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.

All Obstructive Sleep Apnea Events Are Not Created Equal: The Relationship between Event-related Hypoxemia and Physiologic Response.

Rationale: Obstructive sleep apnea (OSA) severity is typically assessed by the apnea-hypopnea index (AHI), a frequency-based metric that allocates equal weight to all respiratory events. However, more severe events may have a greater physiologic impact. Objectives: The purpose of this study was to determine whether the degree of event-related hypoxemia would be associated with the postevent physiologic response. Methods: Patients with OSA (AHI, ⩾5/h) from the multicenter Canadian Sleep and Circadian Network cohort were studied. Using mixed-effect linear regression, we examined associations between event-related hypoxic burden (HBev) assessed by the area under the event-related oxygen saturation recording with heart rate changes (ΔHRev), vasoconstriction (vasoconstriction burden [VCBev] assessed with photoplethysmography), and electroencephalographic responses (power ratio before and after events). Results: Polysomnographic recordings from 658 patients (median [interquartile range] age, 55.00 [45.00, 64.00] yr; AHI, 27.15 [14.90, 64.05] events/h; 42% female) were included in the analyses. HBev was associated with an increase in all physiologic responses after controlling for age, sex, body mass index, sleep stage, total sleep time, and study centers; for example, 1 standard deviation increase in HBev was associated with 0.21 [95% confidence interval, 0.2, 0.22], 0.08 [0.08, 0.09], and 0.22 [0.21, 0.23] standard deviation increases in ΔHRev, VCBev, and ß-power ratio, respectively. Conclusions: Increased event-related hypoxic burden was associated with greater responses across a broad range of physiologic signals. Future metrics that incorporate information about the variability of these physiologic responses may have promise in providing a more nuanced assessment of OSA severity.

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.

Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing.

STUDY OBJECTIVES: Although cognitive impairment in obstructive sleep apnea (OSA) is primarily attributed to intermittent hypoxemia and sleep fragmentation, hypercapnia may also play a role in patients whose OSA is complicated by hypoventilation. This study investigated the impact of hypercapnia on cognitive function in severe sleep-disordered breathing (OSA accompanied by hypoventilation). METHODS: Patients with severe OSA (apnea-hypopnea index >30 events/h; n = 246) underwent evaluation for accompanying hypoventilation with polysomnography that included continuous transcutaneous carbon dioxide (TcCO2) monitoring and awake arterial blood gas analysis. Patients were categorized as having no hypoventilation (n = 84), isolated sleep hypoventilation (n = 40), or awake hypoventilation (n = 122). Global cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), memory with the Rey Auditory Verbal Learning Test (RAVLT), and processing speed with the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV), Digit Symbol Coding subtest (DSC). RESULTS: Apnea-hypopnea index was similar across groups (P = .15), but the sleep and awake hypoventilation groups had greater nocturnal hypoxemia compared with the no-hypoventilation group (P < .01). Within all groups, mean MoCA scores were < 26, which is the validated threshold to indicate mild cognitive impairment; RAVLT scores were lower than age-matched norms only in the awake-hypoventilation group (P ≤ .01); and DSC scores were lower than age-matched norms within all groups (P < .01). In multivariable regression analyses, higher arterial partial pressure of carbon dioxide (PaCO2) and TcCO2 during wakefulness were associated with lower MoCA and DSC scores (P ≤ .03), independent of confounders including overlap syndrome (OSA + chronic obstructive pulmonary disease). CONCLUSIONS: Awake hypoventilation is associated with greater deficits in cognitive function in patients with severe sleep-disordered breathing. CITATION: Beaudin AE, Raneri JK, Ayas NT, Skomro RP, Smith EE, Hanly PJ; on behalf of Canadian Sleep and Circadian Network. Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing. J Clin Sleep Med. 2022;18(1):245-254.

Cognitive Function in a Sleep Clinic Cohort of Patients with Obstructive Sleep Apnea.

