The Association Between Obstructive Sleep Apnea and Alzheimer's Disease: A Meta-Analysis Perspective

Farnoosh Emamian, Habibolah Khazaie, Masoud Tahmasian, Guy D Leschziner, Mary J Morrell, Ging-Yuek R Hsiung, Ivana Rosenzweig, Amir A Sepehry, Farnoosh Emamian, Habibolah Khazaie, Masoud Tahmasian, Guy D Leschziner, Mary J Morrell, Ging-Yuek R Hsiung, Ivana Rosenzweig, Amir A Sepehry

Abstract

Alzheimer's disease (AD) and obstructive sleep apnea (OSA) are highly prevalent, chronic conditions with intriguing, yet poorly understood epidemiological overlap. To date, the amount of OSA syndrome present in patients with AD across literature remains unknown. To address this question, we collected all available published clinical data and analyzed them through a quantitative meta-analytical approach. The results of our quantitative meta-analysis suggest that the aggregate odds ratio for OSA in AD vs. healthy control was 5.05 and homogeneous. This reflects that patients with AD have a five times higher chance of presenting with OSA than cognitively non-impaired individuals of similar age. Moreover, these data suggest that around half of patients with AD have experienced OSA at some point after their initial diagnosis. The additive impact of progressive changes in sleep quality and structure, changes in cerebral blood flow and the cellular redox status in OSA patients may all be contributing factors to cognitive decline and may further aggravate AD progression. It is hoped that the high OSA rate in AD patients, as suggested by the findings of our meta-analysis, might provide a sufficient clinical incentive to alert clinicians the importance of screening patients for OSA in AD, and stimulate further research in this area.

Keywords: Alzheimer’s disease; meta-analysis; obstructive sleep apnea; prevalence; sleep-disordered breathing.

Figures

Figure 1
Figure 1
Flow chart depicting article selection strategy.
Figure 2
Figure 2
Forest plot shows the aggregate comparison between patients with Alzheimer’s disease (AD) and healthy controls in terms of obstructive sleep apnea (OSA). CI, confidence interval.

