A systematic review of patient-reported outcome instruments measuring sleep dysfunction in adults

Sleep dysfunction can manifest in several ways, ranging from insomnia to somnolence, and from disrupted sleep to lack of restful sleep. Measuring sleep dysfunction is an area of active research and there exist a number of patient-reported outcome instruments that measure various aspects of sleep dysfunction. However, these instruments have not been evaluated systematically. We used a conceptual model of sleep that included four physical domains of general interest to patients and investigators, and cover the breadth of this disorder: sleep initiation; sleep maintenance; sleep adequacy; and somnolence. We next considered the additional health-related quality-of-life (HR-QOL) domains of psychological and social functioning, progressing along the continuum to include health perceptions and opportunity. We then conducted a literature review to identify instruments and, using criteria developed by the Medical Outcomes Trust Scientific Advisory Committee, evaluated these instruments for their potential use in measuring sleep dysfunction. Twenty-two instruments were identified. Six instruments were found to include the four physical domains defined a priori (Basic Nordic Sleep Questionnaire, Leeds Sleep Evaluation Questionnaire, Medical Outcomes Study - Sleep Problems Measures, Pittsburgh Sleep Diary, Pittsburgh Sleep Quality Index, Self-Rated Sleep Questionnaire and the Sleep Dissatisfaction Questionnaire). Several additional instruments addressed at least some of the domains and thus may be useful for specific purposes. A few instruments addressed overall HR-QOL, but did not include all four domains of interest (Functional Outcomes of Sleep Questionnaire, Quality of Life in Insomniacs and the Sleep-Wake Activity Inventory). Two instruments had undergone extensive psychometric evaluation (Medical Outcomes Study - Sleep Problems Measures and Pittsburgh Sleep Quality Index), with only the latter reporting information about interpretability. Our review indicates that measuring sleep dysfunction in adults is an area of active research and that much work still needs to be completed, specifically the study of interpretability and the application of patient preferences or item response theory. The specific research focus should dictate instrument selection.     

Sleep disorders in Parkinson's disease: epidemiology and management

Sleep problems are an under-emphasised cause of disability in Parkinson's disease (PD) and may be seen independently of PD, associated with primary PD pathology, or as a result of antiparkinsonian medications. Common sleep disorders include excessive daytime sleepiness, rapid eye movement (REM) sleep behaviour disorder, night-time wakefulness and restless legs syndrome. A number of strategies may be used to improve sleep cycle disturbances, and often these interventions do not require pharmacological manipulation. Restoring traditional mealtimes and scheduling activities during predicted periods of sleepiness may help alleviate daytime somnolence; the use of controlled-release levodopa preparations or administration of a catechol-O-methyl transferase (COMT) inhibitor with levodopa at bedtime may reduce periods of night-time wakefulness. Administration of clonazepam at bedtime may assist with REM sleep behaviour disorder but, because this agent can result in daytime somnolence, experimentation with dosage times is recommended. Sleep attacks are described as a sudden, unavoidable transition from wakefulness to sleep and, although rare, have been described with pramipexole, ropinirole and other dopamine agonists. Although the condition has yet to be recognised by the International Association of Sleep Disorders, patients with PD who report rapid sleep onset should be evaluated for the possibility of sleep attacks. If sleep attacks are suspected, it is reasonable to strongly caution patients regarding potentially risk-associated activities such as driving, and to consider careful withdrawal of dopaminergic therapy.     

Sleep-Dependent Declarative Memory Consolidation—Unaffected after Blocking NMDA or AMPA Receptors but Enhanced by NMDA Coagonist D-Cycloserine

Sleep has a pivotal role in the consolidation of declarative memory. The coordinated neuronal replay of information encoded before sleep has been identified as a key process. It is assumed that the repeated reactivation of firing patterns in glutamatergic neuron assemblies translates into plastic synaptic changes underlying the formation of longer-term neuronal representations. Here, we tested the effects of blocking and enhancing glutamatergic neurotransmission during sleep on declarative memory consolidation in humans. We conducted three placebo-controlled, crossover, double-blind studies in which participants learned a word-pair association task. Afterwards, they slept in a sleep laboratory and received glutamatergic modulators. Our first two studies aimed at impairing consolidation by administering the NMDA receptor blocker ketamine and the AMPA receptor blocker caroverine during retention sleep, which, paradoxically, remained unsuccessful, inasmuch as declarative memory performance was unaffected by the treatment. However, in the third study, administration of the NMDA receptor coagonist D-cycloserine (DCS) during retention sleep facilitated consolidation of declarative memory (word pairs) but not consolidation of a procedural control task (finger sequence tapping). Administration of DCS during a wake interval remained without effect on retention of word pairs but improved encoding of numbers. From the overall pattern, we conclude that the consolidation of hippocampus-dependent declarative memory during sleep relies on NMDA-related plastic processes that differ from those processes leading to wake encoding. We speculate that glutamatergic activation during sleep is not only involved in consolidation but also in forgetting of hippocampal memory with both processes being differentially sensitive to DCS and unselective blockade of NMDA and AMPA receptors.     

