Diabetes Mellitus and the Brain : Special Emphasis on Cognitive Function : Review

ABSTRACT

Diabetes mellitus (DM) is a major public health problem. Cognitive deficits are common with DM which range from subclinical or subtle to severe deficits such as dementia. Both hypoglycaemia and hyperglycaemia are causes of cognitive impairment with DM. In patients with DM; not only severe hypoglycaemia but also recurrent mild or moderate hypoglyacemia have deleterious effect on the brain. Recurrent mild/moderate hypoglycaemia is associated with intellectual decline; reduced attention; impaired mental abilities and memory deficits. Hypoglycaemia may result in abnormalities of neuronal plasticity; synaptic weakening and scattered neuronal death in the cerebral cortex and hippocampus. Chronic hyperglycaemia 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 such 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 hyperglycaemia-related cognitive dysfunction include; macro- and microvascular disease or vasculopathy; hyperlipidaemia; hypertension; insulin resistance and hyperinsulinaemia; stress response; direct toxic effect of chronic hyperglycaemia on the brain; advanced glycation end-products; inflammatory cytokines and oxidative stress. Hyperglycaemia causes oxidative stress; amyloidosis; angiopathy; abnormal lipid peroxidation; accumulation of ?-amyloid and tau phosphorylation; neuro-inflammation; 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 an early age; frequency of hypoglycaemia; poor glycaemic control and presence of risk factors negatively affect cognitive functions in DM will have important implications for treatment and research purposes: