Cognitive impairment in type 2 diabetes mellitus

Abstract

The worldwide epidemic of type 2 diabetes mellitus places a burden on health system. Type 2 diabetes mellitus has been associated with high morbidity, mortality and poor quality of life as it is linked with obesity, dyslipidemia, and organs damage including retinopathy, heart disease, kidney disease, and stroke. The disease is also associated with decline of cognitive function that further impairs the patients' ability to self management and increases risk of hospitalization. Several studies have reported that poor glycemic control, duration of the disease and presence of microvascular complications increase the risk of mild to moderate impairment in several cognitive domains including memory, language and executive function (psychomotor speed, attention and concentration). The basic pathophysiology of cognitive impairment in type 2 diabetes mellitus has yet to be identified but some mechanisms have been hypothesized responsible to the condition. Chronic hyperglycemia induces oxidative stress and facilitate neuro-inflammation state result in pathological changes in substansia alba especially of frontal lobe and temporal lobe and disruption of blood brain barrier causing risk of parenchym exposure by neurotoxic protein from circulation. Insulin resistance impairs the regulation of neurotransmitters essensial for memory formation. Autonomical dysfunction related with peripheral autonomic neuropathy and central autonomic dysfunction including hippocampus and prefrontal cortex has hypothesized to play a significant role in cognitive dysfunction in type 2 diabetes mellitus patients. All of the mechanisms lead to pathological change in several structures of the brain responsible for cognitive function including hippocampus medial temporal lobe and prefrontal cortex. Several future therapies have been identified to improve cognitive function and increase the patients' quality of life. Several clinicals trials are performed to evaluate the efficacy and safety of the promising theraphies.