Physiological sleep-dependent changes in arterial blood pressure: central autonomic commands and baroreflex control

Sleep is a heterogeneous behaviour. As a first approximation, it is subdivided objectively into two states: non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). The mean value and variability of arterial blood pressure (ABP) decrease physiologically from wakefulness to NREMS. In REMS, there may be a further decrease or increase in mean ABP as well as phasic hypertensive events, which enhance the variability of ABP. The reduced mean ABP during NREMS results from a decrease in either heart rate or sympathetic vasoconstrictor tone. During REMS, sympathetic activity to the different cardiovascular effectors undergoes a substantial repatterning. Thus, the mean ABP in REMS reflects a balance between changes in cardiac output and constriction or dilatation of different vascular beds. In both sleep states, the phasic changes in ABP are driven by bursts of vasoconstriction, which may be accompanied by surges of heart rate. The available evidence supports the hypothesis that the sleep-dependent changes in ABP, either tonic or phasic, result from the integration between cardiovascular reflexes and central autonomic commands that are specific to each sleep state.     

The effects of estazolam on sleep, performance, and memory: a long-term sleep laboratory study of elderly insomniacs.

Insomnia, a common complaint among the elderly, is generally treated with benzodiazepines. Long-acting benzodiazepines (e.g., flurazepam) often produce daytime somnolence and performance deficits, whereas short-acting drugs (e.g., triazolam) have been associated with marked rebound insomnia and anterograde memory loss. The authors designed a pilot study to evaluate the efficacy of an intermediate-acting benzodiazepine, estazolam (e.g., ProSom), as well as its side effects. The parameters studied were sleep, daytime performance, and memory. Ten geriatric patients (greater than 60 years of age) with insomnia participated in the study. They received placebo nightly for 2 weeks (baseline), estazolam 1 mg nightly for the next 4 weeks (treatment phase), and placebo again for 2 weeks (withdrawal period). Sleep was monitored by polysomnography the first two nights of each week in a sleep laboratory. Estazolam significantly decreased sleep latency, nocturnal awakenings, and wake time after sleep onset. Total sleep time increased an average of 63 minutes the first night of treatment. Significant improvements in wake time after sleep onset and total sleep time also were observed in the fourth week of estazolam treatment. Rebound insomnia occurred on the first withdrawal night only for wake time and total sleep time. By the next night, these sleep parameters returned to baseline. Neither day-time performance nor anterograde memory was adversely affected by estazolam treatment or its withdrawal. A 1-mg dose of estazolam appears to be a safe and effective hypnotic for elderly patients with insomnia.     

Effects of sleep deprivation on retrieval and reconsolidation of morphine reward memory in rats

Relapse induced by exposure to cues associated with drugs of abuse is a major challenge to the treatment of drug addiction. Drug seeking can be inhibited by manipulation of the reconsolidation of drug-related memory. Sleep has been proposed to be involved in various memory processes. However, the role of sleep in drug reward memory is not clear. The present study used conditioned place preference to examine the effects of total sleep deprivation on retrieval and reconsolidation of morphine reward memory in rats. Six-hour total sleep deprivation had no effect on the retrieval of morphine reward memory. However, sleep deprivation from 0-6 h, but not 6-12 h, after re-exposure disrupted the reconsolidation of morphine reward memory. This impairment was not attributable to the formation of an aversive associative memory between the drug-paired context and sleep deprivation. Our findings suggest that sleep plays a critical role in morphine reward memory reconsolidation, and sleep deprivation may be a potential non-pharmacotherapy for the management of relapse associated with drug-related memory.     

