|Ahead of print publication
Continuous positive airway pressure improved daytime sleepiness and memory function in patients with obstructive sleep apnea
Ya-Ling Hong1, Yu-Chih Shen2, En-Ting Chang3, Shu-Chin Kung4
1 Speak to the Heart Combined Clinics, Tainan; School of Medicine, Tzu Chi University, Hualien, Taiwan
2 School of Medicine, Tzu Chi University; Department of Psychiatry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
3 School of Medicine, Tzu Chi University; Department of Chest Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
4 School of Medicine, Tzu Chi University, Hualien, Taiwan
|Date of Submission||07-Jan-2022|
|Date of Decision||21-Feb-2022|
|Date of Acceptance||01-Apr-2022|
|Date of Web Publication||23-Aug-2022|
Department of Chest Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 707, Section 3, Chung-Yang Road, Hualien
Source of Support: None, Conflict of Interest: None
Objectives: Obstructive sleep apnea (OSA) is a sleep disorder which results in daytime sleepiness and impaired memory function. The aim of this study was to investigate the effect of continuous positive airway pressure (CPAP) on daytime sleepiness and memory function in OSA patients. We also investigated whether CPAP compliance impacted the effect of this treatment. Materials and Methods: The nonrandomized, nonblinded clinical trial enrolled 66 patients with moderate-to-severe OSA subjects. All subjects completed a polysomnographic study, daytime sleepiness questionnaires (the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index), and four memory function tests (working memory; processing speed [PS]; logical memory [LM]; face memory [FM]). Results: Before CPAP treatment, no significant differences (P < 0.05) were noted in the demographic data, daytime sleepiness, or memory function between two groups (with/without CPAP). However, OSA patients treated with CPAP for 2 months showed significant improvements in daytime sleepiness, PS, mostly of LM, and FM comparing to 2 months ago. As compared to those who did not receive CPAP treatment, CPAP can improve only parts of LM (delayed LM [DLM] and LM percentage [LMP]). In addition, compared to control group, a significant improvement of daytime sleepiness and LM (LM learning, DLM, and LMP) in good compliance with CPAP treatment group and of DLM and LMP in the low compliance with CPAP treatment group was found. Conclusion: CPAP treatment for 2 months could improve some of LM in OSA patients, especially in patients exhibiting good CPAP compliance.
Keywords: Continuous positive airway pressure therapy, Daytime sleepiness, Memory function, Obstructive sleep apnea
|How to cite this URL:|
Hong YL, Shen YC, Chang ET, Kung SC. Continuous positive airway pressure improved daytime sleepiness and memory function in patients with obstructive sleep apnea. Tzu Chi Med J [Epub ahead of print] [cited 2022 Oct 6]. Available from: https://www.tcmjmed.com/preprintarticle.asp?id=354283
| Introduction|| |
Obstructive sleep apnea (OSA) is characterized by recurrent collapse of the upper airway, leading to episodes of hypoxemia and arousal during sleep . The clinical features of OSA include snoring, daytime sleepiness, and sleep fragmentation . Many studies have reported that OSA patients have significant impairments in cognitive function, attention, and memory function ,,,,. Recently, a large randomized clinical trial of Sleep Apnea Cardiovascular Endpoints (SAVE) study shows improvement of depression and Epworth Sleepiness Scale (ESS) but not anxiety score (hospital anxiety and depression scale) during 48-month follow-up . Other studies have shown that OSA patients have significant impairments in episodic memory, procedural memory, and working memory (WM) ,,. Furthermore, in a recent study by Jackson et al., OSA patients exhibited greater daytime sleepiness and impairments in the backward digit span test, trail making test, and quality of life compared to a nonsleep apneic community sample .
