Diabetes and the brain
Cognitive dysfunction in type 2 diabetes: course of development and relation to vascular disease

It is increasingly recognised that type 2 diabetes (DM2) is associated with long-term complications in the brain. These complications are reflected in cognitive dysfunction and abnormalities on brain imaging.

Cross-sectional neuropsychological studies of older individuals with DM2 typically show modest performance deficits across several cognitive domains. Psychomotor efficiency and learning and memory are affected most consistently. On these domains the average performance of DM2 patients is around the 20-30th percentile of performance on the normal distribution in the general population. Longitudinal studies show that the rate of decline of cognitive functioning in DM2 patients is approximately 1.5 times that of what would be expected from normal ageing. The risk of developing dementia is 1.5 to 2 times as high as in individuals without DM2. This risk involves both Alzheimer’s disease and vascular dementia, as diagnosed on clinical criteria.

Recent brain imaging studies provide insight into the structural correlates of these cognitive impairments. DM2 is associated with a moderate degree of cortical and subcortical atrophy, relative to non-diabetic age-matched controls. In addition, vascular lesions, in particular lacunar infarcts, are encountered more frequently on brain scans of DM2 patients. The severity of so-called “white matter hyperintensities” also appears to be increased, although there are inconsistencies between studies. Both atrophy and these vascular lesions appear to be determinants of impaired cognition.

The relation of functional and structural brain changes to metabolic and vascular risk factors has not been fully clarified yet. On the one hand, chronic exposure to hyperglycaemia may play a role. On the other, vascular risk factors are likely to be involved. In fact, some of the cerebral changes may already develop in “pre-diabetic stages” in which risk factors, such as hypertension, dyslipidemia and insulin resistance already exist in the absence of frank hyperglycaemia.

The main challenges for the near future will be to further clarify the course of development ad risk factors for cerebral complications in DM2. Eventually this will lead to the development of preventive treatment for those patients that are at increased risk for developing clinically relevant forms of cognitive impairment, such as dementia.