Cognition and obstructive sleep apnoea in Parkinson’s disease, effect of positive airway pressure therapy (COPE-PAP trial): protocol of a randomized controlled trial
DOI:
https://doi.org/10.18203/2349-3259.ijct20210143Keywords:
Parkinson’s disease, Neurodegenerative disorders, Obstructive sleep apnea, Sleep-disordered breathing, Cognitive functionAbstract
Background: Parkinson’s disease (PD) is the second most frequent neurodegenerative disease and is associated with cognitive dysfunction. Obstructive sleep apnea (OSA) has been linked with cognitive dysfunction in the general population and in PD. Treatment with positive airway pressure (PAP), can improve cognition in the general population and in patients with other neurodegenerative diseases. However, the effect of PAP therapy on cognitive function has not been well studied in PD.
Methods: This randomized controlled trial will assess the effect of 6 months of PAP therapy versus placebo on global cognitive function in PD patients with OSA and reduced baseline cognition. Secondary outcomes will include quality of life and other non-motor symptoms of PD. Exploratory outcomes will be specific domains of neurocognitive function and symptoms of REM sleep behaviour disorder.
Conclusions: PD-related cognitive dysfunction often evolves towards dementia and has substantial personal, social and healthcare costs. Few interventions have been shown to improve cognition in PD to date. If positive, results from our study could prove OSA to be a new therapeutic target relevant to cognition and would support more systematic screening for OSA in PD patients with cognitive decline.
Trial Registration: Trial registration number is NCT02209363.
References
Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29(13):1583-90.
Braak H, Tredici K Del, Rüb U, Vos RAI De, Jansen Steur ENH, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197-211.
Huang X, Ng SYE, Chia NSY, Setiawan F, Tay KY, Au WL, et al. Non-motor symptoms in early Parkinson’s disease with different motor subtypes and their associations with quality of life. Eur J Neurol. 2019;26(3):400-6.
Levy G, Tang MX, Louis ED, Côté LJ, Alfaro B, Mejia H, et al. The association of incident dementia with mortality in PD. Neurology. 2002;59(11):1708-13.
Hely MA, Reid WGJ, Adena MA, Halliday GM, Morris JGL. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837-44.
Wallace A, Bucks RS. Memory and Obstructive Sleep Apnea: A Meta-Analysis. Sleep. 2013;36(2):203-20.
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(10):1237-45.
Silva-Júnior FP da, Prado GF do, Barbosa ER, Tufik S, Togeiro SM. Sleep disordered breathing in Parkinson’s disease: a critical appraisal. Sleep Med Rev. 2014;18(2):173-8.
Shafazand S, Wallace DM, Arheart KL, Vargas S, Luca CC, Moore H, et al. Insomnia, sleep quality, and quality of life in mild to moderate parkinson’s disease. Ann Am Thorac Soc.2017;14(3):412-9.
Meng L, Benedetti A, Lafontaine AL, Mery V, Robinson AR, Kimoff J, et al. Obstructive sleep apnea, CPAP therapy and Parkinson’s disease motor function: A longitudinal study. Park Relat Disord. 2020;70:45-50.
Mery VP, Gros P, Lafontaine A-L, Robinson A, Benedetti A, Kimoff RJ, et al. Reduced cognitive function in patients with Parkinson disease and obstructive sleep apnea. Neurology. 2017;88(12):1120-8.
Patil SP, Ayappa IA, Caples SM, John Kimoff R, Patel SR, Harrod CG. Treatment of adult obstructive sleep apnea with positive airway pressure: An American academy of sleep medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2019;15(2):301-34.
Ferini-Strambi L, Baietto C, Gioia MR Di, Castaldi P, Castronovo C, Zucconi M, et al. Cognitive dysfunction in patients with obstructive sleep apnea (OSA): Partial reversibility after continuous positive airway pressure (CPAP). Brain Res Bull. 2003;61(1):87-92.
Engleman HM, Cheshire KE, Deary IJ, Douglas NJ. Daytime sleepiness, cognitive performance and mood after continuous positive airway pressure for the sleep apnoea/hypopnoea syndrome. Thorax. 1993;48(9):911-4.
Kushida CA, Nichols DA, Holmes TH, Quan SF, Walsh JK, Gottlieb DJ, et al. Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep. 2012;35(12):1593-602.
Olaithe M, Bucks RS. Executive dysfunction in OSA before and after treatment: a meta-analysis. Sleep. 2013;36(9):1297-305.
Dalmases M, Solé-Padullés C, Torres M, Embid C, Nuñez MD, Martínez-Garcia MÁ, et al. Effect of CPAP on cognition, brain function, and structure among elderly patients with OSA a randomized pilot study. Chest. 2015;148(5):1214-23.
Neikrug AB, Liu L, Avanzino JA, Maglione JE, Natarajan L, Bradley L, et al. Continuous positive airway pressure improves sleep and daytime sleepiness in patients with Parkinson disease and sleep apnea. Sleep. 2014;37(1):177-85.
Kaminska M, Mery VP, Lafontaine AL, Robinson A, Benedetti A, Gros P, et al. Change in Cognition and Other Non-Motor Symptoms With Obstructive Sleep Apnea Treatment in Parkinson Disease. J Clin Sleep Med. 2018;14(05):819-28.
Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591-601.
Arnulf I, Konofal E, Merino-Andreu M, Houeto JL, Mesnage V, Welter ML, et al. Parkinson’s disease and sleepiness: An integral part of PD. Neurology. 2002;58(7):1019-24.
Iber C, Ancoli-Israel S, Chesson A, Quan S. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. 2007.
