Obstructive sleep apnea and cognitive functioning in the older general population: The moderating effect of age, sex, ApoE4, and obesity.

Research on the relationship between obstructive sleep apnea and cognitive functioning has yielded conflicting results, particularly in the older population, and moderators of this association have rarely been studied. Here we investigated the cross-sectional association between obstructive sleep apnea and cognitive functioning as well as the moderating effect of age, sex, apolipoprotein E4, and obesity on this association among community-dwelling older people. We analysed data from 496 participants (71.4 ± 4.4 years; 45.6% men) of the HypnoLaus study who underwent polysomnography and a battery of neuropsychological tests. The sample was categorised as no-to-mild obstructive sleep apnea (apnea-hypopnea index 0-14.9/h; reference), moderate obstructive sleep apnea (apnea-hypopnea index 15.0-29.9/h), or severe obstructive sleep apnea (apnea-hypopnea index ≥30/h). Regression and moderation analyses were performed with adjustment for confounders. Apolipoprotein E4 and obesity moderated the association between severe obstructive sleep apnea and processing speed, whereas no moderating effects were found for age and sex. In apolipoprotein E4 carriers only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.13, p = 0.024). In obese participants only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.02, p = 0.025) and Stroop condition 2 (B = 3.30, p = 0.034). Severe obstructive sleep apnea was also associated with lower executive function in the whole sample according to Stroop condition 3 (B = 3.44, p = 0.020) and Stroop interference score (B = 0.24, p = 0.006). Our findings support associations of severe obstructive sleep apnea (but not moderate obstructive sleep apnea) with lower performance in processing speed and executive function in the older general population. Apolipoprotein E4 and obesity appear to be vulnerability factors that strengthen the association between severe obstructive sleep apnea and lower performance in processing speed.

Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea.

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus (N = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) (N = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or <15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P = 0.031; and 2.35 [1.12-4.93], P = 0.024) and in the PLSC (1.36 [1.13-1.63], P = 0.001; and 1.44 [1.06-1.94], P = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P = 0.031; and HR, 0.91 [0.86-0.96], P < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

Obstructive sleep apnoea and 5-year cognitive decline in the elderly.

BACKGROUND: The relationship between obstructive sleep apnoea (OSA) and cognitive decline remains controversial, especially in the elderly population. We used data from the HypnoLaus study to assess associations between OSA and longitudinal cognitive changes in a sample of community-dwelling elderly individuals. METHODS: We studied associations between polysomnographic OSA parameters (of breathing/hypoxaemia and sleep fragmentation) and cognitive changes over a 5-year period, after adjustment for potential confounders. The primary outcome was the annual change in cognitive scores. The moderating effects of age, sex and apolipoprotein E4 (ApoE4) status were also examined. RESULTS: 358 elderly individuals without dementia were included (mean±sd age 71.0±4.2 years; 42.5% males). A lower mean peripheral oxygen saturation (S pO2 ) during sleep was associated with a steeper decline in Mini-Mental State Examination (B= -0.12, p=0.004), Stroop test condition 1 (B=0.53, p=0.002) and Free and Cued Selective Reminding Test delayed free recall (B= -0.05, p=0.008). A longer time spent asleep with S pO2 <90% was associated with a steeper decline in Stroop test condition 1 (B=0.47, p=0.006). Moderation analysis showed that apnoea-hypopnoea index and oxygen desaturation index were associated with a steeper decline in global cognitive function, processing speed and executive function only in older participants, men and ApoE4 carriers. CONCLUSIONS: Our results provide evidence of the contribution of OSA and nocturnal hypoxaemia to cognitive decline in the elderly population.

Prenatal stress induces changes in PAR2- and M3-dependent regulation of colon primitive cells.

