Bright Light Therapy: Improved Sensitivity to Its Effects on Rest-Activity Rhythms in Alzheimer Patients by Application of Nonparametric Methods

Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.     

Dim nighttime illumination interacts with parametric effects of bright light to increase the stability of circadian rhythm bifurcation in hamsters

The endogenous circadian pacemaker of mammals is synchronized to the environmental day by the ambient cycle of relative light and dark. The present studies assessed the actions of light in a novel circadian entrainment paradigm where activity rhythms are bifurcated following exposure to a 24-h light:dark:light:dark (LDLD) cycle. Bifurcated entrainment under LDLD reflects the temporal dissociation of component oscillators that comprise the circadian system and is facilitated when daily scotophases are dimly lit rather than completely dark. Although bifurcation can be stably maintained in LDLD, it is quickly reversed under constant conditions. Here the authors examine whether dim scotophase illumination acts to maintain bifurcated entrainment under LDLD through potential interactions with the parametric actions of bright light during the two daily photophases. In three experiments, wheel-running rhythms of Syrian hamsters were bifurcated under LDLD with dimly lit scotophases, and after several weeks, dim scotophase illumination was either retained or extinguished. Additionally, "full" and "skeleton" photophases were employed under LDLD cycles with dimly lit or completely dark scotophases to distinguish parametric from nonparametric effects of bright light. Rhythm bifurcation was more stable in full versus skeleton LDLD cycles. Dim light facilitated the maintenance of bifurcated entrainment under full LDLD cycles but did not prevent the loss of rhythm bifurcation in skeleton LDLD cycles. These studies indicate that parametric actions of bright light maintain the bifurcated entrainment state; that dim scotophase illumination increases the stability of the bifurcated state; and that dim light interacts with the parametric effects of bright light to increase the stability of rhythm bifurcation under full LDLD cycles. A further understanding of the novel actions of dim light may lead to new strategies for understanding, preventing, and treating chronobiological disturbances.     

The suitability of actigraphy, diary data, and urinary melatonin profiles for quantitative assessment of sleep disturbances in schizophrenia: a case report

Sleep disruption is a commonly encountered clinical feature in schizophrenic patients, and one important concern is to determine the extent of this disruption under "real" life situations. Simultaneous wrist actigraphy, diary records, and repeated urine collection for urinary 6-sulphatoxymelatonin (aMT6s) profiles are appropriate tools to assess circadian rhythms and sleep patterns in field studies. Their suitability for long-term recordings of schizophrenic patients living in the community has not been evaluated. In this case report, we document long-term simultaneous wrist actigraphy, light detection, repeated urine collection, and diary records as a suitable combination of non-invasive techniques to quantify and assess changes in sleep-wake cycles, light exposure, and melatonin profiles in a schizophrenic patient. The actigraph was well-tolerated by the patient, and compliance to diary records and 48 h urine collection was particularly good with assistance from family members. The data obtained by these techniques are illustrated, and the results reveal remarkable abnormal patterns of rest-activity patterns, light exposure, and melatonin production. We observed various rest-activity patterns, including phase-shifts, highly delayed sleep on- and offsets, and irregular rest-activity phases. The period of the rest-activity rhythm, light-dark cycle, and melatonin rhythm was longer than 24 h. These circadian abnormalities may reinforce the altered sleep patterns and the problems of cognitive function and social engagement associated with schizophrenic.     

