老年神经变性疾病相关睡眠障碍的管理

<正>神经系统变性疾病常发生于老年人,神经变性病的患者常合并多种睡眠障碍,如:失眠、睡眠呼吸障碍、嗜睡、异态睡眠(如快速动眼睡眠行为障碍)、昼夜节律紊乱、睡眠相关运动障碍(如不宁腿综合征)等。如果不能识别和处理这些睡眠障碍,会导致患者生活质量下降及神经系统相关症状加重。本文对     

针刺与药物治疗女性更年期失眠症30例

更年期女性由于体内雌激素水平下降可导致体温调节过程、昼夜节律、应激反应等改变,从而导致睡眠障碍。约三分之二的更年期女性会出现一系列由于体内雌激素变化所引起的各种相关症状,33%～51%的更年期妇女存在睡眠障碍。更年期失眠虽极少危及生命,但极大影响着女性心理及生理健     

昼夜节律失调性睡眠障碍的研究进展

良好的睡眠是生长发育、机体恢复、保持心理健康等的需要,但随着现代人生活节奏的加快,睡眠问题也日益增多.据2005年国际睡眠疾病分类第二版(ICSD-Ⅱ),睡眠障碍分为8类:失眠、睡眠相关呼吸障碍、睡眠过度、昼夜节律失调性睡眠障碍、睡眠行为障碍、睡眠运动障碍、孤立的睡眠症状、其他睡眠障碍[1].其中,昼夜节律失调性睡眠障碍又可以分为:睡眠时相滞后(delayed sleep phase,DSP)、睡眠时相超前(advanced sleep phase,ASP)、无规则型睡眠-觉醒节律(irregular sleep-wake cycle)紊乱、时区改变睡眠障碍(jet lag disorder)、轮班工作睡眠障碍(shiftwork disorder)、自激型睡眠-觉醒节律(free-running type)6种类型,常见的是DSP、ASP和无规则型睡眠-觉醒节律紊乱[2].     

老年睡眠障碍患者营养干预专家共识

睡眠障碍是常见的身体功能障碍，表现为睡眠-觉醒过程中的各种功能紊乱。根据国际睡眠疾病分类第三版（ICSD-3），睡眠障碍的种类包括失眠、睡眠相关呼吸障碍、中枢性嗜睡障碍、昼夜节律睡眠-觉醒障碍、异态睡眠、睡眠相关运动障碍和其他睡眠障碍。不同类型常常同时存在，最常见的为失眠障碍和睡眠相关呼吸障碍。睡眠障碍严重影响老年人心理卫生和日常生活满意度，本共识从营养筛查、评定、干预等方面推荐营养素调节睡眠，以及合并睡眠障碍的特殊人群的营养指导等方面着手制定本共识，强调全面生活方式干预的重要性，积极寻求有效方法帮助老年人提高睡眠质量。     

睡眠障碍同慢性肝病相关性的研究进展

各种原因所致的慢性肝病在进展过程中往往伴随不同程度或不同类型的睡眠障碍,如：入睡困难、早醒、多梦、日间嗜睡、昼夜颠倒等。慢性肝病患者出现睡眠障碍的主要机制包括昼夜节律紊乱、肝性脑病、肠道菌群失调等,同时越来越多的证据表明,睡眠障碍会严重影响肝病患者的日常生活质量及疾病预后。本文就近年来关于睡眠障碍与慢性肝病之间相互作用的研究作一综述,以期提高临床医师对于肝病患者睡眠障碍的重视程度,并为改善慢性肝病患者的睡眠情况提供新思路。     

老年神经系统疾病患者睡眠障碍的处理

神经系统的某些疾病可出现程度不同的睡眠障碍，但产生睡眠障碍的机制不明，可能与病变累及睡眠调节结构，或由于疾病（如脑血管病导致瘫痪等）长期卧床引起睡眠-觉醒节律紊乱，或睡眠障碍本身就是疾病的主要表现（如家族性致死性失眠），或由于病症产生的各种不适（如睡眠相关性头痛）干扰了睡眠。本章就神经系统疾病相关性睡眠障碍分别予以介绍。     

血府逐瘀汤配合穴位埋注治疗顽固性失眠临床观察

失眠是指睡眠的始发和睡眠维持发生障碍，致使睡眠质量不能满足个体生理需要而明显影响患者白天活动的一种睡眠障碍综合征，是临床常见病、多发病。长期失眠容易引起多脏器功能紊乱和免疫功能下降，并与溃疡病、高血压病、冠心病、糖尿病以及其他精神疾病密切相关。如果长期服用安眠类药物仍然使睡眠状况得不到改善或离开安眠药就不能睡觉者则称为顽固性失眠，病程一般持续数月或数年。采用常法治疗往往难以见效，临床颇为棘手。     

