Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?

Abstract

Diabetes is associated with cognitive dysfunction and an increased risk of dementia. This article addresses findings with brain MRI that may underlie cognitive dysfunction in diabetes. Studies in adults with type 1 diabetes show regional reductions in brain volume. In those with a diabetes onset in childhood, these volume reductions are likely to reflect the sum of changes that occur during brain development and changes that occur later in life due to exposure to diabetes-related factors. Type 2 diabetes is associated with global brain atrophy and an increased burden of small-vessel disease. These brain changes occur in the context of aging and often also in relation to an adverse vascular risk factor profile. Advanced imaging techniques detect microstructural lesions in the cerebral gray and white matter of patients with diabetes that affect structural and functional connectivity. Challenges are to further unravel the etiology of these cerebral complications by integrating findings from different imaging modalities and detailed clinical phenotyping and by linking structural MRI abnormalities to histology. A better understanding of the underlying mechanisms is necessary to establish interventions that will improve long-term cognitive outcomes for patients with type 1 and type 2 diabetes.Interest in the effect of diabetes on the brain is growing. It is now clear that type 1 diabetes is associated with modest decrements in cognitive functioning, which are most marked in patients with an early childhood diabetes onset (1). These decrements in adults with type 1 diabetes are most evident in the domains of general intelligence, psychomotor speed, and mental flexibility (2). On these domains, the magnitude of the decrements is ;0.3 to 0.7 SD units relative to people without diabetes (2). This implies that, on average, the performance of people with diabetes on these domains is at the 30th to the 40th percentile of control values. The progression of cognitive decrements in adults with type 1 diabetes, relative to people without diabetes, is generally slow, except in subgroups of patients with marked microvascular complications, who may show more marked decline (1).Modest decrements in cognitive functioning, evident on the domains of verbal and visual memory, information processing speed, and executive functioning, have also been noted in people with type 2 diabetes across all age groups (3). Similar to type 1 diabetes, effect sizes are small to moderate (0.3 to 0.4 SD units) (4) and follow a slow progression over time, only modestly exceeding the rate of normal aging-related cognitive decline (3). In older people, however, particularly older than the age of 65, type 2 diabetes is also associated with more severe forms of cognitive impairment. Data from large epidemiological surveys link diabetes to an increased dementia risk. A meta-analysis estimated that people with type 2 diabetes have a relative risk of vascular dementia of 2.5 (95% CI 2.1-3.0) and that of Alzheimer disease is 1.5 (95% CI 1.2-1.8) relative to indiv...

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