Insulin Resistance Syndrome and Alzheimer Disease:... : Alzheimer Disease & Associated Disorders (original) (raw)

Review Articles

Insulin Resistance Syndrome and Alzheimer Disease: Pathophysiologic Mechanisms and Therapeutic Implications

Department of Psychiatry and Behavioral Sciences, Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington School of Medicine

Supported by the Department of Veterans Affairs, the Institute for the Study of Aging, NIA RO1 AG-10880, and GlaxoSmithKline.

Reprints: Suzanne Craft, PhD, GRECC S-182, VAPSHCS, 1660 S. Columbian Way, Seattle, WA, 98108 (e-mail [email protected]).

Received for publication September 11, 2006; accepted September 19, 2006

Dr Craft is a consultant for GlaxoSmithKline.

Abstract

Insulin plays a key role in cognition and other aspects of normal brain function. Insulin resistance induces chronic peripheral insulin elevations, reduces insulin activity, and reduces brain insulin levels. The insulin resistance syndrome and associated conditions such as type 2 diabetes mellitus and hypertension, are associated with age-related memory impairment and Alzheimer disease. Our work has focused on potential mechanisms through which this association is forged, including the effects of peripheral hyperinsulinemia on memory, inflammation, and regulation of the β-amyloid peptide. We have shown that raising plasma insulin to levels that characterize patients with insulin resistance invokes synchronous increases in levels of β-amyloid and inflammatory agents. These convergent effects may impair memory and induce AD pathology. Therapeutic strategies focused on preventing or correcting insulin abnormalities may thus benefit adults with age-related memory impairment and AD.