Prenatal stress is associated with a high risk of developing adult intestinal pathologies, such as irritable bowel syndrome, chronic inflammation, and cancer. Although epithelial stem cells and progenitors have been implicated in intestinal pathophysiology, how prenatal stress could impact their functions is still unknown. We have investigated the proliferative and differentiation capacities of primitive cells using epithelial crypts isolated from colons of adult male and female mice whose mothers have been stressed during late gestation. Our results show that stem cell/progenitor proliferation and differentiation in vitro are negatively impacted by prenatal stress in male progeny. This is promoted by a reinforcement of the negative proliferative/differentiation control by the protease-activated receptor 2 (PAR2) and the muscarinic receptor 3 (M3), two G protein-coupled receptors present in the crypt. Conversely, prenatal stress does not change in vitro proliferation of colon primitive cells in female progeny. Importantly, this maintenance is associated with a functional switch in the M3 negative control of colonoid growth, becoming proliferative after prenatal stress. In addition, the proliferative role of PAR2 specific to females is maintained under prenatal stress, even though PAR2-targeted stress signals Dusp6 and activated GSK3ß are increased, reaching the levels of males. An epithelial serine protease could play a critical role in the activation of the survival kinase GSK3ß in colonoids from prenatally stressed female progeny. Altogether, our results show that following prenatal stress, colon primitive cells cope with stress through sexually dimorphic mechanisms that could pave the way to dysregulated crypt regeneration and intestinal pathologies.NEW & NOTEWORTHY Primitive cells isolated from mouse colon following prenatal stress and exposed to additional stress conditions such as in vitro culture, present sexually dimorphic mechanisms based on PAR2- and M3-dependent regulation of proliferation and differentiation. Whereas prenatal stress reinforces the physiological negative control exerted by PAR2 and M3 in crypts from males, in females, it induces a switch in M3- and PAR2-dependent regulation leading to a resistant and proliferative phenotype of progenitor.

Abnormal brain iron accumulation in obstructive sleep apnea: A quantitative MRI study in the HypnoLaus cohort.

Obstructive sleep apnea syndrome (OSA) may be a risk factor for Alzheimer's disease. One of the hallmarks of Alzheimer's disease is disturbed iron homeostasis leading to abnormal iron deposition in brain tissue. To date, there is no empirical evidence to support the hypothesis of altered brain iron homeostasis in patients with obstructive sleep apnea as well. Data were analysed from 773 participants in the HypnoLaus study (mean age 55.9 ± 10.3 years) who underwent polysomnography and brain MRI. Cross-sectional associations were tested between OSA parameters and the MRI effective transverse relaxation rate (R2*) - indicative of iron content - in 68 grey matter regions, after adjustment for confounders. The group with severe OSA (apnea-hypopnea index ≥30/h) had higher iron levels in the left superior frontal gyrus (F3,760  = 4.79, p = 0.003), left orbital gyri (F3,760  = 5.13, p = 0.002), right and left middle temporal gyrus (F3,760  = 4.41, p = 0.004 and F3,760  = 13.08, p < 0.001, respectively), left angular gyrus (F3,760  = 6.29, p = 0.001), left supramarginal gyrus (F3,760  = 4.98, p = 0.003), and right cuneus (F3,760  = 7.09, p < 0.001). The parameters of nocturnal hypoxaemia were all consistently associated with higher iron levels. Measures of sleep fragmentation had less consistent associations with iron content. This study provides the first evidence of increased brain iron levels in obstructive sleep apnea. The observed iron changes could reflect underlying neuropathological processes that appear to be driven primarily by hypoxaemic mechanisms.

The effect of tongue elevation muscle training in patients with obstructive sleep apnea: A randomised controlled trial.

BACKGROUND: Oropharyngeal myofunctional therapy is a multi-component therapy effective to reduce the severity of obstructive sleep apnoea (OSA). However, existing protocols are difficult to replicate in the clinical setting. There is a need to isolate the specific effectiveness of each component of the therapy. OBJECTIVE: To assess the effects of a 6 weeks tongue elevation training programme in patients with OSA. METHODS: We conducted a multicentre randomised controlled trial. Eligible participants were adults diagnosed with moderate OSA who presented low adherence to continuous positive airway pressure therapy (mean use <4 h per night). The intervention group completed a 6 weeks tongue elevation training protocol that consisted in anterior tongue elevation strength and endurance tasks with the Iowa Oral Performance Instrument. The control group completed a 6 weeks sham training protocol that involved expiratory muscle training at very low intensity. Polygraphy data, tongue force and endurance, and OSA symptoms were evaluated pre- and post-intervention. The primary outcome was apneoa-hypopnea index (AHI). RESULTS: Twenty-seven patients (55 ± 11 years) were recruited. According to modified intention-to-treat analysis (n = 25), changes in AHI and c did not significantly differ between groups. Daytime sleepiness (Epworth Sleepiness Scale) and tongue endurance significantly improved in the intervention group compared to the control group (p = .015 and .022, respectively). In the intervention group, 75% of participants had a decrease in daytime sleepiness that exceeded the minimal clinically important difference. CONCLUSION: Six weeks of tongue elevation muscle training had no effect on OSA severity.

