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Sleeping brain, learning brain. The role of sleep for memory systems.

The hypothesis that sleep participates in the consolidation of recent memory traces has been investigated using four main paradigms: (1) effects of post-training sleep deprivation on memory consolidation, (2) effects of learning on post-training sleep, (3) effects of within sleep stimulation on the sleep pattern and on overnight memories, and (4) re-expression of behavior-specific neural patterns during post-training sleep. These studies convincingly support the idea that sleep is deeply involved in memory functions in humans and animals. However, the available data still remain too scarce to confirm or reject unequivocally the recently upheld hypothesis that consolidations of non-declarative and declarative memories are respectively dependent upon REM and NREM sleep processes.

Animals↗

Evolution of sleep quantity, sleep deprivation, mood disturbances, empathy, and burnout among interns.

PURPOSE: To explore the relationships between sleep deprivation and the evolution of mood disturbances, empathy, and burnout among a cohort of interns. METHOD: In 2002-03, 47 interns in the internal medicine resident program at the University of Pennsylvania School of Medicine completed the following instruments at baseline and at year end: sleep quantities, Epworth Sleepiness Scale, the Beck Depression Inventory-Short Form, the Interpersonal Reactivity Index, and the Maslach Burnout Inventory-Human Services Survey. The prevalences of acute and chronic sleep deprivation, subjective sleepiness, burnout, empathy, and depression at the beginning of the year were compared to prevalences at the end of internship. Associations between sleep deprivation and mood, empathy, or burnout were explored. RESULTS: The prevalence of chronic sleep deprivation, depression, burnout, and empathy increased from baseline to year end. Specifically, the prevalence of "high" scores changed for chronic sleep deprivation (9% to 43%, p = .0001). The prevalence of moderate depression increased from 4.3% to 29.8% (p = .0002). Only 4.3% reported a high level of burnout initially compared with 55.3% at year end (p < .0001). Scores that were originally more favorable than general population norms (p < .001) approached norms at the end of the year for empathic concern (p = .15). There was an association between becoming chronically sleep deprived and becoming depressed (OR = 7, p = .014). CONCLUSIONS: Given the association between chronic sleep deprivation and mood disturbances during internship, outcome assessment is warranted to see if duty-hour reform will translate into more hours slept or fewer hours worked, coincident with improved mood.

Analysis of Variance↗

Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition.

OBJECTIVE: To compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factors, to self-reported sleep difficulty in middle-aged women. DESIGN: A community-based survey of women's health and menopausal symptoms was conducted between November 1995 and October 1997 at each of the seven US sites participating in the Study of Women's Health Across the Nation. A multiethnic sample of 12,603 Caucasian, African American, Chinese, Japanese, and Hispanic women aged 40 to 55 years was categorized into six groups: premenopausal, early perimenopausal, late perimenopausal, naturally postmenopausal, surgically postmenopausal, and postmenopausal receiving hormone replacement therapy. The women were asked whether they had experienced difficulty sleeping in the past 2 weeks. RESULTS: Difficulty sleeping was reported by 38%. Age-adjusted rates were highest in the late perimenopausal (45.4%) and surgically postmenopausal (47.6%) groups. Among ethnic groups, rates ranged from 28% in Japanese women to 40% in Caucasian women. In the multivariate analysis, menopausal status was significantly associated with difficulty sleeping. Ethnicity, vasomotor and psychological symptoms, self-perceived health and health behaviors, arthritis, and education also were significantly associated with difficulty sleeping. CONCLUSIONS: These results suggest that stage of the menopausal transition, independent of other potential explanatory factors, is associated with self-reported sleep difficulty. Older age per se was not significantly associated with difficulty sleeping.

Adult↗

Posttraining increases in REM sleep intensity implicate REM sleep in memory processing and provide a biological marker of learning potential.

Posttraining rapid eye movement (REM) sleep has been reported to be important for efficient memory consolidation. The present results demonstrate increases in the intensity of REM sleep during the night of sleep following cognitive procedural/implicit task acquisition. These REM increases manifest as increases in total number of rapid eye movements (REMs) and REM densities, whereas the actual time spent in REM sleep did not change. Further, the participants with the higher intelligence (IQ) scores showed superior task acquisition scores as well as larger posttraining increases in number of REMs and REM density. No other sleep state changes were observed. None of the pretraining baseline measures of REM sleep were correlated with either measured IQ or task performance. Posttraining increases in REM sleep intensity implicate REM sleep mechanisms in further off-line memory processing, and provide a biological marker of learning potential.

Adult↗

The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.

