Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to both motor symptoms (e.g., tremor, rigidity, gait disturbances) and non-motor symptoms. PD is classified into three subtypes: postural instability gait difficulty (PIGD), tremor-dominant (TD), and indeterminate. The PIGD subtype is associated with worse outcomes, while TD tends to have a better prognosis. Recent research indicates that PD's pathophysiology extends beyond dopamine depletion, involving structural changes in the cerebellum and cerebral cortex. Advanced neuroimaging techniques, particularly quantitative susceptibility mapping (QSM), provide detailed insights into brain alterations associated with PD.
Methods: Forty-three PD patients and 22 healthy controls (HC) were recruited from the University Medical Center Hamburg-Eppendorf. PD diagnosis followed UK Brain Bank criteria, excluding individuals with other neurological disorders, MRI-incompatible implants, or CNS-affecting medications. Clinical assessments included MDS-UPDRS, MoCA for cognition, and Hoehn and Yahr staging. MRI was performed on a 3T Siemens Prisma scanner using T1-weighted MPRAGE and QSM sequences. Image processing included Freesurfer for cortical segmentation and CERES for cerebellar regions. Regions of interest (ROIs) such as the dentate nucleus, thalamus, primary motor cortex (M1), red nucleus, substantia nigra, and subthalamic nucleus were segmented and analyzed using ANCOVA, adjusting for age, sex, disease stage, and dominant symptom side.
Results: Significant differences in cerebellar volumes were found, with a notable difference in lobule VIIIA (right side) between TD and PIGD patients (p < 0.01), and in lobule VI (left side) between PIGD patients and HC (p < 0.05). Additionally, lobule X volume was positively correlated with the severity of rest tremor. Thalamic volume was larger in the TD group compared to both HC and PIGD patients, while M1 volume was larger in TD than in PIGD patients.
Conclusion : This study identifies distinct structural differences between PD subtypes, particularly in cerebellar and cortical regions. These findings may improve understanding of PD’s pathophysiology and inform more targeted therapeutic approaches. Further analysis of additional brain regions is ongoing.
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