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Sleep–wake disturbances belong to the most frequent non-motor symptoms in patients with Parkinson’s disease. They encompass insomnia, excessive daytime sleepiness, different forms of parasomnias, sleep-related breathing disorders, restless legs syndrome, and circadian sleep–wake disorders. All of these sleep–wake disorders have the potential to severely impact the quality of life of patients and their bedpartners, and some of them not only get more frequent with longer disease duration, but may even precede motor manifestations of Parkinson’s disease. Isolated REM sleep behavior disorder in particular is a specific biomarker heralding synuclein-related neurodegenerative disease. Although very common, both diagnostic and therapeutic approaches for Parkinson-related sleep–wake disorders are still under evaluation. This chapter discusses the current knowledge on the pathophysiology and clinical manifestations of Parkinson-related sleep–wake disorders, and contributes a clinical guide on how to diagnose and treat them.
The depression, obstructive sleep apnea and cognitive impairment (DOC) screen assesses three post-stroke comorbidities, but additional information may be gained from the time to complete the screen. Cognitive screening completion time is rarely used as an outcome measure.
Objective:
To assess DOC screen completion time as a predictor of cognitive impairment in stroke/transient ischemic attack clinics.
Methods:
Consecutive English-speaking stroke prevention clinic patients consented to undergo screening and neuropsychological testing (n = 437). DOC screen scores and times were compared to scores on the NINDS-CSC battery using multiple linear regression (controlling for age, sex, education and stroke severity) and receiver operating characteristic (ROC) curve analysis.
Results:
Completion time for the DOC screen was 3.8 ± 1.3 minutes. After accounting for covariates, the completion time was a significant predictor of the speed of processing (p = 0.002, 95% CI: −0.016 to −0.004), verbal fluency (p < 0.001, CI: −0.012 to −0.006) and executive function (p = 0.004, CI: −0.006 to −0.001), but not memory. Completion time above 5.5 minutes was associated with a high likelihood of impairment on executive and speed of processing tasks (likelihood ratios 3.9–5.2).
Conclusions:
DOC screen completion time is easy to collect in routine care. People needing over 5.5 minutes to be screened likely have deficits in executive functioning and speed of processing – areas commonly impaired, but challenging to screen for, after stroke. DOC screen time provides a simple, feasible approach to assess these under-identified cognitive impairments.
To assess the potential cost-effectiveness of neuromuscular electrical stimulation (NMES) for treatment of mild obstructive sleep apnea (OSA).
Methods
A decision-analytic Markov model was developed to estimate health state progression, incremental cost, and quality-adjusted life year (QALY) gain of NMES compared to no treatment, continuous airway pressure (CPAP), or oral appliance (OA) treatment. The base case assumed no cardiovascular (CV) benefit for any of the interventions, while potential CV benefit was considered in scenario analyses. Therapy effectiveness was based on a recent multi-center trial for NMES, and on the TOMADO and MERGE studies for OA and CPAP. Costs, considered from a United States payer perspective, were projected over lifetime for a 48-year-old cohort, 68% of whom were male. An incremental cost-effectiveness ratio (ICER) threshold of USD150,000 per QALY gained was applied.
Results
From a baseline AHI of 10.2 events/hour, NMES, OA and CPAP reduced the AHI to 6.9, 7.0 and 1.4 events/hour respectively. Long-term therapy adherence was estimated at 65-75% for NMES and 55% for both OA and CPAP. Compared to no treatment, NMES added between 0.268 and 0.536 QALYs and between USD7,481 and USD17,445 in cost, resulting in ICERs between USD15,436 and USD57,844 per QALY gained. Depending on long-term adherence assumptions, either NMES or CPAP were found to be the preferred treatment option, with NMES becoming more attractive with younger age and assuming CPAP was not used for the full night in all patients.
Conclusions
NMES might be a cost-effective treatment option for patients with mild OSA.