Rationale: Obstructive sleep apnea (OSA) is associated with an increased risk of mild cognitive impairment (MCI) within the general population. However, MCI risk in sleep-clinic populations of patients with OSA is poorly characterized.Objectives: To determine the prevalence of MCI in a sleep-clinic population of patients with OSA and which patients are at the greatest risk for this complication.Methods: Adults (n = 1,084) referred to three academic sleep centers for suspected OSA who had home sleep apnea testing or in-laboratory polysomnography were recruited. Patients completed sleep and medical history questionnaires, the Montreal Cognitive Assessment Test (MoCA) of global cognition, the Rey Auditory Verbal Learning Test of memory, and the Wechsler Adult Intelligence Scale-Fourth Edition Digit-Symbol Coding (DSC) subtest of information processing speed.Results: A MoCA score <26 (range 0-30) was operationally defined as MCI. MCI was present in 47.9% of our entire patient cohort, increasing to >55.3% in patients with moderate and severe OSA. Patients with a MoCA <26 were predominantly older males with more severe OSA, hypoxemia, and vascular comorbidities. Moderate and severe OSA were independently associated with >70% higher odds for MCI compared with patients with no OSA (P = 0.003). Memory and information processing speed was lower than age-matched normal values (P < 0.001), with lower MoCA and DSC scores associated with a higher oxygen desaturation index and nocturnal hypoxemia.Conclusions: Cognitive impairment is highly prevalent in patients referred to sleep clinics for suspected OSA, occurring predominantly in older males with moderate to severe OSA and concurrent vascular comorbidities. Moderate to severe OSA is an independent risk factor for MCI.

Symptom subtypes and cognitive function in a clinic-based OSA cohort: a multi-centre Canadian study.

BACKGROUND: Distinct symptom subtypes are found in patients with OSA. The association between these subtypes and neurocognitive function is unclear. OBJECTIVE: The purposes of this study were to assess whether OSA symptom subtypes are present in a cohort of Canadian patients with suspected OSA and evaluate the relationship between subtypes and neurocognitive function. METHODS: Patients with suspected OSA who completed a symptom questionnaire and underwent testing for OSA were included. Symptom subtypes were identified using latent class analysis. Associations between subtypes and neurocognitive outcomes (Montreal Cognitive Assessment [MoCA], Rey Auditory Verbal Learning Test [RAVLT], Wechsler Adult Intelligence Scale [WAIS-IV], Digit-Symbol Coding subtest [DSC]) were assessed using analysis of covariance (ANCOVA), controlling for relevant covariates. RESULTS: Four symptom subtypes were identified in patients with OSA (oxygen desaturation index ≥5 events/hour). Three were similar to prior studies, including the Excessively Sleepy (N=405), Disturbed Sleep (N=382) and Minimally Symptomatic (N=280), and one was a novel subtype in our sample defined as Excessively Sleepy with Disturbed Sleep (N=247). After covariate adjustment, statistically significant differences among subtypes (p=0.037) and among subtypes and patients without OSA (p=0.044) were observed in DSC scores; the Minimally Symptomatic subtype had evidence of higher DSC scores than all other groups, including non-OSA patients. No differences were seen in MoCA or RAVLT. CONCLUSIONS: Results support the existence of previously identified OSA symptom subtypes of excessively sleepy, disturbed sleep and minimally symptomatic in a clinical sample from Canada. Subtypes were not consistently associated with neurocognitive function across multiple instruments.

Residents' and attendings' perceptions of a night float system in an internal medicine program in Canada.

BACKGROUND: The Night Float system (NFS) is often used in residency training programs to meet work hour regulations. The purpose of this study was to examine resident and attendings' perceptions of the NFS on issues of resident learning, well-being, work, non-educational activities and the health care system (patient safety and quality of care, inter-professional teams, workload on attendings and costs of on-call coverage). METHODS: A survey questionnaire with closed and open-ended questions (26 residents and eight attendings in an Internal Medicine program), informal discussions with the program and moonlighting and financial data were collected. RESULTS AND DISCUSSION: The main findings included, (i) an overall congruency in opinions between resident and attendings across all mean comparisons, (ii) perceptions of improvement for most aspects of resident well-being (e.g. stress, fatigue) and work environment (e.g. supervision, support), (iii) a neutral effect on the resident learning environment, except resident opinions on an increase in opportunities for learning, (iv) perceptions of improved patient safety and quality of care despite worsened continuity of care, and (v) no increases in work-load on attendings or the health care system (cost-neutral call coverage). Patient safety, handovers and increased utilization of moonlighting opportunities need further exploration.

Sleep tight: exploring the relationship between sleep and attachment style across the life span.

Based on early life experiences in which developmental, genetic, and environmental components interact, humans learn to trust themselves and others and connect emotionally in consistent ways that are broadly defined as "attachment styles." These relatively stable patterns of interpersonal interaction are associated with either vulnerability to various health risks or resilience. Similarly, the mechanisms involved in sleep regulation undergo developmental changes that overlap temporally with attachment formation and remain sensitive to a series of biological, environmental and psychological influences. Interestingly, while sleep has been conceptualized as a fundamental attachment behavior given its dyadic context, few studies have explored its relationship with attachment style in various ages. We present the first systematic review of the published literature examining the relationship between attachment style and sleep in humans across the life span. While levels of evidence and methods of assessment vary significantly, the results suggest a possible life-long relationship between individual attachment style and sleep. These findings are particularly useful in understanding relatively ingrained psychological mechanisms that can affect and be affected by sleep. Clinical and research implications are discussed.

