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.

Sleep Efficiency and Sleep Onset Latency in One Saskatchewan First Nation.

BACKGROUND: Sleep efficiency and sleep onset latency are two measures that can be used to assess sleep quality. Factors that are related to sleep quality include age, sex, sociodemographic factors, and physical and mental health status. This study examines factors related to sleep efficiency and sleep onset latency in one First Nation in Saskatchewan, Canada. METHODS: A baseline survey of the First Nations Sleep Health project was completed between 2018 and 2019 in collaboration with two Cree First Nations. One-night actigraphy evaluations were completed within one of the two First Nations. Objective actigraphy evaluations included sleep efficiency and sleep onset latency. A total of 167 individuals participated, and of these, 156 observations were available for analysis. Statistical analysis was conducted using logistic and linear regression models. RESULTS: More females (61%) than males participated in the actigraphy study, with the mean age being higher for females (39.6 years) than males (35.0 years). The mean sleep efficiency was 83.38%, and the mean sleep onset latency was 20.74 (SD = 27.25) minutes. Age, chronic pain, ever having high blood pressure, and smoking inside the house were associated with an increased risk of poor sleep efficiency in the multiple logistic regression model. Age, chronic pain, ever having anxiety, heart-related illness, and smoking inside the house were associated with longer sleep onset latency in the multiple linear regression model. CONCLUSIONS: Sleep efficiency and sleep onset latency were associated with physical and environmental factors in this First Nation.

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.

Identification of SARS-CoV-2 biomarkers in saliva by transcriptomic and proteomics analysis.

The detection of SARS-CoV-2 biomarkers by real time PCR (rRT-PCR) has shown that the sensitivity of the test is negatively affected by low viral loads and the severity of the disease. This limitation can be overcome by the use of more sensitive approaches such as mass spectrometry (MS), which has not been explored for the detection of SARS-CoV-2 proteins in saliva. Thus, this study aimed at assessing the translational applicability of mass spectrometry-based proteomics approaches to identify viral proteins in saliva from people diagnosed with COVID-19 within fourteen days after the initial diagnosis, and to compare its performance with rRT-PCR. After ethics approval, saliva samples were self-collected by 42 COVID-19 positive and 16 healthy individuals. Samples from people positive for COVID-19 were collected on average on the sixth day (± 4 days) after initial diagnosis. Viable viral particles in saliva were heat-inactivated followed by the extraction of total proteins and viral RNA. Proteins were digested and then subjected to tandem MS analysis (LC-QTOF-MS/MS) using a data-dependent MS/MS acquisition qualitative shotgun proteomics approach. The acquired spectra were queried against a combined SARS-CoV-2 and human database. The qualitative detection of SARS-CoV-2 specific RNA was done by rRT-PCR. SARS-CoV-2 proteins were identified in all COVID-19 samples (100%), while viral RNA was detected in only 24 out of 42 COVID-19 samples (57.1%). Seven out of 18 SARS-CoV-2 proteins were identified in saliva from COVID-19 positive individuals, from which the most frequent were replicase polyproteins 1ab (100%) and 1a (91.3%), and nucleocapsid (45.2%). Neither viral proteins nor RNA were detected in healthy individuals. Our mass spectrometry approach appears to be more sensitive than rRT-PCR for the detection of SARS-CoV-2 biomarkers in saliva collected from COVID-19 positive individuals up to 14 days after the initial diagnostic test. Based on the novel data presented here, our MS technology can be used as an effective diagnostic test of COVID-19 for initial diagnosis or follow-up of symptomatic cases, especially in patients with reduced viral load.

Sleep Architecture and Daytime Sleepiness in Patients with Erectile Dysfunction.