Although there exists significant evidence on memory impairments in OSA patients, the effect of continuous positive airway pressure (CPAP) treatment on these memory impairments remains controversial ,. Indeed, very few studies have investigated the effect of CPAP on memory impairments. A randomized controlled study by Joyeux-Faure et al. showed no significant impact of CPAP on memory impairment . However, the drop-out rate of CPAP usage was high and only 10 OSA patients completed the study. Therefore, given the limitations of this previous study, we aimed to investigate the effect of CPAP compliance on sleepiness and memory function in OSA patients.
| Materials and Methods|| |
Study participants and experimental protocol
This nonrandomized, nonblinded clinical trial was conducted at the Sleep Center of Hualien Tzu Chi General Hospital from 2016 to 2017, and 66 moderate-to-severe adult OSA patients (apnea–hypopnea index [AHI] ≥15/h; age ranging from 20 to 75 years) were enrolled. Patients who had previously been diagnosed with, or treated for, any psychological disease or chronic disease that could have interfered with the accuracy of the neurocognitive tests were excluded from the study. Patients unable to cooperate with the tasks were also excluded. The baseline characteristics of the subjects such as age, sex, and body mass index were recorded. All enrolled subjects underwent polysomnography and completed the ESS, the Pittsburgh Sleep Quality Index (PSQI), and memory tests. The subjects were then divided into two groups – patients in one group received 2 months of CPAP treatment (S8 AutoSet, ResMed Inc., San Diego, CA, USA) and patients in the other did not receive CPAP treatment (controlled group), but rather sleep hygiene education (a program including weight loss, changing sleep position, and avoid of sedative drugs or alcoholic use before sleep) every month. After 2 months, all patients once again completed the ESS, PSQI, and memory tests as well. Data on CPAP compliance were also collected.
All patients underwent one night of standard Type 1 attended polysomnography (Embla A10, Embla, Broomfield, CO, USA) at our Sleep Center. Sleep and arousals were scored according to the standard criteria. The AHI and 3% oxygen desaturation index (ODI) were determined and utilized as markers of disease severity .
Sleep questionnaires were conducted before and after 2-month CPAP treatment period. The ESS is an eight-item questionnaire that asks respondents to rate their likelihood of falling asleep during eight different everyday situations. Each question is rated on a scale from 0 (not at all likely to fall asleep) to 3 (very likely to fall asleep), and the total score of the ESS ranges from 0 (minimum) to 24 (maximum) . All enrolled subjects also completed the PSQI, a commonly used instrument designed to measure sleep disturbance and sleep habits within a 1-month period . This questionnaire consists of 19 items including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.
All memory tests were conducted before and after 2-month CPAP treatment period, according to previously published data ,. Here, we employed two components of the Wechsler Memory Scale-Third Edition, namely face memory (FM) and logical memory (LM) subtests. The FM subtest includes (1) immediate FM (IFM), (2) delayed FM (DFM), and (3) FM percentage. The LM subtest includes (1) immediate LM (ILM), (2) LM learning (LML), (3) delayed LM (DLM), (4) LM percentage (LMP), and (5) LM recognition (LMR). All study participants completed the memory tests in the morning in a quiet isolation room at 23°C without any interference.
Continuous positive airway pressure compliance
Although there exists no exact definition of CPAP compliance, we defined good CPAP compliance as the use of CPAP for more than 4 h per night for more than 70% of the days monitored. Low CPAP compliance was defined with those who cannot tolerate more than 4 h CPAP treatment in one night.
Independent t-tests were used to compare age, sex, body mass index, AHI, ODI, arousal index, ESS, PSQI, and memory test scores between two OSA groups (with/without CPAP treatment) at baseline. Data are presented as mean ± standard deviation (SD). P < 0.05 was considered to indicate statistical significance. Paired t-tests were used to compare ESS, PSQI, and memory test scores before and after CPAP treatment. Data are presented as mean ± SD. P < 0.05 was considered to indicate statistical significance. The subjects were divided into three groups (good compliance group (≥4 h/night), low compliance group (<4 h/night), and control group (denied CPAP used), and the previous test scores were tested by ANCOVA. All statistical analyses were performed using SPSS for Windows Version 14.0 software (SPSS, Chicago, IL, USA).