Dim Nighttime Illumination Interacts With Parametric Effects of Bright Light to Increase the Stability of Circadian Rhythm Bifurcation in Hamsters

The endogenous circadian pacemaker of mammals is synchronized to the environmental day by the ambient cycle of relative light and dark. The present studies assessed the actions of light in a novel circadian entrainment paradigm where activity rhythms are bifurcated following exposure to a 24-h light:dark:light:dark (LDLD) cycle. Bifurcated entrainment under LDLD reflects the temporal dissociation of component oscillators that comprise the circadian system and is facilitated when daily scotophases are dimly lit rather than completely dark. Although bifurcation can be stably maintained in LDLD, it is quickly reversed under constant conditions. Here the authors examine whether dim scotophase illumination acts to maintain bifurcated entrainment under LDLD through potential interactions with the parametric actions of bright light during the two daily photophases. In three experiments, wheel-running rhythms of Syrian hamsters were bifurcated under LDLD with dimly lit scotophases, and after several weeks, dim scotophase illumination was either retained or extinguished. Additionally, “full” and “skeleton” photophases were employed under LDLD cycles with dimly lit or completely dark scotophases to distinguish parametric from nonparametric effects of bright light. Rhythm bifurcation was more stable in full versus skeleton LDLD cycles. Dim light facilitated the maintenance of bifurcated entrainment under full LDLD cycles but did not prevent the loss of rhythm bifurcation in skeleton LDLD cycles. These studies indicate that parametric actions of bright light maintain the bifurcated entrainment state; that dim scotophase illumination increases the stability of the bifurcated state; and that dim light interacts with the parametric effects of bright light to increase the stability of rhythm bifurcation under full LDLD cycles. A further understanding of the novel actions of dim light may lead to new strategies for understanding, preventing, and treating chronobiological disturbances. (Author correspondence: jevans@msm.edu)     

Randomized,DIM Light Controlled,Crossover test of Morning Bright Light Therapy for Rest-Activity Rhythm Disorders in Patients with Vascular Dementia and Dementia of Alzheimer's type

The authors compared the therapeutic effect of morning bright and dim light exposure on rest-activity (R-A) rhythm disorders in patients with vascular dementia (VD) and patients with dementia of Alzheimer's type (DAT). Participants in this study were 12 patients with VD (M/F = 5/7; average age = 81 years) and 10 patients with DAT (M/F = 4/6; average age = 78 years). They were exposed to 2 weeks of bright light (BL; 5000-8000 lux) and 2 weeks of dim light (DL; 300 lux) in the morning (09:00-11:00) in a randomized crossover design in which the 2-week treatment period took place between pretreatment (1 week) and posttreatment (1 week) periods. Continuous R-A monitoring was performed at 1-minute intervals throughout the study using an actigraph around the nondominant wrist. The BL exposure for 2 weeks induced a significant reduction in both nighttime activity and percentages of nighttime activity to total activity compared with the pretreatment period, as well as compared with the DL condition in the VD group, but not in the DAT group. These findings support the assumption that the therapeutic efficacies of morning BL exposure are prominent in VD patients and are mainly due to its photic effect rather than nonphotic effects such as the intensification of social interaction accompanying light therapy. (Chronobiology International, 15(6), 647-654, 1998)     

Entraining effects of variations in light spectral composition on the rest-activity rhythm of a nocturnal rodent

