Gait analysis with wearables predicts conversion to Parkinson disease

Ulrike Suenkel,Walter Maetzler,Morad Elshehabi,Silvia Del Din,Clint Hansen,Florian Metzger,Daniela Berg,Lynn Rochester,Kathrin Brockmann,Brook Galna,Elke Warmerdam,Markus A. Hobert

doi:10.1002/ana.25548

Abstract

ObjectiveQuantification of gait with wearable technology is promising; recent cross‐sectional studies showed that gait characteristics are potential prodromal markers for Parkinson disease (PD). The aim of this longitudinal prospective observational study was to establish gait impairments and trajectories in the prodromal phase of PD, identifying which gait characteristics are potentially early diagnostic markers of PD.MethodsThe 696 healthy controls (mean age = 63 ± 7 years) recruited in the Tubingen Evaluation of Risk Factors for Early Detection of Neurodegeneration study were included. Assessments were performed longitudinally 4 times at 2‐year intervals, and people who converted to PD were identified. Participants were asked to walk at different speeds under single and dual tasking, with a wearable device placed on the lower back; 14 validated clinically relevant gait characteristics were quantified. Cox regression was used to examine whether gait at first visit could predict time to PD conversion after controlling for age and sex. Random effects linear mixed models (RELMs) were used to establish longitudinal trajectories of gait and model the latency between impaired gait and PD diagnosis.ResultsSixteen participants were diagnosed with PD on average 4.5 years after first visit (converters; PDC). Higher step time variability and asymmetry of all gait characteristics were associated with a shorter time to PD diagnosis. RELMs indicated that gait (lower pace) deviates from that of non‐PDC approximately 4 years prior to diagnosis.InterpretationTogether with other prodromal markers, quantitative gait characteristics can play an important role in identifying prodromal PD and progression within this phase. ANN NEUROL 2019;86:357–367

Highlights

To reduce the number of models, we focused on gait characteristics which changed over time in the PD converters (PDCs) group in conjunction with a group difference at the time of Parkinson disease (PD) diagnosis
We were able to show that gait discriminates future PD converters from healthy controls (HCs) up to approximately 4 years prior to clinical diagnosis
We show that gait characteristics have the potential to predict conversion to PD and can relevantly add to a panel of prodromal markers for the definition of persons at substantially increased risk for PD

Summary

Objective

Quantification of gait with wearable technology is promising; recent cross-sectional studies showed that gait characteristics are potential prodromal markers for Parkinson disease (PD). More than 50% convert to PD or similar diseases (such as dementia with Lewy bodies) with an average duration of the overall prodromal phase of 13 years[8] and a motor phase of 4.5 years.[9,10,11] A study using simple methods for description of motor abnormalities (UPDRS and Timed Up and Go test) suggests that first abnormalities in gait precede diagnosis by up to 4.4 to 6.3 years.[10] A quantitative cross-sectional evaluation of normal-pace walking in RDB participants found subtle changes of velocity, cadence, and variability of gait compared to controls.[12] Comparable results were found in a quantitative crosssectional evaluation of gait—here, only during challenging (dual-task) conditions—in LRRK2 mutation carriers who showed increased gait variability and decreased amplitude of the dominant peak of the accelerometer signal.[13] Another cross-sectional study[14] showed increased arm-swing variability in LRRK2 mutation carriers that was basically visible in non-PD and PD state under challenging conditions (ie, dual-task conditions) These latter studies cannot differentiate between initial abnormalities in the central gait network of RBD and LRRK2 cohorts (which can be entirely independent of dynamic processes happening in a prodromal PD phase) and “real” prodromal PD markers, highlighting the need for prospective longitudinal and populationbased studies. We hypothesized that (1) selected gait characteristics predict future PD conversion, (2) gait declines continuously during the prodromal phase, and (3) first gait changes in future PD converters (PDCs) appear 4 to 5 years prior to diagnosis

Subjects and Methods

Results

Discussion

Limitations