Identification of Parkinson's disease subtypes with distinct brain atrophy progression and its association with clinical progression

Abstract

Backgr ound: 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 pr ogr es- sion. 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 employ ed to assess the r ates of re gional GMV loss. Hier ar c hical cluster analysis was conducted to explore potential subtypes based on individual rates of GMV loss. Clinical score c hanges w er e then compar ed acr oss these subtypes. Results: Tw o PD subtypes w ere identified based on br ain atrophy r ates. Subtype 1 (n = 63) show ed moder ate atr ophy, nota b l y in the pr efr ontal and lateral temporal lobes, while Subtype 2 (n = 44) had faster atrophy across the brain, particularly in the lateral temporal region. Furthermor e, subtype 2 exhibited faster deterioration in non-motor (MDS-UPDRS-Part I , β= 1.26 ±0.18, P = 0.016) and motor (MDS-UPDRS-Part II , β= 1.34 ±0.20, P = 0.017) symptoms, autonomic dysfunction (SCOPA-AUT, β= 1.15 ±0.22, P = 0.043), memory (HVLT-Retention, β= -0.02 ±0.01, P = 0.016) and de pr ession (GDS, β= 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 ma y ha ve implications for de v eloping personalized tr eatment strategies.