Risk factors of excessive daytime sleepiness in a prospective population-based cohort.

Although excessive daytime sleepiness is commonly evaluated in clinical and research settings using the Epworth Sleepiness Scale, few studies have assessed the factors associated with its incidence in the general population. We prospectively investigated the predictors of incident and persistent excessive daytime sleepiness in 2,751 subjects (46.1% men, mean age 56.0 ± 9.8 years) from the CoLaus-PsyCoLaus population-based cohort (Lausanne, Switzerland) over 5 years. Participants completed the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index, and underwent a full clinical evaluation at baseline and 5 years afterwards. Ambulatory polysomnography was performed at baseline in a sub-sample of 1,404 subjects. Among the 2,438 subjects without excessive daytime sleepiness (Epworth Sleepiness Scale ≤ 10) at baseline, the 5-year incidence of excessive daytime sleepiness was 5.1% (n = 124). Multivariate logistic regression revealed that male sex, depressive symptoms, reported poor sleep quality and moderate to severe obstructive sleep apnea were independent predictors of incident excessive daytime sleepiness, while older age, moderate coffee consumption, periodic leg movement during sleep and hypertension were independent protective factors. Stratified analysis according to sex and age showed some distinctive associations. Among the 313 patients with excessive daytime sleepiness at baseline, 137 (43.8%) had persistent excessive daytime sleepiness 5 years later. Our findings provide new insights into the predictors of incident excessive daytime sleepiness, but interventional studies are needed to understand the impact of treating these risk factors on the incidence of excessive daytime sleepiness.

Longer-term effects of supervised physical activity on obstructive sleep apnea and subsequent health consequences.

Although recent trials have shown promising benefits of exercise on obstructive sleep apnea (OSA) severity, the long-term effect of these interventions remains unknown. The aim of this study was to assess the effect of a 9-month community physical activity program on OSA severity one year later in free-living conditions. OSA patients, previously included in a 9-month randomized controlled trial (EXESAS study) evaluating the effects of supervised community physical activity on OSA severity, were invited to participate in an extra one-year observational study. Twenty-eight patients completed the study. Although OSA severity did not significantly worsen over the real-life period (9 to 21 months of follow-up), reductions in apnea-hypopnea index (AHI) and oxygen desaturation index were no longer significant after 21 months of follow-up compared to baseline (baseline AHI: 22.2 ± 6.3 /h; 9 months: 16.3 ± 6.4 /h; 21 months: 18.7 ± 8.9 /h). Benefits observed at 9 months on daytime sleepiness and mental health were preserved at 21 months, whereas cardiorespiratory fitness slightly decreased. Per-protocol analysis revealed that patients who stopped exercise at 9 months had worsened OSA severity compared to those who continued exercise during the real-life period (AHI: +9.0 ± 8.8 vs. -1.3 ± 5.3 /h; p < .01). In conclusion, our study suggested that improvements in OSA severity remain transient and is dependent on long-term adherence to regular physical activity practice.

Effect of exercise training on heart rate variability in patients with obstructive sleep apnea: A randomized controlled trial.

While obstructive sleep apnea (OSA) increases chemoreflex, leading to an autonomic dysfunction in the long term, no studies have yet assessed the potential benefit of exercise on cardiac autonomic activity in these patients. The aim of this study was to evaluate potential improvement in cardiac autonomic function (CAF) measured through heart rate variability (HRV) after a 9-month physical activity program in patients with OSA. Seventy-four patients with moderate OSA, aged 40-80 years, were randomly assigned to an exercise group (n = 36, 3 × 1 h/wk) or a control group (n = 38) during 9 months. Linear and nonlinear HRV parameters were measured during night using a Holter ECG. After 9 months, mean R-R intervals increased in the exercise group without any changes in HRV parameters, while controls decreased global (standard deviation of normal-to-normal intervals, total power) and parasympathetic (root mean square successive difference of N-Ns, very low frequency, high frequency, and standard deviation of the instantaneous beat-to-beat variability) indices of HRV (P < 0.05 for all). Significant correlations with moderate effect size were found between changes in apnea severity and changes in R-R intervals (P < 0.05). Improvement in moderate-to-vigorous physical activity was also correlated to improvement in nocturnal oxygen parameters (P < 0.05). In conclusion, supervised community physical activity may prevent a decline in nighttime CAF observed in nontreated community-dwelling patients with moderate OSA over a 9-month period. Thus, beyond apnea-hypopnea index improvement, exercise may be cardioprotective in OSA patients through bradycardia, CAF preservation, and VO2peak increase.

