Association of Relative Brain Hyperperfusion Independent of Dopamine Depletion With Motor Dysfunction in Patients With Parkinson Disease

Background and Objectives Parkinson disease (PD) exhibits a characteristic pattern of brain perfusion or metabolism, thereby being considered network disorder. Using dual-phase N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) PET, we investigated the role of brain perfusion in motor symptoms and disease progression, independent of striatal dopamine depletion. Methods We recruited patients with de novo PD and healthy controls (HCs) who underwent dual-phase ¹⁸F-FP-CIT PET and brain MRI. All patients underwent the Unified PD Rating Scale (UPDRS) and were followed up for ≥5 years. A subset of patients (n = 51) underwent followup UPDRS and brain MRI. Early-phase images evaluated brain perfusion, while delayed-phase images evaluated dopamine transporter availability. We compared early-phase ¹⁸F-FP-CIT uptakes (SUVR_E) between PD and HC groups. Then, we investigated the association of SVUR_E and delayed-phase ¹⁸F-FP-CIT uptakes (SUVR_D) with motor symptoms in PD. Standardized residuals (SRs) of the SUVR_E in the hyperperfusion region (SUVR_E-HYPER) were obtained from the linear regression of the SUVR_D in the posterior putamen (SUVR_D-PP), the main region of dopamine deficit. Subsequently, we investigated the association of the SR with baseline and longitudinal motor symptoms and brain atrophy. Results Compared with HC (n = 30), patients with PD (n = 168) showed relative hyperperfusion in the primary motor cortex, thalamus, pons, hippocampus, and cerebellum and relative hypoperfusion in the prefrontal and temporo-parieto-occipital cortices, which is consistent with a PD-related metabolic pattern. Motor symptoms were negatively correlated with SUVR_D-PP (standardized β = 0.402, p < 0.001) and positively correlated with SUVR_E-HYPER (standardized β = 0.292, p < 0.001), but not with SUVR_E in the hypoperfusion regions. Regardless of SUVR_D-PP, SUVR_E-HYPER was independently associated with motor dysfunction, especially rigidity (standardized β = 0.214, p = 0.012). The SR of SUVR_E-HYPER was significantly associated with the UPDRS part III total score. Longitudinally, the baseline SR of SUVR_EHYPER was not associated with long-term motor complications but with an increase in the UPDRS part III total score (p = 0.017) and a decrease in brain volume. Discussion These results suggest that aberrant relative brain hyperperfusion, independent of striatal dopamine depletion, was associated with baseline and longitudinal motor deficits and progression of neurodegeneration in PD.