To attempt a categorization of sleep disorders in children, we developed a 27 item Likert-type rating scale (Sleep Disturbance Scale for Children: SDSC) and assessed the psychometric properties was developed. The scale was distributed to the mothers of 1304 children (1157 controls, mean age 9.8 y; 147 sleep disorder subjects, mean age 9.2y, composed of four clinical groups: Insomnia 39 subjects, Hypersomnia 12 subjects, Respiratory disturbances during sleep 25 subjects and Parasomnias 71 subjects). The internal consistency was high in controls (0.79) and remained at a satisfactory level in sleep disorder subjects (0.71); the test/retest reliability was adequate for the total (r = 0.71) and single item scores. The factor analysis (variance explained 44.21%) yielded six factors which represented the most common areas of sleep disorders in childhood and adolescence. Enuresis was the only item with a factor loading lower than 0.40 and with a low inter-item correlation and was therefore eliminated, resulting in a final scale of 26 items. The re-evaluation of the sample, using the factor scores, supported the validity and the discriminating capacity of the scales between controls and the four clinical groups. The correlation between factor scores corroborated the hypothesis that childhood sleep disturbances are not independent entities nor do they cluster into different groupings related to each other. The SDSC appears to be a useful tool in evaluating the sleep disturbances of school-age children in clinical and non-clinical populations.

Adolescent↗

Effect of two antidepressant drugs on REM sleep and EMG activity during sleep.

In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine and dexnafenodone, an antidepressant drug under development, were investigated in young, healthy volunteers. In contrast to placebo, both drugs suppressed REM sleep substantially after acute and repeated administration. As a consequence, REM sleep latencies increased under active treatment to mean values which were about two to four times larger than baseline values. Since the active inhibition of the muscle tone is a distinct feature of REM sleep, we studied the influence of the two antidepressant drugs on this variable. By means of computerised EMG analysis, tonic and transient EMG activity were computed for total recording time and for the different sleep stages. While tonic EMG activity during sleep was increased with both drugs, transient EMG events remained unaffected. Computerised analysis of the microstructure of sleep is an effective tool for studying the effect of antidepressant drugs on sleep.

Adrenergic Uptake Inhibitors↗

Menopausal status and sleep-disordered breathing in the Wisconsin Sleep Cohort Study.

Menopause is considered to be a risk factor for sleep-disordered breathing, but this hypothesis has not been adequately tested. The association of premenopause, perimenopause, and postmenopause with sleep-disordered breathing was investigated with a population-based sample of 589 women enrolled in the Wisconsin Sleep Cohort Study. Menopausal status was determined from menstrual history, gynecologic surgery, hormone replacement therapy, follicle-stimulating hormone, and vasomotor symptoms. Sleep-disordered breathing was indicated by the frequency of apnea and hypopnea events per hour of sleep, measured by in-laboratory polysomnography. Multivariable logistic regression was used to estimate odds ratios for having 5 or more and 15 or more apnea and hypopnea events per hour. Odds ratios (95% confidence interval), adjusted for age, body habitus, smoking, and other potential confounding factors, for 5 or more apnea and hypopnea events per hour were 1.2 (0.7, 2.2) with perimenopause and 2.6 (1.4, 4.8) with postmenopause; odds ratios for 15 or more apnea and hypopnea events per hour were 1.1 (0.5, 2.2) with perimenopause and 3.5 (1.4, 8.8) with postmenopause. The menopausal transition is significantly associated with an increased likelihood of having sleep-disordered breathing, independent of known confounding factors. Evaluation for sleep-disordered breathing should be a priority for menopausal women with complaints of snoring, daytime sleepiness, or unsatisfactory sleep.

Adult↗

Clinical and parental assessment of sleep in children with attention-deficit/hyperactivity disorder referred to a pediatric sleep medicine center.

Frequently reported sleep problems in children with attention deficit-hyperactivity disorder (ADHD) referred to a pediatric sleep medicine center were assessed and compared with objective sleep assessments. A retrospective review of 97 children with ADHD (mean age of 8.3+/-3.0 years) was conducted. Polysomnography in 69 children revealed periodic limb movement disorder (PLMD) in 36% and sleep-disordered breathing in 7%, while actigraphy uncovered substantial variability in sleep schedules of 16 patients. Although parental subjective sleep complaints were verified by objective sleep assessments in a small proportion of cases, PLMD and night-to-night variability in sleep patterns were common.

Adolescent↗

A molecular window on sleep: changes in gene expression between sleep and wakefulness.

Sleep is thought to be "by the brain and for the brain," but despite decades of behavioral and neurophysiologic research, we still do not know why the brain actually needs to sleep. Recently, gene expression studies have allowed researchers to investigate the molecular correlates of sleep and wakefulness and to gain new insights into the benefits that sleep may bring at the cellular level. In the latest series of studies, a genome-wide screening of brain gene expression was performed in rats that had been asleep, spontaneously awake, or sleep deprived for 8 hours. It was found that of approximately 15,000 transcripts expressed in the cerebral cortex, about 5% change their expression levels depending on behavioral state but independently of time of day. Half of the modulated genes increase in wakefulness and half in sleep. Moreover, wakefulness-related and sleep-related transcripts belong to different functional categories. Waking-related transcripts are involved in energy metabolism, excitatory neurotransmission, transcriptional activation, synaptic potentiation and memory acquisition, and the response to cellular stress. Sleep-related transcripts are involved in brain protein synthesis, synaptic consolidation/depression, and membrane trafficking and maintenance, including cholesterol metabolism, myelin formation, and synaptic vesicle turnover.

