The long-term effects of Small Vessel Disease

Small vessel disease (SVD) is a slowly progressive vasculopathy of the small
perforating cerebral vessels and is now considered to be the most important
vascular contributor to stroke and cognitive decline, ultimately leading to
dementia and loss of functional independence. It has been assumed that SVD is a
more dynamic and heterogeneous disease than previously thought, showing
inter-individual variability in progression as well as regression on MRI over
time. Yet, the mechanisms underlying progression as well the long-term effects
of SVD progression are still poorly understood. We therefore propose to perform
another follow-up study, including novel advanced perfusion imaging (assessing
BBB-function and brain perfusion), and neuropsychological examinations among
survivors of our RUN DMC study with already known moderate to severe SVD. We
will hereby be collecting 13-14 years of follow up data of SVD including
imaging and neuropsychological assessments, which is as far as we know the
longest follow-up of SVD-patients in literature. By doing so, we aim to gain
more insights in the long-term (> 13 years after diagnosis) clinical effects of
SVD, assess the clinical outcome of temporal dynamics of SVD, and identify
potential causes (such as BBB dysfunction) and risk factors that may play an
important role in the progression of the disease.

Primary Objective
Our primary objective is to investigate the effect of SVD-progression on the
long-term clinical outcome.

Secondary Objectives
- To identify causes and risk factors related to an unfavourable clinical
outcome over time
- To identify causes and risk factors related to the temporal dynamics of SVD
- To assess the correlation between SVD-severity and BBB dysfunction

The RUN DMC study is a prospective cohort study, initiated to investigate risk
factors and clinical consequences of SVD.

The participants, previously diagnosed as SVD, will be asked to undergo the
following procedures: standardized MRI protocol, vena puncture to collect blood
and neuropsychological examinations. Some participants will additionally
receive gadolinium-based contrast agent to assess the BBB impairment; in case
of adverse effects, they will be treated reasonably and professionally.