Possible mechanism involved in sleep deprivation-induced memory dysfunction

Sleep deprivation disrupts various vital biological and metabolic processes that are necessary for health. The present study was designed to investigate the possible mechanisms of sleep deprivation-induced memory dysfunction by using different behavioral, biochemical and neurochemical parameters. Male Wistar rats were sleep deprived for 72 h using a grid suspended over water. Elevated plus maze, passive avoidance and Morris water maze tests were used to assess memory retention in 72-h sleep-deprived animals. Various electrophysiological (sleep-wake cycle), biochemical (lipid peroxidation, reduced glutathione, nitrite, catalase, acetylcholinesterase) and neurochemical parameters (norepinephrine, dopamine and serotonin) were also assessed. Sleep deprivation resulted in memory dysfunction in all the behavioral paradigms, alteration in the sleep-wake cycle (delayed sleep latency, shortening of rapid eye movement [REM] and non-REM [NREM] sleep and increased waking period) and oxidative stress (increased lipid peroxidation and nitrite levels, depletion of reduced glutathione and catalase activity). In addition, increased levels of acetylcholinesterase (AChE; the enzyme responsible for the degradation of acetylcholine) and reduction in norepinephrine and dopamine levels were seen in 72-h sleep-deprived animals. In conclusion, sleep deprivation-induced memory deficits may possibly be due to the combined effect of oxidative damage and alterations in neurotransmitter levels.     

Zebrafish as a Tool in the Study of Sleep and Memory-related Disorders

Sleep is an evolutionarily conserved phenomenon, being an important biological necessity for the learning process and memory consolidation. The brain displays two types of electrical activity during sleep: slow-wave activity or Non-Rapid Eye Movement (NREM) sleep, and desynchronized brain wave activity or Rapid Eye Movement (REM) sleep. There are many theories regarding “Why we need to sleep?”; one of them is the synaptic homeostasis. This theory suggests the role of sleep in the restoration of synaptic homeostasis, which is destabilized by synaptic strengthening triggered by learning during waking and by synaptogenesis during development. Sleep diminishes the plasticity load on neurons and other cells to normalize synaptic strength whereas it reestablishes neuronal selectivity and the ability to learn, leading to the consolidation and integration of memories. The use of zebrafish as a tool to assess sleep and its disorders is growing, although sleep in this animal is not yet divided, for example, into REM and NREM states. However, zebrafish are known to have a regulated daytime circadian rhythm, and their sleep state is characterized by periods of inactivity accompanied by an increase in arousal threshold, preference for resting place, and the “rebound sleep effect” phenomenon, which causes an increased slow-wave activity after a forced waking period. In addition, drugs known to modulate sleep, such as melatonin, nootropics, and nicotine have been tested in zebrafish. In this review, we discuss the use of zebrafish as a model to investigate sleep mechanisms and their regulation, demonstrating this species as a promising model for sleep research.     

The relationship between subjective ratings of sleep and mental functioning in healthy subjects and patients with chronic fatigue syndrome

The present study examined the relationships between subjective reports of sleep and mental functioning. This was done both for healthy subjects and chronic fatigue syndrome patients, a group who frequently report sleep disorders. Sleep abnormalities were found to be related to personality and to state measures of physical and mental health. Distractability, as measured by the Stroop task, was also related to sleep disorder. The psychomotor slowing observed in the chronic fatigue syndrome patients was not modified by sleep status. However, the problems of memory and sustained attention found in the patients were restricted to those subgroups with sleep disorders.     

Antidepressants and sleep: a qualitative review of the literature

Most antidepressants change sleep; in particular, they alter the physiological patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months. Sleep initiation and maintenance are also affected by antidepressants, but the effects are much less consistent between drugs. Some antidepressants such as clomipramine and the selective serotonin receptor inhibitors (SSRIs), particularly fluoxetine, are sleep-disturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects are fairly short-lived and there are very few significant differences between drugs after a few weeks of treatment. In general, the objectively measured sleep of depressed patients improves during 3-4 weeks of effective antidepressant treatment with most agents, as does their subjective impression of their sleep. Sleep improvement earlier in treatment may be an important clinical goal in some patients, perhaps when insomnia is particularly distressing, or to ensure compliance. In these patients, the choice of a safely used and effective antidepressant which improves sleep in short term is indicated. Patients with other sleep disorders such as restless legs syndrome and REM sleep behaviour disorder should be identified before choosing a treatment, as some antidepressants worsen these conditions. Conversely, there is evidence that some antidepressants may be useful in the treatment of sleep disorders such as night terrors.     

