Inflammation, glucocorticoids and microvascular disease in the aetiology of cognitive impairment in type 2 diabetes

People with adult-onset (type 2) diabetes are at increased risk of developing problems with certain functions of the brain, including memory, attentional and problem-solving abilities. These difficulties can significantly impair the ability of a person to carry out routine daily tasks and can have substantial impact on employment and the lives of family and friends. At its severest level, dementia can develop. The prevalence of type 2 diabetes is set to rise dramatically in the years ahead. Therefore, diabetes-related memory impairment could have substantial future social and economic implications.

The cause of these brain function abnormalities is not understood. A range of risk factors, including damage to small blood vessels, inflammation and/or hormonal imbalances can occur in the brains of people with diabetes and it is proposed that this may be a cause of diabetes-related memory impairment.

We plan to test the brain function of 1000 people with type 2 diabetes. At the same time we will take photographs of the back of subjects eyes to determine whether or not there is small vessel disease and measure other potential risk factors for memory impairment in a blood sample. By comparing the brain function of people with and without risk factors, important information about the cause of diabetes-related memory problems will be obtained.

Traditionally, memory problems in elderly people have been regarded as irreversible, but with a better understanding of the causes of brain function abnormalities in type 2 diabetes, it should be possible to start to develop strategies to prevent, reverse or ameliorate the problem.

People with type 2 diabetes are at increased risk of cognitive impairment and dementia. This is of major concern given the predicted future increase in the prevalence of type 2 diabetes. However, the aetiology of cognitive impairment in people with diabetes is unknown. There are strong theoretical grounds, supported by experimental animal data and observational studies in humans, to suggest that microvascular disease, inflammation and/or dysregulation of the HPA axis are likely to explain a significant proportion of the variation in cognitive function in people with type 2 diabetes and an examination of these potential associations forms the basis of the proposed study. A range of cognitive tests, assessing the major domains of mental function, will be administered to one thousand patients with established type 2 diabetes aged over 60 years, at baseline and again after 4 years. The association between cognitive decline and baseline risk factors will be determined and the independence of any relationship with respect to macrovascular disease (and other risk factors) will be assessed. The cohort will also provide the basis for future cerebral neuroimaging and dynamic HPA axis studies. Traditionally, cognitive decrements in elderly people have been regarded as irreversible, but with a better understanding of the aetiology of cognitive impairment in type 2 diabetes, it should be possible to start to develop preventive and/or therapeutic strategies.