Heterogeneous Patterns of Wearing-Off in Parkinson's Disease

Background: Wearing-off (WO) in Parkinson's disease (PD) refers to the recurrence of motor and non-motor symptoms between levodopa doses. Its prevalence, inter-individual variability, and temporal relationship to medication remain incompletely characterized in real-world settings. Methods: Twenty-three PD participants with self-reported WO completed a digitized Wearing-Off Questionnaire-19 (WOQ-19) hourly during waking hours over three consecutive days (72 h), yielding 894 valid surveys. Symptom heterogeneity was quantified using the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Symptom changes time-locked to medication intake were assessed using Cochran's Q test. Results: Mean compliance was 91.86% ± 6.31%. All 19 WOQ-19 symptoms were endorsed at least once, with participants reporting a median of 8 distinct symptoms (IQR: 5-11). Prevalence differed significantly across symptoms (Kruskal-Wallis test, p < 0.001). Tremor was the most prevalent symptom overall, while other symptoms were rare, episodic, and highly variable across individuals. Participants' relative symptom burden was consistent between Days 2 and 3 (Spearman's rho = 0.682, p < 0.001), and diurnal worsening showed a non-significant positive trend (β = 0.031/hour, p = 0.117). Five symptoms showed significant peri-dose modulation: weakness, muscle cramping, experience of hot or cold, tremor, and abdominal discomfort (all p < 0.05). WO burden did not significantly correlate with standard clinical severity measures. Conclusions: WO symptom expression is highly heterogeneous across individuals but largely consistent from day to day within individuals. Weakness and experience of hot or cold are candidates for future wearable sensor-based studies of levodopa cycling, supporting individualized approaches to WO assessment in PD.