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Background: Obstructive sleep apnea (OSA) is a common disease caused by repeated episodes of collapse of the upper airway during sleep and is associated with the development of cardiovascular disease (CVD). However, there is high heterogeneity in the impact of OSA on patients. Until now, the profile of OSA patients at risk of developing CVD has not been defined, including the measurable variables that could be used to predict the CVD risk of a patient with OSA. Objective: The aim of this study was to identify the microRNA (mi­RNA) profile associated with CVD in patients with OSA. Method: This is an observational, cross-sectional study that included 132 male patients. Three groups were defined as OSA patients, OSA patients with hypertension, and OSA patients who developed a major cardiovascular event. Polysomnography and ambulatory blood pressure measurements were performed. The expression profiling of 188 miRNAs in plasma was performed in 21 subjects (matched by BMI and age) by the TaqMan low density array (TLDA). miRNAs differentially expressed in the different subgroups of patients and miRNAs that correlated with the cardiovascular risk SCORE were selected for validation by RT-qPCR in the 111 remaining patients. Results: From the TLDA analysis, 7 miRNAs were selected for validation. Differential expression was not confirmed in any of the miRNAs. miR-143 was associated with nocturnal systolic blood pressure. miR-107 correlated with 24-h blood pressure parameters and with nocturnal hypertension. miR-486 was associated with the cardiovascular risk SCORE. Conclusions: The circulating profile of miRNAs does not seem to be different in any of the subgroups of patients with OSA and different cardiovascular risk factors. Nevertheless, miR-107 and miR-143 are associated with specific blood pressure parameters in patients with OSA and miR-486 is associated with the cardiovascular risk SCORE.

Introduction: Obstructive sleep apnea (OSA) is a chronic, heterogeneous and multicomponent disorder with associated cardiovascular and metabolic alterations. Despite being the most common sleep-disordered breathing, it remains a significantly undiagnosed condition. Objective: We examined the plasma metabolome and lipidome of patients with suspected OSA, aiming to identify potential diagnosis biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease. Additionally, we evaluated the impact of continuous positive airway pressure (CPAP) treatment on the circulating metabolomic and lipidomic profile. Material and methods: Observational-prospective-longitudinal study including 206 consecutive subjects referred to the sleep unit. OSA was defined as an apnea-hypopnoea index ≥ 15 events/h after polysomnography (PSG). Patients treated with CPAP were followed-up for 6 months. Untargeted plasma metabolomic and lipidomic profiling was performed using liquid chromatography coulpled to massspectrometry. Results: A plasma profile composed of 33 metabolites (mainly glycerophospholipids and bile acids) was identified in OSA vs. non-OSA patients. This profile correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses disclosed a 4-metabolites-signature that provided an accuracy (95% CI) of 0.98 (0.95-0.99) for OSA detection. CPAP treatment was associated with changes in 5 plasma metabolites previously altered by OSA. Conclusions: This analysis of the circulating metabolome and lipidome reveals a molecular fingerprint of OSA, which was modulated after effective CPAP treatment. Our results suggest blood-based biomarker candidates with potential application in the personalized management of OSA and suggest the activation of adaptive mechanisms in response to OSA-derived hypoxia. We thank the individuals who participated in this trial, their families, and the clinical and research team in the sleep department. LP is the recipient of a predoctoral fellowship from the Ministry of Universities of Spain (FPU19/01555). MJ is a “Serra Húnter” Fellow. MSdT has received financial support from the “Ramon ´ y Cajal” grant (RYC2019- 027831-I) from the “Ministerio de Ciencia e Innovacion ´ - Agencia Estatal de Investigacion´ ” cofunded by the European Social Fund (ESF) / “Investing in your future”

Background A close relationship between obstructive sleep apnoea (OSA) and Alzheimer's disease (AD) has been described in recent years. OSA is a risk factor for AD, but the diagnosis and clinical characteristics of OSA in patients with AD is not well understood. This study evaluated the clinical utility of two screening questionnaires, the STOP-Bang questionnaire (SBQ) and the Berlin questionnaire (BQ), to identify which patients with mild AD are at higher risk of having OSA and to determine the clinical predictors of OSA in this population. Methods In this study, 91 consecutive outpatients with mild AD were prospectively evaluated with the SBQ and the BQ. All patients underwent level 1 in-laboratory polysomnography. The predictive performance of the questionnaires were calculated for different apnoea-hypopnoea index (AHI) cut-offs. Results The median age of the patients was 76.0 (73.0; 80.0) years, and 58 (63.7%) were female. Of those, 81 patients (89.02%) were found to have OSA defined by an AHI > 5 events/h. Comparing the predictive performances of the SBQ and the BQ, the SBQ was found to have a higher diagnostic sensitivity (85% vs 4%), a lower specificity (35% vs. 96%), a higher positive predictive value (PPV) (44% vs 33%) and negative predictive value (NPV) (80% vs 65%) for detecting severe OSA at an AHI cut-off of 30 events/h. None of the items alone in the two questionnaires predicted the risk of OSA. A modified version of the SBQ, with new cut-off points for several variables according to the characteristics of AD patients, showed a slightly greater AUC than the standard SBQ (AUC 0.61 vs 0.72). Conclusion There is a high prevalence of OSA among patients with mild AD. The SBQ and the BQ are not good screening tools for detecting OSA in patients with AD. A modified version of SBQ could increase the detection of these patients.

Rationale: Evidence suggests that the physiopathologic consequences of obstructive sleep apnea (OSA) resemble those induced by aging. Some studies report that the deleterious effects associated wit...

