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The timing and nutritional composition of food intake are important zeitgebers for the biological clocks in humans. Thus, eating at an inappropriate time (e.g., during the night) may have a desynchronizing effect on the biological clocks and, in the long term, may result in adverse health outcomes (e.g., weight gain, obesity, and poor metabolic function). Being a very late or early chronotype not only determines preferred sleep and wake times but may also influence subsequent mealtimes, which may affect the circadian timing system. In recent years, an increased number of studies have examined the relation between chronotype and health outcomes, with a main focus on absolute food intake and metabolic markers and, to a lesser extent, on dietary intake distribution and eating behavior. Therefore, this review aimed to systematically determine whether chronotype indirectly affects eating behaviors, dietary intake (timing, choice, nutrients), and biomarkers leading to body composition outcomes in healthy adults. A systematic literature search on electronic databases (PubMed, CINAHL, MEDLINE, SCOPUS, Cochrane library) was performed (International Prospective Register of Systematic Reviews number: CRD42020219754). Only studies that included healthy adults (aged18 y), classified according to chronotype and body composition profiles, using outcomes of dietary intake, eating behavior, and/or biomarkers, were considered. Of 4404 articles, 24 met the inclusion criteria. The results revealed that late [evening type (ET)] compared with early [morning type (MT)] chronotypes were more likely to be overweight/obese with poorer metabolic health. Both MT and ET had similar energy and macronutrient intakes, consuming food during their preferred sleep-wake timing: later for ET than MT. Most of the energy and macronutrient intakes were distributed toward nighttime for ET and exacerbated by unhealthy eating behaviors and unfavorable dietary intakes. These findings from our systematic review give further insight why higher rates of overweight/obesity and unhealthier metabolic biomarkers are more likely to occur in ET.

Light exposure fundamentally influences human physiology and behavior, with light being the most important zeitgeber of the circadian system. Throughout the day, people are exposed to various scenes differing in light level, spectral composition and spatio-temporal properties. Personalized light exposure can be measured through wearable light loggers and dosimeters, including wrist-worn actimeters containing light sensors, yielding time courses of an individual’s light exposure. There is growing interest in relating light exposure patterns to health outcomes, requiring analytic techniques to summarize light exposure properties. Building on the previously published Python-based pyActigraphy module, here we introduce the module pyLight. This module allows users to extract light exposure data recordings from a wide range of devices. It also includes software tools to clean and filter the data, and to compute common metrics for quantifying and visualizing light exposure data. For this tutorial, we demonstrate the use of pyLight in three examples: (1) loading, accessing and visual inspection of a dataset, (2) truncation, masking, filtering and binarization of the dataset, (3) calculation of summary metrics, including time above threshold (TAT) and mean light timing above threshold (MLit). The pyLight module paves the way for open-source, large-scale automated analyses of light-exposure data.

New Zealand (NZ) enforced a rigorous lockdown in response to the outbreak of COVID-19 in 2020. Infection rates remained remarkably low, yet social and personal routines were affected. Factors associated with reporting worsening sleep were explored using an anonymous online survey launched during New Zealand’s 2020 lockdown. Participants were 723 adults aged 20–85 years (median: 45 years, 82% women). Bed and wake times occurred significantly later compared to pre-lockdown estimates and resulted in shorter social jetlag (15 min). During lockdown, 54.5% were identified as “poor sleepers” [i.e. score > 5 on the Pittsburgh Sleep Quality Index (PSQI)]. Overall, 45% rated their sleep quality to worsen compared to pre-lockdown, 22% reported an improvement. Reports of worsening sleep were significantly related to increased sleep latency, reduced sleep efficiency, and heightened PSQI scores compared to those with better sleep or no change. Subjectively worse sleep was significantly associated with less time engaging in physical activity, less exposure to daylight, and social interactions compared to pre-lockdown estimates (p < .05). Logistic regression models identified significant relationships between having more vivid dreams and worsening sleep. Worse sleepers also had increased likelihoods of reporting poorer mood and they also scored higher for anxiety compared to those with no change or improved sleep during lockdown (p < .05). Pandemic-related restrictions contributed to poorer self-reported sleep which was linked to deterioration of mood. Negative affect was comparatively lower than reported elsewhere. These findings provide unique insights to the psychosocial impact of the initial COVID-19 lockdown in New Zealand, where the disease outbreak remained low.

We describe the time course of bone formation marker (P1NP) decline in men exposed to ~ 3 weeks of sleep restriction with concurrent circadian disruption. P1NP declined within 10 days and remained lower with ongoing exposure. These data suggest even brief exposure to sleep and circadian disruptions may disrupt bone metabolism. A serum bone formation marker (procollagen type 1 N-terminal, P1NP) was lower after ~ 3 weeks of sleep restriction combined with circadian disruption. We now describe the time course of decline. The ~ 3-week protocol included two segments: “baseline,” ≥ 10-h sleep opportunity/day × 5 days; “forced desynchrony” (FD), recurring 28 h day (circadian disruption) with sleep restriction (~ 5.6-h sleep per 24 h). Fasted plasma P1NP was measured throughout the protocol in nine men (20–59 years old). We tested the hypothesis that PINP would steadily decline across the FD intervention because the magnitude of sleep loss and circadian misalignment accrued as the protocol progressed. A piecewise linear regression model was used to estimate the slope (β) as ΔP1NP per 24 h with a change point mid-protocol to estimate the initial vs. prolonged effects of FD exposure. Plasma P1NP levels declined significantly within the first 10 days of FD ($$ \hat{\beta} $$ = − 1.33 μg/L per 24 h, p

