Therapies For Sleep Disorders Research Articles

Associations of sleep disorders with all-cause MCI/dementia and different types of dementia - clinical evidence, potential pathomechanisms and treatment options: A narrative review.

Due to worldwide demographic change, the number of older persons in the population is increasing. Aging is accompanied by changes of sleep structure, deposition of beta-amyloid (Aß) and tau proteins and vascular changes and can turn into mild cognitive impairment (MCI) as well as dementia. Sleep disorders are discussed both as a risk factor for and as a consequence of MCI/dementia. Cross-sectional and longitudinal population-based as well as case-control studies revealed sleep disorders, especially sleep-disorderded breathing (SDB) and excessive or insufficient sleep durations, as risk factors for all-cause MCI/dementia. Regarding different dementia types, SDB was especially associated with vascular dementia while insomnia/insufficient sleep was related to an increased risk of Alzheimer's disease (AD). Scarce and still inconsistent evidence suggests that therapy of sleep disorders, especially continuous positive airway pressure (CPAP) in SDB, can improve cognition in patients with sleep disorders with and without comorbid dementia and delay onset of MCI/dementia in patients with sleep disorders without previous cognitive impairment. Regarding potential pathomechanisms via which sleep disorders lead to MCI/dementia, disturbed sleep, chronic sleep deficit and SDB can impair glymphatic clearance of beta-amyloid (Aß) and tau which lead to amyloid deposition and tau aggregation resulting in changes of brain structures responsible for cognition. Orexins are discussed to modulate sleep and Aß pathology. Their diurnal fluctuation is suppressed by sleep fragmentation and the expression suppressed at the point of hippocampal atrophy, contributing to the progression of dementia. Additionally, sleep disorders can lead to an increased vascular risk profile and vascular changes such as inflammation, endothelial dysfunction and atherosclerosis which can foster neurodegenerative pathology. There is ample evidence indicating that changes of sleep structure in aging persons can lead to dementia and also evidence that therapy of sleep disorder can improve cognition. Therefore, sleep disorders should be identified and treated early.

0489 Sleep Disordered Medicine: A Residents Perspective

0489 Sleep Disordered Medicine: A Residents Perspective

Peculiarities of current melatonin application — successful experience and new opportunities

The paper presents current information about the physiological functions and pharmacological properties of hormone melatonin. Consideration was given to the results of clinical trials, confirming melatonin efficacy in the treatment of insomnia of various etiology in patients of different age groups in comparison of other hypnotics, both as monotherapy and combined therapy of arterial hypertension with the purpose of regulation of circadian rhythms in case of desynchronosis (jet lug, shift work, syndromes sleep phase disturbances). An experience of exogenous melatonin application at coronavirus disease (COVID‑19) has been analyzed. The review is based on search results in the PubMed, Medline, Scopus databases for the period 1997–2021 for the keywords melatonin, therapeutic use, insomnia, hypertension, circadian rhythm disturbances, COVID‑19.
 Data showed that melatonin was an effective and safe medication that can be recommended in all cases of sleep disturbances and for patients of any age with or without concomitant pathology. It is well tolerated and goes well with other drugs. Melatonin efficacy and safety was registered at its simultaneous use with antihypertensive, hypoglycemic and anti‑inflammatory drugs in elderly and middle‑aged people with arterial hypertension. Owing to its anti‑inflammatory, immunoregulatory, antioxidant effects, melatonin diminishes the risk of infections, inflammation, and oxidative stress in case of disease development, it promotes health in people at risk, has a neuroprotective effect in patients with COVID‑19, can serve as an adjuvant to boost anti‑SARS‑CoV‑2 vaccines. As an antioxidant and anti‑inflammatory agent, melatonin counteracts acute lung injury/acute respiratory distress syndrome caused by viral and bacterial infections.
 Melatonin preparation Melafresh (Prime Health Ltd., Canada) proved to be an effective addition to the therapy of sleep disorders of various etiology, especially in cases of their onset due to inconsistent circadian rhythms, it prevents or attenuates desynchronosis of circadian rhythms, violation of daily sleep/wakefulness cycles, decreases the number of episodes of awakening at night, restores full sleep after psycho‑emotional overload and stress, and promotes easy awakening. One of Melafresh advantages is its drug form (sublingual tablets) as it increases its bioavailability and concentration in blood.