Improved Sleep Efficiency after Anti-Tumor Necrosis Factor α Therapy in Rheumatoid Arthritis Patients.

BACKGROUND: Poor sleep health is increasingly recognized as contributing to decreased quality of life, increased morbidity/mortality and heightened pain perception. Our purpose in this study was to observe the effect on sleep parameters, specifically sleep efficiency, in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor alpha (anti-TNF-α) therapy. METHODS: This was a prospective observational study of RA patients with hypersomnolence/poor sleep quality as defined by the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Study patients underwent overnight polysomnograms and completed questionnaire instruments assessing sleep prior to starting anti-TNF-α therapy and again after being established on therapy. The questionnaire included the ESS, PSQI, the Berlin instrument for assessment of obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS) diagnostic criteria, and measures of disease activity/impact. RESULTS: A total of 12 RA patients met inclusion criteria, of which 10 initiated anti-TNF-α therapy and underwent repeat polysomnograms and questionnaire studies approximately 2 months later. Polysomnographic criteria for OSA were met by 60% of patients. Following anti-TNF-α therapy initiation, significant improvements were observed by polysomnography (PSG) for sleep efficiency, increasing from 73.9% (SD 13.5) to 85.4% (SD 9.6) (p = 0.031), and 'awakening after sleep onset' time, decreasing from 84.1 minutes (SD 43.2) to 50.7 minutes (SD 36.5) (p = 0.048). Questionnaire instrument improvements were apparent in pain, fatigue, modified Health Assessment Questionnaire (mHAQ), and Rheumatoid Arthritis Disease Activity Index (RADAI) scores. CONCLUSIONS: Improved sleep efficiency and 'awakening after sleep onset' time were observed in RA patients treated with anti-TNF-α therapy.

Outcomes of home-based diagnosis and treatment of obstructive sleep apnea.

BACKGROUND: Home diagnosis and therapy for obstructive sleep apnea (OSA) may improve access to testing and continuous positive airway pressure (CPAP) treatment. We compared subjective sleepiness, sleep quality, quality of life, BP, and CPAP adherence after 4 weeks of CPAP therapy in subjects in whom OSA was diagnosed and treated at home and in those evaluated in the sleep laboratory. METHODS: A randomized trial was performed consisting of home-based level 3 testing followed by 1 week of auto-CPAP and fixed-pressure CPAP based on the 95% pressure derived from the auto-CPAP device, and in-laboratory polysomnography (PSG) (using mostly split-night protocol) with CPAP titration; 102 subjects were randomized (age, 47.4 +/- 11.4 years; 63 men; BMI, 32.3 +/- 6.3 kg/m(2); Epworth Sleepiness Scale [ESS]: 12.5 +/- 4.3). The outcome measures were daytime sleepiness (ESS), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), quality of life (Calgary Sleep Apnea Quality of Life Index [SAQLI], 36-Item Short-Form Health Survey [SF-36], BP, and CPAP adherence after 4 weeks. RESULTS: After 4 weeks of CPAP therapy, there were no significant differences in ESS (PSG 6.4 +/- 3.8 vs home monitoring [HM] 6.5 +/- 3.8, P = .71), PSQI (PSG 5.4 +/- 3.1 vs HM 6.2 +/- 3.4, P = .30), SAQLI (PSG 4.5 +/- 1.1 vs HM 4.6 +/- 1.1, P = .85), SF-36 vitality (PSG 62.2 +/- 23.3 vs HM 64.1 +/- 18.4, P = .79), SF-36 HM (PSG 84.0 +/- 10.4 vs HM 81.3 +/- 14.9, P = .39), and BP (PSG 129/84 +/- 11/0 vs HM 125/81 +/- 13/9, P = .121). There was no difference in CPAP adherence (PSG 5.6 +/- 1.7 h/night vs HM 5.4 +/- 1.0 h/night, P = .49). CONCLUSIONS: Compared with the home-based protocol, diagnosis and treatment of OSA in the sleep laboratory does not lead to superior 4-week outcomes in sleepiness scores, sleep quality, quality of life, BP, and CPAP adherence. TRIAL REGISTRATION: clinicaltrials.gov; Identifier: NCT00139022.

Sleep and neuromuscular disorders in children.

