Differential brain iron deposition in Parkinson’s disease subtypes: a comparative quantitative susceptibility mapping study of tremor-dominant versus postural instability/gait difficulty phenotypes

Introduction This study used quantitative susceptibility mapping (QSM) to investigate brain iron deposition patterns in different motor subtypes of Parkinson’s disease (PD). We compared tremor-dominant (TD) and postural instability/gait difficulty (PIGD) patients, analyzed the association between iron deposition and core motor symptoms, and further explored its potential as an imaging feature associated with clinical subtypes. Methods The study included 45 PD patients (25 TD-PD, 20 PIGD-PD) and 23 healthy controls. QSM values were measured in the bilateral caudate nucleus (CN), dentate nucleus (DN), globus pallidus (GP), putamen (PUT), red nucleus (RN), substantia nigra (SN), and thalamus (TH). Results Compared to controls, both PD groups showed elevated iron levels in multiple brain regions. Notably, TD patients exhibited significantly higher magnetic susceptibility in the DN than both PIGD patients and controls, and DN susceptibility also showed a positive correlation with tremor severity in the overall PD cohort (rs = 0.339, p = 0.023). A combined model incorporating DN susceptibility and levodopa equivalent daily dose effectively distinguished TD from PIGD subtypes with an area under the curve of 0.898. Discussion These findings suggest that the motor subtypes of Parkinson’s disease exhibit distinct brain iron distribution patterns, with the TD subtype showing increased DN iron deposition. This supports the role of the cerebello-thalamo-cortical (CTC) circuit in tremor and highlights dentate nucleus iron deposition as a potential imaging feature associated with the tremor-dominant phenotype.