Clinical manifestations of small vessel disease

Cardiovascular disease is a major health problem worldwide. However, the mortality risk in patients with cardiovascular disease has decreased due to early detection of the disease and improved treatment possibilities. The downside of increased survival rates are higher rates of long-term functional disability. Cardiovascular disease and an increased cardiovascular risk are associated with loss of function such as cognitive dysfunction, motor dysfunction, and depression. Vascular damage on brain MRI, reflected in markers of small vessel disease, is increasingly recognized as potential underlying factor for age-related function loss that is frequently found in patients with cardiovascular disease. The present thesis aimed to gain more insight in the cross-sectional, but particularly in the longitudinal relationship between risk factors, MRI markers of small vessel disease, and functional disability. In the first part of the thesis we investigated the association between risk factors, MRI markers of small vessel disease, and cognitive decline. We found that potentially modifiable risk factors (e.g. diabetes mellitus and physical activity) may have small impact on slowing down cerebral vascular damage and cognitive dysfunction in middle-aged patients already burdened with vascular disease. Cognitive dysfunction is a slowly developing process that may follow a stepwise progression over time. MRI markers of small vessel disease may be more sensitive to detect the influence of modifiable risk factors and may precede differences in cognitive decline. In part II of the thesis we were interested in the relationship of subclinical features of small vessel disease on brain MRI with motor dysfunction. We performed an explorative study to examine the association of microstructural abnormalities in specific white matter tracts with motor dysfunction in patients with type 2 diabetes mellitus with and without cognitive impairment. We found that in a small group of older patients with type 2 diabetes mellitus with slightly impaired motor performance scores, microstructural abnormalities in the corpus callosum were associated with motor performance scores in the expected directions, although the results were not statistically significant. In part III of the thesis we investigated the course of depression in patients with cardiovascular disease. 30% of these patients had an intermittent or chronic course of depression. Furthermore, of the patients with a history of vascular disease, those with cerebrovascular disease most often showed a chronic course of depression. Cerebral small vessel disease, on top of existing cardiovascular disease contributes to depression. Depression is therefore an important clinical manifestation of both large (e.g. stroke) and small vessel disease in patients with high vascular burden. Patients with cardiovascular disease may require more careful clinical monitoring and management of depressive symptoms.