Progression of daily-life tremor measures in early Parkinson disease: a longitudinal continuous monitoring study

BackgroundSensitive outcome measures are critical for evaluating the efficacy of novel treatments for Parkinson disease (PD). Recently, we demonstrated that a tremor detection algorithm could reliably detect and quantify real-life PD tremor from wearable sensor data. Here, we assess the sensitivity to change of sensor-derived daily-life tremor measures over two years in an unmedicated and medicated cohort of persons with early PD. MethodsWe used two-year continuous wrist sensor data (median wear time: 22 hours/day) from the Personalized Parkinson Project (n=462 medicated; n=78 unmedicated at baseline), in combination with annual clinical evaluations of tremor severity. From the raw gyroscope data, we derived previously validated weekly measures for tremor time and power, which were smoothed over time using piecewise linear trend estimation. One- and two-year standardized response means (SRMs) were computed to compare the sensitivity to change between the sensor-derived tremor measures and clinical tremor scores. FindingsIn unmedicated participants with tremor, sensor-derived tremor measures demonstrated a high sensitivity to progression (two-year SRMs ranged from 0.67 to 1.09), which was significantly larger than clinical tremor scores (two-year SRMs ranged from 0.21 to 0.41). In medicated participants, sensor-derived tremor time decreased (two-year SRM of -0.18 in participants with tremor), which was associated with both an increase in dopaminergic medication dose and higher disease duration. In contrast, the sensor-derived tremor power measures and clinical rest tremor scores (measured in the OFF state) increased slightly (two-year SRMs ranging from 0.11 to 0.27). InterpretationPrior to initiation of symptomatic treatment, sensor-derived daily-life tremor measures are substantially more sensitive to disease progression than clinical tremor scores, making them a promising tool to evaluate the efficacy of disease-modifying treatments in early PD.