Differential Implications of Cerebral Hypoperfusion and Hyperperfusion in Parkinson's Disease

Background: Patients with Parkinson's disease (PD) exhibit widespread brain perfusion changes. Objective: This study investigated whether cerebral regions with hypoperfusion and hyperperfusion have differential effects on motor and cognitive symptoms in PD using early-phase ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) positron emission tomography (PET) scans. Methods: We enrolled 394 patients with newly diagnosed PD who underwent dual-phase ¹⁸F-FP-CIT PET scans. Indices reflecting associated changes in regional cerebral hypoperfusion and hyperperfusion on early-phase ¹⁸F-FP-CIT PET scans were calculated as PD_[hypo] and PD_[hyper], respectively. The associations of PD_[hypo] and PD_[hyper] on motor and cognitive symptoms at baseline were assessed using multivariate linear regression. Also, Cox regression and linear mixed models were performed to investigate the effects of baseline PD_[hypo] and PD_[hyper] on longitudinal outcomes. Results: There was a weak correlation between PD_[hypo] and PD_[hyper] (γ = −0.19, P < 0.001). PD_[hypo] was associated with baseline Unified Parkinson's Disease Rating Scale Part III scores (β = −1.02, P = 0.045), rapid increases in dopaminergic medications (β = −18.02, P < 0.001), and a higher risk for developing freezing of gait (hazard ratio [HR] = 0.67, P = 0.019), whereas PD_[hyper] was not associated. Regarding cognitive function, PD_[hypo] was more relevant to the baseline cognitive performance levels of visuospatial, memory, and frontal/executive function than PD_[hyper]. However, greater PD_[hyper] was associated with future dementia conversion (HR = 1.43, P = 0.004), whereas PD_[hypo] was not associated. Conclusions: These findings suggest that PD_[hypo] and PD_[hyper] may differentially affect motor and cognitive functions in patients with PD.