Structural MRI Differences Between Parkinson’s Disease Motor Subtypes in Early-Stage: A Multicontrast Imaging Study

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ABSTRACT Background Parkinson’s disease (PD) is characterized by dopaminergic neuron degeneration, leading to motor and neuropsychological symptoms. PD is clinically divided into tremor-dominant (TD) and postural instability-gait disorder (PIGD) subtypes, which may differ in neuroanatomical changes. Neuroimaging explores these differences, enhancing understanding of PD heterogeneity. Objectives This study examines neuroanatomical differences between subtypes using MRI, focusing on subcortical volumes, cortical thickness, iron deposition, and white matter changes. Methods This cross-sectional study included 51 PD patients and controls. Participants underwent clinical assessments and MRI. Cortical and subcortical segmentation was automated using FreeSurfer, and quantitative susceptibility mapping was used to assess brain iron content. Diffusion-weighted MRI data were processed using Tractseg for tractometry analysis. Results The PD-TD group exhibited higher iron levels in the substantia nigra compared to healthy controls. Iron deposition in the thalamus correlated with MDS-UPDRS-part-III and PIGD scores. Tractometry showed differences in fractional anisotropy (FA) between PD-TD and PD-PIGD in the bilateral fronto-pontine tract (FPT). The PD-PIGD group had decreased FA in the middle cerebellar peduncle (MCP) compared to controls. FA in the left FPT correlated with tremor scores, while FA in the MCP correlated with PIGD scores. Conclusions This study highlights distinct neuroimaging signatures between PD motor subtypes. Elevated iron deposition in the substantia nigra is a shared feature, particularly in the TD subtype. Subtype-specific white matter changes, including reduced FA in the FPT and MCP, correlate with tremor and PIGD scores. These findings underscore the potential of neuroimaging biomarkers in unraveling PD heterogeneity and guiding tailored approaches.

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