Enhancing lighting conditions in institutions for individuals with dementia improves their sleep, circadian rhythms and well-being. Here, we tested whether a greater long-term daily light exposure supports the immune response to the annual influenza vaccination. Eighty older institutionalised patients suffering from dementia (54 women and 26 men) continuously wore an activity tracker for 8 weeks to assess individual light exposure and rest-activity cycles. The patients’ immune response was analysed from two blood samples taken before and 4 - 5 weeks after the annual influenza vaccination. Individual antibody concentrations to three influenza virus strains (H3N2, H1N1, IB) were quantified via hemagglutination inhibition assays. By quantifying individual light exposure profiles (including daylight), we classified the patients into a low and a high light exposure group based on a median illuminance of 392.6 lux. The two light exposure groups did not differ in cognitive impairment severity, age or gender distribution. However, patients in the high light exposure group showed a significantly greater circadian rest-activity amplitude (i.e., more daytime activity and less nighttime activity) along with a significantly greater antibody titer increase to the H3N2 vaccine than patients in the low light exposure group, despite similar pre-vaccination concentrations. Sufficient seroprotective responses to all three influenza virus strains were attained for ≥ 75% of participants. These data provide first evidence for a potentially enhanced immune response in patients with dementia when they received more daily light. Increasing daily light exposure may have beneficial effects on the human immune system, either directly or via circadian rhythm stabilisation.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Current patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, SI-compliant standard provides a way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert-scientific consensus and expressed according to this new measurement standard. These recommendations are supported by a comprehensive analysis of the sensitivity of human ‘non-visual’ responses to ocular light, are centred on an easily measured quantity (melanopic equivalent daylight (D65) illuminance), and provide a straightforward framework to inform lighting design and practice.

Purpose The purpose of this work is to determine whether an uncoupling of bone turnover markers (BTMs) occurs in women exposed to the combination of sleep restriction with circadian disruption (SRCD), as previously reported in men. Methods Four bone biomarkers (N-terminal propeptide of type I procollagen [P1NP] and osteocalcin = bone formation; C-telopeptide [CTX] = bone resorption; sclerostin = bone formation inhibitor) were measured in bihourly samples over 24 hours at baseline and after approximately 3 weeks of sleep restriction (~5.6 hours of sleep/24 hours) with concurrent circadian disruption (SRCD, recurring 28-hour “day” in dim light). Maximum likelihood estimation in a repeated-measures model was used to assess the effects of SRCD and age on bone biomarkers. Results Five women were young (22 ± 2.8 years) and four were older (58 ± 1.8 years). Baseline bone biomarker levels did not differ by age (all P ≥ .07). Bone formation markers were lower after SRCD (estimate ± SEE, ΔP1NP = –9.5 ± 2.8 μg/L, P = .01; Δosteocalcin = –2.3 ± 0.9 ng/mL, P = .04). The P1NP decline was greater in young women (ΔP1NP = –12.9 ± 3.7 μg/L, P = .01). After SRCD, CTX was significantly higher in young women (0.182 ± 0.069 ng/mL, P = .04) but did not change in older women. Conclusions These pilot data are similar to previous findings in men and suggest that SRCD negatively altered bone metabolism in women by decreasing markers of bone formation and, in young women, increasing a marker of bone resorption. If sustained, this pattern of BTM uncoupling may lead to bone loss and lower bone mineral density.

Daylight stems solely from direct, scattered and reflected sunlight, and undergoes dynamic changes in irradiance and spectral power composition due to latitude, time of day, time of year and the nature of the physical environment (reflections, buildings and vegetation). Humans and their ancestors evolved under these natural day/night cycles over millions of years. Electric light, a relatively recent invention, interacts and competes with the natural light−dark cycle to impact human biology. What are the consequences of living in industrialised urban areas with much less daylight and more use of electric light, throughout the day (and at night), on general health and quality of life[1, 2]? In this workshop report, we have classified key gaps of knowledge in daylight research into three main groups: (I) uncertainty as to daylight quantity and quality needed for “optimal” physiological and psychological functioning, (II) lack of consensus on practical measurement and assessment methods and tools for monitoring real (day) light exposure across multiple time scales, and (III) insufficient integration and exchange of daylight knowledge bases from different disciplines. Crucial short and long-term objectives to fill these gaps are proposed.

Glaucoma damages retinal ganglion cells, including intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells modulate various non-visual physiological and psychological functions which are modulated by light. In patients with glaucoma, we assessed the effect of daily bright light exposure (LE) on several melanopsin-dependent functions, such as the pupil constriction, circadian rest-activity cycles, sleep and subjective well-being including relaxation, alertness and mood. Twenty patients participated in the study (9 women, 11 men, mean age = 67.6 ± 7.5 y). Pupillometry was performed before the LE weeks and repeated on the last day of LE. The post-illumination pupil response (PIPR) was calculated as a proxy for melanopsin-dependent activation. Participants continuously wore an activity monitor and self-assessed sleep quality, well-being and visual comfort for 7 days before and during 4 weeks of daily bright LE (30 min to 10,000 lux polychromatic bright white light). After the LE, there was a significantly greater PIPR and higher subjective sleep quality when compared to the pre-LE week (p < 0.05), but no significant changes in 24-h rhythms or sleep parameters. A greater PIPR was correlated with an increase in circadian amplitude and higher inter-daily stability (derived from rest-activity cycles; p < 0.05). In a small group of patients with glaucoma, scheduled daily bright light exposure could improve subjective sleep quality. These findings highlight the importance to evaluate and maintain non-visual functions at different levels in patients with progressive loss of ipRGCs.