Obstructive sleep apnea is considered a risk factor for erectile dysfunction. The aim of this study was to determine sleep architecture and assess daytime sleepiness in patients with erectile dysfunction. The study group included 280 patients. The 107 enrolled patients had reported erectile dysfunction. The control group consisted of 173 patients who had no history of erectile dysfunction. The Epworth sleepiness scale (ESS) was used to measure the subjects' level of daytime sleepiness. All patients underwent a standardized overnight, single-night polysomnography in sleep laboratory. In the erectile dysfunction group, we observed increased ESS total score and N1 sleep phase duration. Mean and minimal oxygen saturation and mean oxygen desaturation were decreased in comparison to the control group. In summary, subjects with erectile dysfunction have altered sleep architecture, oxygen saturation parameters and increased daytime sleepiness.

Contribution of obstructive sleep apnea to disrupted sleep in a large clinical cohort of patients with suspected obstructive sleep apnea.

STUDY OBJECTIVES: The response of sleep depth to CPAP in patients with OSA is unpredictable. The odds-ratio-product (ORP) is a continuous index of sleep depth and wake propensity that distinguishes different sleep depths within sleep stages, and different levels of vigilance during stage wake. When expressed as fractions of time spent in different ORP deciles, nine distinctive patterns are found. Only three of these are associated with OSA. We sought to determine whether sleep depth improves on CPAP exclusively in patients with these three ORP patterns. METHODS: ORP was measured during the diagnostic and therapeutic components of 576 split-night polysomnographic (PSG) studies. ORP architecture in the diagnostic section was classified into one of the nine possible ORP patterns and the changes in sleep architecture were determined on CPAP for each of these patterns. ORP architecture was similarly determined in the first half of 760 full-night diagnostic PSG studies and the changes in the second half were measured to control for differences in sleep architecture between the early and late portions of sleep time in the absence of CPAP. RESULTS: Frequency of the three ORP patterns increased progressively with the apnea-hypopnea index. Sleep depth improved significantly on CPAP only in the three ORP patterns associated with OSA. Changes in CPAP in the other six patterns, or in full diagnostic PSG studies, were insignificant or paradoxical. CONCLUSIONS: ORP architecture types can identify patients in whom OSA adversely affects sleep and whose sleep is expected to improve on CPAP therapy.

STOP-Bang Score and Prediction of Severity of Obstructive Sleep Apnea in a First Nation Community in Saskatchewan, Canada.

The STOP-Bang questionnaire is an easy-to-administer scoring model to screen and identify patients at high risk of obstructive sleep apnea (OSA). However, its diagnostic utility has never been tested with First Nation peoples. The objective was to determine the predictive parameters and the utility of the STOP-Bang questionnaire as an OSA screening tool in a First Nation community in Saskatchewan. The baseline survey of the First Nations Sleep Health Project (FNSHP) was completed between 2018 and 2019. Of the available 233 sleep apnea tests, 215 participants completed the STOP-Bang score questionnaire. A proportional odds ordinal logistic regression analysis was conducted using the total score of the STOP-Bang as the independent variable with equal weight given to each response. Predicted probabilities for each score at cut-off points of the Apnea Hypopnea Index (AHI) were calculated and plotted. To assess the performance of the STOP-Bang questionnaire, sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and area under the curve (AUC) were calculated. These data suggest that a STOP-Bang score ≥ 5 will allow healthcare professionals to identify individuals with an increased probability of moderate-to-severe OSA, with high specificity (93.7%) and NPV (91.8%). For the STOP-Bang score cut-off ≥ 3, the sensitivity was 53.1% for all OSA and 72.0% for moderate-to-severe OSA. For the STOP-Bang score cut-off ≥ 3, the specificity was 68.4% for all OSA and 62.6% for moderate-to-severe OSA. The STOP-Bang score was modestly superior to the symptom of loud snoring, or loud snoring plus obesity in this population. Analysis by sex suggested that a STOP-Bang score ≥ 5 was able to identify individuals with increased probability of moderate-to-severe OSA, for males with acceptable diagnostic test accuracy for detecting participants with OSA, but there was no diagnostic test accuracy for females.

The effect of continuous positive airway pressure and mandibular advancement device on sleep bruxism intensity in obstructive sleep apnea patients.