Sleep disorders are very prevalent in late life, though they are often unrecognized, underdiagnosed, and poorly treated. Epidemiological evidence suggests that over 50% of elderly people suffer from one of several different sleep disorders, with the most common sleep disorders being insomnia and sleep apnea. Both insomnia and sleep apnea carry many serious negative physical, mental, and social consequences. Epidemiology, diagnosis, and treatment management for both insomnia and sleep apnea in older adults are reviewed. Diagnosis of insomnia in older adults is based on self-report, while sleep apnea diagnosis requires a sleep study. Treatment of insomnia in late life is guided by behavioral and cognitive principles, with the gold-standard treatment approach being cognitive-behavioral therapy or CBT. Positive airway pressure (PAP) therapy is the recommended treatment approach for sleep apnea. Contextual factors that complicate the diagnosis and management of insomnia and sleep apnea in late life are reviewed with the aim of providing practical information for the medical professional working with older patients.
Since elephant seals are submerged 90% of the time they are at sea and they are at sea 8 to 10 months of the year, depending on sex, when do they sleep? They hold their breath while sleeping on land, as if they are diving. This suggests that they do not sleep at sea during the short periods at the surface. A good case can be made that they sleep during dives. This is reasonable because heart rate slows and metabolism decreases during diving just as it does during sleep. On land, elephants sleep whenever they can, day or night, that is, when the entire colony is quiet.
Missatributing symptoms to already established conditions often represents a missed opportunity to improve management. These cases provide some examples.
Aging is marked by cognitive decline, which in the case of Alzheimer’s disease is associated with tremendous global economic burden. Identifying modifiable risk factors for cognitive decline is therefore of paramount importance. In this chapter, we describe how aging compromises sleep quality and sleep architecture at a rate that parallels normal age-related cognitive decline. We argue that understanding the neurocognitive functions of sleep – frontal lobe restoration, memory consolidation, and metabolite clearance – and how such functions change in later life will be key to informing why some older individuals maintain healthy cognitive functioning and other older individuals do not. Critically, by investigating how sleep, cognition, and aging interact, researchers and clinicians can develop sleep-related treatments that target preventing, or at least ameliorating, pathologies such as Alzheimer’s disease.
Patients with untreated obstructive sleep apnea often report depressive symptoms, such as low mood, loss of interest and reduction of drive. In this study we examined the frequency of significant depressive symptoms amongst patients with untreated obstructive sleep apnea over a one year period.
Methods
From January to December 2008 we screened 1260 consecutive patients with untreated obstructive sleep apnea (AHI > 9) seen at our Center for Sleep Medicine were screened for depression. Based on self-administered questionnaires, patients with significant depressive symptoms were defined as having either a BDI II score ≥ 14 or WHO-5 ≤ 13. Additionally, severity of depression was rated based on BDI II scores.
Results
Depressive symptoms were reported frequently. Based on BDI-II, 27.9% of patients report significant depressive symptoms. Of these, 46.2% were mild, 35.9% moderate and 17.9% severe. In addition, 52.6% of patients self-reported feeling unwell based on their WHO-5 scores.
Conclusions
Significant depressive symptoms measured by standardised self-rating scales were detected in over a quarter of our patients with untreated sleep apnea. It remains unknown whether treatment of OSA alone abolishes depressive symptoms, or whether depressive mood may reduce the compliance with treatment. Patients may need an interdisciplinary approach to initial treatment.
We sought to investigate the risk of incident major depressive disorder (MDD) attributable to a range of sleep disorders in the Danish population. Data were obtained by linking longitudinal Danish population-based registers. A total of 65,739 individuals who had first onset of depression between 1995 and 2013 were selected as cases. For each case, a set of 20 controls of the same sex, birth month and year and who had not had depression by the date that the case was diagnosed were selected at random form the population (N = 1,307,580 in total). We examined whether there was an increased rate of prior sleep disorders in MDD cases compared to controls using conditional logistic regression. An increased risk of incident depression in cases was found for all sleep disorders analyzed. Highest incidence rate ratios (IRRs) were found for circadian rhythm disorders (IRR = 7.06 [2.78–17.91]) and insomnia of inorganic origin (IRR = 6.76 [4.37–10.46]). The lowest estimated IRR was for narcolepsy (IRR = 2.00 [1.26–3.17]). Those diagnosed with a sleep disorder in the last 6 months were at highest risk of developing depression compared to those with at least 1 year since diagnosis (3.10 vs. 2.36). Our results suggest that having any sleep disorder is a risk factor for incident depression. Depression screening should be considered for patients with sleep disorders, and where possible, long-term follow-up for mental health problems is advisable.
