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 follow-up 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_E-HYPER 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.