Insulin resistance syndrome and Alzheimer disease: pathophysiologic mechanisms and therapeutic implications

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 beta-amyloid peptide. We have shown that raising plasma insulin to levels that characterize patients with insulin resistance invokes synchronous increases in levels of beta-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.