Sleep disturbances and incident risk of major depressive disorder in a population-based cohort.

Sleep disturbances are well-known symptoms of major depressive disorder (MDD). However, the prospective risk of MDD in the presence of sleep disturbances in a general population-based cohort is not well known. This study investigated associations between both polysomnography (PSG)-based or subjective sleep features and incident MDD. Participants representative of the general population who had never had MDD completed sleep questionnaires (n = 2000) and/or underwent PSG (n = 717). Over 8 years' follow-up, participants completed psychiatric interviews enabling the diagnosis of MDD. Survival Cox models were used to analyze associations between sleep features and MDD incidence. A higher Epworth Sleepiness Scale and presence of insomnia symptoms were significantly associated with a higher incidence of MDD (hazard ratio [HR] [95 % confidence interval (CI)]: 1.062 [1.022-1.103], p = 0.002 and 1.437 [1.064-1.940], p = 0.018, respectively). Higher density of rapid eye movements in rapid eye movement (REM) sleep was associated with a higher incidence of MDD in men (HR 1.270 [95 % CI 1.064-1.516], p = 0.008). In women, higher delta power spectral density was associated with a lower MDD incidence (HR 0.674 [95 % CI 0.463-0.981], p = 0.039). This study confirmed the associations between subjective and objective sleep features and the incidence of MDD in a large community dwelling cohort.

A human anti-matriptase-2 antibody limits iron overload, α-globin aggregates, and splenomegaly in ß-thalassemic mice.

ABSTRACT: Iron plays a major role in the deterioration of ß-thalassemia. Indeed, the high levels of transferrin saturation and iron delivered to erythroid progenitors are associated with production of α-globin precipitates that negatively affect erythropoiesis. Matriptase-2/TMPRSS6, a membrane-bound serine protease expressed in hepatocytes, negatively modulates hepcidin production and thus is a key target to prevent iron overload in ß-thalassemia. To address safety concerns raised by the suppression of Tmprss6 by antisense oligonucleotides or small interfering RNA, we tested a fully human anti-matriptase-2 antibody, RLYB331, which blocks the protease activity of matriptase-2. When administered weekly to Hbbth3/+ mice, RLYB331 induced hepcidin expression, reduced iron loading, prevented the formation of toxic α-chain/heme aggregates, reduced ros oxygen species formation, and improved reticulocytosis and splenomegaly. To increase the effectiveness of RLYB331 in ß-thalassemia treatment even further, we administered RLYB331 in combination with RAP-536L, a ligand-trapping protein that contains the extracellular domain of activin receptor type IIB and alleviates anemia by promoting differentiation of late-stage erythroid precursors. RAP-536L alone did not prevent iron overload but significantly reduced apoptosis in the erythroid populations of the bone marrow, normalized red blood cell counts, and improved hemoglobin and hematocrit levels. Interestingly, the association of RLYB331 with RAP-536L entirely reversed the ß-thalassemia phenotype in Hbbth3/+ mice and simultaneously corrected iron overload, ineffective erythropoiesis, splenomegaly, and hematological parameters, suggesting that a multifunctional molecule consisting of the fusion of RLYB331 with luspatercept (human version of RAP-536L) would allow administration of a single medication addressing simultaneously the different pathophysiological aspects of ß-thalassemia.

Periodic leg movements during sleep and cognitive functioning in the older general population.

