The Circadian Brain and Cognition.

Circadian rhythms are inherent to living organisms from single cells to humans and operate on a genetically determined cycle of approximately 24 hours. These endogenous rhythms are aligned with the external light/dark cycle of the Earth's rotation and offer the advantage of anticipating environmental changes. Circadian rhythms act directly on human cognition and indirectly through their fundamental influence on sleep/wake cycles. The strength of the circadian regulation of performance depends on the accumulated sleep debt and the cognitive domain, and it has been suggested to involve the activation of ascending arousal systems and their interaction with attention and other cognitive processes. In addition, attention-related cortical responses show extensive circadian rhythms, the phases of which vary across brain regions. This review discusses the impact of the circadian system on sleep/wake regulation and cognitive performance. It further addresses the health implications of circadian disruption, particularly in relation to mental and neurological disorders.

A Protocol to Determine Circadian Phase by At-Home Salivary Dim Light Melatonin Onset Assessment.

Internal circadian phase assessment is increasingly acknowledged as a critical clinical tool for the diagnosis, monitoring, and treatment of circadian rhythm sleep-wake disorders and for investigating circadian timing in other medical disorders. The widespread use of in-laboratory circadian phase assessments in routine practice has been limited, most likely because circadian phase assessment is not required by formal diagnostic nosologies, and is not generally covered by insurance. At-home assessment of salivary dim light melatonin onset (DLMO, a validated circadian phase marker) is an increasingly accepted approach to assess circadian phase. This approach may help meet the increased demand for assessments and has the advantages of lower cost and greater patient convenience. We reviewed the literature describing at-home salivary DLMO assessment methods and identified factors deemed to be important to successful implementation. Here, we provide specific protocol recommendations for conducting at-home salivary DLMO assessments to facilitate a standardized approach for clinical and research purposes. Key factors include control of lighting, sampling rate, and timing, and measures of patient compliance. We include findings from implementation of an optimization algorithm to determine the most efficient number and timing of samples in patients with Delayed Sleep-Wake Phase Disorder. We also provide recommendations for assay methods and interpretation. Providing definitive criteria for each factor, along with detailed instructions for protocol implementation, will enable more widespread adoption of at-home circadian phase assessments as a standardized clinical diagnostic, monitoring, and treatment tool.

Effects of evening smartphone use on sleep and declarative memory consolidation in male adolescents and young adults.

Exposure to short-wavelength light before bedtime is known to disrupt nocturnal melatonin secretion and can impair subsequent sleep. However, while it has been demonstrated that older adults are less affected by short-wavelength light, there is limited research exploring differences between adolescents and young adults. Furthermore, it remains unclear whether the effects of evening short-wavelength light on sleep architecture extend to sleep-related processes, such as declarative memory consolidation. Here, we recorded polysomnography from 33 male adolescents (15.42 ± 0.97 years) and 35 male young adults (21.51 ± 2.06 years) in a within-subject design during three different nights to investigate the impact of reading for 90 min either on a smartphone with or without a blue-light filter or from a printed book. We measured subjective sleepiness, melatonin secretion, sleep physiology and sleep-dependent memory consolidation. While subjective sleepiness remained unaffected, we observed a significant melatonin attenuation effect in both age groups immediately after reading on the smartphone without a blue-light filter. Interestingly, adolescents fully recovered from the melatonin attenuation in the following 50 min before bedtime, whereas adults still, at bedtime, exhibited significantly reduced melatonin levels. Sleep-dependent memory consolidation and the coupling between sleep spindles and slow oscillations were not affected by short-wavelength light in both age groups. Nevertheless, adults showed a reduction in N3 sleep during the first night quarter. In summary, avoiding smartphone use in the last hour before bedtime is advisable for adolescents and young adults to prevent sleep disturbances. Our research empirically supports general sleep hygiene advice and can inform future recommendations regarding the use of smartphones and other screen-based devices before bedtime.

Inverse association between slow-wave sleep and low-grade inflammation in children and adolescents with major depressive disorder.

OBJECTIVE: To investigate the relationship between both self-reported and objective sleep variables and low-grade inflammation in children and adolescents with major depressive disorder (MDD) of moderate to severe symptom severity. METHODS: In this cross-sectional study, we examined twenty-nine children and adolescents diagnosed with MDD and twenty-nine healthy controls (HC). Following a one-week actigraphy assessment, comprehensive sleep evaluations were conducted, including a one-night sleep EEG measurement and self-reported sleep data. Plasma high-sensitivity C-reactive protein (hsCRP) was employed as a marker to assess low-grade inflammation. RESULTS: No significant difference in hsCRP levels was observed between participants with MDD and HC. Furthermore, after adjusting for sleep difficulties, hsCRP exhibited no correlation with the severity of depressive symptoms. In HC, levels of hsCRP were not linked to self-reported and objective sleep variables. In contrast, depressed participants showed a significant correlation between hsCRP levels and increased subjective insomnia severity (Insomnia Severity Index; r = 0.41, p < 0.05), increased time spent in the N2 sleep stage (r = 0.47, p < 0.01), and decreased time spent in slow-wave sleep (r = - 0.61, p < 0.001). Upon additional adjustments for body mass index, tobacco use and depression severity, only the inverse association between hsCRP and time spent in slow-wave sleep retained statistical significance. Moderation analysis indicated that group status (MDD vs. HC) significantly moderates the association between slow-wave sleep and hsCRP. CONCLUSION: Our findings suggest that alterations in the architecture of slow-wave sleep may have a significant influence on modulating low-grade inflammatory processes in children and adolescents with MDD.

