Excessive daytime sleepiness and antipathogen drug consumption in the elderly: a test of the immune theory of sleep.
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ABSTRACT:
SUBMITTER: Berticat C
PROVIDER: S-EPMC4800730 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
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Excessive daytime sleepiness and antipathogen drug consumption in the elderly: a test of the immune theory of sleep.
Berticat Claire C Thomas Frédéric F Dauvilliers Yves Y Jaussent Isabelle I Ritchie Karen K Helmer Catherine C Tzourio Christophe C Raymond Michel M Artero Sylvaine S
Scientific reports 20160321
The evolutionary reasons for sleep remain controversial. The immune theory of sleep suggests that sleep is essential to the immune system, allowing organisms to allocate more energy to their immunity. This hypothesis was tested by exploring the links between excessive daytime sleepiness (EDS) and vulnerability to infectious diseases in a large (n = 9294) cohort of elderly individuals, with information on socio-demographics, daily habits, and medical characteristics. At the two-year and four-year ...[more]
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Project description:Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.
| S-EPMC8086534 | biostudies-literature
Project description:An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF.We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB.Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m(2), and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low (R(2) = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively.Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.
| S-EPMC3318950 | biostudies-other
Project description:ObjectiveTo assess sleepiness, TNF-? plasma levels, and genomic variance in the TNF-? gene in children with obstructive sleep apnea (OSA).Study designChildren being evaluated for OSA (n = 60) and matched control children (n = 80) were assessed with a modified Epworth Sleepiness Scale questionnaire and underwent a blood draw the morning after nocturnal polysomnography. TNF-? plasma concentrations were assayed using ELISA, and genomic DNA was extracted. Genotyping and allelic frequencies were determined for 4 TNF-? single nucleotide polymorphisms using real-time polymerase chain reaction genotyping assays.ResultsMorning TNF-? levels and Epworth Sleepiness Scale scores were increased in the presence of OSA, but substantial variability was present. Although TNF-? plasma concentrations were globally increased in OSA, most of the variance was attributable to the presence or absence of TNF-? -308G gene polymorphism.ConclusionsTNF-? levels are increased in a subset of children with OSA, particularly among those harboring the TNF-? -308G single nucleotide polymorphism. Among the latter, significant increases in excessive daytime sleepiness symptoms are also present. The relatively high variability of excessive daytime sleepiness in pediatric OSA may be related to underlying TNF-? gene polymorphisms, particularly -308G.
| S-EPMC3005990 | biostudies-literature
Project description:To develop the Barcelona Sleepiness Index (BSI), an interviewer-administered instrument for assessing excessive daytime sleepiness (EDS) in sleep-disordered breathing (SDB) that correlates well with objective measures of EDS and which is sensitive to change with treatment.(1) Generation of a preliminary item list: Fifty-three consecutive SDB patients complaining of EDS and their bed partners were interviewed using a focus group methodology to generate a list of situations prone to cause sleepiness. Sixty different consecutive SDB patients were then evaluated using cognitive interviews to refine this list. (2) Construct validity: The maintenance of wakefulness test (MWT), the multiple sleep latency test (MSLT) and the sustained attention to response task (SART) test were used in an additional 98 consecutive SDB patients with and without EDS. The item combination that best correlated with the objective tests constituted the BSI. Cutoff values were determined to differentiate between patients with and without EDS. (3) Sensitivity to change: Thirty patients requiring continuous positive airway pressure (CPAP) were evaluated after satisfactory treatment.A combination of two items, "in the morning, when relaxing" and "in the afternoon, standing inactive, in a public place," presented the highest correlations with the MWT (r: -0.50, p < 0.001), the MSLT (r: -0.21, p = 0.07), and the SART (r: 0.27, p < 0.02) and constituted the BSI. The BSI significantly correlated with oxyhemoglobin saturation measures (nadir SpO2: r: -0.28, p = 0.01; CT 85: r: 0.23, p = 0.04) and showed a high sensitivity to change with CPAP treatment (t: 3.4, p = 0.002). A score of 2 or more identified patients with objective EDS (sensitivity = 64.9%, specificity = 72.1%).The Barcelona Sleepiness Index is a simple, brief instrument for measuring subjective EDS in SDB.
| S-EPMC4623127 | biostudies-other
Project description:The aim of the study was to compare REM-dependent and REM-independent, obstructive sleep apnea syndrome (OSA) patients in relation to their daily sleepiness assessed by Epworth sleepiness scale (ESS). The study included 1863 consecutive patients, who were referred to a sleep centre with a presumed diagnosis of OSA. Following polysomnography, 292 patients fulfilled criteria for either REM-dependent OSA (REM-OSA, n = 102) or REM-independent OSA (nREM-OSA, n = 190). Both study groups were matched regarding sex and age. REM-OSA group had two times lower median apnoea-hypopnea index (AHI) compared to nREM-OSA (p < 0.001), yet day-time sleepiness measured by ESS was similar: median score 9.0 (6.0-11.0) and 8.0 (4.8-11.0), p = 0.109, respectively. Subsequent post-hoc ANCOVA analysis, with covariates (BMI, percent of total sleep time spent in REM stage, percent of total sleep time spent in the supine position), has shown statistically significant difference between study groups regarding AHI (p < 0.001) and no difference regarding ESS score (p = 0.063). Despite two times lower AHI, patients with REM-OSA present with similar day-time sleepiness as those with REM independent OSA. Daily sleepiness may be stronger associated with apneas/hypopneas occurring in REM than nREM sleep.
