Enhancing sleep slow waves with auditory stimulation in people with Parkinson's disease: a randomized...

Deep sleep supports restorative functions and has emerged as a potential therapeutic target in neurodegenerative diseases, such as Parkinson's (PD). Phase-targeted auditory stimulation (PTAS) non-invasively enhances slow waves, the electrophysiological hallmark of deep sleep.

To investigate, for the first time, whether PTAS can be successfully applied in PD, using a wearable device at home.

Single-center, randomized, sham-controlled, double-blind, cross-over study.

Of 43 screened PD patients, 33 had subjective sleep disturbance and qualified for home screening with the device; of these, eight were excluded due to non‑feasibility of PTAS (procedural difficulties n = 1, worsened insomnia n = 2, limited neurophysiological target engagement n = 5) and two withdrew. Twenty‑three participants with confirmed feasibility were randomized.

Three nights of PTAS compared to sham stimulation using wearable devices at participants' homes. PTAS was applied in ON and OFF windows for the entire night in 14 participants and the first 2.5 h after the first stimulus (part-night) in nine.  Main outcome: Slow-wave enhancement measured by slow-wave activity (SWA).

PTAS increased low-frequency SWA by almost 30% during ON windows, with corresponding increases in slow-wave amplitudes, in 21 analyzed participants (two posthoc excluded). Whole-night PTAS - but not part-night PTAS - showed a trend toward longer wake after sleep onset and lower sleep efficiency. Participants receiving part-night PTAS reported improved subjective daytime sleepiness after the third night. No relevant adverse events occurred. Conclusions: This proof-of-concept study demonstrates successful enhancement of slow waves with PTAS in PD, in participants with confirmed feasibility during screening. Our observation of the potential advantages of part-night PTAS warrants further exploration. Our data encourage longer and larger trials to determine the therapeutic potential of PTAS in PD and other neurodegenerative diseases.

ClinicalTrials.gov: NCT04589182 (29/09/2020).