Longitudinal Iron Changes in the Substantia Nigra of Early‐Stage Parkinson's Disease

BACKGROUND: Progression of substantia nigra pars compacta (SNc) iron content in early-stage Parkinson's patients (PD) is poorly understood. OBJECTIVE: To determine if nigral iron measured by quantitative susceptibility mapping (QSM) with zero-referencing can track disease progression in early-stage PD. METHODS: Thirty-four early-stage PD patients and 35 matched controls were recruited. Iron content in the SNc and related regions were obtained using QSM with zero-referencing at both baseline and 1-year follow-up, along with clinical metrics. RESULTS: Of seven clinic metrics and five regional iron measures, only Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part II (MDS-UPDRS-II) (P = 0.046) and SNc iron (P = 0.0025 for cerebrospinal fluid zero-referencing; P = 0.014 for whole-brain zero-referencing) showed significant changes in PD subjects in the 1-year epoch. The changes in SNc iron were also correlated with changes in MDS-UPDRS-II (P = 0.004). CONCLUSION: Nigral iron content measured by zero-referencing QSM can be used to track disease progression in early-stage PD over the 1-year epoch. © 2026 International Parkinson and Movement Disorder Society.