Identification of Parkinson's Disease Subtypes with Distinct Brain Atrophy Progression and Its Association with Clinical Progression

Background: Parkinson's disease (PD) patients suffer from progressive gray matter volume (GMV) loss, but whether distinct patterns of atrophy progression exist within PD are still unclear. Objective This study aims to identify PD subtypes with different rates of GMV loss and assess their association with clinical progression. Methods: This study included 107 PD patients (mean age: 60.06 +/- 9.98 years, 70.09% male) with baseline and >= 3-year follow-up structural MRI scans. A linear mixed-effects model was employed to assess the rates of regional GMV loss. Hierarchical cluster analysis was conducted to explore potential subtypes based on individual rates of GMV loss. Clinical score changes were then compared across these subtypes. Results: Two PD subtypes were identified based on brain atrophy rates. Subtype 1 (n = 63) showed moderate atrophy, notably in the prefrontal and lateral temporal lobes, while Subtype 2 (n = 44) had faster atrophy across the brain, particularly in the lateral temporal region. Furthermore, subtype 2 exhibited faster deterioration in non-motor (MDS-UPDRS-Part I, beta = 1.26 +/- 0.18, P = 0.016) and motor (MDS-UPDRS-Part II, beta = 1.34 +/- 0.20, P = 0.017) symptoms, autonomic dysfunction (SCOPA-AUT, beta = 1.15 +/- 0.22, P = 0.043), memory (HVLT-Retention, beta = -0.02 +/- 0.01, P = 0.016) and depression (GDS, beta = 0.26 +/- 0.083, P = 0.019) compared to subtype 1. Conclusion: The study has identified two PD subtypes with distinct patterns of atrophy progression and clinical progression, which may have implications for developing personalized treatment strategies.