Objective: To test the feasibility and effectivity of a new method for non-pharmacological enhancement of deep sleep in Parkinson disease (PD).

Background: Sleep-wake disturbances and non-restorative sleep are common, burdensome symptoms of PD. Deep sleep is restorative and has been linked with slower progression and better cognition in PD [1,2]. Phase-targeted auditory stimulation (PTAS) of sleep slow waves is a novel non-pharmacological method for enhancing deep sleep [3]. Thus, PTAS may exploit restorative properties of sleep for therapeutic purposes in PD. However, the effects of PTAS in people with PD are unknown.

Method: We conducted a remote, double-blinded, randomized, crossover study in 14 PD patients with subjective poor sleep quality. Participants used a wearable device for automatic delivery of PTAS [4,5] over three consecutive nights with PTAS followed by three nights with sham stimulation, or vice versa. During PTAS, the device played non-arousing tones, targeting the up-phase of slow waves in alternating 6-second windows with (ON) and without (OFF) stimulation, for the entire night. During sham stimulation, the device played no tones. Outcomes included subjective sleep quality, sleepiness, and mood, objective sleep architecture, and low-frequency slow-wave activity (SWA, 0.75-1.25 Hz), a quantitative marker of sleep depth.

Results: The at-home intervention was well tolerated, without dropouts. PTAS enhanced SWA within PTAS nights (+25.9±2.3% mean SWA during ON- compared to OFF-windows, p<0.001) and in PTAS compared to sham nights (+13.2±4.2% mean SWA in ON-windows during PTAS compared to ON-windows during sham stimulation, p<0.01). Subjective clinical outcomes did not differ between conditions. Enhanced SWA correlated with a reduced duration of rapid eye movement sleep (REMS) during PTAS relative to sham stimulation (r=-0.67, p<0.05). In turn, reduced REMS related to worse mood the next day (r=0.73, p<0.05).

Conclusion: At-home PTAS using a wearable device is feasible and enhances deep sleep in PD patients. PTAS is a promising non-pharmacological method, ready to be applied in large-scale PD studies. However, we recommend to adapt whole-night PTAS to the first half of the night, to minimize impact on REMS and fully exploit the potential of deep sleep enhancement.

This project was part of the Hochschulmedizin Zürich Flagship “SleepLoop” and partly presented at the ERSRS meeting (09/27/2022).

References: 1. Schreiner SJ, Imbach LL, Werth E, Poryazova R, Baumann-Vogel H, Valko PO, Murer T, Noain D, Baumann CR. Slow-wave sleep and motor progression in Parkinson disease. Ann Neurol. 2019
2. Schreiner SJ, Imbach LL, Valko PO, Maric A, Maqkaj R, Werth E, Baumann CR, Baumann-Vogel H. Reduced Regional NREM Sleep Slow-Wave Activity Is Associated With Cognitive Impairment in Parkinson Disease. Front Neurol. 2021
3. Ngo HV, Martinetz T, Born J, Mölle M. Auditory Closed-Loop Stimulation of the Sleep Slow Oscillation Enhances Memory. Neuron 2013
4. Ferster ML, Lustenberger C, Karlen W. Configurable Mobile System for Autonomous High-Quality Sleep Monitoring and Closed-Loop Acoustic Stimulation. IEEE Sensors Letters 2019
5. Lustenberger C, Ferster ML, Huwiler S, Brogli L, Werth E, Huber R, Karlen W. Auditory deep sleep stimulation in older adults at home: a randomized crossover trial. Commun Med. 2022

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