Abstract
PURPOSE: The effect of therapeutic versus partially therapeutic levels of hypoglossal nerve stimulation (HGNS) therapy on cognitive measures and patient-reported outcomes (PROs) was evaluated in patients with moderate-severe obstructive sleep apnea (OSA). METHODS: In a 10-week, double-blind, randomized crossover therapy trial, subjects optimized on HGNS therapy underwent 4 weeks each of active and control (partially therapeutic) HGNS therapy. Cognitive measures (psychomotor vigilance test [PVT], digit symbol substitution test [DSST]) and sleep-related PROs were assessed after each 4-week treatment period. RESULTS: Sixty subjects were randomized and completed the primary study protocol, including PROs. A subset of randomized subjects (n = 43) underwent cognitive testing. This subset was, on average, older (65.7 ± 10.2 years), overweight/obese (body mass index [BMI] 29.7 ± 4.6 kg/m(2)), and had severe OSA at baseline (apnea-hypopnea index [AHI] 34.2 ± 15.0 events/h). There were no differences in cognitive performance measures between active and control (partially therapeutic) HGNS conditions in all subjects; in the per-protocol analysis, however, improvement in DSST reaction time with active HGNS was demonstrated (mean [95% CI] change on active therapy = - 153.6 [- 285.3, - 22.0] ms; p = 0.025). Significant improvements in all PROs (Epworth Sleepiness Scale, Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire, and Snoring Visual Analog Scale) were observed in the active HGNS condition. CONCLUSIONS: In this secondary analysis of the CARDIOSA-12 randomized crossover trial of subjects using HGNS, subjective PROs, but not objective cognitive measures, were improved with active HGNS compared to control (partially therapeutic) HGNS therapy. These findings warrant additional investigation examining the relationship between subjective and objective neurocognitive outcomes in OSA. The effect of hypoglossal nerve stimulation (HGNS), a novel and promising therapy for obstructive sleep apnea (OSA), on neurocognitive deficits remains underexplored. This study evaluated whether HGNS therapy improves cognitive performance using the psychomotor vigilance test (PVT) and digit symbol substitution test (DSST), along with patient-reported outcomes (PROs) related to sleepiness, snoring, insomnia, and sleep-related function. In the modified intention-to-treat analysis, no significant differences in PVT or DSST outcomes were observed between active and control (partially therapeutic) HGNS therapy; however, in a subset of participants with ≥ 50% reduction in AHI with active HGNS, improvement in DSST reaction time was noted. All PROs significantly improved with active HGNS, suggesting benefits in subjective measures without substantial changes in objective cognitive measures.