Objective: To explore the potential contribution of dopamine loss, perfusion deficit, and cognition to spatiotemporal gait parameters in patients with Parkinson’s disease (PD).

Background: Gait disturbance is one of the debilitating symptoms of PD, significantly impacting quality of life and prognosis. Gait impairment is not solely determined by dopamine depletion but characterized by a complex interplay of dopaminergic deficits, cerebral metabolism, and cognition. However, the relationship between these factors remains unclear. Dual-phase 18F-FP-CIT positron emission tomography (PET) provides both striatal dopamine transporter (DAT) availability (delayed phase) and perfusion imaging (early phase), thus serving as an attractive modality to investigate the neural correlates of gait parameters in PD.

Method: In this retrospective study, we included 150 drug-naïve patients with PD who underwent dual-phase 18F-FP-CIT PET, neuropsychological assessments, and quantitative gait analysis using GAITRite system. Multivariate linear regression analyses were performed to identify the potential determinants of spatiotemporal gait parameters derived from self-paced walking, which were adjusted for age, sex, motor phenotype and white matter hyperintensity.

Results: Caudate DAT availability revealed positive correlation with stride length and cadence, while step time difference was associated with the asymmetry index in the putamen. Functional ambulation profile (FAP) score and gait velocity revealed significant positive correlation with DAT availability in the caudate nucleus and cerebral perfusion in prefrontal and inferior parietal regions, and performance in attention and frontal/executive domains. Path analyses revealed that the influence of the frontoparietal hypoperfusion on gait disturbance (gait velocity and FAP) were mediated by frontal/executive dysfunction. In a serial mediation analysis model incorporating the DAT availability, perfusion, cognition, and gait parameters, the influence of caudate DAT availability on FAP score and gait velocity was completely mediated by prefrontal hypoperfusion and frontal/executive dysfunction.

Conclusion: Our findings demonstrate that dopaminergic loss in the caudate nucleus, altered cerebral perfusion in frontoparietal association cortices, and cognitive performance in the frontal/executive domain may serve as neural substrates underlying gait disturbance in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/contribution-of-dopamine-depletion-cerebral-perfusion-and-cognition-to-gait-dysfunction-in-parkinsons-disease/