References

    1. Ancoli-Israel S., Coy T. (1994). Are breathing disturbances in elderly equivalent to sleep apnea syndrome? Sleep 17, 77–83.
    1. Ancoli-Israel S., Klauber M. R., Butters N., Parker L., Kripke D. F. (1991). Dementia in institutionalized elderly: relation to sleep apnea. J. Am. Geriatr. Soc. 39, 258–263. 10.1111/j.1532-5415.1991.tb01647.x
    1. Ancoli-Israel S., Palmer B. W., Cooke J. R., Corey-Bloom J., Fiorentino L., Natarajan L., et al. . (2008). Cognitive effects of treating obstructive sleep apnea in Alzheimer’s disease: a randomized controlled study. J. Am. Geriatr. Soc. 56, 2076–2081. 10.1111/j.1532-5415.2008.01934.x
    1. Bliwise D. L. (2013). Alzheimer’s disease, sleep apnea and positive pressure therapy. Curr. Treat. Options Neurol. 15, 669–676. 10.1007/s11940-013-0262-5
    1. Borenstein M. H. L., Higgins J., Rothstein H. (2005). Comprehensive Meta-Analysis. 2nd Edn. Englewood, NJ: Biostat.
    1. Bucks R. S., Olaithe M., Eastwood P. (2013). Neurocognitive function in obstructive sleep apnoea: a meta-review. Respirology 18, 61–70. 10.1111/j.1440-1843.2012.02255.x
    1. Carmona P., Molina M., Toledano A. (2016). Blood-based biomarkers of Alzheimer’s disease: diagnostic algorithms and new technologies. Curr. Alzheimer Res. 13, 450–464. 10.2174/1567205013666151116130301
    1. Chan K. Y., Wang W., Wu J. J., Liu L., Theodoratou E., Car J., et al. . (2013). Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990–2010: a systematic review and analysis. Lancet 381, 2016–2023. 10.1016/s0140-6736(13)60221-4
    1. Christensen A., Pike C. J. (2015). Menopause, obesity and inflammation: interactive risk factors for Alzheimer’s disease. Front. Aging Neurosci. 7:130. 10.3389/fnagi.2015.00130
    1. Cooke J. R., Ancoli-Israel S., Liu L., Loredo J. S., Natarajan L., Palmer B. S., et al. . (2009a). Continuous positive airway pressure deepens sleep in patients with Alzheimer’s disease and obstructive sleep apnea. Sleep Med. 10, 1101–1106. 10.1016/j.sleep.2008.12.016
    1. Cooke J. R., Ayalon L., Palmer B. W., Loredo J. S., Corey-Bloom J., Natarajan L., et al. . (2009b). Sustained use of CPAP slows deterioration of cognition, sleep and mood in patients with Alzheimer’s disease and obstructive sleep apnea: a preliminary study. J. Clin. Sleep Med. 5, 305–309.
    1. Daurat A., Foret J., Bret-Dibat J. L., Fureix C., Tiberge M. (2008). Spatial and temporal memories are affected by sleep fragmentation in obstructive sleep apnea syndrome. J. Clin. Exp. Neuropsychol. 30, 91–101. 10.1080/13803390701236116
    1. Franklin K. A., Lindberg E. (2015). Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. J. Thorac. Dis. 7, 1311–1322. 10.3978/j.issn.2072-1439.2015.06.11
    1. Harris P., Fernandez Suarez M., Surace E. I., Chrem Mendez P., Martin M. E., Clarens M. F., et al. . (2015). Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina-Alzheimer’s disease neuroimaging initiative). Neuropsychiatr. Dis. Treat. 11, 2599–2604. 10.2147/NDT.S84292
    1. Heinzer R., Vat S., Marques-Vidal P., Marti-Soler H., Andries D., Tobback N., et al. . (2015). Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir. Med. 3, 310–318. 10.1016/s2213-2600(15)00043-0
    1. Heneka M. T., Carson M. J., El Khoury J., Landreth G. E., Brosseron F., Feinstein D. L., et al. . (2015a). Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14, 388–405. 10.1016/S1474-4422(15)70016-5
    1. Heneka M. T., Golenbock D. T., Latz E. (2015b). Innate immunity in Alzheimer’s disease. Nat. Immunol. 16, 229–236. 10.1038/ni.3102
    1. Hoch C. C., Reynolds C. F., III, Kupfer D. J., Houck P. R., Berman S. R., Stack J. A. (1986). Sleep-disordered breathing in normal and pathologic aging. J. Clin. Psychiatry 47, 499–503.
    1. Hoch C. C., Reynolds C. F., III, Nebes R. D., Kupfer D. J., Berman S. R., Campbell D. (1989). Clinical significance of sleep-disordered breathing in Alzheimer’s disease. Preliminary data. J. Am. Geriatr. Soc. 37, 138–144. 10.1111/j.1532-5415.1989.tb05872.x
