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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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-804/coif). This work was supported by the National Key Research and Development Program of China (Nos. 2022YFC2406900 and 2022YFC2406904). The authors have no other conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)