Animals↗

Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP.

Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable. Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope. CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP application (from 6.5+/-2.4 to 7.5+/-2.9 ms x mmHg(-1)), mostly in response to decreasing blood pressure. The change in BRS did not correlate with changes in arterial oxygen saturation or apnoea/hypopnoea index. The small change in baroreflex control of heart rate during sleep at first application of continuous positive airway pressure in severe obstructive sleep apnoea was unrelated to the acute resolution of nocturnal hypoxaemia, and might reflect autonomic adjustments to positive intrathoracic pressure, and/or improved sleep architecture. The small increase in baroreflex control of heart rate during sleep may be of clinical relevance as it was accompanied by reduced cardiovascular variability, which is acknowledged as an independent cardiovascular risk factor.

Adult↗

REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease.

OBJECTIVE: To determine the frequency of REM sleep behavior disorder (RBD) among patients with PD using both history and polysomnography (PSG) recordings and to further study REM sleep muscle atonia in PD. BACKGROUND: The reported occurrence of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency of RBD using PSG recordings or analyzed in detail the characteristics of REM sleep muscle atonia in a large group of unselected patients with PD. METHODS: Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were studied. Each subject underwent a structured clinical interview and PSG recording. REM sleep was scored using a method that allows the scoring of REM sleep without atonia. RESULTS: One third of patients with PD met the diagnostic criteria of RBD based on PSG recordings. Only one half of these cases would have been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16 control subjects had REM sleep without atonia. Of these 19 patients with PD, 8 (42%) did not present with behavioral manifestations of RBD, and their cases may represent preclinical forms of RBD associated with PD. Moreover, the percentage of time spent with muscle atonia during REM sleep was lower among patients with PD than among healthy control subjects (60.1% vs 93.2%; p = 0.003). CONCLUSIONS: RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.

Aged↗

Respiratory effort. A factor contributing to sleep propensity in patients with obstructive sleep apnea.

To test the hypothesis that respiratory effort during obstructive apneas contributes, together with hypoxemia and sleep fragmentation, to excessive daytime sleepiness, we investigated the relationship between daytime sleepiness and polysomnographic variables in 44 patients with obstructive sleep apnea (OSA). In all patients, daytime sleep propensity was assessed by an 11-item standardized self-questionnaire yielding a sleepiness score and by a modified sleep latency test yielding a mean sleep latency. Respiratory effort during apneas was evaluated by measuring esophageal pressure swings using an esophageal balloon. Within each apneic cycle, we measured the esophageal pressure swings during the first three and the last three occluded efforts during the apnea to define the overall increase, its ratio to apnea duration, and the maximal effort developed during obstruction. In the group of patients as a whole, the sleepiness score was negatively correlated with the mean sleep latency (r=-0.38, p=0.01). The sleepiness score was correlated with the indexes of respiratory effort during apneas (ie, the overall increase, its ratio to apnea duration, and the maximal end-apneic swing in esophageal pressure) and with the apnea+hypopnea index. The mean sleep latency was correlated with all indexes of nocturnal hypoxemia (ie, the mean lowest oxyhemoglobin saturation [SaO2] and the index of apnea associated with a fall in SaO2 below 90% and 80%). We conclude that the degree of respiratory effort during obstructive apneas contributes to self-rated sleep propensity in patients with OSA.

Adult↗

Periodic sleep apnea: chronic sleep deprivation related to intermittent upper airway obstruction and central nervous system disturbance.

Periodic sleep apnea may be due to repeated episodes of upper airway obstruction in patients who have a short thick neck and/or large jowls. Apnea due to complete cessation of breathing may occur to a lesser extent. Anaylsis of the sleep electroencephalogram shows that these patients rarely achieve deep sleep and have less stage 1-REM sleep than normal subjects of comparable age. They are chronically sleep-deprived, a manifestation expressed by daytime somnolence, chronic fatigue and often by personality disturbances marked by paranoia, agitated depression and hostility. The definitive diagnosis of this syndrome may be established by monitoring during sleep, the electroencephalogram, measuring abdominal excursions through a mercury-in-Silastic-strain gauge and recording air flow at the nose by means of a thermocouple. As demonstrated by other investigators, chronic hypoventilation during sleep leads to both pulmonary and systemic arterial hypertension, which may produce generalized cardiac enlargement and congestive heart failure. The abnormalities in the periodic sleep apnea syndrome are abolished by establishing a patent airway either through tracheostomy or weight reduction.

