Objective: To determine whether digital mobility outcomes (DMOs) differ between individuals with relatively advanced PD grouped according to the clinical criteria of the Neuronal α-Synuclein Disease Integrated Staging System (NSD-ISS).

Background: PD progression is traditionally characterised by motor and non-motor symptoms with functional impairment, commonly quantified using clinical rating scales. The NSD-ISS offers a biologically grounded framework for staging PD, though biological criteria currently exist for stages 0–2; later stages are defined by clinical criteria in conjunction with biomarkers. DMOs have the potential to serve as these anchors for classifying stages 3 and 4.

Method: As part of the Mobilise-D study, real-world mobility was assessed over seven consecutive days in individuals with PD (n=461 with DMO and clinical staging data available, mean age 65.8 ± 9.6, 65% male) and healthy controls (HC; n=221 with DMO data, mean age 66.8 ± 8.4, 67% male), using a wearable device worn on the lower back. As biological markers (neuronal α-synuclein, dopaminergic neuron dysfunction) were unavailable, PD participants were stratified using the clinical components of the NSD-ISS, including motor (MDS-UPDRS part II), non-motor (MDS-UPDRS part I) and cognitive criteria (MoCA/MDS-UPDRS item 1.1), into stage 3 (n=290) and stage 4 (n=171). Demographic and clinical variables, along with 24 technically validated DMOs, were compared across HC and NSD stages using Kruskal–Wallis or one-way ANOVA tests.

Results: All groups were well matched for age, sex, height, weight, and body mass index. Individuals in NSD stage 4 had a greater proportion of fallers, freezers, and walking aid users compared with NSD stage 3 and HC (all p < .001). After controlling for multiple comparisons, 22 DMOs differed significantly across groups. Post-hoc analyses revealed significant differences in DMOs between HC and PD across several domains, while three walking speed DMOs and one walking speed variability DMO differed between NSD stages 3 and 4.

Conclusion: Pace- and variability-related DMOs differed between NSD stages 3 and 4 stratified by the clinical components of NSD-ISS, supporting their potential utility as objective staging anchors within this framework. These findings require replication in biologically confirmed cohorts and expansion to other stages to determine whether DMOs can anchor the full NSD-ISS spectrum.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/do-digital-mobility-outcomes-differ-across-clinically-defined-nsd-iss-stages-in-parkinsons-disease/