Children suffering from neuromuscular diseases are at an increased risk of sleep-related breathing disorders (SRBD) such as obstructive sleep apnea syndrome (OSAS) and hypoventilation as well as central sleep apnea, which is frequent in these patients due to diaphragmatic weakness. They are at higher risk for developing complications of nocturnal hypoxemia, including pulmonary hypertension, cor pulmonale and neurocognitive dysfunction. Neuromuscular disorders and OSAS are both prevalent disorders and frequently overlap. Sleep-related hypoventilation/hypoxemia due to neuromuscular diseases may be exacerbated in the presence of OSAS; these children are likely to experience greater severity and duration of sleep-related hypoxemia than are children with either disorder alone. Additionally, some of these children have reduced central neural chemoresponsiveness. The development of SRBD in these patients further impairs their quality of life and worsens their respiratory status. We review the literature on the diagnosis and treatment of SRBD in children with a variety of neuromuscular disorders.

An orientation session improves objective sleep quality and mask acceptance during positive airway pressure titration.

The aim of this study was to determine whether an orientation session led by a polysomnography (PSG) technician during the night of positive airway pressure (PAP) titration can improve objective sleep quality and acceptance of nasal mask in patients referred to a sleep laboratory. Consecutive patients (n = 1,481), referred for PAP titration during PSG, were retrospectively evaluated. Patients were distributed in two groups: the control group, patients referred for PAP titration (n = 699) who did not undertake an orientation session led by a PSG technician, and the oriented group, patients referred to PAP titration (n = 782) who followed the orientation session. Demographic data were similar (p > 0.05) between groups (control vs oriented) for: male/female proportion (76:24 vs 75:25%), age (mean +/- SD; 53 +/- 12 vs 52 +/- 12 years), Epworth Sleepiness Scale score (12 +/- 6 vs 12 +/- 6), and body mass index (31 +/- 6 vs 31 +/- 6 kg/m(2)). PSG data were different (p < 0.05) between the groups for: total sleep time (312 +/- 81 vs 326 +/- 85 min), sleep efficiency (74 +/- 17 vs 77 +/- 14%), sleep latency (22 +/- 24 vs 18 +/- 29 min), S1 (8 +/- 8 vs 6 +/- 5%), S3 4 (19 +/- 11 vs 21 +/- 13%), rapid eye movement sleep (17 +/- 9 vs 18 +/- 9%), and wake after sleep onset (106 +/- 68 vs 93 +/- 58 min). After the orientation session, the number of patients who did not accept nasal mask during PSG recording was higher in the control group than the oriented group (80 vs 44; p = 0.001). An orientation session led by a PSG technician can improve objective sleep quality and nasal mask acceptance during the night of PAP titration. Such an addition to PAP titration could be an efficient intervention to improve PAP compliance.

An empirical continuous positive airway pressure trial for suspected obstructive sleep apnea.

BACKGROUND: Standard practice in obstructive sleep apnea (OSA) management requires that a positive diagnostic, overnight polysomnography (PSG) test be obtained before initiating treatment. However, long waiting times due to lack of access to PSG testing facilities may delay the initiation of definitive treatment for OSA. OBJECTIVES: To evaluate the response of patients who had a high clinical suspicion for OSA and who were waiting for a PSG test to an empirical continuous positive airway pressure (CPAP) trial. METHODS: A retrospective study of all patients who had been offered empirical CPAP therapy for suspected OSA was conducted. After outpatient assessment, 183 patients with a high pretest probability of having OSA began empirical CPAP testing using an arbitrary CPAP pressure. The presence of OSA, the accuracy of empirical CPAP pressure prescription, the adherence to empirical CPAP and the improvement in daytime somnolence were evaluated at the time of PSG. RESULTS: Of 183 patients on a CPAP trial, 91% had OSA, which was at least moderate (more than 15 apneas and hypopneas per hour of sleep) in 75% of the patients. Eighty per cent of the patients had significant daytime somnolence (Epworth Sleepiness Scale [ESS] greater than 10, mean +/- SD ESS 14+/-5), which improved with CPAP (ESS 9.0+/-5, P<0.01). In 40% of the patients, the arbitrary CPAP pressure was lower than that determined by manual titration. Adherence to a trial of CPAP (longer than 2 h/night) predicted OSA with a sensitivity of 82% and a specificity of 41%; the positive and negative predictive values were 92% and 22%, respectively. CONCLUSIONS: At the time of PSG testing, OSA was present in 91% of the patients who had received empirical CPAP. An empirical CPAP provided satisfactory interim treatment for excessive somnolence, despite the fact that the CPAP pressure was suboptimal in 40% of the patients.