Vascular Cognitive Impairment: risk factors and brain MRI correlates

Abstract

Vascular disease plays an important role in the development of dementia, also in patients diagnosed with Alzheimer’s disease. Risk factors such as hypertension, obesity, and type 2 diabetes, are associated with a two-fold increased risk of cognitive dysfunction and dementia. The development of cognitive impairment due to vascular disease is potentially preventable if patients are recognized and treated early. The present thesis gives more insight in the early stages of cognitive impairment in the context of vascular disease by examining 1) the development of cognitive decline, 2) the relation between vascular risk factors and late-life cognitive dysfunction, and 3) cerebral white matter correlates of cognitive dysfunction in people at risk of vascular disease. The studies in the first part of the thesis were conducted in patients with type 2 diabetes. We show that the development of cognitive decline in the majority of patients with diabetes develops slowly over time, over the course of years. However, we identified a subgroup of patients with accelerated cognitive decline, which seems to be triggered by the progression of both vascular brain lesions and a loss of brain volume on MRI. In the second part of the thesis we evaluated the time-course of vascular risk factors over 15 years in relation to late-life cognitive functioning in a large population-based cohort. We showed that late-life cognitive impairment (~70 years) was most strongly related to the presence of hypertension, adiposity, and hyperglycemia 15-20 years earlier. This indicates that long-term exposure to vascular risk factors, starting at midlife, is harmful to the brain, probably through the slow accumulation of vascular brain damage over the course of decades. Furthermore, we were also able to predict late-life cognitive impairment based on the vascular risk factor profile at midlife. This relation was independent of age and education, which supports the notion that vascular risk factor play an important role in the development of late-life cognitive dysfunction and dementia. The third part of the thesis focused on brain MRI correlates of cognitive dysfunction in patients with Alzheimer’s disease and type 2 diabetes. We demonstrated that the use of advanced brain imaging techniques: diffusion tensor imaging (DTI) and ‘deconvolution based tractography’ can increase the sensitivity to detect microstructural white matter correlates of memory dysfunction in patients with Alzheimer’s disease. This same technique also proved to be more sensitive than conventional brain imaging techniques to white matter abnormalities in patients with diabetes. These white matter abnormalities were related to reduced memory performance and slowing of information processing speed in patients. These findings suggest that microscopic white matter lesions play an important role in the pathogenesis of cognitive impairment in individuals with vascular disease, by disrupting structural and functional connectivity between brain areas. Our findings contribute to a better understanding of the pathogenesis of vascular-related cognitive impairment and contribute to identify individuals at increased risk of dementia at an early stage. This may help to delay or prevent the development of dementia in the near future