Instability of post-respiratory delta activity is associated with neurocognitive dysfunction in obstructive sleep...

Conventional polysomnographic severity indices poorly capture inter-individual vulnerability to neurocognitive dysfunction in obstructive sleep apnea (OSA). Although respiratory event-related physiological responses have recently gained attention, whether instability of these neural responses reflects impaired cortical resilience and contributes to cognitive dysfunction remains unknown.

We performed a secondary analysis of baseline polysomnographic data from the Apnea Positive Pressure Long-term Efficacy Study (APPLES), including 1077 adults with OSA. Event-related EEG responses were quantified from signals time-locked to respiratory event termination. Variability of post-event spectral dynamics across respiratory events was assessed, with a particular focus on delta-band instability. Multivariable linear regression models evaluated associations between respiratory event-related physiological metrics and multiple neurocognitive domains after adjustment for demographics, comorbidities, lifestyle factors, apnea-hypopnea index (AHI), and conventional sleep parameters.

A total of 399,968 respiratory events were analyzed. Greater variability of post-respiratory delta-band activity was independently associated with poorer global cognitive performance measured by the Wechsler Abbreviated Scale of Intelligence (β = -1.50, 95% CI -2.30 to -0.71; p =0.001) and reduced objective wakefulness assessed by Maintenance of Wakefulness Test mean sleep latency (β = -0.38, 95% CI -0.64 to -0.11; p = 0.005). Greater delta instability was also associated with slower psychomotor performance, although this association did not survive false discovery rate correction. A secondary exploratory analysis showed a nominal positive association between median post-event theta responses and global cognition.

Instability of post-respiratory delta activity represents a potential electrophysiological marker of impaired cortical resilience to nocturnal respiratory stress and is independently associated with neurocognitive dysfunction in OSA.