睡眠紊乱与糖尿病关系的研究进展

长期睡眠紊乱可改变机体神经-内分泌功能,使血中升血糖激素、细胞因子水平升高,引起胰岛素抵抗、肥胖等病理生理改变,导致糖尿病的患病风险明显升高.同时,糖尿病引起的中枢神经系统与神经递质异常,急、慢性并发症的发生、发展,及其所带来的心理负担等,都极易影响患者的睡眠模式和质量,引起睡眠紊乱.糖尿病与睡眠紊乱关系密切,改善睡眠质量可明显提高胰岛素敏感性,改善血糖控制,起到辅助治疗糖尿病的作用.     

睡眠知觉障碍的研究进展

1有关睡眠知觉障碍诊断的研究现状 睡眠知觉障碍（以前通称主观性失眠）是指睡眠状态感知不良，表现为入睡困难、睡眠不足或增多、根本不能入睡。虽然患者主诉失眠或白天过度思睡，但并无睡眠紊乱的客观证据。主诉睡眠不好是所有类型失眠患者的主要临床特点，患者夸大其入睡困难和低估其睡眠维持时间是普遍现象，这一点在睡眠知觉障碍患者表现更为显著。     

睡眠与脑血管疾病的关系

脑血管病患者可发生睡眠结构紊乱、交感神经活动活跃、快速眼动睡眠减少或消失、睡眠昼夜节律消失 ,合并或加重睡眠呼吸紊乱的现象明显增多。从而使睡眠也成为脑血管病的独立危险因素。文章阐述了睡眠中出现的独特的睡眠结构改变、自主神经活动、血压变化和睡眠呼吸紊乱与脑血管病 ,尤其是缺血性脑血管病的关系     

Circadian rhythm abnormalities in totally blind people: incidence and clinical significance.

When people are completely isolated from environmental time cues, their circadian rhythms free run with a nearly 24-h cycle, generated by an internal body clock. Free-running temperature, cortisol, and melatonin rhythms have also been described in totally blind people, even though they were living in normal society and had access to abundant time cues; thus an intact visual system may be essential for synchronization of the circadian system. However, because of the small numbers of subjects studied, the incidence and clinical significance of circadian rhythm abnormalities among the blind has remained uncertain. In this study, plasma melatonin (n = 20), cortisol (n = 4), and sleep propensity (n = 1) were measured in serial samples taken from totally blind subjects for 24 h. Most totally blind subjects had circadian rhythm abnormalities. In about half of the subjects, the rhythms were free-running. Some blind subjects suffered recurrent insomnia and daytime sleepiness that were maximal when the internal rhythms were out of phase with the preferred sleep times. The high incidence of abnormal circadian rhythms in blind people underscores the importance of the light-dark cycle as an important environmental synchronizer for the human circadian system.     

Circadian rhythm sleep disorders

Humans exhibit endogenous circadian rhythms that are regulated by the master circadian clock of the body, the suprachiasmatic nucleus. These endogenous circadian rhythms are aligned to the outside world by social and environmental cues. Circadian rhythm sleep disorders (CRSD) occur when there is an alteration of the internal timing mechanism or a misalignment between sleep and the 24-h social and physical environment. CRSD are often underrecognized yet should be considered in the differential of patients presenting with symptoms of insomnia and/or hypersomnia. Because behavioral and environmental factors often are involved in the development and maintenance of these conditions, a multimodal treatment approach of behavioral and/or pharmacologic approaches is usually required to synchronize a patient's circadian rhythm to the 24-h environment, consolidate sleep, and improve alertness. Rapid advances in our understanding of the physiologic, cellular, and molecular basis of circadian rhythm and sleep regulation will likely lead to improved diagnostic tools and treatments for CRSD.     

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18-74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.     

