Diabetes and the brain: Cognitive performance in type 1 and type 2 diabetes mellitus

Abstract

Both type 1 and type 2 diabetes mellitus are associated with altered brain function, a complication referred to as diabetic encephalopathy. The issues surrounding the cognitive and emotional status in chronic, older diabetic patients remain complex. The literature shows contrasting findings and especially the role of recurrent hypoglycemic episodes remains controversial. The research of this thesis was designed to further unravel the clinical and cognitive characteristics of altered central nervous system functioning in type 1 as well as type 2 diabetes and to identify risk factors. Two groups of older patients with type 1 and type 2 diabetes were compared to a group of age-matched non-diabetic control participants with respect to their performance on a broad range of cognitive parameters. Furthermore, levels of physical and psychological complaints were assessed and magnetic resonance imaging (MRI) of the brain was performed to explore the presence of abnormalities in brain structure (e.g., atrophy or white-matter lesions). The first part of this thesis focuses on the characteristics of diabetic encephalopathy in type 1 diabetic patients. A quantitative analysis of previous findings shows that type 1 diabetes is associated with modest cognitive impairments in young to middle-aged adult patients. Lowered cognitive performance was associated with the presence of microvascular complications, but not with the occurrence of severe hypoglycemic episodes. More or less the same deficits were found in older people with type 1 diabetes. Surprisingly, the magnitude of these deficits was similar to the magnitude seen in younger adults. Also, these cognitive deficits were not accompanied by obvious changes in brain structure . The second part of this thesis focuses on type 2 diabetic patients. There is a clear relationship between cognitive deficits and brain MRI abnormalities in older patients with type 2 diabetes. Patients had significantly more cortical and subcortical atrophy, more deep white-matter lesions and infarcts than controls. Patients with type 2 diabetes showed impairments across several cognitive domains, notably in information processing speed, learning and retrieval of information, and executive functioning. It appears that patients have a diminished ability to efficiently process unstructured information and to flexibly use stored information. Another important finding is that structural and functional brain effects in patients with over thirty years of type 1 diabetes are similar to those seen in patients of a similar age and education with only seven years of type 2 diabetes. We could not find differences in cognitive profile or levels of psychological well-being between these two groups, although patients with type 1 diabetes had slightly better MRI ratings than patients with type 2 diabetes. In conclusion. the cognitive deficits and brain abnormalities of patients with diabetes are subtle and the cognitive impairment can best be characterised as mental slowing. Risk factors for the development of this diabetic encephalopathy are chronic hyperglycemia and atherosclerotic vascular disease. The occurrence of repeated episodes of hypoglycemia probably does not induce neurocognitive dysfunction.