Objective: To determine the longitudinal change in the Movement Disorder Society –Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) in Parkinson’s disease (PD) participants who were untreated at baseline.

Background: MDS-UPDRS is a validated revised version of UPDRS that is increasingly used in clinical research. One current barrier to increased utilization of the MDS-UPDRS as the primary outcome in clinical trials is lack of the longitudinal data on the rate of change specifically in the de novo population.

Methods: Parkinson’s Progression Markers Initiative (PPMI) is an observational international cohort study of at baseline untreated PD participants and matched healthy controls (HCs). MDS-UPDRS is assessed longitudinally every 6 months.  Once participants start dopaminergic therapy (DT), MDS-UPDRS is assessed annually in the OFF medications state (>6 hours post last dose of DT) and ON state. We report analysis of the MDS-UPDRS change over 5 years and baseline predictors of change.

Results: 423 PD patients were recruited into the study. Presented data include subset of participants with available OFF scores.  MDS-UPDRS Part I-III at baseline was 32.4 (SD 13.1), at year 1= 39.2(16)(N=334), year 2= 42.8(17) (N=283), year 3= 46 (18.6)(N=255), year 4 =51.9 (21.3)(N=185) and year =53(22.4)(N=73). Baseline to year one change of MDS-UPDRS was 7.45 (11.6) in the overall cohort, but was 10 (10.6) in subjects who did not require DT (N=162, 41%) and 5.0 (12) (p<.0001) (OFF state) in subjects who required DT (N=172). In a multivariate model after adjusting for age, gender, disease duration, DT status, and baseline score, larger MDS-UPDRS 12 mon change was associated with the lower baseline contralateral putamen DAT scores and cerebrospinal fluid alpha-synuclein levels.

Conclusions: This is the largest dataset to report longitudinal change of MDS-UPDRS in de novo PD patients. These data can be used for the sample size estimate for the interventional studies in de novo PD population. Association of the rate of change of MDS-UPDRS with the putamen DAT scores and alpha-synuclein levels suggest that the scale captures “biological state” of the disease and that these biomarkers could be used as outcome measure and/ or for stratification of participants into clinical trials.

References: Authorship: Ken Marek on behalf of the PPMI Investigators

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MDS Abstracts - https://www.mdsabstracts.org/abstract/five-year-longitudinal-change-in-the-mds-updrs-scores-in-early-parkinsons-disease-participants-results-from-the-ppmi-study/