Music therapy for sleep disorders based on the Biorhythm theory of Ayurveda

Music therapy for sleep disorders based on the Biorhythm theory of Ayurveda

P0963MANAGEMENT OF SLEEP DISORDERS IN END-STAGE RENAL DISEASE, IS IT REALLY IMPORTANT?

Abstract Background and Aims Sleep apnoea (SA), either obstructive and central (OSA and CSA, respectively) associated with and excessive daytime sleepiness (EDS) are common sleep disorders among patients with end-stage renal disease (ESRD). Fluid overload characterizes end-stage kidney disease and plays an important role in the pathogenesis of OSA, CSA and EDS. In our study we assessed the prevalence of sleep apnoea and excessive daytime sleepiness in patients from a nephrology and dialysis unit from south-eastern Romania. Method 86 patients with ESRD pre-dialysis (eGFR < 15 ml/min/1,73 m) or on maintenance haemodialysis were monitored for an interval of 2 years. We used questionnaires to assess the prevalence of SA and EDS. All subjects underwent overnight polysomnography (PSG). Extracellular fluid volume of the total body, neck, thorax and right leg were measured using bioelectrical impedance. We also examined the association between sleep apnoea, EDS, the underlying causes of ESRD, co-morbidities, medication used, and other demographic data. Results The mean patients age was 57.5 years ± 14.9 years; 65.1% were male, and 34.9% were female. The prevalence of SA as defined by the Berlin questionnaire (BQ) was 49.5% in males and 34.8% in females, which was not a statistically significant difference (P = 0.029). Sleep apnoea was significantly associated with age, obesity, diabetes, hypertension, fluid overload and 2nd or 3rd haemodialysis shift (P-values, 0.001, < 0.0001, < 0.002, < 0.008, <0.0001, and < 0.005. Sleep apnoea was also significantly associated with other sleep disorders such as restless leg syndrome, insomnia, habitual snoring, and EDS (P-values, < 0.001, < 0.001, < 0.001, and < 0.001, respectively). The prevalence of EDS was 35,5%, and EDS was significantly associated with age (over 60 years old), diabetes mellitus, hypertension and obesity. 18 patients (20.9%) had refractory hypertension, that improved after CPAP administration, and 10 of these patients (over 50% with refractory HT), that refused the application of appropriate therapy of sleep disorders, suffered a major cardiovascular event during our study. Conclusion Sleep apnoea, excessive daytime sleepiness and other sleep disorders are relatively common in pre-dialysis and haemodialysis patients and are significantly associated with refractory hypertension and severe cardio-vascular events. That is why a greater attention should be given to the diagnosis and management of sleep disorders, as one of the important steps in nursing and our patients’ rehabilitation.

Basic chronobiology: what do sleep physicians need to know?

Sleep is an essential physiological process, which profoundly affects a wide range of biological activities. It is now known that sleep supports myriad vital functions in the central nervous system. This includes neural plasticity, learning, memory, cognition and emotional regulation. Additionally, it affects basic processes such as cardiovascular, immunological and metabolic activity. Evidence from multiple lines of research has thus shown that good quality of sleep is essential for both survival and optimal functioning of life. Considerable evidence also supports the conclusion that even minimal dysfunctions in circadian regulation can significantly disrupt sleep and broadly affect body physiology. As a consequence, it is now appreciated that the therapy of sleep disorders is more complex than was once thought. At present, several clinical disciplines have recognized the significance of the biological clock in health and illness, and are incorporating this knowledge into treatment programs. Recent decades have seen the emergence of chronotherapies, i.e., treatment strategies that are aimed at producing adjustments in the circadian clock. The final objective of these approaches is to affect basic cellular and physiological processes, which in turn may be at the root of disorders such as physiological aging, immune functioning, metabolic activity, and psychiatric disturbance. It is suggested that the integration of chronobiological perspectives into many mainstream medical disciplines would be of significant benefit, both for the reduction of the prevalence of diseases and their treatment. This review considers the physiology of sleep and the importance of timekeeping mechanisms in the regulation of overall health.

Cognitive behavioral theory and therapy for sleep disorders

Cognitive behavioral theory and therapy for sleep disorders

Neuroendocrine Control of Sleep.

