Diabetes Mellitus And The Brain: Special Emphasis To Cognitive Function

Diabetes mellitus (DM) is a major public health problem. Cognitive deficits are common with DM which range from subclinical or subtle to severe deficits as dementia. Both hypoglycemia and hyperglycemia are causes of cognitive impairment with DM. In patients with DM, not only severe hypoglycemia but also recurrent mild or moderate hypoglycemia have deleterious effect on the brain. Recurrent mild/moderate hypoglycemia is associated with intellectual decline, reduced attention, impaired mental abilities and memory deficits. Hypoglycemia may result in abnormalities of neuronal plasticity, synaptic weakening and scattered neuronal death in the cerebral cortex and the hippocampus. Chronic hyperglycemia in type 1 and type 2 DM is associated with low IQ (verbal, performance and total) and abnormalities in testing for different domains of cognitive function as verbal relations, comprehension, visual reasoning, pattern analysis, quantitation, memory, learning, mental control, psychomotor efficiency, mental and motor processing speed and executive function. The suggested mechanisms incriminated in the pathogenesis of hyperglycemia related cognitive dysfunction include, macro- and micro-vascular disease or vasculopathy, hyperlipidemia, hypertension, insulin resistance and hyperinsulinemia, stress response, direct toxic effect of chronic hyperglycemia on the brain, advanced glycation end products, inflammatory cytokines and oxidative stress. Hyperglycemia causes oxidative stress, amyloidosis, angiopathy, abnormal lipid peroxidation, accumulation of β-amyloid and tau phosphorylation, neuroinflammation, mitochondrial pathology, apoptosis and neuronal degeneration in the cortex and hippocampus. Depression has been identified as a risk for accelerated cognitive decline with DM. The knowledge that diagnosis at early age, frequency of hypoglycemia, poor glycemic control and presence of risk factors which negatively affect cognitive functions in DM, will have important implications for treatment and for research purposes.