Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Esther van Leijsen (Donders series 345)

19 November 2018

Promotor: prof. dr. H. de Leeuw
Co-promotors: dr. ir. M. Verbeek, dr. A. Tuladha

Unraveling the heterogeneity of cerebral small vessel disease - From local to remote effects

Cerebral small vessel disease (SVD) has been recognized as the most important vascular contributor to cognitive decline and the development of dementia. However, clinical symptoms in patients with a virtually identical SVD burden are often remarkably heterogeneous, both in nature and severity. Where SVD goes clinically unnoticed in the majority of patients, it leads to major cognitive deficits or dementia in others. In addition, the spectrum of cognitive symptoms attributable to SVD is more diverse than previously thought. Where SVD was previously thought to be mainly associated with psychomotor speed, the spectrum of cognitive symptoms attributable to SVD seems to be much broader than previously thought and cannot solely be explained by the severity and location of SVD markers on neuroimaging. In this thesis, I therefore examined additional explanations for the remarkable variation of SVD-related cognitive symptoms.

Cerebral small vessel disease is highly heterogeneous, reflected in inter-individual variability in the temporal dynamics, etiology and cognitive consequences. SVD might exert its effects throughout the brain by inducing a cascade of events that spread from the visible SVD markers to remote brain areas, which might explain the variability in cognitive symptoms in patients with apparently similar SVD burden.