AbstractBackgroundPatients with Parkinson's disease (PD) exhibit widespread brain perfusion changes.ObjectiveThis 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.MethodsWe 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.ResultsThere 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.ConclusionsThese findings suggest that PD_[hypo] and PD_[hyper] may differentially affect motor and cognitive functions in patients with PD. © 2023 International Parkinson and Movement Disorder Society.