Quantitative susceptibility mapping found increased dentate nucleus iron deposition in tremor-dominant PD versus PIGD and controls, with DN susceptibility correlating with tremor severity and, combined with levodopa dose, distinguishing subtypes (AUC 0.898).

Provides a noninvasive imaging biomarker tied to tremor-related CTC circuit pathology and iron dysregulation that could help stratify patients for subtype-specific trials and suggest exploration of iron-modulating therapies.

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.