The ability to predict and adjust physiology and behavior to recurring environmental events has been necessary for survival on Earth. Recent discoveries revealed that not only changes in irradiance but also light spectral composition can stimulate the suprachiasmatic nucleus (SCN), ensuring the body’s synchronization to the environment. Therefore, using a lighting system that modulates spectral composition during the day using combined red-green-blue (RGB) lights, we evaluated the effect of variations in light spectral composition on the rest-activity rhythm of rodents. Male Wistar rats (n = 17) were gestated and raised under different lighting conditions and exposed to a long photoperiod (16 h light: 8 h dark). The difference between groups was the presence of variations in light spectral composition during the day (RGB-v) to simulate daily changes in natural light, or not (RGB-f). After weaning, spontaneous motor activity was recorded continuously for rhythm evaluation. Our results indicated that animals under RGB-v did not present a reactive peak of activity after the beginning of the light phase, suggesting that this group successfully detected the variations aimed at mimicking daily alterations of natural light. Furthermore, RGB-v animals exhibited an earlier activity acrophase in comparison to animals under RGB-f (RGB-v = 12:16 – “hh:mm”, RGB-f = 13:02; p < 0.001), which might have been due to the capability to predict the beginning of the dark phase when exposed to variations in light spectrum. However, this earlier activity acrophase can be also explained by the blue-light peak that occurred in RGB-v. The spectral and waveform analysis of daily patterns of motor activity revealed that rats in the RGB-v group were better entrained to a circadian rhythm throughout the experiment. RGB-v showed higher interdaily stability (IS) values (29.75 ± 6.5, n = 9) than did RGB-f (t₍₁₅₎ = 2.74, p = 0.015). Besides, the highest power content (PC) on the first harmonic (circadian) was reached earlier in the RGB-v group. The circadianity index (CI) of the whole period was higher in the RGB-v group (t₍₁₅₎ = 3.47, p = 0.003). Thus, we could consider that locomotor activity rhythm was entrained to the light-dark cycle in the RGB-v rats earlier compared to the RGB-f rats. Our results provide additional evidence for the effect of variations in light spectral composition on the rest-activity pattern of nocturnal rodents. This suggests that these animals might predict the arrival of the activity phase by its advanced acrophase when exposed to RGB-v, demonstrating a better synchronization to a 24-h rhythm.     

Monitoring of rest-activity rhythm in cancer patients paves the way for the adoption of patient-specific chronotherapeutic approach

The status and phases of the circadian timing system (CTS) can be ascertained through measuring several biological functions. Of those measurements, rest-activity rhythm is considered as a reliable circadian biomarker to evaluate the function of CTS among oncology population. Its amenable non-invasive monitoring over longitudinal time scale makes it more appropriate and convenient. Its use as reference rhythm for timing the medications is widely accepted in cancer and sleep clinics. Current mini review highlights the present knowledge on different actigraphy devices used for the measurement of circadian rest-activity rhythm. Further, this review presents recent data dealing with the status of circadian rest-activity rhythm in cancer patients and discusses its association with health-related patients’ quality of life. Application of this concept supports that the interventions with abilities to reverse CTS dysfunction in cancer patients might prolong their survival with improved and acceptable level of health-related quality of life.     

pyActigraphy: Open-source python package for actigraphy data visualization and analysis

Over the past 40 years, actigraphy has been used to study rest-activity patterns in circadian rhythm and sleep research. Furthermore, considering its simplicity of use, there is a growing interest in the analysis of large population-based samples, using actigraphy. Here, we introduce pyActigraphy, a comprehensive toolbox for data visualization and analysis including multiple sleep detection algorithms and rest-activity rhythm variables. This open-source python package implements methods to read multiple data formats, quantify various properties of rest-activity rhythms, visualize sleep agendas, automatically detect rest periods and perform more advanced signal processing analyses. The development of this package aims to pave the way towards the establishment of a comprehensive open-source software suite, supported by a community of both developers and researchers, that would provide all the necessary tools for in-depth and large scale actigraphy data analyses.     

Activation of the dorsal raphe nucleus and locus coeruleus by transcutaneous electrical nerve stimulation in Alzheimer's disease: a reconsideration of stimulation-parameters derived from animal studies

In 1990 a series of studies started in which the effects of Transcutaneous Electrical Nerve Stimulation (TENS) was examined on cognition, behaviour, and the rest-activity rhythm of patients with Alzheimer's disease (AD). In these studies, TENS aimed primarily at stimulating the dorsal raphe nucleus (DRN) and the locus coeruleus (LC) by a combination of low- and high-frequency stimulation (2 Hz and 160 Hz, respectively), a pulse width of 0.1 ms, and an intensity that provokes muscular twitches. TENS was applied 30 min a day, during a six-week period. In order to make reliable comparisons between studies, identical stimulation-parameters were used in all studies thus far. TENS appeared to have a positive effect on cognition, behaviour, and the rest-activity rhythm but the effects disappeared after cessation of stimulation. In order to optimise TENS treatment in AD, the present paper is meant to reconsider the once selected stimulation-parameters by reviewing the relevant literature published since 1991. The results derived from animal experimental studies show that for an optimal stimulation of the LC and DRN, the pulse width should be more than 0.1 ms. Limitations and suggestions for future research will be discussed.     