Sleep in babies born to chronically heroin addicted mothers. A follow up study

The effects of chronic addiction to, and withdrawal from, opiates on sleep have been described in experimental animals, in human adults and infants born to addicted mothers. These sleep alterations are seen through the first weeks of life. Thirteen maternally addicted babies were studied. Sleep samples were recorded and scored within a few days following birth and repeated 4 or 5 weeks later after recovery from the abstinence syndrome. A significant decrease in quiet sleep and increase of active sleep were found. The same alterations, although less marked, were observed in a follow up recording performed during the second month of life. Sleep alterations in addicted newborns could be related to central nervous system (CNS) distress caused by withdrawal. The authors however propose a perturbation of endogenous opiates subsequent to fetal addiction as a cause of sleep alterations.     

鼻用糖皮质激素联合孟鲁司特钠对轻度阻塞性睡眠呼吸暂停综合征患儿睡眠状况及记忆能力的影响

目的 研究鼻用糖皮质激素联合孟鲁司特钠对轻度阻塞性睡眠呼吸暂停综合征患儿睡眠状况及记忆能力的影响.方法 抽选2014年2月至2015年5月就诊于我院的睡眠呼吸暂停综合征患儿98例,随机法分为观察组(n=49)和对照组(n=49),对照组患儿给予鼻用糖皮质激素治疗,观察组在此基础上加用孟鲁司特钠口服治疗.比较两组患儿睡眠及记忆能力改善情况,检测半胱氨酰白三烯(Cys-LTs)水平.结果 两组患儿治疗后睡眠总时间和快速眼动睡眠期均显著增加,且观察组明显长于对照组,差异均有统计学意义(P＜0.05).两组患儿治疗后AHI异常次数显著下降,观察组显著低于对照组,差异有统计学意义(P＜0.05).两组患儿治疗后MQ优秀率均显著上升,且观察组优秀率明显高于对照组(87.76％ vs.71.43％),差异有统计学意义(P＜0.05).观察组治疗后尿Cys-LTs/尿肌酐比值低于对照组,差异有统计学意义(P＜0.05).结论 鼻用糖皮质激素联合孟鲁司特钠治疗轻度阻塞性睡眠呼吸暂停综合征患儿,能显著提升患儿睡眠质量,提高其记忆能力.     

Self-report of memory and affective dysfunction in association with medication use in a sample of individuals with chronic sleep disturbance

Benzodiazepines produce memory disturbance after acute administration. It is not clear whether chronic use of benzodiazepines is hazardous to memory processes. Epidemiological data indicate that a large proportion (10-30 per cent) of individuals with sleep dysfunction take hypnotic aids for a year or longer. The purpose of the present study was to evaluate self-reported memory dysfunction in a sample of individuals who considered their sleep disturbance sufficiently severe to seek investigation in sleep clinics. It was hypothesized that individuals taking benzodiazepines for sleep would report greater perceived everyday memory failures than individuals taking other sleep aids or no medication. Questionnaires were given to 368 individuals referred into the study by investigators in six sleep disorders clinics. All respondents completed a lengthy (700-item) questionnaire, which included scales assessing memory difficulties, affective status and sleep disturbance. Respondents also reported any medication use for sleep problems and duration of use of the current drug. Information on medication use was reported by 289 participants. Fifty-six per cent of respondents reported using some form of psychoactive medication (antidepressants, benzodiazepines, Zopiclone). Twenty-two per cent reported using no medication. Analysis of covariance showed that these medications had no detectable effect on subjective memory difficulties during chronic use, F(4,226)=1.34, p=0.25. Copyright 2000 John Wiley & Sons, Ltd.     

Sleep dysfunction in patients with gastro-oesophageal reflux disease: prevalence and response to GERD therapy, a pilot study

BACKGROUND: There is little information on the prevalence of pathological sleep disorders in patients with gastro-oesophageal reflux disease and whether pharmacological treatment of patients with gastro-oesophageal reflux disease will lead to improvement in sleep. AIMS: This pilot study determined the prevalence of sleep disorder in patients with erosive gastro-oesophageal reflux disease, correlated subjective (questionnaire) and objective (actigraphy - a watch worn on the wrist that monitors motion to help differentiate sleep from awake states) assessment of sleep dysfunction and determined whether therapeutic resolution of oesophageal symptoms was associated with an improvement in sleep. METHODS: Eighteen patients with erosive gastro-oesophageal reflux disease received esomeprazole 40 mg once daily for 8 weeks. Assessments at 0, 4 and 8 weeks included: Gastrointestinal Symptoms Rating Scale, Pittsburgh Sleep Quality Index questionnaire and ambulatory wrist actigraphy. RESULTS: Unrecognized sleep disturbance occurred in 81% of this cohort of patients with gastro-oesophageal reflux disease and erosive oesophagitis. Median reflux syndrome score (heartburn and acid regurgitation) on Gastrointestinal Symptoms Rating Scale decreased from 2 at baseline to 0 at weeks 4 and 8 (P 相似文献   

Sleep homeostasis: a role for adenosine in humans?

