors, including type 2 diabetes mellitus (T2DM), have been associated with increased risk of AD decades later and may serve as targets for AD prevention. Studies to date suggest that T2DM and hyperinsulinemia increase risk for AD, possibly through their effects on amyloid-β metabolism and cerebrovascular dysfunction – two early findings in preclinical AD pathology. This paper reviews the evidence supporting a relationship between T2DM, hyperinsulinemia, and diabetic dyslipidemia on the development of AD, discusses DM treatment trials and their preliminary results on cognitive function, and proposes some strategies for optimizing future AD prevention trial design.