Alterations of the characteristics of the circadian rest-activity rhythm of cancer in-patients

The aim of the present study was to evaluate the characteristics of the circadian rest-activity rhythm of cancer patients. Thirty-one in-patients, consisting of 19 males and 12 females, were randomly selected from the Regional Cancer Center, Pandit Jawaharlal Nehru Medical College, Raipur, India. The rest-activity rhythm was studied non-invasively by wrist actigraphy, and compared with 35 age-matched apparently healthy subjects (22 males and 13 females). All subjects wore an Actiwatch (AW64, Mini Mitter Co. Inc., USA) for at least 4-7 consecutive days. Fifteen-second epoch length was selected for gathering actigraphy data. In addition, several sleep parameters, such as time in bed, assumed sleep, actual sleep time, actual wake time, sleep efficiency, sleep latency, sleep bouts, wake bouts, and fragmentation index, were also recorded. Data were analyzed using several statistical techniques, such as cosinor rhythmometry, spectral analysis, ANOVA, Duncan's multiple-range test, and t-test. Dichotomy index (I相似文献   

Worsening of rest-activity circadian rhythm and quality of life in female breast cancer patients along progression of chemotherapy cycles

Chemotherapy and its associated side effects can induce the disruption of circadian rest-activity rhythm and may have negative consequences on health-related quality of life (HRQoL) of cancer patients. In the current study, repeated-measures cross-sectional design was implemented to determine the status of circadian rest-activity rhythm and to assess the HRQoL of newly diagnosed female breast cancer patients those were planned to receive six cycles of chemotherapy. Rest activity and HRQoL were assessed in twenty-five patients during chemotherapy cycles 1st (C1), 3rd (C3), and 6th (C6) immediately after they reported to the outdoor ward of the Regional Cancer Center, Pt. J.N.M. Medical College, Dr. B.R. Ambedkar Memorial Hospital, Raipur, India. Wrist actigraphs for consecutive spans of 3–4 days were used to record the rest-activity rhythm, and its parameters were computed with the help of Cosinor Rhythmometry. Quality of life (QoL) parameters were assessed using EORTC QLQ-C30 and QLQ-BR23. Results revealed that average scores of all rhythm parameters, such as MESOR, amplitude, acrophase, rhythm quotient, circadian quotient, peak activity, dichotomy index, and autocorrelation coefficient; and all functional scales of QLQ-C30, such as physical, role, emotional, cognitive, and social, and global quality of life statistically significantly decreased with the increasing number of chemotherapy cycles (C1 to C3 and C6). Scores of symptom scales of QLQ-C30, such as fatigue, pain, dyspnoea, insomnia, appetite loss, and diarrhea increased significantly from C1 to C6. Among the QLQ-BR23 scales, scores of sexual functioning, sexual enjoyment, breast symptoms, and arm symptoms significantly decreased, whereas scores of systemic therapy side effects, and upset by hair loss significantly increased across the chemotherapy cycles. We conclude that rest-activity rhythm disrupted and HRQoL of breast cancer patients worsened along the increasing number of chemotherapy cycles. We suggest that along with the treatment protocol, level of disruption of these parameters should be assessed and managed with the proper interventions that prominently include timing of the chemotherapy administration. The latter is pivotal for maintenance of these parameters, which are likely to enhance the physiological ability of patients for better treatment responses and may improve the overall QoL and survival of the patients.     