| S-EPMC6949253 | biostudies-literature
Project description:Importance:Aging is associated with excessive daytime sleepiness (EDS), which has been linked to cognitive decline in the elderly. However, whether EDS is associated with the pathologic processes of Alzheimer disease remains unclear. Objective:To investigate whether EDS at baseline is associated with a longitudinal increase in regional β-amyloid (Aβ) accumulation in a cohort of elderly individuals without dementia. Design, Setting, and Participants:This prospective analysis included participants enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study in Olmsted County, Minnesota. Of 2900 participants, 2172 (74.9%) agreed to undergo carbon 11-labeled Pittsburgh compound B positron emission tomography (PiB-PET). We included 283 participants 70 years or older without dementia who completed surveys assessing sleepiness at baseline and had at least 2 consecutive PiB-PET scans from January 1, 2009, through July 31, 2016, after excluding 45 (13.7%) who had a comorbid neurologic disorder. Main Outcomes and Measures:Excessive daytime sleepiness was defined as an Epworth Sleepiness Scale score of at least 10. The difference in Aβ levels between the 2 consecutive scans (ΔPiB) in Aβ-susceptible regions (prefrontal, anterior cingulate, posterior cingulate-precuneus, and parietal) was determined. Multiple linear regression models were fit to explore associations between baseline EDS and ΔPiB while adjusting for baseline age, sex, presence of the apolipoprotein E ε4 allele, educational level, baseline PiB uptake, global PiB positivity (standardized uptake value ratio ≥1.4), physical activity, cardiovascular comorbidities (obesity, hypertension, hyperlipidemia, and diabetes), reduced sleep duration, respiratory symptoms during sleep, depression, and interval between scans. Results:Of the initial 283 participants, mean (SD) age was 77.1 (4.8) years; 204 (72.1%) were men and 79 (27.9%) were women. Sixty-three participants (22.3%) had EDS. Baseline EDS was significantly associated with increased regional Aβ accumulation in the anterior cingulate (B coefficient = 0.031; 95% CI, 0.001-0.061; P = .04), posterior cingulate-precuneus (B coefficient = 0.038; 95% CI, 0.006-0.069; P = .02), and parietal (B coefficient = 0.033; 95% CI, 0.001-0.065; P = .04) regions. Association of EDS with longitudinal Aβ accumulation was stronger in participants with baseline global PiB positivity in the anterior cingulate (B coefficient = 0.065; 95% CI, 0.010-0.118; P = .02) and cingulate-precuneus (B coefficient = 0.068; 95% CI, 0.009-0.126; P = .02) regions. Conclusions and Relevance:Baseline EDS was associated with increased longitudinal Aβ accumulation in elderly persons without dementia, suggesting that those with EDS may be more vulnerable to pathologic changes associated with Alzheimer disease. Further work is needed to elucidate whether EDS is a clinical marker of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers. Early identification of patients with EDS and treatment of underlying sleep disorders could reduce Aβ accumulation in this vulnerable group.
| S-EPMC5885188 | biostudies-literature
Project description:Study objectivesExcessive daytime sleepiness (EDS) is highly prevalent in the general population and is associated with occupational and public safety hazards. However, no study has examined the clinical and polysomnographic (PSG) predictors of the natural history of EDS.DesignRepresentative longitudinal study.SettingSleep laboratory.ParticipantsFrom a random, general population sample of 1,741 individuals of the Penn State Adult Cohort, 1,395 were followed up after 7.5 years.Measurements and resultsFull medical evaluation and 1-night PSG at baseline and standardized telephone interview at follow-up. The incidence of EDS was 8.2%, while its persistence and remission were 38% and 62%, respectively. Obesity and weight gain were associated with the incidence and persistence of EDS, while weight loss was associated with its remission. Significant interactions between depression and PSG parameters on incident EDS showed that, in depressed individuals, incident EDS was associated with sleep disturbances, while in non-depressed individuals, incident EDS was associated with increased physiologic sleep propensity. Diabetes, allergy/ asthma, anemia, and sleep complaints also predicted the natural history of EDS.ConclusionsObesity, a disorder of epidemic proportions, is a major risk factor for the incidence and chronicity of EDS, while weight loss is associated with its remission. Interestingly, objective sleep disturbances predict incident EDS in depressed individuals, whereas physiologic sleep propensity predicts incident EDS in those without depression. Weight management and treatment of depression and sleep disorders should be part of our public health policies.
