Skip to main content

Advertisement

Log in

Sleep Apnea Is a Risk Factor for Stroke and Vascular Dementia

  • Sleep (M Thorpy and M Billiard, Section Editors)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

In this article, we review the cerebrovascular complications of sleep apnea (SA). SA is the major sleep disorder associated with stroke and vascular dementia.

Recent Findings

Sleep apnea syndrome of moderate to severe intensity affects 17% of 50–70-year-old men and 9% of 50–70-year-old women, making SA a notorious and prevalent disorder. SA increases the risk of hypertension, stroke, myocardial infarction, and atrial fibrillation (AF) and is closely linked to vascular dementia. In addition, SA may worsen the neurologic outcome in acute stroke patients and interferes with rehabilitation after stroke.

Summary

Proper management of SA may decrease the clinical impact of stroke risk factors, improve neurologic outcome after stroke, and lessen the progression of subcortical ischemic vascular disease. In this article, we will cover the most salient pathologies that associate SA and cerebrovascular pathology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. Culebras A editor. Sleep, stroke and cardiovascular disease. Cambridge University Press, 2013.

  2. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006–14.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Culebras A. Sleep apnea and stroke. Curr Neurol Neurosci Rep. 2015;15(1):503. Review

    Article  PubMed  Google Scholar 

  4. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008;5:136–43.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gastaut H, Tassinari CA, Duron B. Polygraphic study of diurnal and nocturnal (hypnic and respiratory) episodal manifestations of Pickwick syndrome. Rev Neurol (Paris). 1965;112:568–79.

    CAS  Google Scholar 

  6. Dickens C. The posthumous papers of the Pickwick Club. 1867.

  7. Lugaresi E. Snoring. Electroencephalogr Clin Neurophysiol. 1975;39:59–64.

    Article  PubMed  CAS  Google Scholar 

  8. •• American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed. Darien, ILL; American Academy of Sleep Medicine. 2014. Codifies all sleep disorders .

  9. American Academy of Sleep Medicine - Hidden Health Crisis report, 2016. Prevalence, Diagnosis and treatment of sleep apnea in the United States.

  10. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034–41.

    Article  PubMed  CAS  Google Scholar 

  11. Gami AS, Hodge DO, Herges RM, Olson EJ, Nykodym J, Kara T, et al. Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J Am Coll Cardiol. 2007;49(5):565–71.

  12. Román GC. In: Culebras A, editor. Sleep, stroke and cardiovascular disease. Cambridge University Press, 2013.

  13. Siccoli MM, Valko PO, Hermann DM, Bassetti CL. Central periodic breathing during sleep in 74 patients with acute ischemic stroke—neurogenic and cardiogenic factors. J Neurol. 2008;255(11):1687–92.

    Article  PubMed  CAS  Google Scholar 

  14. Robbins J, Redline S, Ervin A, Walsleben JA, Ding J, Nieto FJ. Associations of sleep-disordered breathing and cerebral changes on MRI. J Clin Sleep Med. 2005;1:159–65.

    PubMed  Google Scholar 

  15. Muñoz R, Durán-Cantolla J, Martínez-Vila E, et al. Central sleep apnea is associated with increased risk of ischemic stroke in the elderly. Acta Neurol Scand. 2012;126(3):183–8.

    Article  PubMed  Google Scholar 

  16. Dyken ME, Im KB. Obstructive sleep apnea and stroke. Chest. 2009;136(6):1668–77.

    Article  PubMed  Google Scholar 

  17. Culebras A. Sleep, stroke and poststroke. Neurol Clin. 2012;30(4):1275–84.

    Article  PubMed  Google Scholar 

  18. Martínez-García MA, Capote F, Campos-Rodríguez F, Lloberes P, Díaz de Atauri MJ, Somoza M, et al. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA. 2013;310(22):2407–15.