Sleep is a phenomenon in animal behavior as enigmatic as it is ubiquitous, and one deeply tied to endocrine function. Though there are still many unanswered questions about the neurochemical basis of sleep and its functions, extensive interactions have been identified between sleep and the endocrine system, in both the endocrine system's effect on sleep and sleep's effect on the endocrine system. Unfortunately, until recent years, much research on sleep behavior largely disregarded its connections with the endocrine system. Use of both clinical studies and rodent models to investigate interactions between neuroendocrine function, including biological sex, and sleep therefore presents a promising area of further exploration. Further investigation of the neurobiological and neuroendocrine basis of sleep could have wide impact on a number of clinical and basic science fields. In this review, we summarize the state of basic sleep biology and its connections to the field of neuroendocrine biology, as well as suggest key future directions for the neuroendocrine regulation of sleep that may significantly impact new therapies for sleep disorders in women and men.

Modular organization of a hypocretin gene minimal promoter.

Orexins or hypocretins are neurotransmitters produced by a small population of neurons in the lateral hypothalamus. This family of peptides modulates sleep-wake cycle, arousal and feeding behaviors; however, the mechanisms regulating their expression remain to be fully elucidated. There is an interest in defining the key molecular elements in orexin regulation, as these may serve to identify targets for generating novel therapies for sleep disorders, obesity and addiction. Our previous studies showed that the expression of orexin was decreased in mice carrying null-mutations of the transcription factor early B-cell factor 2 (ebf2) and that the promoter region of the prepro-orexin (Hcrt) gene contained two putative ebf-binding sites, termed olf-1 sites. In the present study, a minimal promoter region of the murine Hcrt gene was identified, which was able to drive the expression of a luciferase reporter gene in the human 293 cell line. Deletion of the olf1-site proximal to the transcription start site of the Hcrt gene increased reporter gene expression, whereas deletion of the distal olf1-like site decreased its expression. The lentiviral transduction of murine transcription factor ebf2 cDNA into 293 cells increased the gene expression driven by this minimal Hcrt-gene promoter and an electrophoretic mobility shift assays demonstrated that the distal olf1-like sequence was a binding site for ebf2.

ХРОНОБИОЛОГИЧЕСКИЕ АСПЕКТЫ НАРУШЕНИЙ СНА У ЖЕНЩИН КЛИМАКТЕРИЧЕСКОГО ПЕРИОДА: РОЛЬ МЕЛАТОНИНА (ОБЗОР ЛИТЕРАТУРЫ)

The aim of this review is analyze the literature data on the role of the circadian system key element - melatonin in the regulation of the sleep-wake cycle in menopausal women. It is shown that the melatonin level defined in a variety of biological fluids (blood, saliva, urine) depends on age, sex, race, and chronotype. It is detected that morning melatonin can be used as a biological marker for determining human chronotype. Most studies indicate that melatonin decreases with age, and that in women this hormone level is lower than in men. For sleep disorders, lower values of melatonin are revealed, although the results of the studies are ambiguous. Also, the studies show the shift of hormone secretion peaks in the early morning hours. The dependence of circadian rhythm of melatonin secretion on the climacteric phase has been revealed. This determines different approaches to the therapy of sleep disorders. It is extremely important to study the role of melatonin as an adaptogen of the female reproductive system because climacteric syndrome is the realization of a violation of the adaptation of the woman's organism in conditions requiring increased activity of the adaptive system of the body and sleep disorders are common in menopausal women.

Sleep disorders in Parkinson’s disease: approaches to treatment and prevention

Nocturnal sleep disorders are one of the most important non-motor manifestations of Parkinson’s disease (PD). The clinical significance of sleep disorders in PD is determined by their frequency (up to 88%) and negative impact on quality of life in patients. The paper presents the clinical spectrum of sleep disorders in PD, current approaches to their diagnosis. It discusses the multifactorial nature of the pathophysiology of these disorders. Current views on the relationship of sleep disorders to the neurodegeneration of brain structures involved in the regulation of sleep and wakefulness, to circadian disorders and therapy are depicted. On the basis of the heterogeneity of sleep disorders in PD, a differentiated approach to their treatment is substantiated having regard to the nature of dyssomnic disorders and leading pathophysiological factors. Emphasis is focused on the basic principles of differentiated therapy for sleep disorders in PD in relation to the degree of nocturnal motor symptoms of the disease. There are clinical findings indicating an improvement in the characteristics of nocturnal sleep and a reduction in nocturnal sleep disorders during therapy with long- acting ropinirole, a D2-receptor agonist. Approaches to the pharmacotherapy of non-motor disorders of PD, which worsen nocturnal sleep, are depicted. Non-drug therapies for sleep disorders and their efficiency in patients with PD are discussed.

