Objective: To enable prospective identification of individuals with diffuse malignant (DM) Parkinson’s disease (PD) by establishing disease-duration-specific thresholds for motor and non-motor symptom scales.

Background: Heterogeneity in PD progression contributes to the failure of disease-modification trials. Identifying individuals with severe, rapidly progressive PD could enhance trial sensitivity. A validated data-driven model classified PD into DM, intermediate (IM), and mild motor-predominant (MMP) subtypes based on scale scores (>75th percentile for MDS-UPDRS II & III, RBDSQ, SCOPA-AUT; <25th percentile for MoCA). However, prior studies applied these criteria retrospectively, limiting their use in prospective trials.

Method:

Using data from the Parkinson’s Progression Markers Initiative (PPMI), we conducted an observational analysis of idiopathic PD patients, excluding known genetic variants. Composite motor (MDS-UPDRS II & III) and non-motor (MoCA, RBDSQ, SCOPA-AUT) scores were calculated annually post-diagnosis. Disease-duration-specific thresholds were determined each year, classifying patients into DM, IM, or MMP subtypes. Time to disease progression was assessed using 25 PPMI-defined progression milestones across six clinical domains and compared via Kaplan-Meier survival analysis.

Results:

We analyzed 1,036 PD patients. DM-PD prevalence ranged from 18.9% to 21% across the first five years, while IM-PD and MMP-PD ranged from 34.7% to 43.9% and 35.6% to 44.3%, respectively. Motor and non-motor symptom thresholds worsened over time, increasing for MDS-UPDRS II & III, RBDSQ, and SCOPA-AUT, and decreasing for MoCA (Table 1). DM-PD patients had significantly worse baseline symptoms and a shorter time to disease progression milestones than IM-PD and MMP-PD (P<0.0001, Fig 1).

Conclusion: This study provides a framework for prospective PD subtyping using disease-duration-specific criteria, enabling early DM-PD identification. Future studies should validate and implement these criteria to improve patient stratification in clinical trials.

KM survival analysis for progression milestones.

The 75th percentiles of the scores.

References: [1] Fereshtehnejad SM, Romenets SR, Anang JB, Latreille V, Gagnon JF, Postuma RB. New Clinical Subtypes of Parkinson Disease and Their Longitudinal Progression: A Prospective Cohort Comparison With Other Phenotypes. JAMA Neurol. 2015 Aug;72(8):863-73. doi: 10.1001/jamaneurol.2015.0703. PMID: 26076039.

[2] Fereshtehnejad SM, Zeighami Y, Dagher A, Postuma RB. Clinical criteria for subtyping Parkinson’s disease: biomarkers and longitudinal progression. Brain. 2017 Jul 1;140(7):1959-1976. doi: 10.1093/brain/awx118. PMID: 28549077.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/developing-disease-duration-specific-percentiles-for-prospective-subtyping-of-the-diffuse-malignant-parkinsons-disease-a-ppmi-based-study/