Objective: This study seeks to identify structural brain circuitry changes that may help to explain the appearance and severity of parkinsonism symptoms in clinical cohorts of Vascular Parkinsonism (VP), Parkinson’s disease (PD), and healthy controls (HC).

Background: VP is widely-recognized clinically as a diagnosis of a predominantly lower body parkinsonism, but the pathophysiology underlying VP is not well-defined. PD symptoms vary significantly between patients. We hypothesize that differences in structural brain circuitry may contribute to VP and PD symptoms.

Method: We obtained diffusion kurtosis brain imaging in VP (N=7), PD (N=21), and HCs (N=58). The VP and PD groups underwent motor and cognitive testing. We used one-way ANOVA and Tukey post-hoc tests, followed by ANCOVA with covariates age, sex, and whole brain total tract counts to assess differences between cohorts in terms of proportion of long-range fiber degree and strength of connectedness. We assessed network properties: whole brain global network efficiency and modularity, and local network efficiency of the basal ganglia motor loop. In a combined VP and PD cohort, we ran Pearson’s correlations between all imaging measures and the behavioral measures, followed by stepwise multiple regression models with the covariates.

Results: The VP cohort had a lower proportion of long-range fibers, both in terms of degree and strength of connectedness, globally, and in the motor loop (p<0.05). There was no difference between the PD and HC cohorts. Network measures showed VP to have the lowest global and local network efficiencies, followed by PD, and then HC (p<0.05). Global modularity was lower in VP compared to PD and HC, with no difference between PD and HC (p<0.05). Gait and balance impairment score inversely correlated to strength of the long-range fibers within the motor loop (R=-0.46, p=0.016). Cognitive performance directly correlated with the degree of whole brain long-range fiber connectedness (R=0.38, p=0.045) and global network efficiency (R=0.41, p=0.032).

Conclusion: The results of this study present a potential pathophysiological mechanism for development of parkinsonism symptoms in VP and PD. Changes in structural connectivity measures correlate with cognition and gait and balance impairment in VP and PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-and-cognitive-symptoms-in-parkinsonism-are-associated-with-loss-of-long-range-white-matter-fibers-structural-network-changes-in-vascular-parkinsonism-and-parkinsons-disease/