The Impact of Sleep and Hypoxia on the Brain

Potential Mechanisms for the Effects of Obstructive Sleep Apnea

Ivana Rosenzweig; Steve C.R. Williams; Mary J. Morrell


Curr Opin Pulm Med. 2014;20(6):565-571. 

In This Article

Abstract and Introduction


Purpose of review Obstructive sleep apnea (OSA) is a chronic, highly prevalent, multisystem disease, which is still largely underdiagnosed. Its most prominent risk factors, obesity and older age, are on the rise, and its prevalence is expected to grow further. The last few years have seen an exponential increase in studies to determine the impact of OSA on the central nervous system. OSA-induced brain injury is now a recognized clinical entity, although its possible dual relationship with several other neuropsychiatric and neurodegenerative disorders is debated. The putative neuromechanisms behind some of the effects of OSA on the central nervous system are discussed in this review, focusing on the nocturnal intermittent hypoxia and sleep fragmentation.

Recent findings Recent preclinical and clinical findings suggest that neurogenic ischemic preconditioning occurs in some OSA patients, and that it may partly explain variability in clinical findings to date. However, the distinct parameters of the interplay between ischemic preconditioning, neuroinflammation, sleep fragmentation and cerebrovascular changes in OSA-induced brain injury are still largely unclear, and more research is required.

Summary Early diagnosis and intervention in patients with OSA is of paramount importance. Future clinical studies should utilize multimodal investigative approaches to enable more reliable referencing for the acuity of the pathological process, as well as its reversibility following the treatment.


Obstructive sleep apnea (OSA) is a prevalent, chronic and multisystem disease, which can concomitantly lead to acute clinical issues. These can include systemic or pulmonary hypertension, cardiovascular disease, glucose intolerance, impotence, gastroesophageal reflux and a variety of neuropsychiatric and cerebrovascular deficits.[1–5] Population-based studies suggest that up to 19% of middle-aged men and 15% of women may suffer with hypopnoea and apneas above the normative index, the majority of which are undiagnosed.[6,7]

OSA is characterized by the narrowing or occlusion of the pharyngeal airway, which can be caused by a myriad of risk factors, for example, macroglossia, hypertrophy of tonsils, long uvula, increased neck circumference, postmenopausal status, Down's syndrome, Pierre–Robin syndrome, alcohol consumption before bedtime, tobacco and hypnotic use, supine position, etc. The nocturnal episodes of complete or partial pharyngeal obstruction result in intermittent hypoxia, reoxygenation, hypercapnia and sleep fragmentation.[8,9] An increase in respiratory effort, in association with hypoxia or hypercapnia, triggers the frequent sleep arousals, which usually terminate the apnoeic episodes, but also contribute to abnormal sleep architecture and lighter and less restorative sleep[10] Reduced quality of life, labile interpersonal relationships, increased road traffic accidents, and decreased work and school efficiency have all been reported in OSA patients.[11] However, the most widely recognized symptom of OSA is excessive daytime sleepiness.[6]

One of the most effective treatments of OSA is the continuous positive airway pressure therapy (CPAP). It consists of an air pressure generating device and a close fitting mask that maintains upper airway patency and prevents airway obstruction with associated sleep fragmentation.[6] Currently, the National Institute of Clinical Excellence guidelines recommend CPAP as the cost-effective treatment of choice for patients with moderate-to-severe OSA and symptoms of excessive sleepiness.[12,13] However, not all patients with OSA report daytime somnolence, and in some, neurological deficits appear as the leading central nervous system (CNS) manifestation.[6,13,14] Two recent studies (MOSAIC and PREDICT) suggest that the beneficial effects of CPAP use can be extended to minimally symptomatic, and older OSA patients, respectively.[14,15] Understanding the efficacy and cost-effectiveness of OSA treatment is increasingly important, as OSA is predicted to become a highly prevalent health problem in the future, because of the rise of its two most prominent risk factors, obesity and older age.[3,5]