Objective: To compare GBA1-associated PD and sporadic PD progression based on NMS severity, using data from the Parkinson’s Progression Markers Initiative (PPMI) (https://www.ppmi-info.org)
Background: Parkinson’s Disease (PD) progression varies, particularly with non-motor symptoms (NMS), which significantly affect quality of life. GBA1-PD is linked to GBA1-gene mutations, encoding the beta-glucocerebrosidase enzyme. On average, GBA1-PD shows earlier onset and a faster progression compared to sporadic PD (sPD).
Method: PPMI, a multicenter, longitudinal cohort study was used (data-cut: Dec-11th, 2024). Non-motor scales with continuous variables (cognitive, behaviour and sleep-assessments) were included if the sample size at the longest follow-up (6 years) was >= 40. Mixed-Effects-Model for Repeated-Measures (MMRM), corrected for baseline value and disease duration, was employed.
Results: In total, 95 GBA1-PD and 495 sPD patients were included. At baseline, GBA1 vs sPD patients were 62.2 ± 10.55 (mean ± standard deviation) vs 64.1 ± 9.70 years-old and had PD for 3.2 ±1.97 vs 2.2 ±1.18 years, respectively ([Table 1] for first table).
Patients with GBA1-PD consistently showed worse severity and significantly faster progression in 54.5% of the scales vs sPD. Longitudinally, 6 non-motor scales for GBA1-PD and 4 for sPD (out of 11) showed Minimal Clinical Important Difference (MCID) from baseline, with GBA1-PD reaching MCID 1-2 years earlier than sPD. Among group differences ([Figure 1] for first figure), four scales reached MCID: MDS-UPDRS-Part-1A, Symbol-Digit-Modalities-Score, Hopkins-Verbal-Learning-Test, and State-Trait-Anxiety-Index, with scores worse for GBA1-PD vs sPD.
Conclusion: This analysis suggests that, over 6-years, NMS present with more severity and faster progression in GBA1-PD compared to sPD-patients (adjusted for covariates baseline value and disease duration).
Baseline Characteristics
Heatmap of yearly visits.
References: Disclosures:
Daniel S. Ramos, Miguel M. Fonseca, and Valentina Di Foggia are employees of Bial. PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including 4D Pharma, Abbvie, AcureX, Allergan, Amathus Therapeutics, Aligning Science Across Parkinson’s, AskBio, Avid Radiopharmaceuticals, BIAL, BioArctic, Biogen, Biohaven, BioLegend, BlueRock Therapeutics, Bristol-Myers Squibb, Calico Labs, Capsida Biotherapeutics, Celgene, Cerevel Therapeutics, Coave Therapeutics, DaCapo Brainscience, Denali, Edmond J. Safra Foundation, Eli Lilly, Gain Therapeutics, GE HealthCare, Genentech, GSK, Golub Capital, Handl Therapeutics, Insitro, Jazz Pharmaceuticals, Johnson & Johnson Innovative Medicine, Lundbeck, Merck, Meso Scale Discovery, Mission Therapeutics, Neurocrine Biosciences, Neuron23, Neuropore, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi, Servier, Sun Pharma Advanced Research Company, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, the Weston Family Foundation and Yumanity Therapeutics v. 25MAR2024
To cite this abstract in AMA style:
M. Fonseca, D. Ramos, V. Di Foggia, R. Costa, J. Holenz, D. Simon, T. Marker Initiative. A 6-Year Longitudinal Analysis from the Parkinson’s Progression Markers Initiative on Non-Motor Symptom Severity and Progression in GBA1-associated vs. sporadic Parkinson’s Disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/a-6-year-longitudinal-analysis-from-the-parkinsons-progression-markers-initiative-on-non-motor-symptom-severity-and-progression-in-gba1-associated-vs-sporadic-parkinsons-disease/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-6-year-longitudinal-analysis-from-the-parkinsons-progression-markers-initiative-on-non-motor-symptom-severity-and-progression-in-gba1-associated-vs-sporadic-parkinsons-disease/