Technology-based therapy-response and prognostic biomarkers in a prospective study of a de novo Parkinson’s disease cohort

Abstract

Early noninvasive reliable biomarkers are among the major unmet needs in Parkinson’s disease (PD) to monitor therapy response and disease progression. Objective measures of motor performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients’ kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement, p = 0.009) and gait features (velocity of arms and legs, sit-to-stand time, p = 0.007; p = 0.009; p = 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (p = 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.

Longitudinal Monitoring of Progressive Supranuclear Palsy using Body‐Worn Movement Sensors

“…21 Wearable devices introduce the prospect of identifying objective biomarkers to measure the onset, progression, and severity of neurodegenerative conditions; accelerating clinical trials; and facilitating the discovery of new therapeutics. Although a few studies have utilized sensors to monitor motor features longitudinally in typical PD, 22,23 studies focused on PSP patients are virtually nonexistent. The current investigation utilizes a six-sensor IMU array to explore the progression of the walking and swaying kinematic features in PSP participants at 3-month intervals over a 1-year period.…”

Arm swing deviations in patients with Parkinson’s disease at different gait velocities

“…Due to a comparison with PWPD here, an ndASI above 50 was considered pathological (Plate et al 2015 ). Recent developments in sensor-based gait analysis systems (Morris et al 2019 ; Flachenecker et al 2020 ; Di Lazzaro et al 2021 ) enable researchers to evaluate habitual overground walking in a larger area with fewer spatial and optical constraints compared to those in the treadmill trials in laboratory conditions.…”

Antiparkinsonian medication masks motor signal progression in de novo patients

“…Three studies have used wearable devices in de novo patients as they are started on medication, but they have only examined two or three timepoints. Thus although the use of wearable inertial sensors can identify medication-induced improvements of motor features in de novo PD [ [15] , [16] , [17] ], less is known about the effect of levodopa on the longitudinal progression of measurements made using such systems.…”

“… Longitudinal – measure effects of medication – prescribed start of therapy Kwon et al, 2017 [ 36 ] 24 de novo PD/27 HC Tested before and 1 h after starting medication Walking mat Spatio-temporal gait variables, gait variability and asymmetry Stride length, walking speed, and cadence increased, and stride time decreased with medication. Ricci et al [ 16 ], 36 de novo PD 6 and 12 months after start of medication Wearable sensors Bradykinesia, pull test, timed up and go, tremor l -dopa improved features of all but tremor task Di Lazzaro et al, 2021 [ 15 ] 40 de novo PD 6 and 12 months after start of medication Wearable sensors Bradykinesia, timed-up-and-go, pull test, tremor (upper limbs) All motor tasks had at least one feature (except tremor) that improved with levodopa Marras et al, 2011 [ 4 ] 1606 de novo PD (combined) Every 3 months for 2 years UPDRS + other clinical scales Baseline UPDRS, employment, education, age, tremor, MMSE, smoking, asymmetry score, site of onset Higher UPDRS, full time employment, lesser smoking history, onset on the left all associated with initiating levodopa therapy faster Longitudinal – measure effects of medication – natural start of therapy Mancini et al, 17–38 2012 [ 17 ] 13 de novo PD/12 HC After 3, 6 and 12 months Wearable sensors 2-min postural balance test Slight decrease in sway dispersion and velocity compared to an increase in untreated Van den Heuvel et al, 2021 [ 3 ] 432 de novo PD Every 6 months, for 4 years UPDRS + other clinical scales Observed the natural introduction of meds across two-year period in patients, compared earlier vs. later meds …”