    1. Jaussent I., Bouyer J., Ancelin M. L., Berr C., Foubert-Samier A., Ritchie K., et al. . (2012). Excessive sleepiness is predictive of cognitive decline in the elderly. Sleep 35, 1201–1207. 10.5665/sleep.2070
    1. Keage H. A., Banks S., Yang K. L., Morgan K., Brayne C., Matthews F. E. (2012). What sleep characteristics predict cognitive decline in the elderly? Sleep Med. 13, 886–892. 10.1016/j.sleep.2012.02.003
    1. Kendell R. E. (1980). Diagnostic and statistical manual of mental-disorders, 3rd Edn. Am. J. Psychiatry 137, 1630–1631. 10.1176/ajp.137.12.1630
    1. Khaledi-Paveh B. K. H., Nasouri M., Ghadami M. R., Tahmasian M. (2016). Evaluation of Berlin questionnaire validity for sleep apnea risk in sleep clinic populations. Basic Clin. Neurosci. 7, 43–48.
    1. Khazaie H., Heidarpour A., Nikray R., Rezaei M., Maroufi A., Moradi B., et al. . (2013). Evaluation of sleep problems in preeclamptic, healthy pregnant and non-pregnant women. Iran. J. Psychiatry 8, 168–171.
    1. Khazaie H., Maroufi A. (2014). Obstructive sleep apnea syndrome; a neglected cause of traffic collision among Iranian public transport drivers. J. Inj. Violence Res. 6:99. 10.5249/jivr.v6i2.577
    1. Khazaie H., Najafi F., Rezaie L., Tahmasian M., Sepehry A. A., Herth F. J. (2011). Prevalence of symptoms and risk of obstructive sleep apnea syndrome in the general population. Arch. Iran. Med. 14, 335–338.
    1. Koo P., McCool F. D., Hale L., Stone K., Eaton C. B. (2016). Association of obstructive sleep apnea risk factors with nocturnal enuresis in postmenopausal women. Menopause 23, 175–182. 10.1097/GME.0000000000000517
    1. Lavie L. (2015). Oxidative stress in obstructive sleep apnea and intermittent hypoxia–revisited–the bad ugly and good: implications to the heart and brain. Sleep Med. Rev. 20, 27–45. 10.1016/j.smrv.2014.07.003
    1. Malhotra A., Orr J. E., Owens R. L. (2015). On the cutting edge of obstructive sleep apnoea: where next? Lancet Respir. Med. 3, 397–403. 10.1016/s2213-2600(15)00051-x
    1. Mander B. A., Marks S. M., Vogel J. W., Rao V., Lu B., Saletin J. M., et al. . (2015). α-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat. Neurosci. 18, 1051–1057. 10.1038/nn.4035
    1. Mander B. A., Rao V., Lu B., Saletin J. M., Lindquist J. R., Ancoli-Israel S., et al. . (2013). Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat. Neurosci. 16, 357–364. 10.1038/nn.3324
    1. Marshall N. S., Barnes M., Travier N., Campbell A. J., Pierce R. J., Mcevoy R. D., et al. . (2006). Continuous positive airway pressure reduces daytime sleepiness in mild to moderate obstructive sleep apnoea: a meta-analysis. Thorax 61, 430–434. 10.1136/thx.2005.050583
    1. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. (1984). Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology 34, 939–944. 10.1212/wnl.34.7.939
    1. McMillan A., Bratton D. J., Faria R., Laskawiec-Szkonter M., Griffin S., Davies R. J., et al. . (2014). Continuous positive airway pressure in older people with obstructive sleep apnoea syndrome (PREDICT): a 12-month, multicentre, randomised trial. Lancet Respir. Med. 2, 804–812. 10.1016/S2213-2600(14)70172-9
    1. Moher D., Liberati A., Tetzlaff J., Altman D. G., Group P. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6:e1000097. 10.1371/journal.pmed.1000097
    1. Olaithe M., Skinner T. C., Hillman D., Eastwood P. E., Bucks R. S. (2014). Cognition and nocturnal disturbance in OSA: the importance of accounting for age and premorbid intelligence. Sleep Breath 19, 221–230. 10.1007/s11325-014-1000-2
    1. Osorio R. S., Ayappa I., Mantua J., Gumb T., Varga A., Mooney A. M., et al. . (2014). Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer’s disease in cognitively normal elderly individuals. Neurobiol. Aging 35, 1318–1324. 10.1016/j.neurobiolaging.2013.12.030
    1. Osorio R. S., Gumb T., Pirraglia E., Varga A. W., Lu S. E., Lim J., et al. . (2015). Sleep-disordered breathing advances cognitive decline in the elderly. Neurology 84, 1964–1971. 10.1212/WNL.0000000000001566
