Type 2 Diabetes Mellitus and Alzheimer's Disease: from physiopathology to treatment implications.

Abstract

Alzheimer's Disease (AD) is the most common cause of dementia worldwide. Type 2 Diabetes Mellitus (T2DM) is a disease characterized by insulin resistance (IR) and progressive β cell failure, and affected individuals are at increased risk to develop several forms of cognitive dysfunction, including AD. Different mechanisms have already been identified linking visceral obesity, IR and AD. Insulin resistance is associated with a decrease in glucose uptake by neurons, an increase in Amyloid β production and secretion, in the formation of senile plaques, and also in tau protein phosphorylation. Other mechanisms also include a decrease in Insulin Degrading Enzyme (IDE) activity and an increase in oxidative stress secondary to hyperglycemia. Taken together, these mechanisms suggest that drugs used to ameliorate hyperglycemia and IR may also have beneficial effects in diabetic patients with AD. Indeed, manuscripts investigating the effects of metformin, thiazolinediones, leptin, GLP-1 therapies, insulin and bariatric surgery in cognition and AD have been published with very promising results, and may indicate an alternative approach for these patients. This article is protected by copyright. All rights reserved.