Background The circadian clock is a fundamental and pervasive biological program that coordinates 24-hour rhythms in physiology, metabolism, and behavior, and it is essential to health. Whereas therapy adapted to time of day is increasingly reported to be highly successful, it needs to be personalized, since internal circadian time is different for each individual. In addition, internal time is not a stable trait, but is influenced by many factors, including genetic predisposition, age, sex, environmental light levels, and season. An easy and convenient diagnostic tool is currently missing. Methods To establish a validated test, we followed a 3-stage biomarker development strategy: (a) using circadian transcriptomics of blood monocytes from 12 individuals in a constant routine protocol combined with machine learning approaches, we identified biomarkers for internal time; and these biomarkers (b) were migrated to a clinically relevant gene expression profiling platform (NanoString) and (c) were externally validated using an independent study with 28 early or late chronotypes. Results We developed a highly accurate and simple assay (BodyTime) to estimate the internal circadian time in humans from a single blood sample. Our assay needs only a small set of blood-based transcript biomarkers and is as accurate as the current gold standard method, dim-light melatonin onset, at smaller monetary, time, and sample-number cost. Conclusion The BodyTime assay provides a new diagnostic tool for personalization of health care according to the patient's circadian clock. Funding This study was supported by the Bundesministerium fur Bildung und Forschung, Germany (FKZ: 13N13160 and 13N13162) and Intellux GmbH, Germany.

More than a third of US adults report fewer than 6 hours of sleep a night, making chronic sleep restriction a growing public health concern. Sleep curtailment is associated with an increase in industrial accidents, motor vehicle accidents, medical and other occupational errors. Young adults are more vulnerable to acute sleep deprivation than older adults, but less is known about how young vs. older adults respond to the more commonly experienced chronic sleep restriction. To test the hypothesis that young adults are more vulnerable to chronic sleep loss than older adults, we compared data from young and older adults who underwent three weeks of chronic sleep restriction (equivalent to 5.6 hours/24 hours) combined with recurrent circadian disruption in an experiment that enabled us to separate the influences of the sleep-wake homeostatic process, the circadian timing system, and the chronic sleep deficit. We found that while young and older adults reported similar levels of subjective sleepiness, objective measures of sleepiness revealed that young adults were more vulnerable and had more attentional failures than the older adults. These results have important public health implications, particularly related to prevention of sleep-related motor vehicle crashes in young drivers. Further research is needed to understand the neurobiological basis of these age-related differences.

The osteocyte’s role in orchestrating diurnal variations in bone turnover markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte protein). These results suggest that serum sclerostin can be measured at any time of day and the osteocyte does not direct the rhythmicity of other BTMs in men. The osteocyte exerts important effects on bone remodeling, but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-h interval, similar to that of other bone biomarkers. Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 h over a 24-h interval in ten healthy men aged 20–65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm. No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p

Backround:Night-time agitation is a frequent symptom of dementia. It often causes nursing home admission and has been linked to circadian rhythm disturbances. A positive influence of light interventions on night-time agitation was shown in several studies. The aim of our study was to investigate whether there is a long-term association between regional weather data (as indicator for daylight availability) and 24-hour variations of motor activity.Methods:Motor activity of 20 elderly nursing home residents living with dementia was analyzed using recordings of continuously worn wrist activity monitors over a three-year period. The average recording duration was 479 ± 206 days per participant (mean ± SD). Regional cloud amount and day length data from the local weather station (latitude: 52°56′N) were included in the analysis to investigate their effects on several activity variables.Results:Nocturnal rest, here defined as the five consecutive hours with the least motor activity during 24 hours (L5), was the most predictable activity variable per participant. There was a significant interaction of night-time activity with day length and cloud amount (F1,1174 = 4.39; p = 0.036). Night-time activity was higher on cloudy short days than on clear short days (p = 0.007), and it was also higher on cloudy short days than on cloudy long days (p = 0.032).Conclusions:The need for sufficient zeitgeber (time cue) strength during winter time, especially when days are short and skies are cloudy, is crucial for elderly people living with dementia. Activity forecast by season and weather might be a valuable approach to anticipate adequately complementary use of electrical light and thereby foster lower night-time activity.

In single night shifts, extending habitual wake episodes leads to sleep deprivation induced decrements of performance during the shift and re-adaptation effects the next day. We investigated whether short-wavelength depleted (=filtered) bright light (FBL) during a simulated night shift would counteract such effects. Twenty-four participants underwent a simulated night shift in dim light (DL) and in FBL. Reaction times, subjective sleepiness and salivary melatonin concentrations were assessed during both nights. Daytime sleep was recorded after both simulated night shifts. During FBL, we found no melatonin suppression compared to DL, but slightly faster reaction times in the second half of the night. Daytime sleep was not statistically different between both lighting conditions (n = 24) and there was no significant phase shift after FBL (n = 11). To conclude, our results showed positive effects from FBL during simulated single night shifts which need to be further tested with larger groups, in more applied studies and compared to standard lighting.

