Category: Parkinson's Disease: Genetics
Objective: This study aims to investigate the longitudinal disease progression of early-onset Parkinson’s disease (EOPD) in carriers of GBA mutations compared to genetically undefined EOPD (GU-EOPD).
Background: GBA mutations are among the most significant genetic risk factors for PD. However, their impact on disease progression in EOPD remains inadequately characterized. This study examines cognitive decline, motor progression, and key disease milestones in GBA-associated EOPD compared to GU-EOPD.
Method: A total of 76 GBA-EOPD and 474 GU-EOPD patients were included between January 16, 2010, and September 10, 2024. Among them, 33 GBA-EOPD and 163 GU-EOPD patients underwent at least two follow-up visits. Baseline characteristics were compared between groups, and disease progression was assessed using linear mixed-effects models.
Results: Baseline comparisons showed no significant differences between the GBA-EOPD and GU-EOPD groups in age of onset (39.54 vs. 40.06 years, p=0.512), UPDRS-III (med-off) scores (26.67 vs. 26.51, p=0.9512), or MMSE scores (27.15 vs. 28.09, p=0.533), except for a higher LEDD in the GBA group (512.2 mg vs. 462.35 mg, p=0.025).
Longitudinally, the GBA group exhibited a greater annual decline in MMSE (-0.226, p=0.023), memory (-0.08, p=0.03), and visuospatial ability (-0.102, p=0.04), along with a more pronounced increase in GDS (+0.75, p=0.00063) and PDQ-39 scores (+1.668, p=0.036).
GBA mutation carriers had a 15.87-fold increased risk of EOPD. In terms of disease milestones, the GBA-EOPD group had similar times to dementia (5.86 vs. 6.04 years, p=0.912), first falls (7.77 vs. 7.71 years, p=0.430), first freezing episodes (6.39 vs. 7.02 years, p=0.872), first dyskinesias (6.78 vs. 8.47 years, p=0.173), and first hallucinations (7.26 vs. 8.01 years, p=0.5401). However, wearing-off symptoms appeared earlier in the GBA group (5.54 vs. 6.73 years, p=0.023).
Conclusion: GBA mutation carriers with EOPD experience a more aggressive disease course, characterized by accelerated cognitive decline, increased disease burden, and earlier onset of key motor and non-motor complications. These findings highlight the need for genetic screening to inform prognosis and optimize personalized management strategies in EOPD.
To cite this abstract in AMA style:
YM. Sun, PH. Li, ZY. Qi, FT. Liu, JJ. Wu, J. Wang. Longitudinal Analysis of Disease Progression in GBA-Associated Early-Onset Parkinson’s Disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/longitudinal-analysis-of-disease-progression-in-gba-associated-early-onset-parkinsons-disease/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-analysis-of-disease-progression-in-gba-associated-early-onset-parkinsons-disease/