Darkness during early postnatal development is required for normal circadian patterns in the adult rat

Early light experience influences the brain during development. Perinatal light exposure has an important effect on the development of the circadian system, although the role of quantity versus quality of light in this process is still unclear. We tested the development of the circadian rhythm of locomotor activity under constant bright light from the day of weaning, of six groups of rats raised under different light conditions during suckling. Results indicated that when rats received daily darkness during suckling (rats reared under constant darkness or light-dark cycles with dim or bright light) became arrhythmic when exposed to continuous bright light after weaning. However, those rats reared in the absence of darkness (constant dim or bright light, or alternating dim and bright light) developed a circadian rhythm, which was stronger and had a shorter period depending on the quantity of light received during suckling. Vasointestinal polypeptide immunoreactivity in the suprachiasmatic nucleus (SCN) was higher in those rats with weaker rhythms. However, no apparent differences among these groups were found in the melanopsin-expressing retinal ganglion cells, which provide the SCN with light input in the photoentrainment process. When bright light was shifted to dim light in three of the groups on day 57 after weaning, all of them generated a circadian rhythm with a longer period in those rats previously arrhythmic. Our results indicate the importance of the amount of light received at the early stages of life in the development of the circadian system and suggest that darkness is needed for the normal development of circadian behaviour.     

月经周期对女性睡眠-觉醒和静息-活动的影响

目前有关月经周期对睡眠影响的研究结果并不一致,而对月经周期中昼夜睡眠-觉醒及静息-活动节律尚缺乏系统性的研究.本研究旨在观察正常育龄期女性月经周期中睡眠-觉醒及静息-活动昼夜节律的变化.我们采用静息-活动监测仪(actigraphy)和睡眠日志,调查了12个自然生活状态下健康育龄期妇女在月经周期不同阶段,即行经期、围排卵期、黄体早期及黄体晚期中睡眠与活动节律的变化.结果显示,睡眠-觉醒节律参数在四期之间无统计学显著差异;而静息-活动节律方面,所有受试女性静息-活动节律的平均日周期长度为(24.01±0.29)h,并且四期之间无显著性差异.行经期日间稳定系数(interdaily stability,IS)比黄体早期显著增加(P＜0.05).黄体早期日间活动开始时间明显较黄体晚期提前(P＜0.05);黄体早期的活动峰值时相比围排卵期显著提前(P＜0.05).月经周期可以影响静息-活动昼夜节律时相.而总体静息-活动数量与质量未发生显著变化;健康育龄期妇女在月经周期的各阶段中睡眠-觉醒节律亦无明显变异.     

Relationship between infant and mother circadian rest-activity rhythm pre- and postpartum, in comparison to an infant with free-running rhythm

Some infants show a free-running rhythm in their rest-activity. We do not know why, nor do we know exactly what the entrainment factors are for the development of the normal 24-h rest-activity rhythm. Actigraphic recordings on 10 primiparae during late pregnancy and these mothers and their infants during the 2nd, 6th, and 12th wks after birth were made over 3-5 continuous days to investigate maternal and infant entrainment. One infant showed a free-running rest-activity circadian rhythm. In late pregnancy, the period in the autocorrelogram of the mother with the free-running infant was longer than the significant period of the mean autocorrelogram of the mothers with non-free-running infants. The finding of this study indicates the free-running rhythm of infant is not reset by maternal entrainment factors.     

Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons

Increased daytime napping, early morning awakening, frequent nocturnal sleep interruptions, and lowered amplitude and phase advance of the circadian sleep-wake rhythm are characteristic features of sleep-waking and chronobiological changes associated with aging. Especially in elderly patients with dementia, severely fragmented sleep-waking patterns are observed frequently and are associated with disorganized circadian rhythm of various physiological functions. Functional and/or organic deterioration of the suprachiasmatic nucleus (SCN), decreased exposure to time cues such as insufficient social interaction and reduced environmental light, lowered sensitivity of sensory organs to time cues, and reduced ability of peripheral effector organs to express circadian rhythms may cause these chronobiological changes. In many cases of dementia, the usual treatments for insomnia do not work well, and the development of an effective therapy is an important concern for health care practitioner and researchers. Recent therapeutical trials of supplementary administration of artificial bright light and the pineal hormone melatonin, a potent synchronizer for mammalian circadian rhythm, have indicated that these treatments are useful tools for demented elderly insomniacs. Both bright light and melatonin simultaneously ameliorate disorganized thermoregulatory and neuroendocrine systems associated with disrupted sleep-waking times, suggesting a new, potent therapeutic means for insomnia in the demented elderly. Future studies should address the most effective therapeutic design and the most suitable types of symptoms for treatment and investigate the use of these tools in preventive applications in persons in early stages of dementia. (Chronobiology International, 17(3), 419-432, 2000)     

