Abstract
BACKGROUND: The classification of Parkinson disease by age of onset has proven to be a valuable method for subtyping, given its practical application in clinical settings. However, the interactions between the metabolic brain changes, dopaminergic dysfunction, and clinical manifestations in patients with early-onset (early-iPD) and late-onset (late-iPD) idiopathic Parkinson disease have not been adequately evaluated. Therefore, this study aimed to investigate the difference in cerebral metabolism and presynaptic dopaminergic function between patients with early-iPD and those with late-onset disease using (18)F-fluorodeoxyglucose ((18)F-FDG) and [(18)F] 9-fluoropropyl-(+)-dihydrotetrabenazine ((18)F-FP-DTBZ) positron emission tomography (PET). Furthermore, the goal was to further explore the correlation between imaging measurements and clinical manifestations in the early and late idiopathic patients with Parkinson disease. METHODS: This cross-sectional study included 80 patients with idiopathic Parkinson disease and 29 healthy control participants who underwent (18)F-FDG and(18)F-FP-DTBZ PET imaging at Xuanwu Hospital, Capital Medical University from August 2022 to August 2023. The patients were categorized into early-iPD (n=27) and late-iPD (n=53) groups based on an age threshold of 50 years. The mean standardized uptake value of (18)F-FDG and the standardized uptake value ratio (SUVR) of (18)F-FP-DTBZ were compared between the early-iPD and late-iPD groups using unpaired Student t-tests. Furthermore, pairwise correlations among cerebral metabolism, dopaminergic function, and corresponding clinical ratings in all patients were conducted using Pearson correlation analysis. RESULTS: Patients with late-iPD exhibited a significant metabolic decrease in the frontal, parietal, and temporal cortex, along with the globus pallidus, putamen, thalamus, and cerebellum, compared to those with early-iPD in (18)F-FDG PET imaging (all P values <0.05). Furthermore, the (18)F-FP-DTBZ binding potential was significantly lower in the contralateral caudate and anterior putamen of patients with late-iPD compared to those with early-iPD (contralateral caudate: 3.16±1.2 vs. 2.63±0.7, P=0.020; contralateral anterior putamen: 2.49±1.2 vs. 2.05±0.7, P=0.040). Further analysis of the correlations between imaging clinical features revealed that glucose metabolism increases and dopaminergic function decreases with higher motor ratings. CONCLUSIONS: (18)F-FDG and (18)F-FP-DTBZ PET offer an objective molecular imaging basis for distinguishing between early-onset and late-onset idiopathic with Parkinson disease. Additionally, correlation analysis between imaging and clinical data represents a new approach for exploring the potential applications in future studies involving patients with early-iPD and late-iPD.