Sleep is not the mere absence of wakefulness, but an active state which is finely regulated. The homeostatic facet of sleep–wake regulation is keeping track of changes in ‘sleep propensity’ (or ‘sleep need’), which increases during wakefulness and decreases during sleep. Increased sleep propensity following extended prior wakefulness (sleep deprivation) is counteracted by prolonged sleep duration, but also by enhanced non-rapid-eye-movement (nonREM) sleep intensity as measured by electroencephalographic (EEG) slow-wave activity (SWA, power within 1–4 Hz). This highly reliable regulatory feature of nonREM sleep may be the most important aspect of sleep in relation to its function. The neurochemical mechanisms underlying nonREM sleep homeostasis are poorly understood. Here we provide compelling and convergent evidence that adenosinergic neurotransmission plays a role in nonREM sleep homeostasis in humans. Specifically, a functional polymorphism in the adenosine metabolizing enzyme, adenosine deaminase, contributes to the high inter-individual variability in deep slow-wave sleep duration and intensity. Moreover, the adenosine receptor antagonist, caffeine, potently attenuates the EEG markers of nonREM sleep homeostasis during sleep, as well as during wakefulness. Finally, adenosinergic mechanisms modulate individual vulnerability to the detrimental effects of sleep deprivation on neurobehavioral performance, and EEG indices of disturbed sleep after caffeine consumption. While these convergent findings strongly support an important contribution of adenosine and adenosine receptors to nonREM sleep homeostasis, further research is needed to elucidate the underlying mechanisms that mediate the actions of adenosine on sleep and the sleep EEG.     

Hypnosedative-induced complex behaviours : incidence, mechanisms and management

A number of news items and case reports describing complex behaviours (e.g. sleep driving, sleep cooking, sleep eating, sleep conversations, sleep sex) associated with the use of hypnosedative medications have recently received considerable attention. Regulatory agencies examining these reports have subsequently issued warnings regarding the potential of hypnosedative agents to produce complex behaviours. Despite these warnings, little is known about the likelihood, presentation, treatment or prevention of hypnosedative-induced complex behaviours. The purpose of this review is to evaluate the published evidence regarding the clinical presentation, incidence, mechanism and management of sleep-related behaviours induced by nonbenzodiazepine receptor agonists (NBRAs).Review of the literature identified ten published case reports of NBRA-induced complex behaviours involving 17 unique patients. Fifteen of the 17 patients described in the case reports had taken zolpidem, one had taken zaleplon and one had taken zopiclone. The complex behaviours most commonly reported were sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping. Elevated serum concentrations resulting from increased medication dose or drug-drug interactions appeared to play a role in some but not all cases. Sex, age, previous medication exposure and concomitant disease states were not consistently found to be related to the risk of experiencing a medication-induced complex behaviour.From a pharmacological standpoint, enhancement of GABA activity at GABAA receptors (particularly alpha1-GABAA receptors) is a possible mechanism for hypnosedative complex behaviours and amnesia. Evidence suggests that complex behaviour risk may increase with both dose and binding affinity at alpha1-GABAA receptors. The amnesia that accompanies complex behaviours is possibly due to inhibition of consolidation of short- to long-term memory, suggesting that the risk may extend to non-GABAergic hypnosedatives. While amnesia and GABA-related receptor actions are the most frequently discussed mechanisms for complex behaviours in the literature, they do not fully explain such behaviours, suggesting that other mechanisms and factors probably play a role.A number of potential strategies are available to manage or prevent hypnosedative-induced complex behaviours. These include lowering the dose of, or stopping, the offending hypnosedative, switching to a different hypnosedative, treating patients with other classes of medications, using nonpharmacological treatment strategies for patients with sleep disorders, examining drug regimens for potential drug interactions that may predispose patients to experiencing complex behaviours, administering hypnosedative medications appropriately and selecting patients more carefully for treatment in terms of their likelihood of experiencing medication adverse effects.     