Nighttime melatonin suppression is the most commonly used method to indirectly quantify acute nonvisual light effects. Since light is the principal zeitgeber in humans, there is a need to assess its strength during daytime as well. This is especially important since humans evolved under natural daylight but now often spend their time indoors under artificial light, resulting in a different quality and quantity of light. We tested whether the pupillary light response (PLR) could be used as a marker for nonvisual light effects during daytime. We also recorded the wake electroencephalogram to objectively determine changes in daytime sleepiness between different illuminance levels and/or spectral compositions of light. In total, 72 participants visited the laboratory 4 times for 3-h light exposures. All participants underwent a dim-light condition and either 3 metameric daytime light exposures with different spectral compositions of polychromatic white light (100 photopic lux, peak wavelengths at 435 nm or 480 nm, enriched with longer wavelengths of light) or 3 different illuminances (200, 600, and 1200 photopic lux) with 1 metameric lighting condition (peak wavelength at 435 nm or 480 nm; 24 participants each). The results show that the PLR was sensitive to both spectral differences between metameric lighting conditions and different illuminances in a dose-responsive manner, depending on melanopic irradiance. Objective sleepiness was significantly reduced, depending on melanopic irradiance, at low illuminance (100 lux) and showed fewer differences at higher illuminance. Since many people are exposed to such low illuminance for most of their day—living in biological darkness—our results imply that optimizing the light spectrum could be important to improve daytime alertness. Our results suggest the PLR as a noninvasive physiological marker for ambient light exposure effects during daytime. These findings may be applied to assess light-dependent zeitgeber strength and evaluate lighting improvements at workplaces, schools, hospitals, and homes.

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.

Light, through its non-imaging forming effects, plays a dominant role on a myriad of physiological functions, including the human sleep–wake cycle. The non-image forming effects of light heavily rely on specific properties such as intensity, duration, timing, pattern, and wavelengths. Here, we address how specific properties of light influence sleep and wakefulness in humans through acute effects, e.g., on alertness, and/or effects on the circadian timing system. Of critical relevance, we discuss how different characteristics of light exposure across the 24-h day can lead to changes in sleep–wake timing, sleep propensity, sleep architecture, and sleep and wake electroencephalogram (EEG) power spectra. Ultimately, knowledge on how light affects sleep and wakefulness can improve light settings at home and at the workplace to improve health and well-being and optimize treatments of chronobiological disorders.

Light is the most powerful "zeitgeber" signal to synchronize circadian sleep-wake cycles. In dementia, these rhythms are often fragmented - probably due to loss of neuronal function of the suprachiasmatic nuclei (the biological "master clock" in the brain) and/or weakness of external zeitgebers. We investigated the effects of a prototype dawn-dusk simulator (DDS) on circadian rest-activity cycles, sleep, mood and well-being in a balanced crossover design during fall and winter in 20 institutionalized patients with dementia (86 ± 6 y, 17 f). All participants had one baseline week followed by exposure to individually timed DDS over their beds for 7-8 weeks. They spent 8 weeks without DDS as a control. Mood, self-reliant daily activity, social behavior, agitation, and quality of life were assessed by standardized questionnaires and visual analogue scales, regularly rated by trained caregivers. Circadian and sleep characteristics of their rest-activity cycles were analyzed by actimetry over 17 weeks. DDS exposure led to significantly better mood in the morning hours after waking. The effects were most pronounced in the second 4 weeks with DDS, indicating that positive effects emerged gradually. Differences in circadian rest-activity cycles and sleep were mainly age-dependent. We found statistically significant correlations between measures of higher quality of life and better mood, greater alertness and circadian rhythm stability. We conclude that continuous, long-term application of dawn-dusk simulation at the sleep-wake transitions appears to increase external zeitgeber strength in institutionalized patients with dementia. The DDS may provide an effective, non-invasive tool to improve mood and ameliorate patients' quality of life.

Light during the day and darkness at night are crucial factors for proper entrainment of the human circadian system to the solar 24-h day. However, modern life and work styles have led to much more time spent indoors, often with lower daytime and higher evening/nighttime light intensity from electrical lighting than outdoors. Whether this has long-term consequences for human health is being currently investigated. We tested if bright blue-enriched morning light over several days could counteract the detrimental effects of inadequate daytime and evening lighting. In a seminaturalistic, within-between subject study design, 18 young participants were exposed to different lighting conditions on 3 evenings (blue-enriched, bright orange, or dim light), after exposure to 2 lighting conditions (mixed blue-enriched light and control light, for 3 days each) in the mornings. Subjective sleepiness, reaction times, salivary melatonin concentrations, and nighttime sleep were assessed. Exposure to the blue-enriched morning lighting showed acute wake-promoting effects and faster reaction times than with control lighting. Some of these effects persisted until the evening, and performance improved over several days. The magnitude of circadian phase shifts induced by combinations of 3 different evening and 2 morning lighting conditions were significantly smaller with the blue-enriched morning light. During the night, participants had longer total sleep times after orange light exposure than after blue light exposure in the evening. Our results indicate that bright blue-enriched morning light stabilizes circadian phase, and it could be an effective counterstrategy for poor lighting during the day and also light exposure at the wrong time, such as in the late evening.