Sleep-related breathing disorders and dentistry: What is the relationship?

Non-restorative sleep has considerable consequences for daily life. A sleep disorder is recognized by symptoms such as daytime fatigue and performance or concentration disorders. Furthermore, it increases the risk of developing cardiovascular, metabolic, and neurologic diseases. The diagnosis and therapy of sleep disorders is not only in the sleep medicine doctor's hands. A multidisciplinary approach reflects the affected patients' choice. Dentists can make an important contribution, especially to the therapy of sleep-related breathing disorder.

Sleep disorders (insomnia) as a psychoneurological dilemma in the diagnosis and treatment

Approaches of psychiatrists and neurologists to the diagnosis and therapy of sleep disorders are analyzed. On the basis of studying of 37 patients, the phenomenon of «somnic anhedonia» is described. Data on the relationship between insomnia and various mental disorders are presented. Scientifically based schemes of therapy, in particular, with the application of etifoxine (stresam) are described.

Pedunculopontine Nucleus Stimulation in Intractable Epilepsy: A Recent Patent on Deep Brain Stimulation Therapy

The pathogenesis and management of intractable epilepsy (IE) remain challenging to neuroscientists even today. Electrical stimulation therapies like vagal nerve and deep brain stimulation (DBS) are gaining popularity as effective adjunctive treatments with a continued search for newer DBS targets. The strong antiepileptic influence of rapid eye movement sleep (REMS) controlled by acetylcholine neurons (AChN) in the pedunculpontine nucleus (PPN) in humans is well documented, the stimulation of which has been found to induce and enhance REMS. Furthermore, a specific reduction of AChN in the PPN has been observed in autopsy examination of patients with West syndrome (a severe form of epilepsy). Therefore, in view of the strong antiepileptic influence of REMS and its control by AChN in PPN, it is postulated that the PPN may be electrically stimulated as per pre-configurable programming and requirement for enhancing the genesis of REMS during the night sleep time to provide protection against epileptogenesis and seizureoccurrence. The PPN is also responsible for initiation of locomotion and control of gait based on which patents on PPN stimulation in movement disorders like Parkinson’s disease and as therapy for sleep disorders are already available. This brief article presents a recent patent on PPN stimulation in IE. Keywords: Acetylcholine neurons, biomarker of intractability, deep brain stimulation, EEG-desynchronization, EEGsynchronization, electrical stimulation therapy, pedunculopontine nucleus, polysomnography, REM sleep.

Experience with sustained-release melatonin for the treatment of sleep disorders in depression

The data available in the literature on the role of melatonin in the regulation of circadian rhythms and sleep disorders in the population and in patients with mental diseases are analyzed. The cause of insomnia may be circadian rhythm disorders due to the age-related decline in the elaboration of the endogenous hormones that are responsible for the quality and duration of sleep, one of which is melatonin. Sustained-release melatonin is a synthetic analogue of the endogenous human pineal hormone melatonin. According to clinical findings, the main proven clinical effects of sustained-release melatonin 2 mg are a reduction in the latency of sleep, improvement of its quality, and lack of daytime sleepiness. The drug causes no dependence on its long use and rebound symptoms (increased insomnia symptoms), positively affects cognitive functions, and lowers nocturnal blood pressure in hypertensive patients. The paper describes a clinical case of a female patient with recurrent depressive disorder, in whom sustained-release melatonin 2 mg has demonstrated high efficacy and good tolerability in the combination therapy of sleep disorders in the pattern of depression.

Actigraphy, the alternative way?