Although sleep apnea is an important disorder associated with cardiac events, data regarding its prevalence and risk factors in adult patients with congenital heart disease are limited.
Methods:
In this study, patients underwent a sleep study in the hospital. Indications for admission were classified as heart failure, diagnostic catheterisation, interventional catheterisation, or arrhythmia. The prevalence, characteristics, and risk factors of sleep apnea using a type-3 portable overnight polygraph in adult patients with congenital heart disease were evaluated.
Results:
There were 104 patients [median age: 36 (interquartile range: 28–48) years] who were admitted for heart failure 34% (n = 36), diagnostic catheterisation 26% (n = 27), interventional catheterisation 18% (n = 19), or arrhythmia 22% (n = 23). The prevalence of sleep apnea, defined as a respiratory disturbance index ≥5, was 63% (n = 63), with a distribution of 37%, 16%, and 10% for mild (5≤ respiratory disturbance index <15), moderate (15≤ respiratory disturbance index <30), and severe (respiratory disturbance index ≥30) sleep apnea, respectively. A large majority of the sleep apnea cases were categorised as obstructive sleep apnea (92%, n = 58). The respiratory disturbance index ≥15 group had a significantly higher proportion of male patients and higher body mass index, noradrenaline level, and aortic blood pressure than the group without sleep apnea (respiratory disturbance index <5). Multivariable analysis showed that New York Heart Association class ≥II (OR, 4.36; 95% CI, 1.09–20.87) and body mass index ≥25 (OR, 4.29; 95% CI, 1.32–15.23) were independent risk factors for a respiratory disturbance index ≥15.
Conclusion:
Our results showed a high prevalence of sleep apnea in adult patients with congenital heart disease. Its unique haemodynamics may be associated with a high prevalence of sleep apnea. Congestive heart failure and being overweight are important risk factors for sleep apnea. Management of heart failure and general lifestyle improvements will be important for controlling sleep apnea symptoms in these patients.
Sleep difficulties and short sleep duration have been associated with hypertension. Though body mass index (BMI) may be a mediator variable, the mediation effect has not been defined. We aimed to assess the association between sleep duration and sleep difficulties with hypertension, to determine if BMI is a mediator variable, and to quantify the mediation effect. We conducted a mediation analysis and calculated prevalence ratios with 95% confidence intervals. The exposure variables were sleep duration and sleep difficulties, and the outcome was hypertension. Sleep difficulties were statistically significantly associated with a 43% higher prevalence of hypertension in multivariable analyses; results were not statistically significant for sleep duration. In these analyses, and in sex-specific subgroup analyses, we found no strong evidence that BMI mediated the association between sleep indices and risk of hypertension. Our findings suggest that BMI does not appear to mediate the association between sleep patterns and hypertension. These results highlight the need to further study the mechanisms underlying the relationship between sleep patterns and cardiovascular risk factors.
This review examined the efficacy of intranasal corticosteroids for improving adenotonsillar hypertrophy.
Method:
The related literature was searched using PubMed and Proquest Central databases.
Results:
Adenotonsillar hypertrophy causes mouth breathing, nasal congestion, hyponasal speech, snoring, obstructive sleep apnoea, chronic sinusitis and recurrent otitis media. Adenoidal hypertrophy results in the obstruction of nasal passages and Eustachian tubes, and blocks the clearance of nasal mucus. Adenotonsillar hypertrophy and obstructive sleep apnoea are associated with increased expression of various mediators of inflammatory responses in the tonsils, and respond to anti-inflammatory agents such as corticosteroids. Topical nasal steroids most likely affect the anatomical component by decreasing inspiratory upper airway resistance at the nasal, adenoidal or tonsillar levels. Corticosteroids, by their lympholytic or anti-inflammatory effects, might reduce adenotonsillar hypertrophy. Intranasal corticosteroids reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil and adenoid mixed-cell culture system.
