LAUSR

Sleep disturbance from obstructive sleep apnea (OSA) impairs overnight memory processing. This may be mediated by changes to slow wave sleep (SWS) as less slow wave activity (SWA) is associated with worse overnight spatial and declarative memory. We developed a within-subjects model of SWS-specific CPAP-withdrawal to create 3 polysomnologically (PSG)-verified conditions of 1) stable-SWS on CPAP, 2) SWS-fragmentation with intermittent hypoxemia (OSAsws), and 3) SWS-fragmentation with reduced hypoxemia (OSAsws+O2). Using these conditions, we sought to dissociate of effects of SWS disruption and intermittent hypoxemia on overnight spatial navigational memory. We included 33 patients (7 female, average age 54yrs) with moderate-to-severe OSA (AHI4%>20/hr) who were CPAP-treatment adherent. During each PSG visit, they explored one of three 3D maze environments, performing 3 timed trials before and after each of 3 randomized and counterbalanced SWS disruption conditions [1)CPAP, 2)OSASWS & 3)OSASWS+O2]. %SWS, OSA severity during SWS, frontal SWA(0.5-4 Hz), and overnight change in maze completion times were compared according to PSG condition using Friedman Rank Sum and Conover’s tests. The relationship between SWA and maze performance was tested using Pearson correlation coefficient. %SWS was significantly greater during CPAP compared to CPAP-withdrawal conditions (CPAP=17.2%, OSAsws=13.3%, OSAsws+O2=13.8%, p< 0.02). Apnea hypopnea index (AHI3A) in SWS during CPAP-withdrawal was significantly greater compared to CPAP (CPAP=0/hr, OSAsws=24.4/hr, OSAsws+O2=19.3/hr, p< 0.00001). Hypoxic burden in SWS was significantly reduced in the OSAsws+O2 condition vs OSAsws (23 %min/hr vs 37 %min/hr, p < 0.001). No significant differences were observed between the three conditions for SWA or overnight change in maze completion times. When including all PSG visits, greater SWA was significantly associated with better overnight maze improvements (R=0.28,p< 0.01) which approached significance for the CPAP condition in isolation (R=0.33,p=0.068). SWS-specific CPAP-withdrawal resulted in recurrence of mild OSA in SWS; supplemental oxygen reduced the hypoxic burden, but SWA did not differ between OSA with hypoxemia and without. There was, however, an overall positive relationship between SWA and maze performance. These observations suggest that the effect on spatial navigation of hypoxia in OSA is mediated by disruption of SWA. R01AG056682, AASM Focused Project Award.