Thesis defense Anil Man Tuladhar (Donders series 243)

4 October 2016

Promotors: prof. dr. C. Klijn, prof. dr. D. Norris, copromotors: prof. dr. F. de Leeuw, dr E van Dijk

The disconnected brain: mechanisms of clinical symptoms in cerebral small vessel disease

Cerebral small vessel disease (SVD) is an important cause of cognitive impairment and dementia, and is a common finding in elderly participants, including those with normal cognitive function. The mechanisms of how SVD results in clinical manifestations are still not completely understood. The studies in this thesis are aimed at investigating the relation between brain imaging and the clinical symptoms using MRI and network analysis. In the first part of the thesis we showed that the microstructural integrity of the white matter, which cannot be assessed by the conventional MRI, is related to the cognitive and gait disturbances in participants with SVD. In the second part of the thesis, we demonstrated that network measures based on white matter network might be more sensitive in capturing the cumulative effects of SVD-related lesions and are related to cognitive impairment in participants with SVD. Overall the work in this thesis contributes to better understanding of how SVD can cause clinical symptoms. SVD can be considered as a diffuse brain disease, in which network disruption due to visible and non-visible white matter and gray matter damage plays an important role in the pathophysiology of clinical deficits.