Cerebral Small Vessel Disease May Contribute to Parkinsonism

Brain blood vessels
Brain blood vessels
Those who developed vascular parkinsonism had a greater risk if they had microbleeds and low gray matter volume.

Cerebral small vessel disease (SVD) is common among the elderly, and is known to be associated with motor impairment and a decline in gait and balance over time. Now, data indicate that SVD may play a causal role in incident parkinsonism.

Previous autopsy studies in patients with parkinsonism revealed pathologic proof of SVD in patients who otherwise did not exhibit typical tissue evidence related to parkinsonism, including the presence of Lewy bodies or tau inclusions. However, it remained unclear whether parkinsonism was a consequence of SVD or a coincidence.

To better understand the role that SVD plays in parkinsonism, Helena M. van der Holst, MD, of Radboud University Medical Center in the Netherlands, and colleagues investigated the relationship between baseline cerebral SVD  and risk of incident parkinsonism. The study, published in Neurology, is part of the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study.

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A cohort of 503 elderly participants with SVD and without parkinsonism were included in the study. All participants underwent baseline MRI and cognitive (Mini Mental State evaluation) and motor evaluation (Unified Parkinson’s Disease Rating Scale [UPDRS-m]). Follow-up was available for 501 participants (mean age 65.6 years; mean follow-up duration 5.2 years), during which parkinsonism developed in 20 participants (15 with vascular parkinsonism). Participants who had high white matter hyperintensity (WMH) volume (HR 1.8 per SD increase, 95% CI 1.3–2.4) and a high number of lacunes (HR 1.4 per number increase, 95% CI 1.1–1.8) at baseline had an increased five-year risk of any parkinsonism. Risk of parkinsonism among participants who developed vascular parkinsonism was increased based on the presence of microbleeds (HR 5.7, 95% CI 1.9–16.8) and low gray matter volume (HR 0.4 per SD increase, 95% CI 0.2–0.8). In addition, participants with vascular parkinsonism had lower fractional anistrophy values in bifrontal white matter tracts linked to movement control compared to those who did not develop parkinsonism.

The researchers hypothesized that, “SVD disrupts the structural integrity of white matter tracts, including disruption of the thalamocortical fibers, thereby reducing the influence of the basal ganglia on motor, premotor, and supplementary motor cortices. Disconnection of the basal ganglia–thalamocortical circuit possibly leads to (sub) cortical atrophy, ultimately resulting in parkinsonism.”

The researchers admitted that their results should be interpreted with caution, and called for future studies to account for changes in the imaging biomarkers. 


  1. van der Holst HM et al. Neurology. 2015; doi:10.1212/WNL.0000000000002082.