Adult↗

Chronic snoring and sleep in children: a demonstration of sleep disruption.

OBJECTIVE: Chronic snoring that does not adhere to the criteria for a diagnosis of obstructive sleep apnea syndrome may be associated with learning and behavioral problems. We investigated the sleep structure of chronic snorers who had an apnea-hypopnea index of < 1 event per hour and analyzed the cyclic alternating pattern. METHODS: Fifteen successively seen chronic snorers (9.8 +/- 4 years) with an apnea-hypopnea index of <1 and 15 aged-matched control subjects (10.3 +/- 5 years) underwent an investigation of their sleep with the determination of non-apneic-hypopneic breathing abnormalities polysomnographic scoring using current criteria and analysis of the cyclic alternating pattern. RESULTS: Chronic snorers have evidence of flow limitations and tachypnea during sleep even if they do not present with apneas, hypopneas, and decrease in oxygen saturations. They also present with abnormal cyclic alternating pattern rates and changes in phase A of cyclic alternating pattern compared with control subjects. CONCLUSIONS: An apnea-hypopnea index value cannot be the sole determinant in evaluating sleep-disordered breathing in children. Children who have chronic snoring and do not respond to the criteria for obstructive sleep apnea syndrome can present with an abnormal sleep electroencephalogram as evidenced by a significant increase in cyclic alternating pattern rates, with a predominance of abnormalities in slow wave sleep.

Adolescent↗

Effect of sleep position on obstructive sleep apnea.

In order to examine the effect of sleep position on sleep apnea episodes, seven male patients diagnosed as having obstructive sleep apnea syndrome without any organic complication of the upper airway were studied while lying in a supine or lateral position during an all-night polysomnographic study. Apnea index, apnea time/total sleep time (%) and the number of episodes per hour in which oxyhemoglobin saturation dropped below 85% decreased significantly from 51.0 +/- 8.6 (mean +/- S.D.) events/hr, 40.4 +/- 5.8% and 36.2 +/- 9.8 episodes/hr during sleep in supine position to 27.6 +/- 9.1 events/hr, 19.4 +/- 6.0% and 12.9 +/- 5.3 episodes/hr during sleep in lateral position, respectively. Lowest oxyhemoglobin saturation increased significantly from 70.7 +/- 2.6% to 78.0 +/- 2.4%. Thus, sleep in the lateral position may be a simple treatment before essential treatment for patients with obstructive sleep apnea syndrome.

Adult↗

Sleep quality, sleep propensity and academic performance.

We examined associations between measures of sleep propensity on the Epworth Sleepiness Scale, sleep quality on the Pittsburgh Sleep Quality Index and academic performance by GPA and grades in introductory psychology for 414 students. In the total sample, neither sleep propensity nor sleep quality correlated with GPA or introductory psychology grades. However, among students carrying a full course load, those reporting poor sleep quality performed less well on academic measures than those reporting a better quality of sleep. Further research is needed to assess the moderating influence of overall demands of daytime functioning on the association between sleep quality and academic performance.

Achievement↗

Sleep in persons with dementia: Increasing quality of life by managing sleep disorders.

In individuals with dementia, sleep disruptions (e.g., increased number of nighttime awakenings after falling asleep, lower sleep efficiency, increased daytime napping, changes in the amount of rapid eye movement (REM) and non-rapid eye movement (NREM) sleep increase as the dementia increases in severity. Sleep can also be disrupted in individuals with dementia because of primary sleep disorders, such as obstructive sleep apnea, advanced sleep phase syndrome, and restless legs. Other factors that contribute to disrupted sleep in individuals with dementia include age, acute and chronic illness, mood disorders, and medication use.

Aged↗

Sleep disorders: sleep apnea and narcolepsy.

Symptoms of obstructive sleep apnea, a potentially life-threatening disorder, include excessive daytime sleepiness and sleep attacks, nocturnal breath cessation, and snorting and gasping sounds. These symptoms usually become manifest before age 40 and cluster within a few years. Most patients are obese, hypertensive men who eventually develop cardiovascular abnormalities. If sleep apnea is suspected based on clinical information, a sleep laboratory evaluation is indicated. For severe obstructive sleep apnea, tracheostomy is the most effective treatment. Narcolepsy, another sleep disorder, is a life-long and usually disabling condition. In most narcoleptic patients the first symptoms develop during childhood or adolescence, yet many years pass before the proper diagnosis is made. The presence of sleep attacks together with auxiliary symptoms, particularly cataplexy, is diagnostic. Treatment of narcolepsy includes stimulants in combination with therapeutic naps for sleep attacks and tricyclic drugs for cataplexy.

Humans↗