OBJECTIVE: The current evidence of a relationship between periodic leg movements during sleep (PLMS) and cognitive functioning is limited and inconsistent. This cross-sectional study assessed associations between PLMS and cognitive functioning among community-dwelling older adults. METHODS: We included community-dwelling older adults who underwent a polysomnography and a cognitive assessment. The PLMS index (PLMI) and PLMS arousal index (PLMAI) were categorized into tertiles: PLMI <5/h (reference), 5-29.9/h, ≥30/h; and PLMAI <1/h (reference), 1-4.9/h, ≥5/h. The cognitive assessment consisted of ten scores covering the main cognitive domains: global cognition, processing speed, executive function, language, episodic verbal memory, and visuospatial function. Associations between PLMI, PLMAI, and cognitive scores were assessed using regression unadjusted and adjusted models. RESULTS: A total of 579 individuals without dementia were included (mean age: 71.5 ± 4.4 years; men 45.4%). The number of participants in the high-PLMI categories, 5-29.9/h and ≥30/h, was 185 (32.0%) and 171 (29.5%), respectively. Participants in the high-PLMI categories showed no significant difference compared to the reference group regarding their cognitive performance according to the unadjusted and adjusted models. Similarly, we found no association between PLMAI severity and cognitive functioning. CONCLUSIONS: This study shows no cross-sectional association between PLMS severity and cognitive functioning among community-dwelling older adults. However, given the paucity of data in this field, further studies are needed to clarify the relationship between PLMS and cognitive functioning.

Relationship between moderate-to-vigorous, light intensity physical activity and sedentary behavior in a prospective cohort of older French adults: a 18-year follow-up of mortality and cardiovascular events ─ the PROOF cohort study.

Background: It is well documented that moderate-to-vigorous intensity physical activity (MVPA) is effective in the prevention of major chronic diseases. Even though the current international physical activity (PA) guidelines still mainly focus on MVPA, the topic of the most recent epidemiological studies has shifted from MVPA to light intensity physical activity (LPA), owing to the necessity of promoting all activities vs. sedentary behavior (SB). However, the evidence remains currently limited. Thus, the clarification of the effects of LPA and the close relationship with SB is crucial to promote public health. Method: PA and SB were assessed by a validated self-administered questionnaire (POPAQ) investigating 5 different types of PA during the 7 previous days. PA was measured in metabolic equivalent of task (MET)-h, which refers to the amount of energy (calories) expended per hour of PA. SB was measured in hour/day. Medical histories and examinations were taken during each clinical visit to determine clinical events. All-cause mortality was established using the same procedure and by checking local death registries. The relationships between the intensity of PA (light, moderate to vigorous) and mortality and between the periods of SB and mortality or CV events were analyzed by splines and COX models, adjusted for sex and year of birth. Results: From the 1011 65-year-old subjects initially included in 2001 (60% women), the last 18-year follow-up has been currently completed since 2019. A total of 197 deaths (19.2%, including 77 CV deaths) and 195 CV events (19.3%) were reported. Averages (standard deviation) of MVPA, LPA and SB were, respectively, 1.2 h/d (0.3), 5.8 h/d (1.1), and 6.6 h/d (2.3). For all-cause deaths, as well as CV deaths, the splines were significant for LPA (p = 0.04 and p = 0.01), and MVPA (p < 0.001 and p < 0.001), but not for SB (p = 0.24 and p = 0.90). There was a significant reduction in CV events when SB was decreasing from 10.9 to 3.3 h/d. Conclusion: The PROOF cohort study shows a clear dose-response between the dose of LPA, MVPA, SB and risk of mortality. These findings provide additional evidence to support the inclusion of LPA in future PA guidelines.

Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial.