Circadian rhythm of corticosteroids in female hamadryas baboons during long-term hypokinesia

Radioimmunoassay was used to study the effect of restricted motor activity on the circadian rhythms of the content of hydrocortisone, 11-deoxycortisol, corticosterone and aldosterone in the blood plasma of mature female hamadryas baboons in different phases of the menstrual cycle. Intact animals demonstrated distinct circadian rhythms of corticosteroids reproduced stably in both phases of the cycle. Two-week immobilization did not change the general nature of rhythms of the content of glucocorticoids but caused a decrease in their mean daily concentrations which is significant for 11-deoxycortisol and corticosterone of female baboons immobilized in the luteal phase of the cycle. The circadian rhythm of aldosterone got smooth, its level in the blood dropped significantly disregarding a cycle phase at the moment of immobilization. The revealed changes of the circadian rhythms of aldosterone reflect disorders of adrenocortical mineralocorticoid function in female baboons under hypokinesia. Causes of changes in the hormonal activity of the adrenal cortex under clinicostatic hypokinesia are discussed.     

Diurnal rhythms in hypothalamic/pituitary AVT synthesis and secretion in rainbow trout: evidence for a circadian regulation

Arginine vasotocin (AVT) and isotocin (IT) are two neurohypophysial peptide hormones for which a role in adaptation to environmental changes has been suggested in fish. In teleosts, there are only a few available studies about circadian changes of AVT and IT levels, and a role of those peptides in the circadian system has been mainly suggested on the basis of the role of the homologous hormone AVP in mammals. Herein, we evaluated the diurnal rhythms in plasma AVT, pituitary AVT and IT content and the hypothalamic pro-vasotocin (pro-VT) expression in rainbow trout kept under a natural photoperiod, as well as their persistence in constant darkness as a tool for defining circadian dependence. Trout kept under a natural light cycle showed clear diurnal rhythms in both circulating and pituitary AVT levels with peak values around the last hours of the light phase. Hypothalamic pro-VT mRNA was also rhythmically expressed with similar peak characteristics. These rhythms persisted in fish kept under constant darkness for nearly two consecutive days, although peaks were progressively attenuated and phase-advanced. An IT rhythm was also found in pituitary of the trout maintained under a natural photoperiod, but not in those kept under continuous darkness. These results suggest that rhythms of hypothalamic AVT synthesis might be regulated by endogenous circadian mechanisms, and these rhythms contribute to maintain a similar fluctuation in pituitary AVT secretion into the blood. A potential role for AVT in the circadian and seasonal time-keeping system of teleost fish, either as a component of the neural machinery that participates in the adaptation to cyclic environmental changes, or as a circadian/seasonal output signal, is also discussed.     

Diurnal oscillation in glial fibrillary acidic protein in a perisuprachiasmatic area and its relationship to the luteinizing hormone surge in the female rat

It is well known that the reproductive cycle in the female rat is closely associated with the circadian rhythms of motor activity and that this phenomenon requires the presence of estrogens. Estrogens induce plastic changes in neural connectivity and these changes could be the result of glial modifications. We have measured glial fibrillary acidic protein (GFAP) immunoreactivity in order to localize the area in which the coupling of the circadian rhythms to the generation of the luteinizing hormone (LH) surge may occur. As circadian rhythms are driven by the suprachiasmatic nucleus (SCN), GFAP immunoreactivity was measured in 5 areas of the SCN and surrounding regions. It was measured at two times during daylight (10.00 and 17.00 h) in ovariectomized (OVX) females implanted with Silastic capsules containing either estradiol benzoate (EB) or oil (control). Differences between morning and afternoon GFAP immunoreactivity were observed in a peri-SCN area, dorsal to the SCN and close to the 3rd ventricle, in estrogen-treated as well as in control OVX females. However, this difference increased in the subgroup of EB-treated females which displayed the strongest LH rhythmicity. These results suggest that the peri-SCN area could be an important locus for synaptic changes linking circadian rhythms with the estrogen-induced LH surge.     

Circadian rhythms of ocular melatonin in the wrasse Halichoeres tenuispinnis, a labrid teleost

Using in vivo and in vitro methods we studied the regulation of ocular melatonin rhythms in the wrasse Halichoeres tenuispinnis, by either light or the circadian clock. Rhythmic changes in ocular melatonin levels under light-dark (LD) cycles were persistent under constant darkness (DD), and had a circadian periodicity of approximately 24h. However, ocular melatonin levels remained low under constant light conditions. When wrasse were exposed to a single 6-h light pulse at three different circadian phases under DD, phase-dependent phase shifts in the circadian rhythms of ocular melatonin were observed. When eyecups were prepared during mid-light periods or at the onset of darkness, and incubated in vitro in either light or dark periods, both time and light conditions affected melatonin release. These results indicate that the melatonin rhythms in the wrasse eye are driven by an ocular circadian clock that is entrained to LD cycles via local photoreceptors.     