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Board of Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and all participants provided informed consent (IRB 105-20-A, dated August 1, 2016). Informed consent was obtained from all individual participants included in the study.
| Results|| |
Sixty-six subjects were enrolled in our study – 47 OSA patients received CPAP treatment and 19 did not. The demographic data of these two OSA groups (with/without CPAP treatment) showed no significant differences in age, sex, body mass index, AHI, ODI, arousal index, sleepiness scale (ESS and PSQI), or memory test scores (LM, visual memory [VM], WM, and processing speed [PS]) [Table 1].
|Table 1: Baseline characteristics of continuous positive airway pressure and control groups|
Click here to view
Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index questionnaires
The ESS scores of the CPAP and control groups were 10.51 ± 5.09 and 10.53 ± 5.17, respectively, at the baseline. After 2 months of treatment, the ESS score of the CPAP group significantly decreased 3.3 points, compared to its baseline (P = 0.0001). The PSQI scores of the CPAP and control groups were 10.04 ± 5.43 and 10.95 ± 5.07 at the baseline, respectively. After 2 months of treatment, the PSQI score of the CPAP group significantly decreased to 7.13 ± 3.65, compared to its baseline (P = 0.049). Furthermore, PSQI had significant improved in controlled group, compared to its baseline (P = 0.049). However, those two scores of daytime sleepiness at the end of the study showed no significance between these two groups [Table 2].
|Table 2: Changes in daytime sleepiness and memory measures following 2 months of treatment in the continuous positive airway pressure and control groups|
Click here to view
PS (P < 0.001), LM (ILM, DLM, LMP, and LMR), and FM (IFM and DFM) significantly improved after 2 months of CPAP treatment, compared to its baseline. On the other hand, patients who did not undergo CPAP treatment exhibited a significant decrease in LML at the 2-month follow-up, compared to its baseline (P = 0.03). However, compared to the control group, there was only significant improvement on the DML and LMP in the CPAP group at the end of the study [Table 2].
[Table 3] shows the association between daytime sleepiness, memory changes, and CPAP compliance, using ANCOVA with the control group as a baseline. The mean CPAP used was 5.5 ± 0.6 h in good compliant group and 3.6 ± 0.4 h in low compliant group. Compared to the control group, a significant improvement of daytime sleepiness and LM (LML, DLM, and LMP) in good compliance with CPAP treatment group and of DLM and LMP in the low compliance with CPAP treatment group was found.
|Table 3: Associations between daytime sleepiness and memory changes and continuous positive airway pressure compliance by ANCOVA|
Click here to view
| Discussion|| |
In the present study, 2 months of CPAP treatment improved some of memory functions in patients with OSA. Patients exhibiting good CPAP compliance demonstrated greater improvements in daytime sleepiness and some of LM. Although some previous studies showed controversial CPAP effect on memory in OSA patients ,, our study showed the effect of CPAP adherence in improving memory in OSA patients.
CPAP treatment in OSA patients improved daytime sleepiness about ‒3.1 in SAVE study . This value is ‒3.3 points in our study. The improvement of ESS score was significantly larger than the minimal clinical important difference of ESS (‒2 points) in OSA patients . This means that CPAP can significantly decrease daytime sleepiness in OSA patients.
Neurocognitive dysfunction has been well described in OSA patients, and several risk factors for this cognitive impairment have been identified. It has been shown that intermittent hypoxemia affects hippocampal volume, resulting in impairments in memory consolidation and amnesia . In addition, endothelial dysfunction during hypoxemia  and daytime sleepiness  have both been implicated in neurocognitive dysfunction in OSA patients. In our present study, 2 months of CPAP treatment significantly improved daytime sleepiness and, to a lesser degree, WM and LM that may infer difference from recovery of daytime sleepiness and memory function.