Daylight is ubiquitous and is crucial for mammalian vision as well as for non-visual input to the brain via the intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin. The ipRGCs project to the circadian clock in the suprachiasmatic nuclei and thereby ensure entrainment to the 24-hour day-night cycle, and changes in daylength trigger the appropriate seasonal behaviours. The ipRGCs also project to the perihabenular nucleus and surrounding brain regions that modulate mood, stress and learning in animals and humans. Given that light has strong direct effects on mood, cognition, alertness, performance, and sleep, light can be considered a "drug" to treat many clinical conditions. Light therapy is already well established for winter and other depressions and circadian sleep disorders. Beyond visual and non-visual effects via the retina, daylight contributes to prevent myopia in the young by its impact on eye development, and is important for Vitamin D synthesis and bone health via the skin. The sun is the most powerful light source and, dependent on dose, its ultraviolet radiance is toxic for living organisms and can be used as a disinfectant. Most research involves laboratory-based electric light, without the dynamic and spectral changes that daylight undergoes moment by moment. There is a gap between the importance of daylight for human beings and the amount of research being done on this subject. Daylight is taken for granted as an environmental factor, to be enjoyed or avoided, according to conditions. More daylight awareness in architecture and urban design beyond aesthetic values and visual comfort may lead to higher quality work and living environments. Although we do not yet have a factual basis for the assumption that natural daylight is overall "better" than electric light, the environmental debate mandates serious consideration of sunlight not just for solar power but also as biologically necessary for sustainable and healthy living.

Introduction The ability to remember the face and name of a person we have recently met is a critical skill often impacted by cognitive impairment and Alzheimer’s disease. We used a forced desynchrony protocol to explore whether recall of recently-learned face-name pairs is affected by time awake and/or circadian phase in healthy adults. Methods 13 healthy, cognitively normal adults (20-70yrs; 7F) participated in a 39-day inpatient protocol with 3 baseline days (10h time-in-bed/24h) and a 3-week forced desynchrony (FD) segment, where they lived on a 28-h day with sleep restriction (6.5h time-in-bed/28h, equivalent to 5.6h/24h). Core body temperature was collected throughout to estimate circadian period and phase. The face-name test was administered every 4h, beginning 3h after wake. Each test included a learning session with 6 novel face-name pairs. Recall was tested 2h later, when each face was presented twice in random order, once with a correct and once with an incorrect name. Participants were asked to respond whether each face-name pair was correct. Data were averaged across 4-h circadian phase or time awake bins and normalized as a percentage of each participant’s baseline performance. Results Face-name recall varied by time awake (p Conclusion Both duration of prior wake and biological time of day impact the ability to correctly recall face-name pairs. Under normal entrained conditions, opposing circadian- and wake- dependent effects on memory for face-name associations may interact to produce stable performance across the day. Support Study supported by P01 AG009975 and conducted at Brigham and Women’s Hospital Center for Clinical Investigation, part of Harvard Clinical and Translational Science Center supported by UL1 TR001102. Authors supported by T32HL007901 and F32HL143893 (RKY); fellowships from the Novartis Foundation, the W.&T. La-Roche Foundation, and Jazz Pharmaceuticals (MYM); a fellowship from the Natural Sciences and Engineering Research Council of Canada (SWC).

Long-term daylight deprivation such as during the Antarctic winter has been shown to lead to delayed sleep timing and sleep fragmentation. We aimed at testing whether retinal sensitivity, sleep and circadian rest-activity will change during long-term daylight deprivation on two Antarctic bases (Concordia and Halley VI) in a total of 25 healthy crew members (mean age: 34 ± 11y; 7f). The pupil responses to different light stimuli were used to assess retinal sensitivity changes. Rest-activity cycles were continuously monitored by activity watches. Overall, our data showed increased pupil responses under scotopic (mainly rod-dependent), photopic (mainly L-/M-cone dependent) as well as bright-blue light (mainly melanopsin-dependent) conditions during the time without direct sunlight. Circadian rhythm analysis revealed a significant decay of intra-daily stability, indicating more fragmented rest-activity rhythms during the dark period. Sleep and wake times (as assessed from rest-activity recordings) were significantly delayed after the first month without sunlight (p

OBJECTIVES: Exposure to light can have acute alerting and circadian phase-shifting effects. This study investigated the effects of evening exposure to blue-enriched polychromatic white (BEL) vs. polychromatic white light (WL) on sleep inertia dissipation the following morning in older adults. METHODS: Ten healthy older adults (average age = 63.3 yrs; 6F) participated in a 13-day study comprising three baseline days, an initial circadian phase assessment, four days with 2-h evening light exposures, a post light exposure circadian phase assessment and three recovery days. Participants were randomized to either BEL or WL of the same irradiance for the four evening light exposures. On the next mornings at 2, 12, 22 and 32 minutes after each wake time, the participants completed a 90-s digit-symbol substitution test (DSST) to assess working memory, and objective alertness was assessed using a wake EEG recording. DSST and power density from the wake EEG recordings were compared between the two groups. RESULTS: DSST performance improved with time awake (p< 0.0001) and across study days in both light exposure groups (p< 0.0001). There was no main effect of group, although we observed a significant day × group interaction (p=0.0004), whereby participants exposed to BEL performed significantly better on the first two mornings after light exposures than participants in WL (post-hoc, p< 0.05). On those days, the BEL group showed higher EEG activity in some of the frequency bins in the sigma and beta range (p