Alterations in the circadian rhythm of salivary melatonin begin during middle-age

To investigate whether free melatonin may be better suited to reveal age-related changes, we studied the circadian rhythm alterations in saliva melatonin levels during aging. Special attention was paid to the question as to how the free melatonin rhythms change in aging and when such changes take place. A total of 52 healthy volunteers participated in the study consisting of young, middle-aged, old and the oldest groups. In each subject, a total of 12 time-point salivary melatonin samples was taken over 24 hr. Of the 52 data sets, 51 exhibited significant circadian rhythm over 24 hr by using the base cosine function analysis to fit the data. A clear circadian rhythm of salivary melatonin was present in all age groups. The decline in nocturnal peak levels (amplitude) in salivary melatonin was found in old and the oldest subjects. Both the old and the oldest subjects showed an increased daytime (baseline) melatonin levels. The off-set melatonin levels were more than two times higher in the oldest group than that in the other groups indicating a delayed phase of salivary melatonin. Most strikingly, we found that a step-wise decrease in the circadian rhythms of saliva melatonin occurred early in life, around 40 yr of ages. The middle-aged subjects had only 60% of the amplitude of the young subjects. In addition, the middle-aged subjects showed the longest peak levels duration and the lowest daytime melatonin levels. The present study showed that the alterations in the circadian rhythms of salivary melatonin begin during middle-age. Our results showed that salivary melatonin measurement is a reliable, sensitive and easy method to monitor changes in the circadian rhythms of melatonin during the course of aging.     

Persistence of circadian rhythms in gastric acid, gastrin, and pancreatic polypeptide secretions despite loss of cortisol and body temperature rhythms in man under stress

During organic stress, severe dysfunctions of fundamental biological phenomena, such as modification of vagal tone, have been described. These dysfunctions could induce changes in the rhythm of acid secretion and/or its hormonal control. We therefore analyzed the effects of acute respiratory failure on the 24 h variations in intragastric pH, serum gastrin, and pancreatic polypeptide levels, taken as a marker of vagal tone. Body temperature and plasma cortisol circadian rhythms were used as marker rhythms. Twelve patients with chronic obstructive pulmonary disease complicated with acute respiratory failure were studied before and during continuous enteral nutrition; half of the patients received ranitidine, a H2 blocker. During the 3 days of the study, intragastric pH was below 2.5 for only one third of the time. No difference was observed between the placebo and the ranitidine groups. Plasma pancreatic polypeptide was within normal ranges despite increased cortisol levels. Gastrin levels reflected changes in intragastric pH over the 24 h time frame and were noted to increase during ranitidine and enteral nutrition. Despite the loss of cortisol and body temperature circadian rhythmicity all throughout the study, circadian rhythms were maintained or restored during the different therapeutic regimens for intragastric pH, serum gastrin, and pancreatic polypeptide levels. Moreover, an ultradian rhythm for gastrin before any treatment, a circadian rhythm for intragastric pH on enteral nutrition, a circadian rhythm for intragastric pH, plasma gastrin and plasma pancreatic polypeptide on ranitidine regimen were observed. Thus during acute respiratory failure, certain physiological circadian rhythms persisted despite the disappearance of "marker" rhythms. Furthermore, these rhythms for digestive secretions could be pharmacologically restored.     

Effects of exercise on circadian rhythms and mobility in aging Drosophila melanogaster

Daily life functions such as sleep and feeding oscillate with circa 24 h period due to endogenous circadian rhythms generated by circadian clocks. Genetic or environmental disruption of circadian rhythms is associated with various aging-related phenotypes. Circadian rhythms decay during normal aging, and there is a need to explore strategies that could avert age-related changes in the circadian system. Exercise was reported to delay aging in mammals. Here, we investigated whether daily exercise via stimulation of upward climbing movement could improve circadian rest/activity rhythms in aging Drosophila melanogaster. We found that repeated exercise regimen did not strengthen circadian locomotor activity rhythms in aging flies and had no effect on their lifespan. We also tested the effects of exercise on mobility and determined that regular exercise lowered age-specific climbing ability in both wild type and clock mutant flies. Interestingly, the climbing ability was most significantly reduced in flies carrying a null mutation in the core clock gene period, while rescue of this gene significantly improved climbing to wild type levels. Our work highlights the importance of period in sustaining endurance in aging flies exposed to physical challenge.