Longitudinal insights from iron accumulation in motor system of prodromal and clinical Parkinson’s disease

Iron dysregulation is known to play a critical role in the pathogenesis and progression of Parkinson's disease (PD). The specific patterns of regional iron accumulation in PD and in idiopathic rapid eye movement sleep behavior disorder (iRBD), which is considered the prodromal stage of PD, remain incompletely characterized. In this study, we employed an advanced sub-voxel quantitative susceptibility mapping technique (APART-QSM), which separates paramagnetic from diamagnetic sources, thereby enabling in vivo iron quantification based specifically on paramagnetic susceptibility measurement. We applied APART-QSM to 36 healthy controls, 54 patients with iRBD, and 52 patients with early-stage PD (mean disease duration: 5.8 ± 3.6 years; Hoehn and Yahr stage ≤3). Fifteen participants from each group underwent follow-up assessments ranging from 6 to 48 months. Our findings identified novel extrapyramidal and pyramidal regions exhibiting spatial and temporal changes of paramagnetic susceptibility in iRBD and PD. Moreover, paramagnetic susceptibility values were found to serve as potential image biomarkers, reflecting tremor severity (tremor subscore of Movement Disorder Society-Unified Parkinson's Disease Rating Scale III, MDS-UPDRS III) and non-tremor severity (rigidity, bradykinesia, and postural instability subscores of MDS-UPDRS III), with the ability to predict disease progression and track phenoconversion from iRBD to PD.