Study Objectives To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer’s disease. Methods Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer’s disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers). Results The cohort included 125 patients with a median [IQR] of 75.0 [72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of −1.51 (95% CI: −2.43 to −0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose–response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023). Conclusions Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer’s disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline. Clinical Trial Information Role of Hypoxia Ans Sleep Fragmentation in Alzheimer’s Disease. and Sleep Fragmentation. Completed. NCT02814045

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease.In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography.The mean±sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of −3.36 (95% CI 0.19–0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI −1.26–4.64; p=0.445). No significant differences were found among different OSA severity groups.We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.

Background: Sleep-disordered breathing encompasses a group of diseases, of which obstructive sleep apnea (OSA) is most frequent. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease; it is manifested as an initial deficit of episodic memory that evolves into global cognitive and psychosocial dysfunction, and its prevalence is increasing around the world. OSA has been described as a risk factor for AD, and its prevalence is higher in AD patients. However, little is known about the influence of OSA on cognition in the AD population.The aim of this study was to evaluate the impact of nontreated OSA on the cognitive evolution of patients with mild-moderate AD, to investigate whether the magnitude of the cognitive decline is associated with the severity of OSA and to evaluate the influence of OSA on several cognitive subdomains in AD patients. Methods: In this single-center study, patients with mild-moderate AD were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) >15/h. AD severity was assessed using the Mini-Mental State Examination (MMSE). The primary outcome was to measure the change in cognitive score on the Alzheimer’s Disease Assessment Scale-cognitive scale (ADAS-cog) from baseline to 12 months in patients with mild AD with and without OSA. An extensive battery of neuropsychological tests, including the Epworth Sleepiness Scale (ESS), were performed and APOE status was measured. Findings: The cohort included 144 patients with a mean (SD) age of 75.19 (5.30) years; 72 (57.6%) were women, and the mean MMSE score was 23.5 (2.24) points at baseline. The mean (SD) change in the ADAS-cog score at 12 months was 3.19 (5.61) in the non-OSA group and 0.08 (5.62) in the OSA group, with a difference between the groups of -3.36 (95%CI 0.19 to 0.16; p=0.002). Regarding the changes in the ADAS-cog subitems at 12 months, ideational praxis, remembering test instructions and commands showed a significant difference between the groups (p

ObjectiveTo assess the effectiveness and cost-effectiveness of primary care (PC) and sleep unit (SU) models for the management of subjects with suspected obstructive sleep apnoea (OSA).MethodsMulticentre, open-label, two-arm, parallel-group, non-inferiority randomised controlled trial. A total of 302 subjects with suspected OSA and/or resistant hypertension were consecutively enrolled, 149 were treated at 11 PC units and 153 patients at a SU. The primary outcomes were a 6-month change in the Epworth Sleepiness Scale (ESS) score and Health Utilities Index (HUI). The non-inferiority margin for the ESS score was −2.0.ResultsA total of 80.2% and 70.6% of the PC and SU patients were diagnosed with OSA, respectively, and 59.3% and 60.4% of those were treated with CPAP in PC and SU units, respectively. The Apnoea–Hypopnoea Index was similar between the groups (PC vs SU (median (IQR); 23.1 (26.8) events/h vs 21.8 (35.2) events/h), and the baseline ESS score was higher in the PC than in the SU group (10.3 (6.6) vs 9 (7.2)). After 6 months, the ESS score of the PC group decreased from a mean of 10.1 to 7.6 (−2.49; 95% CI −3.3 to −1.69), and that of the SU group decreased from 8.85 to 5.73 (−3.11; 95% CI −3.94 to 2.28). The adjusted difference between groups for the mean change in the ESS score was −1.25 (one-sided 95% CI −1.88; p=0.025), supporting the non-inferiority of PC management. We did not observe differences in the HUI between groups. The cost analysis showed a median savings of €558.14/patient for the PC setting compared with the SU setting.ConclusionsAmong patients with suspected OSA, the PC model did not result in a worse ESS score or HUI than the specialist model and generated savings in terms of management cost. Therefore, the PC model was more cost-efficient than the SU model.Trial registrationResults; >>NCT02234765, Clinical Trials.gov.

To assess the prevalence of obstructive sleep apnea (OSA) in patients with mild-moderate Alzheimer’s Disease (AD) and to evaluate cognitive characteristics according to the severity of OSA. Patients with mild-moderate AD, recruited prospectively from a cognitive impairment unit, underwent overnight polysomnography. OSA was defined as an apnea–hypopnea index > 5/h. AD severity was assessed using the Mini-Mental State Examination and extensive neuropsychological battery. Epworth Sleepiness Scale and APOE status were analyzed. The cohort included 128 patients with a median [IQR] age of 75.0 [72.0;79.2] years and 57.8% were women. OSA was diagnosed in 116 subjects (90.6%). The distribution of mild, moderate and severe severity of OSA was 29 (22.7%), 37 (28.9%) and 50 (39.1%), respectively. Regarding sleep symptoms, the cohort showed normal values of daytime sleepiness (median EES score 5 [3, 8]), while nycturia (89.1%) and snoring (71.1%) were the most common symptoms. Participants with severe OSA included a higher proportion of older men, were associated with snoring and sedentariness. No significant differences in cognitive assessment were found between patients with and without severe OSA in any of the domains. The prevalence of APOE e4 was not significantly different between patients with and without severe OSA. There was a high prevalence of OSA in patients with mild-moderate AD. OSA was not associated with sleepiness or worse cognitive function. APOE e4 was not related to the presence or severity of OSA. Further longitudinal studies will be required to evaluate whether OSA impairs cognitive evolution in AD patients.