Association between sleep microarchitecture and cognition in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. METHODS: Participants with suspected OSA (n=1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 NREM sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP) and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. RESULTS: All spindle characteristics were lower in participants with moderate and severe OSA (p≤0.001, versus no/mild OSA) and positively associated with MoCA, RAVLT and DSC scores (false discovery rate corrected p-value, q≤0.026), except spindle power which was not associated with RAVLT (q=0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p≤0.001) but neither ORPNREM (q≥0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q≥0.166). In mediation analyses, spindle density and EEGNP (p≥0.048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power and %-fast spindles mediated OSA's negative effect on DSC scores (p≤0.018). CONCLUSION: Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.

Adherence and efficacy of mandibular advancement splint treatment of sleep-disordered breathing during pregnancy: a pilot study.

PURPOSE: Sleep-disordered breathing (SDB) is common in pregnancy and is associated with adverse health consequences for both mother and child. Mandibular advancement splints (MAS) have been shown to improve sleep quality, daytime sleepiness and snoring in non-pregnant women. The effectiveness of MAS for treating SDB in pregnancy is unknown. This pilot study aimed to evaluate the efficacy and adherence to MAS in pregnant women with SDB. METHODS: Women with mild-moderate SDB (apnea-hypopnea index (AHI) 10-29/h) on level 2 polysomnography (PSG) performed at 22.0 ± 5.5 weeks' gestation were treated with a MAS during pregnancy to 6 months postpartum. An embedded micro-recorder measured adherence. PSG was repeated while on titrated treatment, and off treatment in the postpartum period. RESULTS: Among 17 women completing the study, MAS was worn ≥ 4 h/night for 57.5 ± 36.7% of nights during the antepartum period. While using MAS, nightly snoring time decreased from 25.9 ± 24.5% at baseline to 6.4 ± 7.8% when treated during pregnancy (p = .003). AHI decreased from 17.6 ± 5.1 to 12.9 ± 6.3 (p = .02) and fell by ≥ 30% and below 15/h in 60% of participants. During the postpartum period, MAS was used for ≥ 4 h/night on 24.8 ± 27.9% of nights. Moreover, the mean AHI off MAS was 17.9 ± 13.1; 88% of women had persistent SDB (AHI ≥ 10). CONCLUSIONS: In this cohort, treatment efficacy and objective adherence were variable. Device use was less frequent in the postpartum period even though a substantial number of women had persistent SDB after delivery. Clinical trial registered with  www. CLINICALTRIALS: gov number: NCT03138291.

Obstructive sleep apnea and its management in patients with atrial fibrillation: An International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT) global survey of practicing cardiologists.

Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.

Association of insomnia and short sleep duration, alone or with comorbid obstructive sleep apnea, and the risk of chronic kidney disease.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA), sleep fragmentation, and short sleep duration (SD) have been associated with chronic kidney disease (CKD). However, these potential mechanisms for CKD have not been compared in the same cohort. This study investigated the independent and combined impact of OSA and insomnia with short sleep duration on the risk of CKD progression in a sleep clinic population. METHODS: In a cross-sectional study design, adults with suspected OSA completed an overnight sleep study and a questionnaire that included the Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI). They also provided blood and urine samples for measurement of the glomerular filtration rate and urine albumin:creatinine ratio, from which the risk of CKD progression was determined. RESULTS: Participants (n = 732, 41% female, 55 ± 13 years) were categorized into four groups: no/mild OSA without insomnia (NM-OSA, n = 203), insomnia with SD without OSA (Insomnia-SD, n = 104), moderate-to-severe OSA without insomnia (MS-OSA, n = 242), and comorbid insomnia and OSA with SD (COMISA-SD, n = 183). After stratification, 12.8% of NM-OSA, 15.4% of Insomnia-SD, 28.9% of MS-OSA, and 31.7% of the COMISA-SD participants had an increased risk of CKD progression. Compared to NM-OSA, the odds ratio (OR) for an increased risk of CKD progression was not increased in Insomnia-SD (OR 0.95, confidence interval [CI]: 0.45-1.99) and was increased to the same degree in MS-OSA (OR 2.79, CI: 1.60-4.85) and COMISA-SD (OR 3.04, CI: 1.69-5.47). However, the ORs were similar between the MS-OSA and COMISA-SD groups across all statistical models (p ≥ .883). CONCLUSIONS: In a sleep clinic population, insomnia with short sleep duration does not increase the risk of CKD progression; nor does it further increase the risk of CKD progression associated with moderate-to-severe OSA.