We aimed to evaluate and compare the effects of continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) in reducing the intensity of sleep bruxism (SB) in patients with obstructive sleep apnea (OSA). Forty-eight adults with OSA were subjected to single-night full polysomnography (PSG) in the Sleep Laboratory of the Wroclaw Medical University. The respiratory events and bruxism episodes were scored according to the standards of the American Academy of Sleep Medicine. The patients were assigned to the CPAP treatment or the MAD treatment in accordance to apnea-hypopnea index (AHI). The second PSG examination was conducted during the MAD or CPAP treatment to assess the effect of treatment on bruxism episode index (BEI) and AHI. The mean AHI and mean BEI in the study material were estimated to be 30.05 ± 15.39 and 5.10 ± 5.31, respectively. The bruxism parameters were significantly decreased in both the CPAP and MAD groups. Compared to the MAD, the CPAP treatment was more effective in reducing AHI; however, there was no significant difference in effectiveness of CPAP and MAD treatment in BEI reduction. Both CPAP and MAD treatments were effective against SB coexisting with OSA. Due to the application of these treatment options, the risk of OSA should be estimated in patients with SB.

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.

Obesity, Sex, Snoring and Severity of OSA in a First Nation Community in Saskatchewan, Canada.

Sleep disorders have been related to body weight, social conditions, and a number of comorbidities. These include high blood pressure and type 2 diabetes, both of which are prevalent in the First Nations communities. We explored relationships between obstructive sleep apnea (OSA) and risk factors including social, environmental, and individual circumstances. An interviewer-administered survey was conducted with adult participants in 2018−2019 in a First Nations community in Saskatchewan, Canada. The survey collected information on demographic variables, individual and contextual determinants of sleep health, and objective clinical measurements. The presence of OSA was defined as an apnea−hypopnea index (AHI) ≥5. Multiple ordinal logistic regression analysis was conducted to examine relationships between the severity of OSA and potential risk factors. In addition to the survey, 233 men and women participated in a Level 3 one-night home sleep test. Of those, 105 (45.1%) participants were reported to have obstructive sleep apnea (AHI ≥ 5). Mild and moderately severe OSA (AHI ≥ 5 to <30) was present in 39.9% and severe OSA (AHI ≥ 30) was identified in 5.2% of participants. Being male, being obese, and snoring loudly were significantly associated with severity of OSA. The severity of OSA in one First Nation appears relatively common and may be related to mainly individual factors such as loud snoring, obesity, and sex.

Top 10 research priorities for people with obstructive sleep apnoea, families and clinicians: James Lind Alliance Priority Setting Partnership.

Obstructive sleep apnoea (OSA) is associated with significant comorbidity, preventable accidents and reduced quality of life. Little is known about the research priorities of patients with OSA, family members and clinicians. A James Lind Alliance research priority setting partnership was conducted. An initial survey (690 respondents who generated 1110 questions), a prioritisation survey (250 respondents), and a final workshop were used to identify the top 10 research priorities. Consensus was achieved on the top-ranked research priorities. Our results will inform the efforts of funders, researchers and policy-makers to align directly with stakeholder priorities related to OSA.

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.

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.

Duration and quality of sleep in 2 rural Cree First Nation communities in Saskatchewan, Canada.

STUDY OBJECTIVES: Estimates of sleep duration and quality are lacking for Canadian First Nations peoples. This study examines the prevalence of and risk factors for short/normal/long sleep duration and sleep quality. METHODS: Five hundred eighty-eight adults participated in the baseline survey of the First Nations Sleep Health Project conducted in 2018-2019 in Saskatchewan, Canada. Sleep duration and quality were self-reported. RESULTS: Mean sleep duration was 8.18 hours per night. About 45.5% slept the recommended 7 hours per night. However, short sleep duration and poor sleep quality were relatively common: about one-quarter of the participants slept fewer hours than recommended. Sleep duration was significantly less for men than women. Women were significantly more likely to report poor sleep quality than males. Multiple regression models revealed that age was significantly related with shorter sleep duration; sex and employment status were significantly related with sleep duration; and sex and income indicators were significantly associated with sleep quality. Nearly half of participants reported having had the recommended hours of sleep, but nearly two-thirds reported poor sleep quality. CONCLUSIONS: Information about the proportion of First Nations adults who sleep the recommended duration and the quality of sleep is important in informing health care and health policy.

