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Abstract
Sleep is a state of reduced awareness and responsiveness, both to internal and external stimuli. It is now recognized as a highly complex and heterogeneous state. Through the time course of the twenty-four hour day on earth there is a pattern of cycling through wakefulness and the states of sleep.
There are two types of sleep; non-rapid eye-movement (NREM) sleep and rapid eye-movement (REM) sleep which alternate cyclically over the course of a period of sleep.
Many physiological changes occur during sleep; changes in blood pressure and heart rate, sympathetic nerve activity, ventilation and respiratory flow, blood flow and metabolism, renal function and hormonal secretion.
Sleep-Wake regulation is regulated by the interplay of two major processes, one that promotes sleep (process S) and one that maintains wakefulness (process C).
Sleep process S is regulated by neurons that shut down the arousal systems, thus allowing the brain to fall asleep. Many of these neurons are found in the preoptic area of the hypothalamus.
Wakefulness is generated by an ascending arousal system from the brainstem that activates forebrain structures to maintain wakefulness.
The activating system has been identified as having a significant role in the maintenance of wakefulness. Some neurotransmitters are involved, including acetylcholine, serotonin, noradrenalin, dopamine, histamine, and hypocretin (orexin).
The proposed functions for sleep are biochemical, physiological, neurological, social and cognitive.
Sleep appears to be involved in consolidation of memory. Post-learning sleep enhances consolidation of declarative, procedural and emotional memories.
Sleep disordered breathing is a process characterized by repetitive partial or complete upper airway occlusion often associated with oxygen desaturation and arousals. It encompasses a spectrum of disorders including; central sleep apnea syndromes (CSA), obstructive sleep apnea syndromes (OSA), sleep related hypoventilation/hypoxemic syndromes, sleep related hypoventilation/hypoxemia due to medical condition and other sleep related breathing disorder.
Prevalence of sleep apnea syndrome (daytime sleepiness and/or non refreshing sleep and an apnea hypoapnea index (AHI) of 5 or greater was estimated at 4% among men and 2% among women in USA.
The most common disorder is obstructive apneas and hypoapneas so most of literatures and studies discuss its effect on cognitive functions.
Obstructive apnea is defined as cessation of nasal/oral airflow for at least 10 seconds, despite persistent ventilatory efforts. The most important factors which determine whether or not OSA develops are small size of upper airway, upper airway compliance and chest wall muscle activity.
The most important causes of OSA are obesity, tobacco, sleeping position, nasal obstruction, tonsil and adenoid enlargement, laryngeal obstruction, craniofacial causes and hormonal factors; all leading to small size of upper airway. Other causes leads to loss of upper airway muscle activity include sleep deprivation and sleep fragmentation, benzodiazepines, alcohol, and neuromuscular conditions.
Clinical features of OSA are noisy breathing in sleep, arousal, restlessness during sleep, nocturia, gastro-esophageal reflux, nocturnal angina, excessive daytime sleepiness and cognitive effects.
OSA show many complications like hypercapnic respiratory failure, cardiac dysrhythmias, myocardial infarction, cerebrovascular stroke, hypertension and pulmonary hypertension.
Full-night polysomnography (NPSG) is the golden standard for diagnosing patients suspected of having OSA. The occurrence of repetitive apnea episodes during sleep is accompanied, among several changes, by a significant reduction in slow-wave sleep which has been indicated as a crucial component of synaptic downscaling during sleep, probably important for cognitive processing.
Central sleep apnea (CSA) is a disorder of decreased breathing rate or depth, particularly during sleep due to a transient reduction or withdrawal of central neural output to the respiratory muscles.
The number of cases of CSA seen in clinical practice is much smaller than the number of cases of obstructive apnea, constituting 5-10% of all sleep apnea cases. CSA may be physiologic central apnea, nonhypercapnic or hypercapnic.
The clinical features of CSA are directly related to the cardiorespiratory and nervous systems including; hypoxemia and hypercapnia, cardiac arrhythmias, pulmonary and systemic vasoconstriction and nervous system changes.
Full polysomnography is required to properly diagnose CSA disorders.
Central apnea is characterized by an absence of airflow and respiratory effort.
Sleep apnea has an effect on the quality of life of the patients and their families. It also leads to motor vehicle crashes and work injuries.
There is evident economic impact of sleep apneas due to the costs of accidents and treatment.
Most researchers currently believe that both transient nocturnal hypoxemia and sleep disruption contribute to cognitive deficits seen in sleep apneas patients.
The effect of sleep apneas on cognitive functions involves many areas.
It is not clear whether CSA may be associated with cognitive impairment, as in OSA. It has been reported as a cause of confusion in the elderly and of impaired daytime performance due to sleep fragmentation.
Long-term memory shows decrements in OSA patients due to hyper somnolence and hypoxemia. Short-term memory was altered due to chronic intermittent oxyhemoglobin desaturations rather than sleepiness.
Short term memory deficits were also reported in CSA patients.
The ability to maintain attention is affected, producing uneven perform¬ance, it is likely the root cause of a significant source of OSA morbidity and mortality in motor vehicle crashes. Inattentive behaviors have been reported also in children with OSA.
Performances related to executive functions maybe the performance parameter that is most affected by OSA. Impairments identified in the OSA population include problems with verbal fluency, plan¬ning, sequential thinking, and constructional ability. Children who were reported to snore frequently also had poorer performance on each executive functions dimension.
Considering intelligence, the preschool age children with OSA are reported to have reduced IQ levels when compared with control children.
Pathogenesis of cognitive dysfunction in sleep apneas includes.
1. Gray matter loss in the cerebellar cortex and deep cerebellar nuclei, hippocampus, cingulate, temporal, and frontal cortices.
2. Metabolic Changes in Central Nervous System, OSA patients demonstrated altered metabolite composition of the cortex and white matter (a decreased ratio of NAA/Cho).
3. Vascular Endothelial dysfunction, due to repetitive episodes of hypoxia/reoxygenation in sleep apneas. Hypoxia/reoxygenation affects several enzymatic systems responsible for increased ROS formation, including enzymes of the mitochondrial respiration chain, xanthine oxidase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
4. There is a susceptibility locus for OSA in the region of the Apolipoprotein E (APOE) on chromosome 19. Memory, attention capacity, and executive functions are affected in non-demented individuals carrying the APOE e4 allele.
5. Alterations in circulating levels of IGF-1 by the presence of OSA. A role of IGF-1 in brain development, and significant positive association between serum IGF-1 levels and IQ was found.
Treatment of sleep apnea is either surgical or non surgical.
Nonsurgical management includes; preventive measures (weight loss, avoidance of alcohol, nicotine and sedatives, positional therapy and good sleep hygiene), pharmacological treatment (Modafanil as a stimulant), oral appliances, nasal continuous positive airway pressure.
Surgical management includes; nasal reconstruction, pharyngeal surgery, genioglossus advancement and hyoid myotomy, maxillomandibular advancement, adenotonsille-ctomy and tracheotomy.
Most studies show that CPAP treatment has a moderate to large effect on cog¬nitive processing, memory, sustained attention, and executive functions. Other studies compared the effect of other lines of treatment (e.g. oral appliances) to the effect of CPAP showing controversial results.
Eventually it is recommended that OSA in children should be a public health priority due to its high prevalence. Also further studies are required to assess the effect of sleep apneas on cognition in Arab countries.