Differential White Matter Regional Alterations in Motor Subtypes of Early Drug-Naive Parkinson's Disease Patients

Background. Parkinson's disease (PD) can be classified into tremor dominant (TD) and postural instability and gait difficulty (PIGD) subtypes with TD considered as the benign subtype. The neural alterations of the 2 subtypes in the early stages before administration of medications remain elusive. Objective. This study assessed the subtype-related white matter (WM) microstructural features in newly diagnosed and drug-naive PD patients from the Parkinson's Progression Markers Initiative (PPMI). Methods. Sixty-five early PDs with stable subtypes (52 TD and 13 PIGD patients) and 61 controls underwent diffusion tensor imaging (DTI) scanning and clinical assessment. Tract-based special statistics (TBSS), graph-theoretical and network-based analyses were used to compare WM regional and network features between groups. Results. No differences in disease stages and duration were found between the 2 patient groups. TD patients showed increased fractional anisotropy (FA), but decreased radial and axial diffusivities (RD and AD) in several projection, association, and commissural tracts, compared with PIGD patients and controls. Motor severity had mild-to-moderate correlations with FA and RD of the corpus callosum (genu) in TD, but strong correlations with FA and RD of multiple association tracts in PIGD. Conversely, no significant network changes were noted. Conclusions. TD patients showed regionally increased FA but decreased diffusivities, implying neural reorganization to compensate PD pathology in early stages. PIGD patients, despite having similar disease stages and duration, exhibited more WM degradation. These results demonstrate differential WM regional features between the 2 subtypes in early PD and support the notion of TD being a benign subtype.