  19. Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364(7):656–65. Review

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Berger S, Lavie L. Sleep apnea, oxidative stress, proinflammatory vascular risk factors and endothelial disease. In: Culebras A, editor. Sleep, stroke and cardiovascular disease. Cambridge University Press, 2013, p. 11.

  21. Wang Y, Zhang SX, Gozal D, et al. Reactive oxygen species and the brain in sleep apnea. Respir Physiol Neurobiol. 2010;174:307–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Capone C, Faraco G, Coleman C, Young CN, Pickel VM, Anrather J, et al. Endothelin 1-dependent neurovascular dysfunction in chronic intermittent hypoxia. Hypertension. 2012;60(1):106–13.

  23. Narkiewicz K, Montano N, Cogliati C, van de Borne PJH, Dyken ME, Somers VK. Altered cardiovascular variability in obstructive sleep apnea. Circulation. 1998;98(11):1071–7.

    Article  PubMed  CAS  Google Scholar 

  24. Nagata K, Osada N, Shimazaki M, et al. Diurnal blood pressure variation in patients with sleep apnea syndrome. Hypertens Res. 2008;31(2):185–91.

    Article  PubMed  CAS  Google Scholar 

  25. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378–84.

    Article  PubMed  CAS  Google Scholar 

  26. Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;283(14):1829–36.

  27. Hla KM, Young T, Finn L, Peppard PE, Szklo-Coxe M, Stubbs M. Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin Sleep Cohort Study. Sleep. 2008;31(6):795–800.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19(12):2271–7.

  29. Walia HK, Li H, Rueschman M, Bhatt DL, Patel SR, Quan SF, et al. Association of severe obstructive sleep apnea and elevated blood pressure despite antihypertensive medication use. J Clin Sleep Med. 2014;10(8):835–43.

  30. Guilleminault C, Connolly SJ, Winkle RA. Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome. Am J Cardiol. 1983;52(5):490–4.

    Article  PubMed  CAS  Google Scholar 

  31. • Culebras A. Double jeopardy: sleep apnea, atrial fibrillation, and stroke. Sleep Med. 2017;30:255–6. The editorial summarizes the state-of-the-art in the association between sleep apnea, atrial fibrillation, and stroke

    Article  PubMed  Google Scholar 

  32. Sauer WH, McKernan ML, Lin D, Gerstenfeld EP, Callans DJ, Marchlinski FE. Clinical predictors and outcomes associated with acute return of pulmonary vein conduction during pulmonary vein isolation for treatment of atrial fibrillation. Heart Rhythm. 2006;3(9):1024–8.

    Article  PubMed  Google Scholar 

  33. • Poli M, Philip P, Taillard J, Debruxelles S, Renou P, Orgogozo JM, et al. Atrial fibrillation is a major cause of stroke in apneic patients: a prospective study. Sleep Med. 2017;30:251–4. A most recent prospective study confirming the association between sleep apnea and atrial fibrillation

  34. Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003;107(20):2589–94.

  35. Patel D, Mohanty P, Di Biase L, et al. Safety and efficacy of pulmonary vein antral isolation in patients with obstructive sleep apnea: the impact of continuous positive airway pressure. Circ Arrhythm Electrophysiol. 2010;3(5):445–51.

    Article  PubMed  Google Scholar 

  36. Holmqvist F, Simon D, Steinberg BA, Hong SJ, Kowey PR, Reiffel JA, et al. Catheter ablation of atrial fibrillation in U.S. community practice—results from outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). J Am Heart Assoc. 2015;4(5):e001901.

  37. Fox H, Bitter T, Horstkotte D, Oldenburg O. Cardioversion of atrial fibrillation or atrial flutter into sinus rhythm reduces nocturnal central respiratory events and unmasks obstructive sleep apnoea. Clin Res Cardiol. 2016;105(5):451–9.

    Article  PubMed  Google Scholar 

  38. Naruse Y, Tada H, Satoh M, et al. Radiofrequency catheter ablation of persistent atrial fibrillation decreases a sleep-disordered breathing parameter during a short follow-up period. Circ J. 2012;76(9):2096–103.

