Issue title: Oxidative Stress, Reactive Metabolites, Inflammation, and RAGE – Building a Bridge from Alzheimer's Disease to Diabetes and Vice Versa
Guest editors: Angelika Bierhaus
Article type: Research Article
Authors: Luchsinger, José A.a; b; c; d; * | Gustafson, Deborah R.e; f
Affiliations: [a] Gertrude H. Sergievsky Center, New York, NY, USA | [b] Taub Institute for Research of Alzheimer's Disease and the Aging Brain, New York, NY, USA | [c] Division of General Medicine, Department of Medicine, College of Physicians and Surgeons, New York, NY, USA | [d] Department of Epidemiology, Joseph P. Mailman School of Public Health, Columbia University, New York, NY, USA | [e] Institute of Neuroscience and Physiology, Section for Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden | [f] Medical College of Wisconsin, Department of Family and Community Medicine, Milwaukee, WI, USA
Correspondence:
[*]
Corresponding author: José A. Luchsinger, MD, 630 West 168th St., PH19, New York, NY 10032, USA. Tel.: +1 212 305 4730; Fax: +1 212 305 2526; E-mail: jal94@columbia.edu.
Abstract: This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of AD. Hyperinsulinemia is a risk factor for T2D, and numerous studies have shown a relation of T2D with higher AD risk. The implication of these associations is that a large proportion of the world population may be at increased risk of AD given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However these associations may present a unique opportunity for prevention and treatment of AD. Several studies in the prevention and treatment of T2D are currently conducting, or have planned, cognition ancillary studies. In addition, clinical trials using insulin sensitizers in the treatment or prevention of AD are under way.
Keywords: Adiposity, Alzheimer's disease, cognitive impairment, glucose, hyperinsulinemia, insulin, obesity, overweight, type 2 diabetes
DOI: 10.3233/JAD-2009-1022
Journal: Journal of Alzheimer's Disease, vol. 16, no. 4, pp. 693-704, 2009
