One-Year Substantia Nigra R 2 * Changes across Parkinson's Disease Stages

Magnetic resonance imaging (MRI) relaxometry using $R_2^{*}$ measurement is a promising non-invasive marker of brain iron-related changes in Parkinson's disease (PD). Although longitudinal susceptibility MRI studies have demonstrated progression over time, the stage-dependent dynamics of $R_2^{*}$ changes across the full spectrum of PD duration remain incompletely characterized.

The goal was to assess 1-year longitudinal $R_2^{*}$ changes across PD stages within a multicenter framework, compared with healthy controls (HC).

In this prospective multicenter study, 95 PD patients and 65 age- and sex-matched HC underwent 3 T MRI and clinical evaluation at baseline and 1 year. PD patients were stratified by disease duration (<5, 5-10, 10-15, >15 years). $R_2^{*}$ values were extracted from basal ganglia regions, focusing primarily on the substantia nigra (SN). Motor and non-motor assessments, performed in the on-medication state, included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Montreal Cognitive Assessment, and mood/apathy scales.

SN $R_2^{*}$ increased significantly over 1 year across PD patients (+5% within-group) and HC (+2% within-group), resulting in a +3% greater longitudinal change in PD versus HC (P < 0.001). Larger SN $R_2^{*}$ changes were observed in patients with longer disease duration (r = 0.28; P = 0.006). Significant $R_2^{*}$ changes were also detected in other basal ganglia regions. No significant change in motor or non-motor disability in the on-medication state was observed over 1 year.

SN $R_2^{*}$ increased over 1 year in PD across disease stages, with larger changes in more advanced patients and no evidence of an early plateau. These findings support the potential of $R_2^{*}$ as a sensitive imaging marker of PD progression over short intervals. © 2026 International Parkinson and Movement Disorder Society.