    Article  PubMed  Google Scholar 

  39. •• Sharma S, Culebras A. Sleep apnoea and stroke. Stroke Vasc Neurol. 2016;1(4):185–91. Review of sleep apnea and stroke

    Article  PubMed  PubMed Central  Google Scholar 

  40. Arzt M, Young T, Finn L, Skatrud JB, Bradley TD. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med. 2005;172(11):1447–51.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Muñoz R, Durán-Cantolla J, Martínez-Vila E, et al. Severe sleep apnea and risk of ischemic stroke in the elderly. Stroke. 2006;37(9):2317–21.

    Article  PubMed  Google Scholar 

  42. Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O’ Connor GT, Resnick HE, et al. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med. 2010;182(2):269–77.

  43. Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31(8):1071–8.

  44. Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754–832.

  45. Lynch JJ, Schuchard GH, Gross CM, Wann LS. Prevalence of right-to-left atrial shunting in a healthy population: detection by Valsalva maneuver contrast echocardiography. Am J Cardiol. 1984;53:1478–806.

    Article  PubMed  CAS  Google Scholar 

  46. Beelke M, Angeli S, Del Sette M, Gandolfo C, Cabano ME, Canovaro P, et al. Prevalence of patent foramen ovale in subjects with obstructive sleep apnea: a transcranial Doppler ultrasound study. Sleep Med. 2003;4(3):219–23.

    Article  PubMed  Google Scholar 

  47. Sanner BM, Doberauer C, Konermann M, Sturm A, Zidek W. Pulmonary hypertension in patients with obstructive sleep apnea syndrome. Arch Intern Med. 1997;157(21):2483–7.

    Article  PubMed  CAS  Google Scholar 

  48. Ciccone A, Proserpio P, Roccatagliata DV, Nichelatti M, Gigli GL, Parati G, et al. Wake-up stroke and TIA due to paradoxical embolism during long obstructive sleep apnoeas: a cross-sectional study. Thorax. 2013;68(1):97–104.

  49. Turkington PM, Bamford J, Wanklyn P, Elliott MW. Prevalence and predictors of upper airway obstruction in the first 24 hours after acute stroke. Stroke. 2002;33:2037–42.

    Article  PubMed  CAS  Google Scholar 

  50. Iranzo A, Santamaría J, Berenguer J, Sánchez M, Chamorro A. Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction. Neurology. 2002;58(6):911–6.

    Article  PubMed  CAS  Google Scholar 

  51. • Menon D,S. Sukumaran,R. Varma,A. Radhakrishnan. Impact of obstructive sleep apnea on neurological recovery after ischemic stroke: a prospective study. Acta Neurol Scand. 2017;136(5):419–26. Prospective study of the impact of sleep apnea on neurological recovery after stroke

    Article  Google Scholar 

  52. Yaggi H, Mohsenin V. Obstructive sleep apnoea and stroke. Lancet Neurol. 2004;3(6):333–42.

    Article  PubMed  Google Scholar 

  53. Mohsenin V, Valor R. Sleep apnea in patients with hemispheric stroke. Arch Phys Med Rehabil. 1995;76(1):71–6.

  54. Parra O, Arboix A, Bechich S, García-Eroles L, Montserrat JM, López JA, et al. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med. 2000;161(2 Pt 1):375–80.

    Article  PubMed  CAS  Google Scholar 

  55. Sandberg O, Franklin KA, Bucht G, Gustafson Y. Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke. J Am Geriatr Soc. 2001;49(4):391–7.

    Article  PubMed  CAS  Google Scholar 

  56. Kaneko Y, Hajek VE, Zivanovic V, Raboud J, Bradley TD. Relationship of sleep apnea to functional capacity and length of hospitalization following stroke. Sleep. 2003;26(3):293–7.

    Article  PubMed  Google Scholar 

  57. Cherkassky T, Oksenberg A, Froom P, Ring H. Sleep-related breathing disorders and rehabilitation outcome of stroke patients: a prospective study. Am J Phys Med Rehabil. 2003;82(6):452–5.

