R D Lawrence Lecture 2010. The brain as a target organ in Type 2 diabetes: exploring the links with cognitive impairment and dementia.

Type 2 diabetes is associated with cognitive impairment and dementia, but the precise underlying mechanisms remain unresolved. Very high blood glucose concentrations are associated with mood changes and poor memory function, possibly by causing alterations in cerebral blood flow or osmotic changes in neurones, and correction of acute hyperglycaemia appears beneficial. Chronic hyperglycaemia may cause structural changes in the brain, such as cerebral microvascular disease, and there are strong associations between the presence of retinal microvascular abnormalities and cognitive function. Functional insulin deficiency in the brain may also be a factor, but trials with rosiglitazone in people with diabetes and other trials in people with Alzheimer's disease have shown no specific benefit of insulin sensitization. There is an association between hypoglycaemia and cognitive impairment in people with Type 2 diabetes; part of that association may simply be a consequence of the fact that people with cognitive impairment find it more difficult to manage their diabetes and so are more prone to hypoglycaemia. The potential for hypoglycaemia to cause harm to the brain has been debated for many years, and the issue remains unresolved. An ongoing prospective study of risk factors for cognitive impairment in people with Type 2 diabetes (Edinburgh Type 2 Diabetes Study) should improve our understanding of the aetiology of cognitive impairment and inform the design of future intervention trials.