Nocturnal Hypoxia Exposure With Simulated Altitude For 14 Days Does Not Significantly Alter Working Memory or Vigilance in Humans

SLEEP-DISORDERED BREATHING IS ASSOCIATED WITH AN ADVERSE IMPACT ON ATTENTION, MOOD, SUBJECTIVE SLEEPINESS, AND EXECUTIVE FUNCTION IN adults and children.1–4 Well-described consequences of disordered respiration during sleep include recurrent oxygen desaturations, chronic partial sleep deprivation, sleep fragmentation from repetitive arousals, hypoxia, and cytokine dysregulation.5, 6 All of these consequences have been implicated as possible contributors to impaired vigilance and executive dysfunction. The effects of intermittent nocturnal hypoxia in mediating sympathoexcitation and daytime hypertension are well established in both patients with sleep-disordered breathing and normal volunteers undergoing hypoxic exposure.7 The relative contributions of sleep fragmentation and nocturnal hypoxia in mediating cognitive dysfunction remain to be fully determined. While correlative analysis suggests that both are important, statistical analysis cannot truly dissociate the effects of hypoxia because increasingly severe sleep-disordered breathing is associated with more severe oxygen desaturations as well as greater degrees of sleep fragmentation. Animal models of intermittent nocturnal hypoxia (rats, mice) have shown convincing evidence of executive dysfunction and excessive sleepiness.8 Sleep quality was not measured during hypoxia exposure in most such studies, and, given the risk for periodic breathing during sleep or direct sleep-disruptive effects of hypoxia itself, there remains a high likelihood that some degree of sleep fragmentation was present in these models. Given this limitation of the current studies to dissect out the independent contribution of intermittent nocturnal hypoxia, effects on cognition independent of sleep fragmentation remain to be completely defined. Contrary to the findings in animal models, studies in patients with sleep apnea, however, do suggest that the role of sleep fragmentation may overwhelm the effects of intermittent hypoxia.9 Studies in humans evaluating changes in cognitive function in response to exposure to nocturnal hypoxia with minimal sleep fragmentation simply have not been completed. The primary purpose of this study was to evaluate the impact of nocturnal hypoxia exposure on daytime vigilance and working memory in normal human volunteers. We hypothesized that recurrent nocturnal hypoxic exposure would result in a significant decline in daytime vigilance and working memory performance. Our exposure utilized a normobaric hypoxic exposure through an “altitude tent” (FiO2 = 0.13) during sleep on 14 consecutive nights. We assessed sleep quality and respiration during sleep utilizing attended 16-channel polysomnography. Attention and working memory were evaluated in the preexposure baseline condition, at the midpoint during, and after 14 nights of hypoxic exposure. Contrary to our expectations, we found no significant change in cognition and subjective sleepiness that, in clinical equivalents of sleep hypoxia in patients with sleep apnea, would reasonably be expected to adversely impact cognition.