| S-EPMC4335535 | biostudies-literature
Project description:Study objectivesExcessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea.MethodsEfficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation).ResultsA systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events.ConclusionsThe results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea.CitationRonnebaum S, Bron M, Patel D, et al. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543-2555.
| S-EPMC8726370 | biostudies-literature
Project description:Importance:Sleep-wake disorders are a common and debilitating nonmotor manifestation of Parkinson disease (PD), but treatment options are scarce. Objective:To determine whether nocturnal administration of sodium oxybate, a first-line treatment in narcolepsy, is effective and safe for excessive daytime sleepiness (EDS) and disturbed nighttime sleep in patients with PD. Design, Setting, and Participants:Randomized, double-blind, placebo-controlled, crossover phase 2a study carried out between January 9, 2015, and February 24, 2017. In a single-center study in the sleep laboratory at the University Hospital Zurich, Zurich, Switzerland, 18 patients with PD and EDS (Epworth Sleepiness Scale [ESS] score >10) were screened in the sleep laboratory. Five patients were excluded owing to the polysomnographic diagnosis of sleep apnea and 1 patient withdrew consent. Thus, 12 patients were randomized to a treatment sequence (sodium oxybate followed by placebo or placebo followed by sodium oxybate, ratio 1:1) and, after dropout of 1 patient owing to an unrelated adverse event during the washout period, 11 patients completed the study. Two patients developed obstructive sleep apnea during sodium oxybate treatment (1 was the dropout) and were excluded from the per-protocol analysis (n = 10) but included in the intention-to-treat analysis (n = 12). Interventions:Nocturnal sodium oxybate and placebo taken at bedtime and 2.5 to 4.0 hours later with an individually titrated dose between 3.0 and 9.0 g per night for 6 weeks with a 2- to 4-week washout period interposed. Main Outcomes and Measures:Primary outcome measure was change of objective EDS as electrophysiologically measured by mean sleep latency in the Multiple Sleep Latency Test. Secondary outcome measures included change of subjective EDS (ESS), sleep quality (Parkinson Disease Sleep Scale-2), and objective variables of nighttime sleep (polysomnography). Results:Among 12 patients in the intention-to-treat population (10 men, 2 women; mean [SD] age, 62 [11.1] years; disease duration, 8.4 [4.6] years), sodium oxybate substantially improved EDS as measured objectively (mean sleep latency, +2.9 minutes; 95% CI, 2.1 to 3.8 minutes; P = .002) and subjectively (ESS score, -4.2 points ; 95% CI, -5.3 to -3.0 points; P = .001). Thereby, 8 (67%) patients exhibited an electrophysiologically defined positive treatment response. Moreover, sodium oxybate significantly enhanced subjective sleep quality and objectively measured slow-wave sleep duration (+72.7 minutes; 95% CI, 55.7 to 89.7 minutes; P < .001). Differences were more pronounced in the per-protocol analysis. Sodium oxybate was generally well tolerated under dose adjustments (no treatment-related dropouts), but it induced de novo obstructive sleep apnea in 2 patients and parasomnia in 1 patient, as detected by polysomnography, all of whom did not benefit from sodium oxybate treatment. Conclusions and Relevance:This study provides class I evidence for the efficacy of sodium oxybate in treating EDS and nocturnal sleep disturbance in patients with PD. Special monitoring with follow-up polysomnography is necessary to rule out treatment-related complications and larger follow-up trials with longer treatment durations are warranted for validation. Trial Registration:clinicaltrials.gov Identifier: NCT02111122.
| S-EPMC5833497 | biostudies-literature
Project description:In the European Union, Czech Republic ranks 3rd and 6th for the incidence of obesity and cardiovascular diseases, respectively. Worldwide, short sleep duration and excessive daytime sleepiness (EDS) characterize obese subjects, which in turn exhibit scarce physical activity and unhealthy diet. We aimed to understand the relationship between irregular sleep patterns, obesity and lifestyle factors, such as diet and physical activity, in a vulnerable Czech population. 1482 members of the Kardiovize cohort, a random sample of the Czech urban population, were included in a cross-sectional study. Exposure variables included self-reported sleep duration and EDS, assessed by the Epworth Sleepiness Scale. Primary outcomes were BMI and waist-to-hip ratio or prevalence of obesity and central obesity. Covariates included physical activity and diet. Associations and interactions between variables were evaluated using logistic regression analyses. After adjustment for covariates, short sleep duration (<7 h) was associated with greater odds of overweight (BMI > 25; OR = 1.42; 95%CI = 1.06?1.90; p = 0.020) and obesity (BMI > 30; OR = 1.40; 95%CI = 1.02?1.94; p = 0.047), while EDS was associated with greater odds of central obesity (OR = 1.72; 95%CI = 1.06?2.79; p = 0.030), independent of diet and physical activity. However, due to the cross-sectional nature of our study, further prospective, large-scale studies are needed to evaluate the etiological link and causality between sleep disturbances and obesity.
| S-EPMC6164828 | biostudies-other