    PubMed  Google Scholar 

  58. Ryan CM, Bayley M, Green R, Murray BJ, Bradley TD. Influence of continuous positive airway pressure on outcomes of rehabilitation in stroke patients with obstructive sleep apnea. Stroke. 2011;42(4):1062–7.

    Article  PubMed  Google Scholar 

  59. Bravata DM, Concato J, Fried T, Ranjbar N, Sadarangani T, McClain V, et al. Auto-titrating continuous positive airway pressure for patients with acute transient ischemic attack: a randomized feasibility trial. Stroke. 2010;41:1464–70.

  60. Yaffe K, Laffan AM, Harrison SL, Redline S, Spira AP, Ensrud KE, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011;306(6):613–9.

  61. •• Blackwell T, Yaffe K, Laffan A, Redline S, Ancoli-Israel S, Ensrud KE, et al. Osteoporotic fractures in men study group. Associations between sleep-disordered breathing, nocturnal hypoxemia, and subsequent cognitive decline in older community-dwelling men: the Osteoporotic Fractures in Men Sleep Study. J Am Geriatr Soc. 2015;63(3):453–61. Points out the impact of hypoxemia in dementia

    Article  PubMed  PubMed Central  Google Scholar 

  62. Shi L, Chen SJ, Ma MY, Bao YP, Han Y, Wang YM, Shi J, Vitiello MV, Lu L. Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis. Sleep Med Rev 2017

  63. •• Leng Y, McEvoy CT, Allen IE, Yaffe K. Association of sleep-disordered breathing with cognitive function and risk of cognitive impairment: a systematic review and meta-analysis. JAMA Neurol. 2017;74:1237–45. Confirms the growing evidence between sleep apnea and cognitive decline

    Article  PubMed  PubMed Central  Google Scholar 

  64. Gelber RP, Redline S, Ross GW, Petrovitch H, Sonnen JA, Zarow C, et al. Associations of brain lesions at autopsy with polysomnography features before death. Neurology. 2015;84(3):296–303.

  65. • Song TJ, Park JH, Choi KH, Chang Y, Moon J, Kim JH, et al. Moderate-to-severe obstructive sleep apnea is associated with cerebral small vessel disease. Sleep Med. 2017;30:36–42. Adds evidence to the association between sleep apnea and periventricular small vessel disease

    Article  PubMed  Google Scholar 

  66. Cho ER, Kim H, Seo HS, Suh S, Lee SK, Shin C. Obstructive sleep apnea as a risk factor for silent cerebral infarction. J Sleep Res. 2013;22(4):452–8.

    Article  PubMed  Google Scholar 

  67. Del Brutto OH, Mera RM, Zambrano M, Castillo PR. Relationship between obstructive sleep apnea and neuroimaging signatures of cerebral small vessel disease in community-dwelling older adults. The Atahualpa Project. Sleep Med. 2017;37:10–2.

    Article  PubMed  Google Scholar 

  68. Urbano F, Roux F, Schindler J, Mohsenin V. Impaired cerebral autoregulation in obstructive sleep apnea. J Appl Physiol (1985). 2008;105(6):1852–7.

    Article  Google Scholar 

  69. Macey PM, Haris N, Kumar R, Thomas MA, Woo MA, Harper RM. Obstructive sleep apnea and cortical thickness in females and males. PLoS One. 2018;13(3):e0193854. https://doi.org/10.1371/journal.pone.0193854.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Román GC. Senile dementia of the Binswanger type. A vascular form of dementia in the elderly. JAMA. 1987;258(13):1782–8.

    Article  PubMed  Google Scholar 

  71. Moon SY, de Souto Barreto P, Rolland Y, Chupin M, Bouyahia A, Fillon L, et al. Prospective associations between white matter hyperintensities and lower extremity function. Neurology. 2018;90(15):e1291–7.

