Enhancing deep sleep with auditory stimulation to boost cognitive training responsiveness in people with Parkinson's disease and mild cognitive impairment: Rationale and design of the double-blind randomized controlled trial PD-CogT-Sleep

Background: Cognitive training (CogT) is an established non-pharmacological intervention for people with Parkinson's disease (PD) and mild cognitive impairment (PD-MCI). However, overall effects on cognitive outcomes are small to moderate and interindividually highly heterogeneous. Sleep -especially deep sleep- could be an important determinant of CogT responsiveness in PD, and may have beneficial effects on PD pathophysiology. Therefore, the enhancement of deep sleep by phase-targeted auditory stimulation (PTAS) could strengthen the effects of CogT on cognitive symptoms and counteract disease progression. Methods: PD-CogT-Sleep is a monocentric, partly decentralized, double-blind, randomized sham-controlled trial that combines two remotely delivered non-pharmacological interventions, to assess the additive effect of PTAS on digital CogT responsiveness in people with PD-MCI. The primary outcome is executive functions; Secondary and exploratory outcomes include further cognitive functions, participant-reported outcome measures, blood-based biomarkers, and high-density sleep electroencephalography markers. Outcomes are assessed at baseline, five weeks post-allocation and at 3-month follow-up. We aim to consecutively recruit N=50 participants, who will be randomized 1:1 to receive CogT+PTAS or CogT+Sham. Discussion: The PD-CogT-Sleep study integrates wearable and digital technologies to systematically combine a novel, non-invasive, sleep-enhancing intervention (PTAS) with established CogT to improve cognition and evaluate PTAS' disease-modifying potential through its effects on blood-based biomarkers in PD-MCI. The expected results will foster our understanding of the interplay of sleep, cognition, and neurodegeneration, and may guide further development of safe, feasible, scalable, patient-centered, technology-based non-pharmacological interventions counteracting cognitive decline in neurodegenerative diseases.