Multimodal PET Imaging Unveils Early Metabolic Compensation Mechanisms and Dopaminergic Degeneration in Parkinson's...

This study aimed to elucidate the interplay between cerebral glucose metabolism and dopaminergic degeneration in Parkinson's disease (PD) using multimodal PET imaging (¹⁸F-FDG and ¹⁸F-FP-DTBZ) and to validate a combined biomarker for enhancing early PD diagnosis. Thirty-two PD patients (Hoehn-Yahr stage ≤ 2, disease duration ≤ 5 years) and 18 healthy controls underwent ¹⁸F-FDG and ¹⁸F-FP-DTBZ PET/MR imaging. Statistical analyses included group comparisons (t-tests, Mann-Whitney U tests) and correlation analyses (Pearson/Spearman). A logistic regression model was employed to integrate frontal cortex SUVR and posterior putamen VMAT2 binding for diagnostic evaluation. PD patients showed significantly reduced metabolism in the frontal cortex (Z = - 4.245, P < 0.0001), parietal cortex (t = - 6.256, P < 0.0001), and temporal cortex (t = - 3.790, P < 0.0001), alongside compensatory metabolic increases were observed in the pons (t = 3.123, P = 0.003) and cerebellum (t = 2.363, P = 0.022). Striatal VMAT2 binding was markedly reduced, particularly in the posterior putamen (contralateral: -66.8%, P < 0.0001), with a progressive decline observed as disease duration increased (r = - 0.357, P = 0.004). The combined biomarker achieved superior diagnostic accuracy (AUC = 0.977). Multimodal PET imaging reveals dynamic interactions between cerebral glucose metabolism and dopaminergic degeneration in PD, highlighting cerebellar-pontine hypermetabolism as a compensatory response to nigrostriatal degeneration. The integration of metabolic and dopaminergic biomarkers significantly enhances early PD detection, offering a robust framework for mechanistic exploration and clinical translation.