2026 ECNP Congress

PS01-1125

Smartphone motor testing detects acute levodopa responsiveness in Parkinson’s disease

Hans Lennard Schneidewind — J. Kasper, L.D. Lotter, C.R. Eickhoff, K.I. Taylor, W.L. Popp, S.B. Eickhoff, J. Dukart · Research Centre Jülich- Institute of Neuroscience and Medicine, Brain and Behaviour INM-7, Jülich, Germany

2026 ECNP Congress

Smartphone-based active testing may provide scalable, objective markers of motor and cognitive symptoms in Parkinson’s disease, complementing sparse clinical assessments1,2. Its value in clinical research and therapy monitoring depends on whether derived digital features are sensitive to clinically meaningful within-patient change. The levodopa OFF/ON challenge provides a pragmatic validation setting, as patients are assessed under two clinically defined medication states. We evaluated whether supervised smartphone-based active tests detect acute levodopa responsiveness in patients with Parkinson’s disease undergoing clinical evaluation for planned deep brain stimulation.

We conducted a single-centre longitudinal observational study in 45 patients with Parkinson’s disease who underwent deep brain stimulation therapy (mean age 63.1 ± 7.9 years, 29 male, 16 female). Patients completed supervised in-clinic smartphone assessments during a routine levodopa challenge. OFF assessments occurred a mean of 14.5 hours (range 13.3-18.4) after last L-DOPA intake. ON assessments occurred after a mean of 94 minutes (range 20-190 minutes). Analysed assessments comprised 13 prespecified digital features from 11 tasks: hand turning, drawing, five U-turn/body turning, static balance, speeded tapping, postural and rest tremor energy, sustained phonation, free speech, information processing speed and trail making. For each feature, recordings within the same medication phase were averaged at patient level, including repeated recordings and left-/right-sided assessments. The primary readout was the within-subject ON-minus-OFF mean feature change and effect size (Cohen’s dz). Exploratory p values were derived from two-sided one-sample t-tests on patient-level ON-minus-OFF differences. Because not all active tests were available or usable for every patient, analyses were performed feature-wise in patients with paired OFF and ON observations. Accordingly, the number of patients analysed differed by task.

MDS-UPDRS III improved from 31.8 ± 15.2 in OFF to 19.0 ± 11.4 in ON (n=42, mean improvement 12.8 points, 39.5%, dz=-1.31, p<0.001), consistent with expected levodopa responsiveness in deep brain stimulation candidates3. Smartphone hand turning, improved in the ON state (n=37, dz=0.41, p=0.018). The strongest effect was observed for the five U-turn/body-turning task, (n=35, dz=0.65, p<0.001). Drawing, static balance, speeded tapping, sustained phonation, free speech and information processing speed did not show significant group-level ON/OFF effects. Trail making showed a trend towards shorter completion time in ON (n=13, dz=-0.56, p=0.066). Tremor energy showed bidirectional changes and no significant group-level ON/OFF effect. Depending on whether the the mean or median energy feature as used, postural tremor energy decreased in 14/37 to 16/37 patients (p=0.440 and p=0.693), whereas rest tremor energy decreased in 20/37 to 22/37 patients (p=0.186 and p=0.213).

Supervised smartphone active testing captured acute levodopa responsiveness most clearly in speed-based motor tasks, particularly turning-related mobility. The limited cognitive and tremor effects are biologically plausible, given the domain-specific cognitive effects of acute dopaminergic stimulation and the variable levodopa responsiveness of Parkinsonian tremor4,5. These findings support smartphone active testing as a potential monitoring tool for treatment-state responsiveness in Parkinson’s disease, while emphasising that digital features require task-specific validation before use as medication-sensitive endpoints.

References

  1. Lipsmeier, F. et al. Evaluation of smartphone-based testing to generate exploratory outcome measures in a phase 1 Parkinson’s disease clinical trial. Mov. Disord. Off. J. Mov. Disord. Soc. 33, 1287–1297 (2018).
  2. Arora, S. et al. Detecting and monitoring the symptoms of Parkinson’s disease using smartphones: A pilot study. Parkinsonism Relat. Disord. 21, 650–653 (2015).
  3. Artusi, C. A., Lopiano, L. & Morgante, F. Deep Brain Stimulation Selection Criteria for Parkinson’s Disease: Time to Go beyond CAPSIT-PD. J. Clin. Med. 9, 3931 (2020).
  4. Wirth, T. et al. Parkinson’s Disease Tremor Differentially Responds to Levodopa and Subthalamic Stimulation. Mov. Disord. Clin. Pract. 10, 1639–1649 (2023).
  5. Poletti, M. & Bonuccelli, U. Acute and chronic cognitive effects of levodopa and dopamine agonists on patients with Parkinson’s disease: a review. Ther. Adv. Psychopharmacol. 3, 101–113 (2013).