Risk of chronic kidney disease in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Chronic kidney disease (CKD) is a global health concern and a major risk factor for cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) may exacerbate this risk by contributing to the development of CKD. This study investigated the prevalence and patient awareness of the risk of CKD progression in individuals with OSA. METHODS: Adults referred to five Canadian academic sleep centers for suspected OSA completed a questionnaire, a home sleep apnea test or in-lab polysomnography and provided blood and urine samples for measurement of estimated glomerular filtration rate (eGFR) and the albumin:creatinine ratio (ACR), respectively. The risk of CKD progression was estimated from a heat map incorporating both eGFR and ACR. RESULTS: 1295 adults (42% female, 54 ± 13 years) were categorized based on the oxygen desaturation index (4% desaturation): <15 (no/mild OSA, n = 552), 15-30 (moderate OSA, n = 322), and >30 (severe OSA, n = 421). After stratification, 13.6% of the no/mild OSA group, 28.9% of the moderate OSA group, and 30.9% of the severe OSA group had a moderate-to-very high risk of CKD progression (p < .001), which was defined as an eGFR <60 mL/min/1.73 m2, an ACR ≥3 mg/mmol, or both. Compared to those with no/mild OSA, the odds ratio for moderate-to-very high risk of CKD progression was 2.63 (95% CI: 1.79-3.85) for moderate OSA and 2.96 (2.04-4.30) for severe OSA after adjustment for CKD risk factors. Among patients at increased risk of CKD progression, 73% were unaware they had abnormal kidney function. CONCLUSION: Patients with moderate and severe OSA have an increased risk of CKD progression independent of other CKD risk factors; most patients are unaware of this increased risk.

Sleep Quality and Nocturnal Symptoms in a Community-Based COPD Cohort.

Small studies have suggested that patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality. Our aim was to examine the prevalence of subjective sleep-related complaints and predictors of poor sleep quality in a large community-based COPD cohort. We analyzed cross-sectional data on sleep questionnaire responses from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, a population-based, prospective longitudinal cohort study across Canada. The cohort comprises a COPD group and two matched non-COPD (never-smokers and ever-smokers) groups. Sleep-related symptoms were assessed using questionnaires including Pittsburgh Sleep Quality Index (PSQI). A total score of PSQI > 5 is indicative of poor sleep quality. Health-related quality of life measures and the presence of mood disturbance were assessed using Short Form-36™ Health Survey (SF-36) multi-item questionnaires and Hospital Anxiety and Depression Scale (HADS), respectively. Predictors of poor sleep quality were analyzed using multivariable logistic regression analysis. Of the 1123 subjects, 263 were healthy controls, 323 at-risk controls, and 537 had COPD (297 had mild, 240 with moderate to severe disease). The mean PSQI score was not significantly different between groups. COPD patients with poor sleep quality had lower diffusion capacity, higher HADS anxiety and depression scores and lower SF-36 mental and physical component summary scores than COPD patients classified as good sleepers. The presence of restless legs and obstructive sleep apnea symptoms, waist circumference, predicted diffusion capacity and HADS anxiety and depression scores were identified as independent predictors of poor sleep quality.

Obstructive sleep apnea, CPAP therapy and Parkinson's disease motor function: A longitudinal study.

INTRODUCTION: We aimed to assess, in patients with Parkinson's disease (PD), the association between obstructive sleep apnea (OSA), progression of motor dysfunction and the effect of OSA treatment. METHODS: Data were analysed from a prospective cohort study of idiopathic PD patients from a movement disorders clinic. Patients found to have OSA on polysomnography (apnea-hypopnea index [AHI] ≥15 events/h, OSA+) were offered treatment using continuous positive airway pressure (CPAP). CPAP+ was defined as an average ≥ 2 h/night use at each follow-up. Motor symptoms were assessed using the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (mUPDRS) and the Timed-Up-And-Go (TUG). Follow-up times were 3, 6 and 12 months. Mixed models were constructed, adjusting for age, sex, body mass index, levodopa equivalent dose and comorbidities. RESULTS: We studied 67 individuals (61.2% male) of mean age 64.7 years (SD = 10.1). Baseline mUPDRS was higher in OSA+ compared to OSA- (24.5 [13.6] vs. 16.2 [7.2], p < 0.001). Motor dysfunction increased at comparable rates in OSA- and OSA+CPAP-. However, in OSA+CPAP+, mUPDRS change was significantly lower compared to OSA- (ß = -0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA+CPAP- [ß = 0.39]) and TUG change was lower compared to OSA+CPAP- (ß = -0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [ß = 0.02]). CONCLUSIONS: In this PD cohort, OSA was associated with higher baseline mUPDRS. In those with OSA, CPAP use was associated with stabilization of motor function (mUPDRS and TUG) over 12 months. These observations support further research to clarify the role of OSA in PD pathophysiology and motor dysfunction.

Impaired Sleep Quality in COPD Is Associated With Exacerbations: The CanCOLD Cohort Study.

BACKGROUND: COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations. METHODS: Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed. RESULTS: A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03). CONCLUSIONS: Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up.