The gold standards for measurement of sleep and wake are polysomnography (PSG) and the multiple sleep latency test (MSLT) and will remain so. Actigraphy is cheap, less labor intensive for the sleep laboratory and gives no burden for the patient. Major features of sleep (time in bed, total sleep time, sleep onset latency, wake after sleep onset and naps during the day) are easily quantified. If done over at least five days the results are in a reasonable way comparable to those of PSG. Obviously, actigraphy provides less details of sleep and the way it is disturbed. From the combination of PSG and one week actigraphy, one gets all details of sleep and wake and their fluctuations over time. As “stand alone” technique, actigraphy is indicated in young children, mentally handicapped patients and in the assessment of therapy for sleep disorders. In our opinion assessment of sleep disorders in children should include actigraphy over at least 5-7 24 hour days, if possible combined with one or two nights PSG. As there are no strict rules and normal values for MSLT in children, actigraphy is also helpful as tool for global assessment of hypersomnia in young patients.

The world epidemic of sleep disorders is linked to vitamin D deficiency

An observation of sleep improvement with vitamin D supplementation led to a 2year uncontrolled trial of vitamin D supplementation in 1500 patients with neurologic complaints who also had evidence of abnormal sleep. Most patients had improvement in neurologic symptoms and sleep but only through maintaining a narrow range of 25(OH) vitamin D3 blood levels of 60–80ng/ml. Comparisons of brain regions associated with sleep–wake regulation and vitamin D target neurons in the diencephalon and several brainstem nuclei suggest direct central effects of vitamin D on sleep. We propose the hypothesis that sleep disorders have become epidemic because of widespread vitamin D deficiency. The therapeutic effects together with the anatomic–functional correspondence warrant further investigation and consideration of vitamin D in the etiology and therapy of sleep disorders.

Sleep disorders in mental diseases and their correction

The authors analyze the data available in the literature on sleep disorders and their correction in the population and in patients with mental disorders and give their experience in using zolpidem (sanval) to treat insomnia in different mental diseases. The clinical features of sleep disorders are characterized in neurotic and affective disorders, schizophrenia, and organic brain injuries. Indications for the use of sanval both alone and in combination with other psychotropic drugs (antidepressants and antipsychotics with a sedative effect) for the therapy of sleep disorders within the framework of mental disorders are discussed. Sanval is shown to be highly effective and well tolerated in 100psychiatric in- and outpatients. No dependence on this drug and withdrawal syndrome permit sanval to be used as long-term courses in patients with chronic permanent insomnia and at an old age.

Emerging therapies for sleep disorders

There has been an upsurge in interest in treatments for sleep disorders recently, as new discoveries in the physiology of sleep-related brain neurotransmitter systems have been made. New targets for therapies have been identified in the field of insomnia, and these will be described in this article.

Orally Administered Melatonin Improves Nocturnal Rest in Young and Old Ringdoves (Streptopelia risoria)

Melatonin possesses chronobiotic properties, which affects sleep/wake rhythms. We investigated a 7-day administration of melatonin (0.25, 2.5 and 5 mg/kg body weight) on the activity/rest rhythms of a diurnal animal (the ringdove, Streptopelia risoria), aged 2-3 (young) and 10-12 (old) years, and its possible relationship with the serum levels of melatonin and serotonin. Total nocturnal and diurnal activity pulses were logged at basal, during, and up to 7 days after the treatments. The animals received 0.1 ml of melatonin orally 1 hr before lights off. The results showed that the administration of whichever melatonin dose decreased both diurnal and nocturnal old ringdove activity, the reduction being larger at night. The young animals also reduced their nocturnal activity with all three melatonin concentrations, whereas their diurnal activity only decreased with the 2.5 and 5 mg/kg body weight treatments. We chose those treatments that gave the best results in terms of nocturnal rest and the least affected diurnal activity (0.25 mg/kg body weight and 2.5 mg/kg in the young and old animals, respectively). Serum melatonin was measured by radioimmunoassay and serotonin by ELISA. In both age groups, the treatment increased both nocturnal and diurnal melatonin levels, with the effect continuing until 1 day after the last dose. Serum serotonin levels were unaffected by the treatments in either age group. The treatment restored the amplitude of the serum melatonin rhythm in the old animals to that of the young group. In summary, treatment with melatonin may be appropriate to improve nocturnal rest, and beneficial as a therapy for sleep disorders.