Beyond heart health: Consequences of obstructive sleep apnea

September 3, 2019|Cleveland Clinic Journal of Medicine
Harneet K. Walia, MD, FAASM
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Harneet K. Walia, MD, FAASM
Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH; Staff, Sleep Disorders Center, Neurological Institute, Cleveland Clinic

Correspondence: Harneet K. Walia, MD, FAASM, Sleep Disorders Center, Neurological Institute, S73, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; waliah@ccf.org

Dr. Walia is principal investigator of a ResMed funded grant.

This article is based on Dr. Walia’s “Beyond Heart Health: Consequences of Obstructive Sleep Apnea” webcast released March 29, 2019, part of the “Obstructive Sleep Apnea: A Cleveland Clinic State-of-the-Art Review” online series (available at www.clevelandclinicmeded.com/online/sleep-apnea). The article was drafted by Cleveland Clinic Journal of Medicine staff and was then reviewed, revised, and approved by Dr. Walia.

Release date: September 1, 2019
Expiration date: August 31, 2022
Estimated time of completion: 0.75 hour

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ABSTRACT

Obstructive sleep apnea (OSA) is a serious condition associated with impaired quality of life, depression, drowsy driving and motor vehicle accidents, metabolic disease, and cognitive decline. The mechanisms accounting for OSA and metabolic disease include hypoxia, sleep fragmentation, and systemic inflammation. OSA appears to advance cognitive decline, and the relationship between the 2 conditions may be bidirectional. Treatment of patients with continuous positive air pressure therapy improves many of the impaired outcomes associated with OSA. Greater awareness, screening, and treatment of patients with OSA can reduce the negative consequences associated with OSA.

KEY POINTS

  • OSA is associated with negative health consequences such as depression, drowsy driving, metabolic disease, and cognitive decline.
  • Several possible mechanisms to explain the health consequences of OSA have been explored.
  • Treatment of patients with OSA may improve outcomes for many of the health consequences associated with OSA.
  • Screening for OSA is important to identify and treat patients to reduce the associated health risks.

COGNITIVE IMPAIRMENT

Data suggest that OSA is linked with cognitive impairment, may advance cognitive decline, and is a bidirectional relationship. Women with OSA were reportedly more likely to develop mild cognitive impairment compared with women without OSA.61 An elevated oxygen desaturation index and a high percentage of time spent with hypoxia was associated with increased risk of developing mild cognitive impairment and dementia.

OSA was found to be an independent risk factor for cerebral white matter changes in middle-age and older individuals. Moderate to severe OSA imparted a 2 times higher risk of cerebral white matter changes compared with individuals without OSA.62 Another study of 20 patients with severe OSA compared with 40 healthy volunteers found diffusion imaging consistent with impaired fibrin integrity in those with OSA, indicative of white matter microstructure damage, and the impairment was associated with increased disease severity and higher systemic inflammation.63

Individuals with hypoxia for a high percentage of time during sleep had a 4 times higher odds of cerebral microinfarcts.64 Cognitive scores decreased less in men. Men typically have more time in slow-wave sleep, suggesting that slow-wave sleep may be protective against cognitive decline. Mild cognitive impairment and Alzheimer disease were found more likely to develop and occur at an earlier age in individuals with sleep-disordered breathing compared with individuals without sleep-disordered breathing.65

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OSA was also associated with increased serum amyloid beta levels in a study of 45 cognitively normal patients with OSA compared with 49 age- and sex-matched control patients. Increased amyloid beta levels correlated with increasing severity of sleep apnea as measured by the AHI.66

Mechanism linking OSA and cognition

One possible mechanism linking sleep quality and cognitive impairment or Alzheimer disease is the role of unfragmented sleep in attenuating the apolipo­protein E e4 allele on the incidence of Alzheimer disease.67 Beta amyloid is released during synaptic activity. Neuronal and synaptic activity decreases during sleep, and disrupted sleep could increase beta amyloid release.68 Sleep has been found to enhance the clearance of beta amyloid peptide from the brain interstitial fluid in a mice model.69

Recent data point toward the bidirectional relationship between the sleep and Alzheimer disease in that excessive and prolonged neuronal activity in the absence of appropriately structured sleep may be the reason for both Alzheimer disease and OSA.70,71

Effect of treatment for OSA on cognition

White matter integrity in 15 patients with OSA before and after treatment with CPAP was compared with 15 matched controls. Over 12 months, there was a nearly complete reversal of white matter abnormalities in patients on CPAP therapy.72 Improvement in memory, attention, and executive function paralleled the changes in white matter after the treatment.

CONCLUSION

OSA is a serious condition with far-reaching consequences associated with impaired quality of life, depressive symptoms, drowsy driving, metabolic disease, and cognitive decline. Treatment of OSA improves many of these health consequences, emphasizing the need for OSA screening. Large randomized studies are needed to assess the efficacy of CPAP on metabolic outcomes, including insulin sensitivity and glucose tolerance, in reducing disease burden. Study of the endophenotypes of patients with OSA is needed to define and target the mechanisms of OSA-induced adverse health outcomes and perhaps lead to personalized care for patients with OSA.