The relevance of daylight for humans.

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.

Can Extra Daytime Light Exposure Improve Well-Being and Sleep? A Pilot Study of Patients With Glaucoma.

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.

Effects of a dawn-dusk simulation on circadian rest-activity cycles, sleep, mood and well-being in dementia patients.

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 ±â€¯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.

High-accuracy determination of internal circadian time from a single blood sample.

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 für Bildung und Forschung, Germany (FKZ: 13N13160 and 13N13162) and Intellux GmbH, Germany.

Improved cognitive morning performance in healthy older adults following blue-enriched light exposure on the previous evening.

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 min 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 x 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 < 0.05) on the wake EEG. CONCLUSION: Exposure to blue-enriched white light in the evening significantly improved DSST performance the following morning when compared to polychromatic white light. This was associated with a higher level of objective alertness on the wake EEG, but not with changes in sleep or circadian timing.

Implementation of Dynamic Lighting in a Nursing Home: Impact on Agitation but not on Rest-Activity Patterns.

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<0.05). Analysis of the CMAI subscores revealed that under the dynamic lighting mainly non-physically aggressive behaviors were reduced. RESULTS: Results from the rest-activity analysis did not show differences of circadian amplitude and other circadian variables before and after the lighting installation. The dynamic lighting in the living room significantly reduced agitated behavior in demented patients, indicating short-term benefits from higher daily light exposures. Whether such lighting also impacts long-term (circadian) rest-activity cycles needs to be further investigated.

Bright Light Delights: Effects of Daily Light Exposure on Emotions, Restactivity Cycles, Sleep and Melatonin Secretion in Severely Demented Patients.

OBJECTIVE: We tested whether the effects of a dynamic lighting system are superior to conventional lighting on emotions, agitation behaviour, quality of life, melatonin secretion and circadian restactivity cycles in severely demented patients. As a comparison, an age matched control patient group was exposed to conventional lighting. For none of the output measures were significant differences between the two lighting conditions found during the 8 study weeks in fall/winter. METHODS: Thus, we divided the patient cohort (n = 89) into two groups, solely based on the median of their daily individual light exposure. Patients with higher average daily light exposure (>417 lx) showed significantly longer emotional expressions of pleasure and alertness per daily observations than patients with lower daily light exposure. Moreover, they had a higher quality of life, spent less time in bed, went to bed later and initiated their sleep episodes later, even though the two groups did not differ with respect to age, severity of cognitive impairment and mobility. In general, men were more agitated, had shorter sleep with more wake episodes, had a lower circadian amplitude of relative rest-wake activity and interdaily circadian stability than women. In particular, lower daily light exposures significantly predicted lower circadian amplitudes of rest-activity cycles in men but not in women. This may indicate sex specific susceptibility to daily light exposures for rest-activity regulation in older demented patients. RESULTS: Our results provide evidence that a higher daily light exposure has beneficial effects on emotions and thus improved quality of life in a severely demented patient group.

Light and chronobiology: implications for health and disease.

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.

Encoding difficulty promotes postlearning changes in sleep spindle activity during napping.

Learning-dependent increases in sleep spindle density have been reported during nocturnal sleep immediately after the learning session. Here, we investigated experience-dependent changes in daytime sleep EEG activity after declarative learning of unrelated word pairs. At weekly intervals, 13 young male volunteers spent three 24 h sessions in the laboratory under carefully controlled homeostatic and circadian conditions. At approximately midday, subjects performed either one of two word-pair learning tasks or a matched nonlearning control task, in a counterbalanced order. The two learning lists differed in the level of concreteness of the words used, resulting in an easier and a more difficult associative encoding condition, as confirmed by performance at immediate cued recall. Subjects were then allowed to sleep for 4 h; afterward, delayed cued recall was tested. Compared with the control condition, sleep EEG spectral activity in the low spindle frequency range and the density of low-frequency sleep spindles (11.25-13.75 Hz) were both significantly increased in the left frontal cortex after the difficult but not after the easy encoding condition. Furthermore, we found positive correlations between these EEG changes during sleep and changes in memory performance between pre-nap and post-nap recall sessions. These results indicate that, like during nocturnal sleep, daytime sleep EEG oscillations including spindle activity are modified after declarative learning of word pairs. Furthermore, we demonstrate here that the nature of the learning material is a determinant factor for sleep-related alterations after declarative learning.