Objective and continuous monitoring of Parkinson’s disease (PD) tremor in free-living conditions could benefit both individual patient care and clinical trials, by overcoming the snapshot nature of clinical assessments. To enable robust detection of tremor in the context of limited amounts of labeled training data, we propose to use prototypical networks, which can embed domain expertise about the heterogeneous tremor and non-tremor sub-classes. We evaluated our approach using data from the Parkinson@Home Validation study, including 8 PD patients with tremor, 16 PD patients without tremor, and 24 age-matched controls. We used wrist accelerometer data and synchronous expert video annotations for the presence of tremor, captured during unscripted daily life activities in and around the participants’ own homes. Based on leave-one-subject-out cross-validation, we demonstrate the ability of prototypical networks to capture free-living tremor episodes. Specifically, we demonstrate that prototypical networks can be used to enforce robust performance across domain-informed sub-classes, including different tremor phenotypes and daily life activities.@en

Background: Wearable sensors have been used successfully to characterize bradykinetic gait in patients with Parkinson disease (PD), but most studies to date have been conducted in highly controlled laboratory environments. Objective: This paper aims to assess whether sensor-based analysis of real-life gait can be used to objectively and remotely monitor motor fluctuations in PD. Methods: The Parkinson@Home validation study provides a new reference data set for the development of digital biomarkers to monitor persons with PD in daily life. Specifically, a group of 25 patients with PD with motor fluctuations and 25 age-matched controls performed unscripted daily activities in and around their homes for at least one hour while being recorded on video. Patients with PD did this twice: once after overnight withdrawal of dopaminergic medication and again 1 hour after medication intake. Participants wore sensors on both wrists and ankles, on the lower back, and in the front pants pocket, capturing movement and contextual data. Gait segments of 25 seconds were extracted from accelerometer signals based on manual video annotations. The power spectral density of each segment and device was estimated using Welch's method, from which the total power in the 0.5- to 10-Hz band, width of the dominant frequency, and cadence were derived. The ability to discriminate between before and after medication intake and between patients with PD and controls was evaluated using leave-one-subject-out nested cross-validation. Results: From 18 patients with PD (11 men; median age 65 years) and 24 controls (13 men; median age 68 years), ≥10 gait segments were available. Using logistic LASSO (least absolute shrinkage and selection operator) regression, we classified whether the unscripted gait segments occurred before or after medication intake, with mean area under the receiver operator curves (AUCs) varying between 0.70 (ankle of least affected side, 95% CI 0.60-0.81) and 0.82 (ankle of most affected side, 95% CI 0.72-0.92) across sensor locations. Combining all sensor locations did not significantly improve classification (AUC 0.84, 95% CI 0.75-0.93). Of all signal properties, the total power in the 0.5- to 10-Hz band was most responsive to dopaminergic medication. Discriminating between patients with PD and controls was generally more difficult (AUC of all sensor locations combined: 0.76, 95% CI 0.62-0.90). The video recordings revealed that the positioning of the hands during real-life gait had a substantial impact on the power spectral density of both the wrist and pants pocket sensor. Conclusions: We present a new video-referenced data set that includes unscripted activities in and around the participants' homes. Using this data set, we show the feasibility of using sensor-based analysis of real-life gait to monitor motor fluctuations with a single sensor location. Future work may assess the value of contextual sensors to control for real-world confounders.

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Background: An important challenge in Parkinson's disease research is how to measure disease progression, ideally at the individual patient level. The MDS-UPDRS, a clinical assessment of motor and nonmotor impairments, is widely used in longitudinal studies. However, its ability to assess within-subject changes is not well known. The objective of this study was to estimate the reliability of the MDS-UPDRS when used to measure within-subject changes in disease progression under real-world conditions. Methods: Data were obtained from the Parkinson's Progression Markers Initiative cohort and included repeated MDS-UPDRS measurements from 423 de novo Parkinson's disease patients (median follow-up: 54 months). Subtotals were calculated for parts I, II, and III (in on and off states). In addition, factor scores were extracted from each part. A linear Gaussian state space model was used to differentiate variance introduced by long-lasting changes from variance introduced by measurement error and short-term fluctuations. Based on this, we determined the within-subject reliability of 1-year change scores. Results: Overall, the within-subject reliability ranged from 0.13 to 0.62. Of the subscales, parts II and III (OFF) demonstrated the highest within-subject reliability (both 0.50). Of the factor scores, the scores related to gait/posture (0.62), mobility (0.45), and rest tremor (0.43) showed the most consistent behavior. Conclusions: Our results highlight that MDS-UPDRS change scores contain a substantial amount of error variance, underscoring the need for more reliable instruments to forward our understanding of the heterogeneity in PD progression. Focusing on gait and rest tremor may be a promising approach for an early Parkinson's disease population.

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