Effect of repeated gaboxadol administration on night sleep and next-day performance in healthy elderly subjects.

Aging is associated with dramatic reductions in sleep continuity and sleep intensity. Since gaboxadol, a selective GABA(A) receptor agonist, has been demonstrated to improve sleep consolidation and promote deep sleep, it may be an effective hypnotic, particularly for elderly patients with insomnia. In the present study, we investigated the effects of subchronic gaboxadol administration on nocturnal sleep and its residual effects during the next days in elderly subjects. This was a randomized, double-blind, placebo-controlled, balanced crossover study in 10 healthy elderly subjects without sleep complaints. The subjects were administered either placebo or 15 mg gaboxadol hydrochloride at bedtime on three consecutive nights. Sleep was recorded during each night from 2300 to 0700 h and tests assessing attention (target detection, stroop test) and memory function (visual form recognition, immediate word recall, digit span) were applied at 0900, 1400, and 1700 h during the following days. Compared with placebo, gaboxadol significantly shortened subjective sleep onset latency and increased self-rated sleep intensity and quality. Polysomnographic recordings showed that it significantly decreased the number of awakenings, the amount of intermittent wakefulness, and stage 1, and increased slow wave sleep and stage 2. These effects were stable over the three nights. None of the subjects reported side effects. Next-day cognitive performance was not affected by gaboxadol. Gaboxadol persistently improved subjective and objective sleep quality and was devoid of residual effects. Thus, at the employed dose, it seems an effective hypnotic in elderly subjects.     

Inflammation, sleep, obesity and cardiovascular disease

Evidence is emerging that disturbances in sleep and sleep disorders play a role in the morbidity of chronic conditions. However, the relationship between sleep processes, disease development, disease progression and disease management is often unclear or understudied. Numerous common medical conditions can have an affect on sleep. For example, diabetes or inflammatory conditions such as arthritis can lead to poor sleep quality and induce symptoms of excessive daytime sleepiness and fatigue. It has also been suggested that poor sleep may lead to the development of cardiovascular disease for which an underlying inflammatory component has been proposed. It is therefore important that the development and progression of such disease states are studied to determine whether the sleep effect merely reflects disease progression or whether it may be in some way causally related. Sleep loss can also have consequences on safety related behaviours both for the individuals and for the society, for example the increased risk of accidents when driving while drowsy. Sleep is a complex phenotype and as such it is possible that there are numerous genes which may each have a number of effects that control an individual's sleep pattern. This review examines the interaction between sleep (both quantity and quality) and parameters of cardiovascular risk. We also explore the hypothesis that inflammation plays an essential role in cardiovascular disease and that a lack of sleep may play a key role in this inflammatory process. AIM: To review current evidence regarding the endocrine, metabolic, cardiovascular and immune functions and their interactions with regard to sleep, given the current evidence that sleep disturbances may affect each of these areas.     

Zolpidem and triazolam do not affect the nocturnal sleep-induced memory improvement

Rationale It is widely accepted that sleep facilitates memory consolidation. Hypnotics (e.g., benzodiazepines), which reportedly increase sleep efficiency but also modify sleep architecture, could affect memory improvement that occurs during sleep. Objectives The present study examined the effects of single doses of two short half-life hypnotics, zolpidem and triazolam, on sleep-induced improvement of memory. Methods Twenty-two healthy volunteers participated in this randomized, double-blind, crossover study. All subjects received a single oral dose of zolpidem (10 mg), triazolam (0.25 mg) or placebo at 9 p.m. and slept for 7.5±0.2 h. The effect of sleep on memory was investigated by comparing the performance of this group of volunteers with a group of 21 subjects in wakefulness condition. Declarative memory was evaluated by using a free-recall test of ten standard word and seven nonword lists. Subjects memorized the word and nonword lists 1 h before dosing and they were asked to recall the memorized lists 10 h after dosing. Digit symbol substitution test (DSST) and forward and backward digit tests were also given 1 h before and 10 h after dosing. Results Subjects who slept remembered more nonwords than those in wakefulness condition, but they did not recall significantly more standard words. Neither zolpidem nor triazolam affected the enhanced nonword recall observed after sleep. Finally, none of the hypnotics affected the improvement in the DSST performance of subjects who slept. Conclusions The hypnotics tested did not interfere with the nocturnal sleep-induced improvement of memory.