Conclusion:
Intranasal corticosteroids have been used in adenoidal hypertrophy and adenotonsillar hypertrophy patients, decreasing rates of surgery for adenotonsillar hypertrophy.
To search for studies on tongue–lip adhesion and tongue repositioning used as isolated treatments for obstructive sleep apnoea in children with Pierre Robin sequence.
Methods:
A systematic literature search of PubMed/Medline and three additional databases, from inception through to 8 July 2016, was performed by two authors.
Results:
Seven studies with 90 patients (59 tongue–lip adhesion and 31 tongue repositioning patients) met the inclusion criteria. Tongue–lip adhesion reduced the mean (± standard deviation) apnoea/hypopnoea index from 30.8 ± 22.3 to 15.4 ± 18.9 events per hour (50 per cent reduction). The apnoea/hypopnoea index mean difference for tongue–lip adhesion was −15.28 events per hour (95 per cent confidence interval = −30.70 to 0.15; p = 0.05). Tongue–lip adhesion improved the lowest oxygen saturation from 75.8 ± 6.8 to 84.4 ± 7.3 per cent. Tongue repositioning reduced the apnoea/hypopnoea index from 46.5 to 17.4 events per hour (62.6 per cent reduction). Tongue repositioning improved the mean oxygen saturation from 90.8 ± 1.2 to 95.0 ± 0.5 per cent.
Conclusion:
Tongue–lip adhesion and tongue repositioning can improve apnoea/hypopnoea index and oxygenation parameters in children with Pierre Robin sequence and obstructive sleep apnoea.
Objectives: Evaluate the association between pediatric sleep-disordered breathing (SDB) and executive functioning. Methods: We searched multiple electronic databases for peer-reviewed journal articles related to pediatric SDB and executive functioning. We included studies that assessed SDB via polysomnography, included objective or questionnaire measures of executive function, and had an age-matched control group. Fourteen articles met inclusion criteria with a total sample of 1697 children ages 5 to 17 years (M=9.81 years; SD=0.34). We calculated an overall effect size for each of the five executive domains (vigilance, inhibition, working memory, shifting, and generativity) as well as effect sizes according to SDB severity: mild, moderate, severe. We also calculated effect sizes separately for objective and subjective questionnaires of executive functioning. Results: We found a medium effect size (−0.427) for just one of five executive function domains on objective neuropsychological measures (generativity). In contrast, effect sizes on all three executive domains measured via questionnaire data were significant, with effect sizes ranging from medium (−0.64) to large (−1.06). We found no difference between executive domains by severity of SDB. Conclusions: This meta-analysis of executive function separated into five domains in pediatric SDB suggested lower performance in generativity on objective neuropsychological measures. There were no differences associated with SDB severity. Questionnaire data suggested dysfunction across the three executive domains measured (inhibition, working memory, shifting). Overall, limited evidence suggested poorer performance in executive function in children with SDB according to objective testing, and subjective ratings of executive function suggested additional worsened performance. (JINS, 2016, 22, 839–850)
To investigate the neutrophil-to-lymphocyte ratio and sleep apnoea severity relationship.
Methods:
Patients (n = 178) were assigned to five groups according to apnoea–hypopnea indices and continuous positive airway pressure use. White blood cell, neutrophil, lymphocyte and neutrophil-to-lymphocyte ratio values were compared for each group.
Results:
The neutrophil-to-lymphocyte ratio values of severe obstructive sleep apnoea syndrome patients (group 4) were significantly higher than those of: control patients (group 1), mild obstructive sleep apnoea syndrome patients (group 2) and patients treated with continuous positive airway pressure (group 5) (p = 0.008, p = 0.008 and p = 0.003). Minimum oxygen saturation values of group 4 were significantly lower than those of groups 1, 2 and 5 (p = 0.0005, p = 0.011 and p = 0.001). There was a positive correlation between apnoea–hypopnea index and neutrophil-to-lymphocyte ratio (r = 0.758, p = 0.034), and a negative correlation between apnoea–hypopnea index and minimum oxygen saturation (r = −0.179, p = 0.012).
Conclusion:
Neutrophil-to-lymphocyte ratio may be used to determine disease severity, complementing polysomnography.
