Arousal threshold modifies the effect of CPAP on executive function among individuals with obstructive sleep apnea.

Abstract

Obstructive Sleep Apnea (OSA) is associated with neurocognitive dysfunction. However, randomized trials evaluating the effects of continuous positive airway pressure (CPAP) on neurocognition in those without dementia do not show a benefit. We thus aimed to assess whether arousal threshold (ArTH) modifies the effect of CPAP on neurocognitive function. We performed a secondary analysis of a randomized, sham-controlled trial, Apnea Positive Pressure Long-term Efficacy Study. ArTH was estimated from polysomnography using a translatable method (Sands et al., SLEEP 2018). Neurocognitive outcomes included the Sustained Working Memory Test-Overall-Mid-Day score (SWMT-OMD, executive function, primary outcome), with the Pathfinder Number Test - total time (attention) and Buschke Selective Reminding Test - sum recall (learning and memory) as secondary outcomes. Generalized linear modeling assessed whether the effect of CPAP was modified by baseline ArTH (treatment-by-ArTH interaction). 833 participants with OSA, [apnea-hypopnea index (AHI) ≥10 events/h], available ArTH, and outcomes were analyzed (CPAP n=437, Sham n=396). For executive function, the effect of CPAP treatment was modified by ArTH (p-interaction=0.042). Specifically, for every 1 sd increase in ArTH, the SWMT-OMD score improved by 0.10 95% CI (0.01, 0.18) in active compared to sham CPAP at 6 months; At ArTH 1 sd above the mean SWMT-OMD improvements were nearly three times that in those with average ArTH (0.139 [0.018, 0.261] versus 0.053 [-0.034, 0.140] respectively. No effect modification was observed for attention (p=0.311) or learning and memory (p=0.744). In OSA, a higher ArTH is associated with greater improvements in executive function following CPAP therapy.