A number of previous studies have shown impairments in episodic memory, procedural memory, and WM in OSA patients ,,, although the effect of CPAP on WM remains controversial ,. Many of the animal data showed impaired spatial WM under intermittent hypoxemia ,, as well as another study in healthy adults . Our study showed that 2 months of CPAP treatment did not have any beneficial effect on WM. WM was found to decrease over the 2-month study period in both groups; however, this decrease was smaller in the CPAP treatment group (‒0.08) than in the control group (‒0.42). Even adjusted to controlled group, good compliance to 2-month CPAP treatment did not significantly improve WM. This implies that the recovery of intermittent hypoxemia over 2 months with CPAP treatment cannot completely recover WM. In the study by Thomas et al., 8 weeks of CPAP therapy was able to achieve complete subjective clinical recovery, but the recovery of neurocognition was still impaired . Further investigation about the recovery time in OSA patients should be studied.
A slow PS was noted in OSA patients, and this was significantly improved by CPAP treatment. A previous pathophysiological study found that white matter integrity was impaired in OSA patients and CPAP treatment reversed this neural injury . In our study, 2 months of CPAP treatment improved the PS of OSA patients, although CPAP compliance did not have an impact on this effect.
LM is a useful tool for assessing memory and, along with a verbal test, tests the recall of a short story. A previous study showed that aspects of verbal memory, including immediate and delayed recall scores, were significant lower than in OSA patients than in healthy control groups . Furthermore, in a recent study, CPAP treatment for 1 month improved DLM in OSA patients . Another study showed that 3 months of CPAP treatment also improved LM but did not demonstrate a dose-dependent effect . Similarly, our study demonstrated a significant improvement in LM after 2 months of CPAP treatment in OSA patients. The improvement in the LML subdomain was found to be greater in those exhibiting good CPAP compliance. The DML and LMP subdomains were significantly improved in the CPAP treatment group compared to the control group, irrespective of compliance.
A meta-analysis showed impaired VM in OSA patients compared to normal healthy subjects . A study from Borak et al. showed that 3 months of CPAP treatment significantly improved visual and spatial memory in OSA patients . Similarly, our study showed that 2 months of CPAP treatment significantly improved IFM and DFM.
There exists a limitation of our study in that a group of healthy subjects was not included as a control. Although the study provided much information in the impact of CPAP in cognitive improvement in OSA, this was a case–control study rather than randomized trial. Besides, the sample size was too small to investigate the impact of treatment effects in different severity of OSA. Therefore, a future randomized study comprising a large sample size and healthy controls should be considered.
| Conclusions|| |
In conclusion, 2 months of CPAP treatment could improve some of LM in OSA patients, especially in patients exhibiting good CPAP compliance. However, daytime sleepiness was not significantly improved after CPAP treatment, compared to control group without CPAP therapy.
Financial support and sponsorship
The study was funded by Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan (TCRD 106-19).
Conflicts of interest
Prof. En-Ting Chang, an editorial board member at Tzu Chi Medical Journal, had no role in the peer review process of or decision to publish this article. The other authors decalared no conflicts of interest in writing this paper.
| References|| |
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230-5.
Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, et al. Rules for scoring respiratory events in sleep: Update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med 2012;8:597-619.
Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea. Chest 2012;141:1601-10.
Verstraeten E, Cluydts R, Pevernagie D, Hoffmann G. Executive function in sleep apnea: Controlling for attentional capacity in assessing executive attention. Sleep 2004;27:685-93.
Twigg GL, Papaioannou I, Jackson M, Ghiassi R, Shaikh Z, Jaye J, et al. Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory. Am J Respir Crit Care Med 2010;182:98-103.
Jackson ML, Howard ME, Barnes M. Cognition and daytime functioning in sleep-related breathing disorders. Prog Brain Res 2011;190:53-68.
Salorio CF, White DA, Piccirillo J, Duntley SP, Uhles ML. Learning, memory, and executive control in individuals with obstructive sleep apnea syndrome. J Clin Exp Neuropsychol 2002;24:93-100.
McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 2016;375:919-31.
Rouleau I, Décary A, Chicoine AJ, Montplaisir J. Procedural skill learning in obstructive sleep apnea syndrome. Sleep 2002;25:401-11.
