Cognitive Dysfunction in Type 1 Diabetes Mellitus

CONTEXT: We have summarized key studies assessing the epidemiology, mechanisms, and consequences of cognitive dysfunction (CD) in type 1 diabetes. EVIDENCE SYNTHESIS: In a number of studies, the severity of CD in type 1 diabetes was affected by the age of onset and duration, and the presence of proliferative retinopathy and autonomic neuropathy. Diabetes-related CD has been observed, not only in adults, but also in children and adolescents. Most neuroimaging studies of patients with type 1 diabetes did not show any differences in whole brain volumes; however, they did reveal selective deficits in gray matter volume or density within the frontal, posterior, and temporal cortex and subcortical gray matter. Studies of middle-age adults with long-standing type 1 diabetes using diffusion tensor imaging have demonstrated partial lesions in the white matter and decreased fractional anisotropy in posterior brain regions. The mechanisms underlying diabetes-related CD are very complex and include factors related to diabetes per se and to diabetes-related cardiovascular disease and microvascular dysfunction, including chronic hyperglycemia, hypoglycemia, macro- and microvascular disease, and increased inflammatory cytokine expression. These mechanisms might contribute to the development and progression of both vascular dementia and Alzheimer disease. CONCLUSIONS: Higher rates of CD and faster progression in type 1 diabetes can be explained by both the direct effects of altered glucose metabolism on the brain and diabetes-related cardiovascular disease. Because the presence and progression of CD significantly worsens the quality of life of patients with diabetes, further multidisciplinary studies incorporating the recent progress in both neuroimaging and type 1 diabetes management are warranted to investigate this problem.