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Background: Although previously thought to be asymptomatic, recent studies have suggested that magnetic resonance imaging–visible perivascular spaces (PVS) in the basal ganglia (BG‐PVS) of patients with Parkinson's disease (PD) may be markers of motor disability and cognitive decline. In addition, a pathogenic and risk profile difference between small (≤3‐mm diameter) and large (>3‐mm diameter) PVS has been suggested. Objective: The aim of this study was to examine associations between quantitative measures of large and small BG‐PVS, global cognition, and motor/nonmotor features in a multicenter cohort of patients with PD. Methods: We performed a cross‐sectional study examining the association between large and small BG‐PVS with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Parts I–IV and cognition (Montreal Cognitive Assessment) in 133 patients with PD enrolled in the Ontario Neurodegenerative Disease Research Initiative study. Results: Patients with PD with small BG‐PVS demonstrated an association with MDS‐UPDRS Parts I (P = 0.008) and II (both P = 0.02), whereas patients with large BG‐PVS demonstrated an association with MDS‐UPDRS Parts III (P < 0.0001) and IV (P < 0.001). BG‐PVS were not correlated with cognition. Conclusions: Small BG‐PVS are associated with motor and nonmotor aspects of experiences in daily living, while large BG‐PVS are associated with the motor symptoms and motor complications. © 2022 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities (WMH) on magnetic resonance imaging may influence clinical presentation in patients with Parkinson's disease (PD), although their significance and pathophysiological origins remain unresolved. Studies examining WMH have identified pathogenic variants in NOTCH3 as an underlying cause of inherited forms of cerebral small vessel disease. Methods: We examined NOTCH3 variants, WMH volumes, and clinical correlates in 139 PD patients in the Ontario Neurodegenerative Disease Research Initiative cohort. Results: We identified 13 PD patients (~9%) with rare (<1% of general population), nonsynonymous NOTCH3 variants. Bayesian linear modeling demonstrated a doubling of WMH between variant negative and positive patients (3.1 vs. 6.9 mL), with large effect sizes for periventricular WMH (d = 0.8) and lacunes (d = 1.2). Negative correlations were observed between WMH and global cognition (r = −0.2). Conclusion: The NOTCH3 rare variants in PD may significantly contribute to increased WMH burden, which in turn may negatively influence cognition. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]