Thomas RJ, Rosen BR, Stern CE, Weiss JW, Kwong KK. Functional imaging of working memory in obstructive sleep-disordered breathing. J Appl Physiol (1985) 2005;98:2226-34.
Naëgelé B, Launois SH, Mazza S, Feuerstein C, Pépin JL, Lévy P. Which memory processes are affected in patients with obstructive sleep apnea? An evaluation of 3 types of memory. Sleep 2006;29:533-44.
Jackson ML, McEvoy RD, Banks S, Barnes M. Neurobehavioral impairment and CPAP treatment response in mild-moderate obstructive sleep apneas. J Clin Sleep Med 2018;14:47-56.
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;267:2823-8.
Vernet C, Redolfi S, Attali V, Konofal E, Brion A, Frija-Orvoen E, et al. Residual sleepiness in obstructive sleep apnoea: Phenotype and related symptoms. Eur Respir J 2011;38:98-105.
Joyeux-Faure M, Naegelé B, Pépin JL, Tamisier R, Lévy P, Launois SH. Continuous positive airway pressure treatment impact on memory processes in obstructive sleep apnea patients: A randomized sham-controlled trial. Sleep Med 2016;24:44-50.
Johns MW. A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep 1991;14:540-5.
Buysse DJ, Reynolds CF 3rd
, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193-213.
Shen YC, Kung SC, Chang ET, Hong YL, Wang LY. The impact of obesity in cognitive and memory dysfunction in obstructive sleep apnea syndrome. Int J Obes (Lond) 2019;43:355-61.
Kung SC, Shen YC, Chang ET, Hong YL, Wang LY. Hypercapnia impaired cognitive and memory functions in obese patients with obstructive sleep apnoea. Sci Rep 2018;8:17551.
Crook S, Sievi NA, Bloch KE, Stradling JR, Frei A, Puhan MA, et al. Minimum important difference of the Epworth Sleepiness Scale in obstructive sleep apnoea: Estimation from three randomised controlled trials. Thorax 2019;74:390-6.
Lavie L. Obstructive sleep apnoea syndrome – An oxidative stress disorder. Sleep Med Rev 2003;7:35-51.
Verstraeten E. Neurocognitive effects of obstructive sleep apnea syndrome. Curr Neurol Neurosci Rep 2007;7:161-6.
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;35:1593-602.
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;37:1465-75.
Kheirandish L, Gozal D, Pequignot JM, Pequignot J, Row BW. Intermittent hypoxia during development induces long-term alterations in spatial working memory, monoamines, and dendritic branching in rat frontal cortex. Pediatr Res 2005;58:594-9.
McCoy JG, McKenna JT, Connolly NP, Poeta DL, Ling L, McCarley RW, et al. One week of exposure to intermittent hypoxia impairs attentional set-shifting in rats. Behav Brain Res 2010;210:123-6.
Champod AS, Eskes GA, Foster GE, Hanly PJ, Pialoux V, Beaudin AE, et al. Effects of acute intermittent hypoxia on working memory in young healthy adults. Am J Respir Crit Care Med 2013;187:1148-50.
Rosenzweig I, Glasser M, Crum WR, Kempton MJ, Milosevic M, McMillan A, et al. Changes in neurocognitive architecture in patients with obstructive sleep apnea treated with continuous positive airway pressure. EBioMedicine 2016;7:221-9.
Antic NA, Catcheside P, Buchan C, Hensley M, Naughton MT, Rowland S, et al. The effect of CPAP in normalizing daytime sleepiness, quality of life, and neurocognitive function in patients with moderate to severe OSA. Sleep 2011;34:111-9.
Wallace A, Bucks RS. Memory and obstructive sleep apnea: A meta-analysis. Sleep 2013;36:203-20.
Borak J, Cieślicki JK, Koziej M, Matuszewski A, Zieliński J. Effects of CPAP treatment on psychological status in patients with severe obstructive sleep apnoea. J Sleep Res 1996;5:123-7.
[Table 1], [Table 2], [Table 3]