Does the MDS-UPDRS provide the precision to assess progression in early Parkinson's disease? Learnings from the Parkinson's progression marker initiative cohort

Abstract

Objectives: Developing disease modifying therapies for Parkinson's disease (PD) calls for outcome measurement strategies focused on characterizing early stage disease progression. We explored the psychometric evidence for using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II (patient motor experience of daily living) and part III (clinician motor examination) in this context.

Methods: MDS-UPDRS-II and -III data were collected at screening, month 12, and month 24 from 384 early stage PD patients (diagnosis ≤ 2 years; Hoehn and Yahr stage 1/2) in the Parkinson's Progression Markers Initiative (PPMI) study. Psychometric analysis, based on Rasch measurement theory (RMT), was performed on both the original MDS UPDRS-II and -III scales and exploratory content-driven scale structures.

Results: RMT analyses showed neither scale was well targeted to early PD. A marked floor effect appeared for most items and a clear item gap was consistently observed in very mild severity of motor signs and levels of motor impact. The original MDS-UPDRS-II and -III scales also displayed disordered thresholds (9/13 and 20/33 items, respectively), indicating response scales not functioning as expected, and misfit (5/13 and 12/33 items, respectively), flagging areas for potential improvement.

Conclusions: The MDS-UPDRS-II and -III have psychometric limitations which limits the precision of measurement of motor symptoms and impact in early PD. This can lead to insensitivity in detecting differences and clinical change. Importantly, the diagnostic psychometric evidence provided by the RMT analysis provides a clear starting point for how to improve the quantification of clinically relevant concepts to characterize the course of early PD.

Keywords: Disease-modifying therapy; Early Parkinson’s disease; Movement Disorder Society Unified Parkinson’s Disease Rating Scale; Rasch measurement theory.

Fig. 1

Heatmap of responses to MDS-UPDRS-III items (baseline PPMI PD cohort; N = 384). Each cell of the map shows the percentage of patients rated at the given level (column) for the given item (raw). Darker fill colours indicate higher percentages

Fig. 2

Scale to sample targeting of MDS-UPRS-III in the PPMI Parkinson’s disease cohort (screening, month 12, and month 24 pooled, N = 1053). The upper panel (pink boxes) shows the distribution of the individuals of the PPMI PD cohort over the continuum of motor sign severity; the lower panel (blue boxes) shows the distribution of the MDS-UPDRS-III items on the continuum of motor sign severity; the green line shows the information function of the MDS-UPDRS-III items, reflecting the accuracy of measurement over the continuum of severity of motor signs

Fig. 3

Heatmap of responses to the MDS-UPDRS-II items (baseline PPMI PD cohort; N = 384). Each cell of the map shows the percentage of patients rated at the given level (column) for the given item (raw). Darker fill colours indicate higher percentages

Fig. 4

Scale to sample targeting of MDS-UPRS-II in the PPMI Parkinson’s disease cohort (screening, month 12, and month 24 pooled, N = 1081). The upper panel (pink boxes) shows the distribution of the individuals of the PPMI PD cohort over the continuum of impact of motor signs; the lower panel (blue boxes) shows the distribution of the MDS-UPDRS-II items on the continuum of impact of motor signs; the green line shows the information function of the MDS-UPDRS-II items, reflecting the accuracy of measurement over the continuum of impact of motor signs