STUDY OBJECTIVES: Although recent investigations combining noradrenergic and antimuscarinic drugs have shown promising short-term results to treat obstructive sleep apnea (OSA), the mid-term effect and optimal dosage remain uncertain. The present study aimed to evaluate the effect of 1 week of 5 mg oxybutynin and 6 mg reboxetine (oxy-reb) on OSA versus placebo. METHODS: We performed a randomized, placebo-controlled, double-blind, crossover trial comparing the effect of 1 week of oxy-reb versus 1 week of placebo on OSA severity. At-home polysomnography was performed at baseline and after each week of intervention. RESULTS: Fifteen participants (male 66.7%) aged 59 [44-62] years (median [interquartile range]) with a mean body mass index of 33.1 ± 6.6 kg/m2 were included. No significant difference in apnea-hypopnea index (AHI) was observed between conditions (estimated marginal means [95% confidence interval] at baseline: 39.7 [28.5-55.3]; oxy-reb: 34.5 [22.7-52.3]; placebo: 37.9 [27.1-52.9]; p = 0.652), but oxy-reb improved average oxygen desaturation (p = 0.016) and hypoxic burden (p = 0.011) and lowered sleep efficiency (p = 0.019) and rapid eye movement sleep (p = 0.002). Moreover, participants reported reduced sleep quality during the week of oxy-reb compared to the week of placebo (4.7 [3.5; 5.9] vs. 6.5 [5.5; 7.5] on a 0-10 visual analogic scale, respectively; p = 0.001). No significant differences in sleepiness, vigilance, and fatigue were observed. No serious adverse events occurred. CONCLUSIONS: Administration of oxybutynin 5 mg and reboxetine 6 mg did not improve OSA severity assessed by AHI, but did alter sleep architecture and sleep quality. Reduced average oxygen desaturation and hypoxic burden were also observed. CLINICAL TRIAL: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04394143.

Objective polysomnography-based sleep features and major depressive disorder subtypes in the general population.

Insomnia and its opposite hypersomnia are part of the diagnostic criteria for major depressive disorder (MDD). However, no study has investigated whether the postulated sleep alterations in clinical subtypes of MDD are reflected in polysomnography (PSG)-derived objective sleep measures. The objective of this study was to establish associations between the melancholic, atypical and unspecified subtypes of MDD and objective PSG-based sleep features. This cross-sectional analysis included 1820 community-dwelling individuals who underwent PSG and a semi-structured psychiatric interview to elicit diagnostic criteria for MDD and its subtypes. Adjusted robust linear regression was used to assess associations between MDD subtypes and PSG-derived objective sleep measures. Current melancholic MDD was significantly associated with decreased absolute delta power and sleep efficiency and with increased wake after sleep onset. Remitted unspecified MDD was significantly associated with increased rapid eye movements density. No other significant associations were identified. Our findings reflect that some PSG-based sleep features differed in MDD subtypes compared with no MDD. The largest number of significant differences were observed for current melancholic MDD, whereas only rapid eye movements density could represent a risk factor for MDD as it was the only sleep measure that was also associated with MDD in remitted participants.

Resistance Training of Inspiratory Muscles After Coronary Artery Disease May Improve Obstructive Sleep Apnea in Outpatient Cardiac Rehabilitation: RICAOS Study.

Background: Obstructive sleep apnea (OSA) affects 5% of the adult population and its prevalence is up to 13 times higher in coronary artery disease (CAD) patients. However, OSA in this population is less symptomatic, leading to lower adherence to positive airway pressure (CPAP). While oropharyngeal exercise showed a significant decrease in apnea-hypopnea index (AHI) in patients with moderate OSA, there have been no studies testing the impact of specific inspiratory muscle training (IMT) for these patients. The aim of our study was to assess the effectiveness of IMT on AHI reduction in CAD patients with moderate OSA. Methods: We included patients with CAD involved in a cardiac rehabilitation program and presenting an AHI between 15 and 30. Patients were randomized in a 1:1 allocation to a control group (CTL - classic training) or an IMT group (classic training + IMT). IMT consisted in 60 deep inspirations a day, 6 days a week, into a resistive load device set at 70% of the maximum inspiratory pressure (MIP). After 6 weeks, we compared AHI, neck circumference, Epworth Sleepiness Scale, Pittsburgh Sleep Quality index, and quality of life with the 12-item Short Form Survey before and after rehabilitation. Results: We studied 45 patient (60 ± 9 y, BMI = 27 ± 6 kg.m-2). The IMT group (n = 22) significantly improved MIP ( p < 0.05) and had a significant decrease in AHI by 25% (-6.5 ± 9.5, p = 0.02). In the CTL group (n = 23), AHI decreased only by 3.5% (-0.7 ± 13.1; p = 0.29). Between groups, we found a significant improvement in MIP ( p = 0.003) and neck circumference ( p = 0.01) in favor of the IMT group. However, we did not find any significant improvement of AHI in the IMT group compared to CTL ( p = 0.09). Conclusion: A specific IMT during cardiac rehabilitation contributes to reduce significantly AHI in CAD patients with moderate OSA. Magnitude of the decrease in OSA severity could be enhanced according to implementation of specific IMT in this population.

