Molecular mechanisms underlying hyperglycemia associated cognitive decline

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. DM can lead to a number of secondary complications affecting multiple organs in the body including the eyes, kidney, heart, and brain. The most common effect of hyperglycemia on the brain is cognitive decline. It has been estimated that 20-70% of people with DM have cognitive deficits. High blood sugar affects key brain areas involved in learning, memory, and spatial navigation, and the structural complexity of the brain has made it prone to a variety of pathological disorders, including T2DM. Studies have reported that cognitive decline can occur in people with diabetes, which could go undetected for several years. Moreover, studies on brain imaging suggest extensive effects on different brain regions in patients with T2D. It remains unclear whether diabetes-associated cognitive decline is a consequence of hyperglycemia or a complication that co-occurs with T2D. The exact mechanism underlying cognitive impairment in diabetes is complex; however, impaired glucose metabolism and abnormal insulin function are thought to play important roles. In this review, we have tried to summarize the effect of hyperglycemia on the brain structure and functions, along with the potential mechanisms underlying T2DM-associated cognitive decline.