Objective: This study aims to explore the effect of cerebral small vessel disease (CSVD) on the clinical heterogeneity of vascular Parkinsonism (VP).

Background: CSVD has been closely linked to VP. However, VP patients with comparable total CSVD burden might exhibit marked clinical heterogeneity. No clinical study has yet established the association between CSVD and the clinical characteristics in VP.

Method: Given that white matter hyperintensity (WMH) was the most common CSVD marker and can be mapped in standard space, WMH was used as the CSVD phenotype in this study. We quantified WMH volume in the whole brain and across 20 regions defined by bullseye parcellation. Associations between regional WMH and clinical manifestations, including motor symptoms (UPDRS-III, TUG), cognitive function (MoCA), and mood (HAMA, HAMD), were tested. Subtype and Stage Inference (SuStaIn) was applied to explore WMH progression patterns and examine their relationships with longitudinal motor progression.

Results: Total WMH volume was significantly higher in VP patients compared to Parkinson’s disease (PD) and healthy controls (HC). Total WMH volume was associated with UPDRS III and MoCA in VP patients. WMH in the deep frontal lobes and basal ganglia showed significant associations with UPDRS III scores and TUG times. SuStaIn identified three distinct WMH progression subtypes in VP. These subtype classifications and their stages accounted for significant variability in the rate of UPDRS III progression over time.

Conclusion: This clinical study demonstrates that CSVD contribute to the clinical heterogeneity of VP. SuStaIn identified three distinct WMH progression subtypes that underlie variability in motor decline, providing a novel approach to stratify VP patients and predict disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebral-small-vessel-disease-associated-with-clinical-heterogeneity-in-vascular-parkinsonism/