The Relationship Between Postoperative Opioid Analgesia and Sleep Apnea Severity in Patients Undergoing Hip Arthroplasty: A Randomized, Controlled, Triple-Blinded Trial.

PURPOSE: Residual postoperative pain after hip arthroplasty is usually treated with oral opioids. While classic opioids are associated with respiratory depression and worsening of sleep apnea, tramadol has been reported to preserve respiratory function. However, this has not been investigated in a prospective trial using respiratory polygraphy. This randomized controlled triple-blinded trial tested the hypothesis that postoperative treatment with oral opioids such as oxycodone would increase sleep apnea severity, measured with a respiratory polygraphy, compared with oral tramadol. PATIENTS AND METHODS: Sixty patients undergoing hip arthroplasty under spinal anesthesia with 15 mg isobaric bupivacaine 0.5% were randomized to receive postoperative pain treatment with either oral oxycodone (controlled-release 10 mg every 12 hours and immediate-release 5 mg every 4 hours as needed) or oral tramadol (controlled-release 100 mg every 8 hours and immediate-release 50 mg every 4 hours as needed). Respiratory polygraphy was performed on the first postoperative night. The primary outcome was the apnea-hypopnea index in the supine position. Secondary outcomes included the oxygen desaturation index, postoperative pain scores and intravenous morphine consumption. RESULTS: Mean supine apnea-hypopnea index on postoperative night 1 was 11.3 events.h-1 (95% confidence interval, 4.8-17.7) in the oxycodone group and 10.7 (4.6-16.8) events.h-1 in the tramadol group (p=0.89). There were no significant differences between the oxycodone and tramadol groups with respect to any secondary sleep-related or pain-related outcomes. CONCLUSION: Oral oxycodone did not increase sleep apnea severity measured using respiratory polygraphy compared with oral tramadol on the first postoperative night after hip arthroplasty. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov - NCT03454217 (date of registration: 05/03/2018).

The effect of a pressure ventilatory support on quadriceps endurance is maintained after exercise training in severe COPD patients. A longitudinal randomized, cross over study.

Purpose: In severe chronic obstructive pulmonary disease (COPD) patients, the application of an inspiratory pressure support (IPS) during exercise increases exercise tolerance and the benefit of exercise training during pulmonary rehabilitation (PR). Moreover, it improves quadriceps endurance after a session of cycling exercise suggesting a reduced muscle fatigue. We looked for the persistence of this effect after PR and sought an association between the improved quadriceps endurance with IPS and the training load during PR. Patients and methods: We studied 20 patients with severe COPD (6 in stage 3and 14 in stage 4 of GOLD) before and after PR. As part of a PR program, patients completed 16 cycling sessions over 6 weeks with the addition of IPS during exercise. As a surrogate of muscular fatigue, quadriceps endurance was measured at 70% of maximal strength in a control condition, after a constant work rate exercise test (CWR) with IPS (TlimQ IPS) or with a sham ventilation (TlimQsham), in a random order. These tests were repeated similarly at the end of PR. Results: PR was associated with a significant increase in maximal power output, cycling endurance, quadriceps strength and endurance. Session training load (power output x duration of the session) increased by 142% during the course of the program. Before PR, CWR duration increases with IPS compared to sham ventilation (Δtime = +244s, p = 0.001). Compared to control condition, post-exercise TlimQ reduction was lower with IPS at isotime than at the end of CWR or than with sham ventilation (-9 ± 21%, -18 ± 16% and -23 ± 18%, respectively, p = 0.09, p < 0.0001 and p < 0.0001). After PR, the post-exercise decrease of TlimQ was reduced after IPS compared to sham (-9 ± 18% vs. -21 ± 17%, respectively, p = 0.004). No relationship was found between the prevention of quadriceps fatigue and the training load. Conclusion: In severe COPD patients, the beneficial effect of a ventilator support on quadriceps endurance persisted after PR with IPS. However, it was not related to the increase in training load, and could not predict the training response to non-invasive ventilation during exercise.