Positive airway pressure therapy for cognitive enhancement in Parkinson’s disease: from statistical signals to clinical practice

We read with great interest the recent randomized controlled trial (RCT) by Lajoie et al. [1], which systematically evaluated the effects of positive airway pressure (PAP) therapy on cognitive function in patients with Parkinson’s disease (PD) and coexisting obstructive sleep apnea (OSA). This study represents a milestone in the field, characterized by a robust sample size and an impressive 6-month follow-up—a feat of feasibility given the inherent heterogeneity of neurodegenerative cohorts. The authors reported potential gains in global cognition, non-motor symptoms, and executive function, providing compelling evidence that sleep disorders represent a modifiable target in PD management. However, several methodological nuances and interpretational challenges merit further discourse to refine future research directions. While the study’s strengths are evident, the primary outcome did not reach conventional significance under a strict intention-to-treat (ITT) analysis. To address this, the authors utilized adjusted ITT, compliance-related analyses, and complier average causal effect (CACE) estimates. While methodologically sound in complex clinical trials, these strategies necessitate a cautious distinction between statistical signals and clinical meaningfulness. As established in methodological literature [2], when primary outcomes yield marginal p-values yet consistent effect directions across supplementary analyses, the focus should shift toward effect sizes and the interval of uncertainty. Defining “clinically relevant” findings in the absence of traditional significance remains a critical challenge for the design and reporting of future neurodegenerative trials.