Characterization of Non-Motor Fluctuations Using the Movement Disorder Society Non-Motor Rating Scale

Background: Non-motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied. Objective: To study NMF in PwP using both the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) NMF subscale and wearable sensors. Methods: We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n = 33), 2–5 years (n = 35), 5–10 years (n = 33), and > 10 years (n = 31). In addition, wearable triaxial sensor output was used as an exploratory outcome for early morning “off” periods. Results: Significant between-group differences were observed for MDS-NMS NMF total scores (P < 0.001), and specifically for depression, anxiety, fatigue and cognition, with both NMF prevalence and burden increasing in those with longer disease duration. Whereas only 9.1% with a short disease duration had NMF (none of whom had dyskinesia), in PwP with a disease duration of >10 years this was 71.0% (P < 0.001). From a motor perspective, dyskinesia severity increased evenly with increasing disease duration, while NMF scores in affected individuals showed an initial increase with largest differences between 2–5 years disease duration (P < 0.001), with plateauing afterwards. Finally, we observed that the most common NMF symptoms in patients with sensor-confirmed early morning “off” periods were fluctuations in cognitive capabilities, restlessness, and excessive sweating. Conclusions: Non-motor fluctuations prevalence in PwP increases with disease duration, but in a pattern different from motor fluctuations. Moreover, NMF can occur in PwP without dyskinesia, and in those with NMF the severity of NMF increases most during years 2–5 after diagnosis.