  72. Swardfager W, Cogo-Moreira H, Masellis M, Ramírez J, Herrmann N, Edwards JD, et al. The effect of white matter hyperintensities on verbal memory: mediation by temporal lobe atrophy. Neurology. 2018;90(8):e673–82.

    Article  PubMed  Google Scholar 

  73. Ramos AR, Gardener H, Rundek T, Elkind MS, Boden-Albala B, Dong C, et al. Sleep disturbances and cognitive decline in the northern Manhattan study. Neurology. 2016;87(14):1511–6.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Lee S, Shin C. Interaction of obstructive sleep apnoea and cognitive impairment with slow gait speed in middle-aged and older adults. Age Ageing. 2017;46(4):653–9.

    PubMed  Google Scholar 

  75. Baillieul S, Wuyam B, Pépin JL, Marillier M, Tamisier R, Pérennou D, et al. Continuous positive airway pressure improves gait control in severe obstructive sleep apnoea: a prospective study. PLoS One. 2018;13(2):e0192442.

  76. Kohler M et al. Effect of CPAP on stroke risk factors and stroke. In: Culebras A, editor. Sleep, stroke and cardiovascular disease. Cambridge University Press; 2013. p. 115.

  77. Walia HK, Griffith SD, Foldvary-Schaefer N, Thomas G, Bravo EL, Moul DE, et al. Longitudinal effect of CPAP on BP in resistant and nonresistant hypertension in a large clinic-based cohort. Chest. 2016;149(3):747–55.

  78. Iftikhar IH, Valentine CW, Bittencourt LR, et al. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis. J Hypertens. 2014;32(12):2341–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Martínez-García MA, Gómez-Aldaraví R, Soler-Cataluña JJ, Martínez TG, Bernácer-Alpera B, Román-Sánchez P. Positive effect of CPAP treatment on the control of difficult-to-treat hypertension. Eur Respir J. 2007;29:951–7.

    Article  PubMed  Google Scholar 

  80. Martínez-García MA, Soler-Cataluña JJ, Ejarque-Martínez L, Soriano Y, Román-Sánchez P, Illa FB, et al. Continuous positive airway pressure treatment reduces mortality in patients with ischemic stroke and obstructive sleep apnea: a 5-year follow-up study. Am J Respir Crit Care Med. 2009;180(1):36–41.

    Article  PubMed  Google Scholar 

  81. Gupta A, Shukla G, Afsar M, Poornima S, Pandey RM, Goyal V, et al. Role of positive airway pressure therapy for obstructive sleep apnea in patients with stroke: a randomized controlled trial. J Clin Sleep Med. 2018;14:511–21.

  82. •• Brill AK, Horvath T, Seiler A, Camilo M, Haynes AG, Ott SR, et al. CPAP as treatment of sleep apnea after stroke: a meta-analysis of randomized trials. Neurology. 2018;90(14):e1222–30. Treatment of sleep apnea may reduce progression of cerebrovascular complications

  83. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, et al. SAVE investigators and coordinators. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375(10):919–31.

  84. Stenzel-Poore MP, Stevens SL, King JS, Simon RP. Preconditioning reprograms the response to ischemic injury and primes the emergence of unique endogenous neuroprotective phenotypes: a speculative synthesis. Stroke. 2007;38(2 Suppl):680–5. Review

    Article  PubMed  Google Scholar 

  85. McDonough A, Weinstein JR. Neuroimmune response in ischemic preconditioning. Neurotherapeutics. 2016;13(4):748–61. Review

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Culebras.

Ethics declarations

Conflict of Interest

Antonio Culebras reports royalties from MedLink and Uptodate.

Sanam Anwar declares no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Sleep

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Culebras, A., Anwar, S. Sleep Apnea Is a Risk Factor for Stroke and Vascular Dementia. Curr Neurol Neurosci Rep 18, 53 (2018). https://doi.org/10.1007/s11910-018-0855-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-018-0855-1

Keywords

Navigation