SUPPLEMENTARY ADMINISTRATION OF ARTIFICIAL BRIGHT LIGHT AND MELATONIN AS POTENT TREATMENT FOR DISORGANIZED CIRCADIAN REST-ACTIVITY AND DYSFUNCTIONAL AUTONOMIC AND NEUROENDOCRINE SYSTEMS IN INSTITUTIONALIZED DEMENTED ELDERLY PERSONS

Increased daytime napping, early morning awakening, frequent nocturnal sleep interruptions, and lowered amplitude and phase advance of the circadian sleep-wake rhythm are characteristic features of sleep-waking and chronobiological changes associated with aging. Especially in elderly patients with dementia, severely fragmented sleep-waking patterns are observed frequently and are associated with disorganized circadian rhythm of various physiological functions. Functional and/or organic deterioration of the suprachiasmatic nucleus (SCN), decreased exposure to time cues such as insufficient social interaction and reduced environmental light, lowered sensitivity of sensory organs to time cues, and reduced ability of peripheral effector organs to express circadian rhythms may cause these chronobiological changes. In many cases of dementia, the usual treatments for insomnia do not work well, and the development of an effective therapy is an important concern for health care practitioner and researchers. Recent therapeutical trials of supplementary administration of artificial bright light and the pineal hormone melatonin, a potent synchronizer for mammalian circadian rhythm, have indicated that these treatments are useful tools for demented elderly insomniacs. Both bright light and melatonin simultaneously ameliorate disorganized thermoregulatory and neuroendocrine systems associated with disrupted sleep-waking times, suggesting a new, potent therapeutic means for insomnia in the demented elderly. Future studies should address the most effective therapeutic design and the most suitable types of symptoms for treatment and investigate the use of these tools in preventive applications in persons in early stages of dementia. (Chronobiology International, 17(3), 419–432, 2000)     

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.     

Correlation between rest-activity rhythm and survival in cancer patients experiencing pain

The purpose of this study was to investigate the influence of rest-activity rhythm on the survival of cancer patients. This study collected data related to cancer patients experiencing pain who had been hospitalized for treatment between August 2006 and October 2007. Data included the Karnofsky Performance Status Index as a representation of functional condition as well as the Brief Pain Inventory and the Pittsburgh Sleep Quality Index. Actigraphic methods were used to record the dichotomy index (I?<?O) of patients' rest-activity rhythms over periods of three consecutive days. Patients were closely followed until 31 July 2013. Results were analyzed using Kaplan–Meier survival analysis, log-rank testing and Cox proportional hazards regression analysis to evaluate whether alterations in the rest-activity rhythm affected the survival rate of the patients. Of the 68 hospitalized cancer patients experiencing pain at the time of admission, 51 subsequently died within the study period. A significant difference was observed in the survival curves between the regular I?<?O group and the disrupted I?<?O group (log rank?=?7.942, p?=?0.005). A multivariable proportional hazard model was used for analysis of overall survival, revealing that the risk of death within the study period among patients with disrupted I?<?O was 4.59 times higher than that of patients with regular I?<?O (95% CI: 1.92–10.96, p?=?0.001). Among patients with poor performance status, the risk of death among patients with disrupted I?<?O was 8.68 times higher than that of patients with regular I?<?O (95% CI: 2.50–30.09, p?=?0.001). Disruptions in rest-activity rhythm were negatively correlated with the survival of hospitalized cancer patients experiencing pain. Effects were particularly pronounced in cancer patients with poor performance status.     