Sleep disordered breathing in children causes disturbance in behaviour and also in cardiorespiratory and neurocognitive function. Subtotal tonsillectomy (‘tonsillotomy’) has been performed to treat sleep disordered breathing, with outcomes comparable to established therapies such as total tonsillectomy or adenoidectomy. This review critically assesses the role of subtotal tonsillectomy in a paediatric setting.
Method:
The Medline database (1966 to October 2012) was electronically searched using key terms including subtotal or intracapsular tonsillectomy, tonsillotomy, tonsillectomy, paediatrics, and sleep disordered breathing.
Results:
Eighteen papers were identified and reviewed. Subtotal tonsillectomy would appear to have an efficacy equal to that of total tonsillectomy for the treatment of sleep disordered breathing, and has significant benefits in reducing post-operative pain and analgesia use. Subtotal tonsillectomy patients appear to have less frequent post-operative haemorrhage compared with total tonsillectomy patients.
Conclusion:
In children, subtotal tonsillectomy is associated with fewer post-operative complications whilst having a comparable effect in improving sleep disordered breathing, compared with total tonsillectomy.
The sleep apnea syndrome occurs in 4% of adult men and 2% of adult women. Inflammation and hypoxia are intertwined at the molecular, cellular, and clinical levels. Sleep apnea influences heart rate variability, during sleep and during wakefulness. It is also an independent risk factor for stroke. Sleep apnea may also lead to cognitive dysfunction from the effects of chronic hypoxia and sympathetic stress associated with small-vessel disease in the brain, white matter ischemia, and lacunar strokes. This syndrome is a modifiable risk factor and therefore efforts to control this condition in patients at risk of vascular disease is a clinical endeavor that should be pursued vigorously, even though clinical research needs to persist in its quest to answer pressing pathophysiological questions. Emerging evidence suggests that restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS) represent risk factors for cardio- and cerebrovascular disease, even leading to stroke.
Anecdotal recognition of the relationship between sleep apnea and atrial fibrillation has recently given way to more rigorous observational data. The risk of recurrence after atrial fibrillation interventions has also been studied longitudinally. There are numerous pathophysiological mechanisms that may link sleep apnea to atrial fibrillation. One of the most important mechanisms may be the significant changes, both acute and chronic, in autonomic tone that occur with obstructive apneas. Most observational data suggest that the success rates of atrial fibrillation interventions, such as cardioversions and ablation, are significantly improved for patients whose sleep apnea is treated. Epidemiological studies suggest that sleep apnea is a risk factor for new-onset atrial fibrillation, and that its presence reflects a poorer prognosis after atrial fibrillation interventions. Randomized controlled trials are necessary to clarify the effects of sleep apnea therapy on atrial fibrillation outcomes in individuals and communities.
There are two principal indications for tonsillectomies or ablation of palatal tonsillar tissue: repeated episodes of tonsillitis (at least 5 times per year in two successive years) and obstructive tonsillar tissue as well as another, more rare, indication, highly asymmetrical blocs of tonsillar tissue that may suggest presence of a lymphoma. When tonsils are obstructive in patients suffering from sleep apnea, the indication for excision is formal and requires prompt attention. In other cases of enlarged tonsils the indication for surgery can be discussed but practitioners must inform parents of the possible maxillofacial complications that may develop because of chronic pharyngeal blockage.
Surgeons perform tonsillectomies on children under general anesthesia, protecting the lower airways by intubation. Post-operative pain after surgery is constant and practitioners must be prepared to manage it in conformity with the age of patients and the difficulties they have in swallowing.
The American Heart Association and others have recommended screening for depression among those with cardiovascular disease (CVD). It has been further suggested that this screening should occur at least quarterly. In addition to an appropriate and targeted work-up for CVD, patients should be screened for conditions related to depression and heart disease, such as sleep apnea. Once the diagnosis of depression has been made, a variety of treatment options are available. These include antidepressants, psychotherapy, and exercise. Relaxation and stress management approaches also may be of benefit. Beta-blockers do not cause depression and should not be avoided in patients with depression and CVD. Although case reports have documented a number of psychiatric adverse effects of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins, such effects have not been reported in systematic studies. Use of statins does not appear to increase risk of suicide.