    1. Pan W. H., Kastin A. J. (2014). Can sleep apnea cause Alzheimer’s disease? Neurosci. Biobehav. Rev. 47, 656–669. 10.1016/j.neubiorev.2014.10.019
    1. Peter-Derex L., Yammine P., Bastuji H., Croisile B. (2015). Sleep and Alzheimer’s disease. Sleep Med. Rev. 19, 29–38. 10.1016/j.smrv.2014.03.007
    1. Reitz C., Mayeux R. (2014). Alzheimer’s disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem. Pharmacol. 88, 640–651. 10.1016/j.bcp.2013.12.024
    1. Reynolds C. F., Kupfer D. J., Hoch C. C., Houck P. R., Stack J. A., Berman S. R., et al. . (1987). Sleep-deprivation as a probe in the elderly. Arch. Gen. Psychiatry 44, 982–990. 10.1001/archpsyc.1987.01800230062011
    1. Reynolds C. F., III, Kupfer D. J., Taska L. S., Hoch C. C., Sewitch D. E., Restifo K., et al. . (1985). Sleep apnea in Alzheimer’s dementia: correlation with mental deterioration. J. Clin. Psychiatry 46, 257–261.
    1. Rhodius-Meester H. F., Koikkalainen J., Mattila J., Teunissen C. E., Barkhof F., Lemstra A. W., et al. . (2015). Integrating biomarkers for underlying Alzheimer’s disease in mild cognitive impairment in daily practice: comparison of a clinical decision support system with individual biomarkers. J. Alzheimers Dis. 50, 261–270. 10.3233/JAD-150548
    1. Rosenzweig I., Glasser M., Polsek D., Leschziner G. D., Williams S. C., Morrell M. J. (2015). Sleep apnoea and the brain: a complex relationship. Lancet Respir. Med. 3, 404–414. 10.1016/s2213-2600(15)00090-9
    1. Rosenzweig I., Williams S. C., Morrell M. J. (2013). CrossTalk opposing view: the intermittent hypoxia attending severe obstructive sleep apnoea does not lead to alterations in brain structure and function. J. Physiol. 591, 383–385; discussion 387–389. 10.1113/jphysiol.2012.241224
    1. Rosenzweig I., Williams S. C., Morrell M. J. (2014). The impact of sleep and hypoxia on the brain: potential mechanisms for the effects of obstructive sleep apnea. Curr. Opin. Pulm. Med. 20, 565–571. 10.1097/MCP.0000000000000099
    1. Roussel B. D., Kruppa A. J., Miranda E., Crowther D. C., Lomas D. A., Marciniak S. J. (2013). Endoplasmic reticulum dysfunction in neurological disease. Lancet Neurol. 12, 105–118. 10.1016/s1474-4422(12)70238-7
    1. Salvatore C., Battista P., Castiglioni I. (2016). Frontiers for the early diagnosis of AD by means of MRI brain imaging and support vector machines. Curr. Alzheimer Res. 13, 509–533.
    1. Smallwood R. G., Vitiello M. V., Giblin E. C., Prinz P. N. (1983). Sleep apnea: relationship to age, sex and Alzheimer’s dementia. Sleep 6, 16–22.
    1. Troussière A. C., Charley C. M., Salleron J., Richard F., Delbeuck X., Derambure P., et al. . (2014). Treatment of sleep apnoea syndrome decreases cognitive decline in patients with Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatr. 85, 1405–1408. 10.1136/jnnp-2013-307544
    1. Veasey S. (2014). Sleep apnea: a redox edge with aging? Sleep 37, 1161–1162. 10.5665/sleep.3828
    1. Willette A. A., Bendlin B. B., Starks E. J., Birdsill A. C., Johnson S. C., Christian B. T., et al. . (2015). Association of insulin resistance with cerebral glucose uptake in late middle-aged adults at risk for Alzheimer’s disease. JAMA Neurol. 72, 1013–1020. 10.1001/jamaneurol.2015.0613
    1. Xu W., Chi L., Row B. W., Xu R., Ke Y., Xu B., et al. . (2004). Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea. Neuroscience 126, 313–323. 10.1016/j.neuroscience.2004.03.055
    1. Yaffe K., Falvey C. M., Hoang T. (2014). Connections between sleep and cognition in older adults. Lancet Neurol. 13, 1017–1028. 10.1016/S1474-4422(14)70172-3
    1. Yaffe K., Laffan A. M., Harrison S. L., Redline S., Spira A. P., Ensrud K. E., et al. . (2011). Sleep-disordered breathing, hypoxia and risk of mild cognitive impairment and dementia in older women. JAMA 306, 613–619. 10.1001/jama.2011.1115

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