Treatment of insomnia in demented nursing home patients: a review

Insomnia and fragmentation are features of the sleep of these patients. In order to list the factors disturbing the sleep of demented nursing home patients and the interventions improving their sleep quality, the literature was reviewed. A Medline search over the period 1966-2000 was performed. This resulted in 22 research articles. Admission to a nursing home is associated with sleep disturbances caused by patient problems (e.g. pain), care routines (e.g. nightly nursing round) and environment (e.g. noise). There are indications that the use of hypnotics in nursing home patients is not always effective and increases the risk of falls. There are several ways to reduce hypnotic consumption in nursing homes. Non-pharmacological interventions to decrease sleep disturbances caused by environmental factors have a favourable although weak effect on sleep itself. By reducing nightly noise, sleep quality does not necessarily improve. Light therapy seems to be the most effective non-pharmacological method to strengthen the circadian sleep/wake rhythm. The struggle against insomnia without using medication perhaps requires a two tracks management: detection and elimination of disturbing environmental factors and implementation of an adequate method to strengthen the circadian sleep/wake rhythm.     

Zeitgebers and their association with rest-activity patterns

Zeitgebers such as light, eating and physical activity provide input to the circadian clock. Chronic circadian misalignment is associated with significant adverse health effects. An improved understanding of the impact of the timing of zeitgebers on the stability of 24-hour rest-activity rhythm in free-living settings may identify behavioural and environmental intervention targets. A total of 133 healthy adults, aged 21–60 years, wore a wrist actigraph for 7 consecutive days. We applied a non-parametric analysis to activity counts to derive rest-activity patterns. We administered a questionnaire through a smartphone app to collect self-reported timing of light exposure, eating episodes and physical activity. To assess the relationship between timing exposures (first and last exposure to outdoor light, first exposure to indoor light, last eating episode, first eating episode, morning physical activity proportion, evening physical activity proportion) and rest-activity or sleep outcomes (bedtimes, total sleep time, inter-daily stability, intra-daily variability, L5 and M10 midpoint), we first calculated Spearman correlations, using the false discovery rate method to control for multiple comparisons. From those significant associations, we then fit regression models adjusting for age, sex, race, household income, education level, study site, body mass index, as well as physical activity. Finally, we tested for interaction between chronotype and each timing-related exposure and stratified the analysis by morning type. All zeitgebers, except for evening physical activity proportion, were correlated with at least four of the seven sleep and rest-activity outcomes. In adjusted analysis, later timing of first (after 6:30 to 7:45 AM versus earlier) and last exposure to indoor light (after 11:00 PM versus earlier) and first (after 7:45–9:45 AM versus earlier) and last eating episode (after 8:00–09:00 PM versus earlier) were associated with a shift of 0.60–1.39 hours to later bedtimes, M10 and L5 midpoints (i.e. timing of peak activities or inactivities). Later timing of first exposure to outdoor light (after 09:30 AM versus earlier) was also associated with 0.51 (95% CI: 0.19 to 0.83) hours longer total sleep time. Higher morning physical activity proportion (> 33%) was associated with 0.95 (95% CI: ?1.38 to ?0.53) hours earlier in-bed time and 0.69 (95% CI: ?1.14 to ?0.24) hours earlier out-of-bed time, 0.92 (95% CI: ?1.41 to ?0.42) hours earlier M10 and 0.96 (95% CI: ?1.42 to ?0.49) min earlier L5 midpoint. The results did not change substantially with further adjustment for total activity. There was a significant interaction between morning chronotype and first eating episode with rest-activity patterns (p < 0.05), with first eating episode associating with timing of activities only in non-morning type adults. Timing of zeitgebers was associated with sleep and rest-activity patterns, including bedtimes, L5 and M10 midpoint. Future research should evaluate the impact of manipulating zeitgebers on both circadian rhythms and health outcomes.