American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events v2.6. Available at: https://learn.aasm.org/Public/Catalog/Details.aspx?id=3HAcgmlK60wJvxPqqan4rg%3d%3d&returnurl=%2fUsers%2fUserOnlineCourse.aspx%3fLearningActivityID%3d3HAcgmlK60wJvxPqqan4rg%253d%253d. Accessed on: 25 November 2020.
Amaro A, Duarte F, Jallad R, Bronstein M, Redline S, Lorenzi-Filho G. The use of nasal dilator strips as placebo for trials evaluating continuous positive airway pressure. Clinics. 2012;67(5):469-74.
Pamidi S, Meltzer SJ, Garfield N, Lavigne L, Olha A, Khalyfa A, et al. A Pilot Randomized-Controlled Trial on the Effect of CPAP Treatment on Glycemic Control in Gestational Diabetes: Study Design and Methods. Front Endocrinol (Lausanne). 2018;9:659.
Rodway GW, Weaver TE, Mancini C, Cater J, Maislin G, Staley B, et al. Evaluation of sham-CPAP as a placebo in CPAP intervention studies. Sleep. 2010;33(2):260-6.
Chasens ER, Drumheller OJ, Strollo PJ. Success in Blinding to Group Assignment With Sham-CPAP. Biol Res Nurs. 2013;15(4):465-9.
Nasreddine ZS, Phillips NA, Badirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment. J Am Geriatr Soc. 2005;53(4):695-9.
Hoops S, Nazem S, Siderowf AD, Duda JE, Xie SX, Stern MB, et al. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology. 2009;73(21):1738-45.
Lessig S, Nie D, Xu R, Corey-Bloom J. Changes on brief cognitive instruments over time in Parkinson’s disease. Mov Disord. 2012;27(9):1125-8.
Peto V, Jenkinson C, Fitzpatrick R, Greenhall R. The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res. 1995;4(3):241-8.
Martinez-Martin P, Jeukens-Visser M, Lyons KE, Rodriguez-Blazquez C, Selai C, Siderowf A, et al. Health-related quality-of-life scales in Parkinson’s disease: Critique and recommendations. Mov Disord. 2011;26(13):2371-80.
Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Mov Disord. 2008;23(15):2129-70.
Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, et al. MDS task force on mild cognitive impairment in Parkinson’s disease: Critical review of PD-MCI. Mov Disord. 2011;26(10):1814-24.
Mery V, Lafontaine AL, Ross Robinson A, Pinto L, Benedetti A, Kimoff RJ, et al. Improvement of REM Sleep Behavior Disorder symptoms with treatment of Obstructive Sleep Apnea in patients with Parkinson’s disease. Sleep. 2013;36:0680.
Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, Dauvilliers Y, et al. A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Mov Disord. 2012;27(7):913-6.
Johns MW. A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep. 1991;14(6):540-5.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An Inventory for Measuring Depression. Arch Gen Psychiatry. 1961;4(6):561-71.
Lachin JM. Introduction to sample size determination and power analysis for clinical trials. Control Clin Trials. 1981;2(2):93-113.
Friedman L, DeMets D. Fundamentals of Clinical Trials. Springer; 4th edition. 2010.
Harmell AL, Neikrug AB, Palmer BW, Avanzino JA, Liu L, Maglione JE, et al. Obstructive Sleep Apnea and Cognition in Parkinson’s disease. Sleep Med. 2016;21:28-34.
Neikrug AB, Maglione JE, Liu L, Natarajan L, Avanzino JA, Corey-Bloom J, et al. Effects of sleep disorders on the non-motor symptoms of Parkinson disease. J Clin Sleep Med. 2013;9(11):1119-29.
Olaithe M, Bucks RS. Executive Dysfunction in OSA Before and After Treatment: A Meta-Analysis. Sleep. 2013;36(9):1297-305.
Ancoli-Israel S, Palmer BW, Cooke JR, Corey-Bloom J, Fiorentino L, Natarajan L, et al. Cognitive effects of treating obstructive sleep apnea in Alzheimer’s disease: A randomized controlled study. J Am Geriatr Soc. 2008;56(11):2076-81.
Richards KC, Gooneratne N, Dicicco B, Hanlon A, Moelter S, Onen F, et al. CPAP Adherence May Slow 1‐Year Cognitive Decline in Older Adults with Mild Cognitive Impairment and Apnea. J Am Geriatr Soc. 2019;15758.
Labarca G, Saavedra D, Dreyse J, Jorquera J, Barbe F. Efficacy of continuous positive airway pressure (CPAP) for improvements in sleepiness, cognition, mood and quality of life in elderly patients with obstructive sleep apnea: Systematic review and meta-analysis of randomized controlled trials. Chest. 2020;158(2):751-64.
Cooke JR, Ayalon L, Palmer BW, Loredo JS, Corey-Bloom J, Natarajan L, Ancoli-Israel S, et al. 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. 2009;5(4):305-9.
Chong MS, Ayalon L, Marler M, Loredo JS, Corey-Bloom J, Palmer BW, et al. Continuous positive airway pressure reduces subjective daytime sleepiness in patients with mild to moderate Alzheimer’s disease with sleep disordered breathing. J Am Geriatr Soc. 2006;54(5):777-81.
Wang G, Goebel JR, Li C, Hallman HG, Gilford TM, Li W. Therapeutic effects of CPAP on cognitive impairments associated with OSA. J Neurol. 2020;267(10):2823-8.
Castronovo V, Scifo P, Castellano A, Aloia MS, Iadanza A, Marelli S, et al. White Matter Integrity in Obstructive Sleep Apnea before and after Treatment. Sleep. 2014;37(9):1465-75.