Thesis defense Ellen van der Holst (Donders series 266)

5 april 2017

Promotors: prof. dr. H. de Leeuw, prof. dr. C. Klijn

copromotors: dr. A. Tuladhar, dr. E. van Dijk

Mind the step in cerebral small vessel disease. Brain changes in motor performance

Cerebral small vessel disease (CSVD) is a disease of the small perforating cerebral arteries, arterioles, venules and capillaries and is very common in the elderly population. CSVD is an important cause of cognitive, mood and motor disturbances. However, it is not well understood which patients are at risk for developing these clinical symptoms. The studies in this thesis are aimed at investigating the relation between brain imaging measures, including traditional CSVD imaging markers and diffusion tensor imaging measures, and the development of motor disturbances and mortality in CSVD. In the first part, we demonstrate that, white matter atrophy and loss of white matter integrity are associated with gait decline after 5 years. Furthermore, we showed that a high white matter hyperintensity volume and a high number of lacunes are associated with an increased 5-year risk of (any) parkinsonism. For vascular parkinsonism, this risk was also increased by the presence of microbleeds, low grey matter volume and low structural integrity of bifrontal white matter tracts.

In the second part of the thesis, we demonstrated that a lower microstructural white matter integrity is also associated with an increased 8-year mortality, next to higher age, lower gait speed and lower grey matter volume. Overall, the work in this thesis contributes to a better understanding of the development of motor disturbances and worse outcome in CSVD. Future studies are needed to investigate whether preventive or treatment strategies on CSVD could improve motor performance and functional outcome in individuals with CSVD.