Body Weight Status and Sleep Disturbances During Pregnancy: Does Adherence to Gestational Weight Gain Guidelines Matter?

BACKGROUND: To determine the effect of preconception body mass index (BMI) and/or gestational weight gain (GWG) on the occurrence of sleep disorders over the whole pregnancy. METHODS: A sample of 2,366 pregnant women, recruited in their 1st trimester (TM), was evaluated until delivery for their sleeping characteristics, using the Pittsburgh Sleep Quality Index (PSQI). Mixed or multinomial logistic modeling was applied, as appropriate. RESULTS: When compared with TM 1, PSQI score was the lowest at TM 2 (ß = -1.03; 95% CI: -1.17 to -0.89) and highest in TM 3 (ß = 0.27; 95% CI: 0.10-0.45). Obese (ß = 0.48; 95% CI: 0.17-0.78) and overweight women (ß = 0.24; 95% CI: 0.00-0.48) exhibited an overall greater PSQI than normal-weight women over the whole pregnancy. When sociodemographic factors were accounted for, the effect size was reduced by 25% among obese women (ß = 0.36; 95% CI: 0.06-0.68), but was no more not significant in overweight women (ß = 0.06; 95% CI: -0.17 to 0.30). Both obese and overweight women still exhibited, although at a lower extend, a greater PSQI than normal-weight women. Further adjustment for GWG had no effect on these observations. Obese women almost had a four-fold increased risk (OR = 3.89; 95% CI: 2.50-6.06) of being snorers in the three TMs. While GWG had only a minor effect (aOR = 3.83; 95% CI: 2.43-6.03), sociodemographic factors increased the odds of being habitual snorer (aOR = 4.04; 95% CI: 2.57-6.35). CONCLUSIONS: High prepregnancy BMI together with sociodemographic correlates appear as the most critical for sleep disturbances across pregnancy. GWG is of marginal importance, especially regarding snoring. These findings confirm the importance of considering the initial body weight status of women in tailoring sleep hygiene advises irrespective of the recommendations for weight gain during pregnancy. The results also underscore the need to providing as early as possible during a pregnancy, supportive tools to ethnic minorities, multiparous, and women from deprived socioeconomic neighborhoods.

Gestational diabetes mellitus and sleep-disordered breathing.

OBJECTIVE: To examine the link between gestational diabetes mellitus (GDM) and sleep-disordered breathing using complete polysomnography and questionnaires in a case-control study of pregnant women. METHODS: Pregnant women (body mass index [BMI] less than 35, no prior diabetes or hypertension) were eligible as cases (n=26) if diagnosed with GDM by routine 75-g oral glucose tolerance test. Women in the control group without GDM (n=26) were matched for gestational age at polysomnography, BMI, and age. Polysomnography were conducted at home at 24-32 weeks of gestation. Sleepiness score (Epworth Sleepiness Scale), subjective sleep quality (Pittsburgh Sleep Quality Index), risk for depression (Edinburgh Postnatal Depression Scale), and restless legs syndrome were assessed by questionnaire. RESULTS: Primary outcome apnea-hypopnea index (4.2±3.9 events per hour in women in the case group compared with 3.8±2.3 events per hour in women in the control group) as well as other objective and subjective sleep measures, including oxygen desaturation index, snoring, and flow limitation, were not significantly different between groups. Sleepiness was greater in women in the case group than in women in the control group (9.8±3.6 compared with 7.2±3.6, P=.05). Additionally, 23% of women in the case group compared with 0% of women in the control group (P<.01) reported an Edinburgh Scale score of at least 10 (suggesting significant depression) and 46% of women with GDM reported restless legs syndrome compared to 19% of women in the control group (P=.07). CONCLUSION: There was no association between GDM and sleep-disordered breathing in pregnant women with prepregnancy BMIs under 35 and no medical comorbidities.

Canadian Sleep Society/Canadian Thoracic Society position paper on the use of portable monitoring for the diagnosis of obstructive sleep apnea/hypopnea in adults.

The present position paper on the use of portable monitoring (PM) as a diagnostic tool for obstructive sleep apnea/hypopnea (OSAH) in adults was based on consensus and expert opinion regarding best practice standards from stakeholders across Canada. These recommendations were prepared to guide appropriate clinical use of this new technology and to ensure that quality assurance standards are adhered to. Clinical guidelines for the use of PM for the diagnosis and management of OSAH as an alternative to in-laboratory polysomnography published by the American Academy of Sleep Medicine Portable Monitoring Task Force were used to tailor our recommendations to address the following: indications; methodology including physician involvement, physician and technical staff qualifications, and follow-up requirements; technical considerations; quality assurance; and conflict of interest guidelines. When used appropriately under the supervision of a physician with training in sleep medicine, and in conjunction with a comprehensive sleep evaluation, PM may expedite treatment when there is a high clinical suspicion of OSAH.