Seasonal adaptation is a ubiquitous behavior seen in many species on both global hemispheres and is conveyed by changing photoperiods. In humans this seasonal adaptation is less apparent, in part because changes in daylength are masked by the use of electrical lighting at night. On the other hand, cataracts which reduce light transmission, may compound seasonal changes related to the reduced daylength of winter. To better understand the effects of different photoperiod lengths in healthy adults without and with cataracts, we tested their melanopsin-mediated light responses in summer vs. winter. Fifty-two participants (mean age 67.4 years; 30 with bilateral cataracts and 22 age-matched controls with clear lenses; pseudophakes) were tested twice, once in summer and once in winter. At each test session we assessed the electroretinogram and pupil responses during daytime and we determined melatonin suppression, subjective sleepiness and mood in response to light exposure in the evening. Circadian rest-activity cycles and sleep from activity recordings were also analyzed for both seasons. Both groups had similar visual function. There were no seasonal differences in the electroretinogram. For the pupil responses to bright blue light, the post- illumination pupil response (PIPR) was greater in winter than summer in pseudophakes, but not in cataract participants, whereas melatonin suppression to acute light exposure showed no differences between both groups and seasons. Overall, intra-daily variability of rest-activity was worse in winter but participants felt sleepier and reported worse mood at the laboratory in evening time in the summer. Those with cataracts had poorer sleep quality with lower sleep efficiency, and higher activity during sleep in winter than summer. In this study, the PIPR showed a seasonal variation in which a larger response was found during winter. This variation was only detected in participants with a clear intraocular lens. In the cataract group, visual function was not impaired yet these participants showed a lack of seasonal changes in the pupil response to blue light and poorer sleep in winter. These findings raise the question for tailored lighting conditions for cataract patients in order to counter potentially deleterious effects of living with chronically lower light exposure.

OBJECTIVE Disturbances of circadian rest-activity rhythms in demented patients often culminate in the clinical problem of evening and nighttime agitation. The aim of the current study was to test the impact of a dynamic lighting system on agitation and rest-activity cycles in patients with dementia. METHODS From midwinter on, a ceiling mounted dynamic lighting system was installed in the common room of a nursing home and programmed to produce high illuminance with higher blue light proportions during the day and lower illuminance without blue light in the evening. Fifteen residents with dementia were regularly assessed with the Cohen Mansfield Agitation Index (CMAI) before and after the lighting intervention. Additionally rest-activity cycles were continuously monitored for 6 months by a wrist worn activity watch. Analysis of CMAI data was performed by using the Wilcoxon-Test for matched pairs (before vs. after the lighting installation). Rest-activity data was compared with t-tests for dependent samples. The dynamic lighting significantly reduced the CMAI sum-scores from 30.2±5.1 to 27.9±2.6 (mean ± SD; N = 12; p

Context Sleep abnormalities are associated with low bone mineral density. Underlying mechanisms are unknown. Objective Investigate the impact of sleep restriction with circadian disruption on bone biomarkers. Design Intervention study. Participants and Methods Four bone biomarkers [C-terminal cross-linked telopeptide of type I collagen (CTX) = bone resorption, N-terminal propeptide of type I procollagen (P1NP) = bone formation, sclerostin and fibroblast growth factor 23 = osteocyte function] were measured in bihourly serum samples over 24 hours at baseline and after ∼3 weeks of sleep restriction (5.6 hours sleep/24 hours) with concurrent circadian disruption (recurring 28-hour “day” in dim light) in 10 men (age groups: 20 to 27 years, n = 6; 55 to 65 years, n = 4). The effects of sleep/circadian disruption and age on bone biomarker levels were evaluated using maximum likelihood estimation in a mixed model for repeated measures. Results P1NP levels were lower after intervention compared with baseline (P < 0.001); the decrease in P1NP was greater for younger compared with older men (28.0% vs 18.2%, P < 0.001). There was no change in CTX (Δ = 0.03 ± 0.02 ng/mL, P = 0.10). Sclerostin levels were higher postintervention in the younger men only (Δ = 22.9% or 5.64 ± 1.10 pmol/L, P < 0.001). Conclusions These data suggest that 3 weeks of circadian disruption with concurrent sleep restriction can lead to an uncoupling of bone turnover wherein bone formation is decreased but bone resorption is unchanged. Circadian disruption and sleep restriction may be most detrimental to bone in early adulthood.

OBJECTIVE At the beginning of this century, a novel photopigment, melanopsin, was discovered in a sub-class of retinal ganglion cells and its action spectrum was described. Shortly after, it became evident that melanopsin is a major contributor to non-visual eye-mediated effects of light on e.g. the circadian, neuroendocrine and neurobehavioral systems. First applied studies pointed out that these non-visual effects of light are relevant for wellbeing, performance and general health. A standardized measurement metric for these nonvisual effects does not exist, but would ease application. Such a metric termed as 'melanopic lux' has been recently introduced and was shown to be superior to describe non-visual effects in animal studies compared to standard metrics. METHODS We aimed at showing some validity of melanopic lux in humans using a seminaturalistic setting. Therefore, we analyzed the impact of different lighting conditions on melatonin suppression and subjective sleepiness by calculating effective illuminance based on single photopigment sensitivities. We retrospectively analyzed data from our laboratory, where young participants were exposed to a total of 19 different polychromatic lighting conditions, for 30 minutes in the evening, one hour prior to habitual bedtime. Saliva samples for melatonin concentration measures and subjective sleepiness were regularly assessed. The photopic illuminance of all lighting conditions ranged from 3 to 604 lx. Stepwise for- and backward regression analyses showed that melanopic lux was the best predictor for changes in melatonin concentrations (but not subjective sleepiness); R²=0.16 (p

Dieser Artikel gibt einen Überblick über mögliche Faktoren für altersbedingte Veränderungen, welche den Schlaf bei gesunden älteren Menschen beeinflussen. Ein wichtiger Beitrag wird hierbei durch die Selbstregulation des Schlaf-Wach Zyklus sowie die innere Uhr geleistet. Eine Quintessenz zeigt sich darin, dass ältere gesunde Erwachsene einen oberflächlicheren Schlaf und meistens frühere Bett- und Aufstehzeiten als noch in jüngeren Jahren haben, was auf altersbedingte Veränderungen in der Schlaf-Wach Homöostase und der inneren Uhr zurückzuführen ist. Zudem reagiert der Schlaf bei gesunden älteren Menschen empfindlicher auf Störungen, wie der circadianen Desynchronisation und einen Mangel an Zeitgebern [zu wenig Licht am Tage].