Seasonal Changes in Sleep Patterns in Two Saskatchewan First Nation Communities.

Sleep is crucial for maintaining the recovery and restoration of the body and brain. Less sleep is associated with poor mental and physical performance. Seasonal changes in sleep patterns can be observed. This paper examines seasonal effects on sleep timing, duration, and problems in two Cree First Nation communities in Saskatchewan, Canada. Data were available from a community survey of 588 adults aged 18 years and older (range: 18-78 years) with 44.2% males and 55.8% females. Results are presented using descriptive statistics and a binary logistic-regression model to identify the association between seasonal changes in sleep patterns, and demographic, social, and environmental factors. The participants reported sleeping the least during the spring and summer months and sleeping the most during the fall and winter months. This was further confirmed by sleep hours and the lower proportion of recommended hours of sleep during the spring and summer, and a higher proportion of longer sleep duration during the fall and winter months. There was no significant variation in sleeping onset and wake-up times by season. Overall, there were no significant differences in the prevalence of sleep deprivation, insomnia, and excessive daytime sleepiness by season. When stratified by age group and sex, some differences existed in the prevalence of sleep problems by season. More than two-thirds (68.6%) of the participants reported that there was a change in sleep patterns across seasons, and about 26.0% reported a very or extremely marked change in sleep patterns across seasons. Changes in sleep patterns by season were related to money left at the end of the month and damage caused by dampness in the house.

Sleep deprivation in two Saskatchewan First Nation communities: a public health consideration.

OBJECTIVES: Sleep deprivation is a common problem in Canada and is associated with many health problems. More than a quarter of Canadians get fewer than the recommended sleep hours (<7 h). This paper examines the prevalence and risk factors for sleep deprivation in two First Nation communities in Saskatchewan, Canada. METHODS: The baseline cross-sectional survey was completed between 2018 and 2019 in collaboration with the two Cree First Nation communities in Saskatchewan, Canada. There were five hundred and eighty-eight participants participated in the survey from two communities. A Multivariate logistic regression model was used for analysis. RESULTS: The prevalence of sleep deprivation (<7 h of sleep) was 25.4%. The multivariate logistics regression revealed that middle and older age groups, visible mold in the house, and being male with nighttime insomnia symptoms were significantly associated with a higher risk of sleep deprivation among study participants in the study. CONCLUSIONS: In these two First Nation communities, a higher proportion of the participants reported having sleep deprivation. This was a unique study, which evolved from ongoing research collaboration with two First Nation communities in Saskatchewan, Canada. Findings will be helpful in the management of patients with sleep deprivation in these communities; as well as for co-creating policy with the communities and future research priorities.

Prevalence of Insomnia in Two Saskatchewan First Nation Communities.

Insomnia is a common problem in Canada and has been associated with increased use of health care services and economic burden. This paper examines the prevalence and risk factors for insomnia in two Cree First Nation communities in Saskatchewan, Canada. Five hundred and eighty-eight adults participated in a baseline survey conducted as part of the First Nations Sleep Health Collaborative Project. The prevalence of insomnia was 19.2% among participants with an Insomnia Severity Index score of ≥15. Following the definition of nighttime insomnia symptoms, however, the prevalence of insomnia was much higher, at 32.6%. Multivariate logistic regression modeling revealed that age, physical health, depression diagnosis, chronic pain, prescription medication use for any health condition, and waking up during the night due to terrifying dreams, nightmares, or flashbacks related to traumatic events were risk factors for insomnia among participants from two Saskatchewan Cree First Nation communities.