Lighting conditions in workplaces contribute to a variety of factors related to work satisfaction, productivity and well-being. We tested whether different photometric variables also influence visual perception and the comfort of the lighting, as well as subjective non-visual variables such as mood, alertness and well-being. Twenty-five young subjects spent two afternoons either under electric light or daylighting conditions (without view from the window). Subjects overall preferred the daylighting for visual acceptance and glare. Changes of photometric variables modulated changes in visual light perception, alertness and mood in the course of the afternoon. Finally, we found several associations of visual and non-visual functions, indicating a potential relationship of visual comfort with other circadian and wake-dependent functions in humans, which consequently could impact office lighting scenarios in the future.

We compared the pupil responses originating from outer versus inner retinal photoreception between patients with isolated hereditary optic neuropathy (HON n=8) and healthy controls (n=8). Three testing protocols were used: a sequence of low intensity blue light stimuli (1 s each) presented after dark adaptation a sequence of photopic red light intensities (1 s each) presented after light adaptation and a single bright (200cd/m2) red and blue light (1 s and 30 s) followed by long inter stimulus dark intervals (30 60 s). For the first two protocols a response function of the maximal pupil contraction versus stimulus light intensity was generated and the intensity at which half of the maximal pupil contraction the half max intensity was determined. For the third protocol the pupil size after light offset the re dilation rate and re dilation amplitude were calculated to assess the post light stimulus response. Patients with HON had bilateral symmetric optic atrophy and significant reduction of visual acuity and visual field compared to controls. There were no significant mean differences in the response curve and pupil response parameters that reflect mainly rod cone or melanopsin activity between patients and controls. In patients there was a significant correlation between the half max intensity of the red light sequence and visual field loss. In conclusion pupil responses derived from outer or inner retinal photoreception in HON patients having mild to moderate visual dysfunction are not quantitatively different from age matched controls. However an association between the degree of visual field loss and the half max intensity of the cone response suggests that more advanced stages of disease may lead to impaired pupil light reflexes.

Age-related disturbances of the sleep-wake cycle can reflect ontogenetic changes in regulatory mechanisms underlying normal and pathological aging, but the exact nature of these changes remains unclear. The present report is the first attempt to apply principal component analysis to the electroencephalographic (EEG) spectrum to examine of whether the observed age-related changes in the objective sleep measures can be linked to the opponent sleep-promoting and wake-promoting processes. The EEG indicators of these processes--scores on the 1st and 2nd principal components of the EEG spectrum, respectively--were compared in 15 older (57-74 years) and 16 younger (20-31 years) healthy volunteers. The scores were calculated for non-REM sleep episodes which occurred during ten 75-min naps scheduled every 150 min throughout a 40-h constant routine protocol. Both, a decrease of the 1st principal component score and an increase of the 2nd principal component score were found to contribute to such most obvious age-related modification of the sleep EEG spectrum as attenuation of EEG slow-wave activity in older people. Therefore, we concluded that the normal aging process can reflect both a weakening of the sleep-promoting process and a strengthening of the wake-promoting process, respectively. Such bidirectional changes in chronoregulatory processes may explain why sleep of older people is characterized by the few profitable and a number of detrimental features (i.e., a better ability to cope with daytime sleepiness and sleep loss vs. difficulty of falling asleep, decreased total nighttime sleep, "lightened" and fragmentized sleep, unwanted early morning awakenings, etc.).

Endogenous rhythms of circalunar periodicity (similar to 29.5 days) and their underlying molecular and genetic basis have been demonstrated in a number of marine species [1, 2]. In contrast, there is a great deal of folklore but no consistent association of moon cycles with human physiology and behavior [3]. Here we show that subjective and objective measures of sleep vary according to lunar phase and thus may reflect circalunar rhythmicity in humans. To exclude confounders such as increased light at night or the potential bias in perception regarding a lunar influence on sleep, we retrospectively analyzed sleep structure, electroencephalographic activity during non-rapid-eye-movement (NREM) sleep, and secretion of the hormones melatonin and cortisol found under stringently controlled laboratory conditions in a cross-sectional setting. At no point during and after the study were volunteers or investigators aware of the a posteriori analysis relative to lunar phase. We found that around full moon, electroencephalogram (EEG) delta activity during NREM sleep, an indicator of deep sleep, decreased by 30%, time to fall asleep increased by 5 min, and EEG-assessed total sleep duration was reduced by 20 min. These changes were associated with a decrease in subjective sleep quality and diminished endogenous melatonin levels. This is the first reliable evidence that a lunar rhythm can modulate sleep structure in humans when measured under the highly controlled conditions of a circadian laboratory study protocol without time cues.

Purpose of review The discovery of a new class of intrinsically photosensitive retinal ganglion cells (ipRGCs) revealed their superior role for various nonvisual biological functions, including the pupil light reflex, and circadian photoentrainment. Recent findings Recent works have identified and characterized several anatomically and functionally distinct ipRGC subtypes and have added strong new evidence for the accessory role of ipRGCs in the visual system in humans. Summary This review summarizes current concepts related to ipRGC morphology, central connections and behavioural functions and highlights recent studies having clinical relevance to ipRGCs. Clinical implications of the melanopsin system are widespread, particularly as related to chronobiology.

Circadian rhythms in physiology and behavior are modulated by external factors such as light or temperature. We studied whether self-selected office lighting during the habitual waking period had a different impact on alertness, cognitive performance and hormonal secretion in extreme morning and evening chronotypes (N = 32), whose preferred bed- and wake-up times differed by several hours. The self-selected lighting condition was compared with constant bright light and a control condition in dim light. Saliva samples for hormonal analyses, subjective ratings of alertness, wellbeing, visual comfort and cognitive performance were regularly collected. Between the self-selected and the bright, but not the dim lighting condition, the onset of melatonin secretion in the evening (as marker for circadian phase) was significantly different for both chronotypes. Morning chronotypes reported a faster increase in sleepiness during the day than evening chronotypes, which was associated with higher cortisol secretion. Wellbeing, mood and performance in more difficult cognitive tasks were better in bright and self-selected lighting than in dim light for both chronotypes, whereas visual comfort was best in the self-selected lighting. To conclude, self-selection of lighting at work might positively influence biological and cognitive functions, and allow for inter-individual differences.

Environmental light synchronizes the primary mammalian biological clock in the suprachiasmatic nuclei, as well as many peripheral clocks in tissues and cells, to the solar 24-hour day. Light is the strongest synchronizing agent (zeitgeber) for the circadian system, and therefore keeps most biological and psychological rhythms internally synchronized, which is important for optimum function. Circadian sleep-wake disruptions and chronic circadian misalignment, as often observed in psychiatric and neurodegenerative illness, can be treated with light therapy. The beneficial effect on circadian synchronization, sleep quality, mood, and cognitive performance depends on timing, intensity, and spectral composition of light exposure. Tailoring and optimizing indoor lighting conditions may be an approach to improve wellbeing, alertness, and cognitive performance and, in the long term, producing health benefits.La luz ambiental sincroniza el reloj biológico primario de los mamíferos en el núcleo supraquiasmático, así como muchos relojes periféricos en tejídos y células, para el día solar de 24 horas. La luz es el agente sincronizador más potente (zeitgeber=dador de tiempo) para el sistema circadíano, y por consiguiente mantiene la mayoría de los ritmos biológicos y psicológicos que se sincronizan internamente, lo que es importante para una óptima función. Las disrupciones circadianas sueño-vigilia y los desajustes circadianos crónicos que se observan con frecuencía en enfermedades psiquiátricas y neurodegenerativas pueden ser tratados con fototerapía. Los efectos favorables sobre la sincronización circadíana, la calidad del sueño, el ánimo y el rendimiento cognitivo dependen de la duración, intensidad y composición espectral de la exposición a la luz. La adaptación y optímízacíón de las condíciones de luz interior pueden constituir una manera de mejorar el bienestar, el alerta y el rendimiento cognitivo, y a largo plazo producir beneficios para la salud.La lumière environnementale synchronise l'horloge biologique primaire des mammifères dans le noyau suprachiasmatique, ainsi que de nombreuses horloges périphériques dans les tissus et les cellules, au jour solaire de 24 h. La lumière est l'agent synchronisant le plus fort (zeitgeber) du système circadien, conservant donc la plupart des rythmes biologiques et psychologiques synchronisés en interne, ce qui est important pour un fonctionnement optimal. Les troubles circadiens veille-sommeil et le décalage circadien chronique, souvent observés dans les maladies psychiatriques et neurodégénératives, peuvent être traités par luminothérapie. L'effet bénéfique sur la synchronisation circadienne, la qualité du sommeil, l'humeur et la performance cognitive dépend de la chronologie, de l'intensité et de la composition spectrale de l'exposition à la lumière. Personnaliser et optimiser les conditions de lumière en intérieur pourraient permettre d'améliorer le bien-être, la vigilance et la performance cognitive et, à long terme, être bénéfique pour la santé.

Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages. Ten healthy older adults with sleep complaints (mean age=63.3 years; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5-8 the subjects were exposed for 2h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed. Subjective alertness and wake EEG activity in the alpha range (9.75-11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p

Ageing is associated with marked changes in sleep timing, structure and electroencephalographic (EEG) activity. Older people exhibit less slow-wave and spindle activity during non-rapid eye movement (NREM) sleep, together with attenuated levels of rapid eye movement (REM) sleep as compared to young individuals. However, the extent to which these age-related changes in sleep impact on dream processing remains largely unknown. Here we investigated NREM and REM sleep EEG activity prior to dream recall and no recall in 17 young (20-31years) and 15 older volunteers (57-74years) during a 40h multiple nap protocol. Dream recall was assessed immediately after each nap. During NREM sleep prior to dream recall, older participants displayed higher frontal EEG delta activity (1-3Hz) and higher centro-parietal sigma activity (12-15Hz) than the young volunteers. Conversely, before no recall, older participants had less frontal-central delta activity and less sigma activity in frontal, central and parietal derivations than the young participants. REM sleep was associated to age-related changes, such that older participants had less frontal-central alpha (10-12Hz) and beta (16-19Hz) activity, irrespective of dream recall and no recall. Our data indicate that age-related differences in dream recall seem to be directly coupled to specific frequency and topography EEG patterns, particularly during NREM sleep. Thus, the spectral correlates of dreaming can help to understand the cortical pathways of dreaming. © 2011 European Sleep Research Society.