The Impact of Pupil Constriction on the Relationship Between Melanopic EDI and Melatonin Suppression in Young Adult Males.

The pupil modulates the amount of light that reaches the retina. Not only luminance but also the spectral distribution defines the pupil size. Previous research has identified steady-state pupil size and melatonin attenuation to be predominantly driven by melanopsin, which is expressed by a unique subgroup of intrinsically photosensitive retinal ganglion cells (ipRGCs) that are sensitive to short-wavelength light (~480 nm). Here, we aimed to selectively target the melanopsin system during the evening, while measuring steady-state pupil size and melatonin concentrations under commonly experienced evening light levels (<90 lx). Therefore, we used a five-primary display prototype to generate light conditions that were matched in terms of L-, M-, and S-cone-opic irradiances, but with high and low melanopic irradiances (~3-fold difference). Seventy-two healthy, male participants completed a 2-week study protocol. The volunteers were assigned to one of the four groups that differed in luminance levels (27-285 cd/m2). Within the four groups, each volunteer was exposed to a low melanopic (LM) and a high melanopic (HM) condition. The two 17-h study protocols comprised 3.5 h of light exposure starting 4 h before habitual bedtime. Median pupil size was significantly smaller during HM than LM in all four light intensity groups. In addition, we observed a significant correlation between melanopic weighted corneal illuminance (melanopic equivalent daylight illuminance [mEDI]) and pupil size, such that higher mEDI values were associated with smaller pupil size. Using pupil size to estimate retinal irradiance showed a qualitatively similar goodness of fit as mEDI for predicting melatonin suppression. Based on our results here, it remains appropriate to use melanopic irradiance measured at eye level when comparing light-dependent effects on evening melatonin concentrations in healthy young people at rather low light levels.

The sleep-circadian interface: A window into mental disorders.

Sleep, circadian rhythms, and mental health are reciprocally interlinked. Disruption to the quality, continuity, and timing of sleep can precipitate or exacerbate psychiatric symptoms in susceptible individuals, while treatments that target sleep-circadian disturbances can alleviate psychopathology. Conversely, psychiatric symptoms can reciprocally exacerbate poor sleep and disrupt clock-controlled processes. Despite progress in elucidating underlying mechanisms, a cohesive approach that integrates the dynamic interactions between psychiatric disorder with both sleep and circadian processes is lacking. This review synthesizes recent evidence for sleep-circadian dysfunction as a transdiagnostic contributor to a range of psychiatric disorders, with an emphasis on biological mechanisms. We highlight observations from adolescent and young adults, who are at greatest risk of developing mental disorders, and for whom early detection and intervention promise the greatest benefit. In particular, we aim to a) integrate sleep and circadian factors implicated in the pathophysiology and treatment of mood, anxiety, and psychosis spectrum disorders, with a transdiagnostic perspective; b) highlight the need to reframe existing knowledge and adopt an integrated approach which recognizes the interaction between sleep and circadian factors; and c) identify important gaps and opportunities for further research.

ICNIRP Statement on Short Wavelength Light Exposure from Indoor Artificial Sources and Human Health.

ABSTRACT: Concerns have been raised about the possibility of effects from exposure to short wavelength light (SWL), defined here as 380-550 nm, on human health. The spectral sensitivity of the human circadian timing system peaks at around 480 nm, much shorter than the peak sensitivity of daytime vision (i.e., 555 nm). Some experimental studies have demonstrated effects on the circadian timing system and on sleep from SWL exposure, especially when SWL exposure occurs in the evening or at night. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has identified a lack of consensus among public health officials regarding whether SWL from artificial sources disrupts circadian rhythm, and if so, whether SWL-disrupted circadian rhythm is associated with adverse health outcomes. Systematic reviews of studies designed to examine the effects of SWL on sleep and human health have shown conflicting results. There are many variables that can affect the outcome of these experimental studies. One of the main problems in earlier studies was the use of photometric quantities as a surrogate for SWL exposure. Additionally, the measurement of ambient light may not be an accurate measure of the amount of light impinging on the intrinsically photosensitive retinal ganglion cells, which are now known to play a major role in the human circadian timing system. Furthermore, epidemiological studies of long-term effects of chronic SWL exposure per se on human health are lacking. ICNIRP recommends that an analysis of data gaps be performed to delineate the types of studies needed, the parameters that should be addressed, and the methodology that should be applied in future studies so that a decision about the need for exposure guidelines can be made. In the meantime, ICNIRP supports some recommendations for how the quality of future studies might be improved.

Ultradian sleep cycles: Frequency, duration, and associations with individual and environmental factors-A retrospective study.

OBJECTIVE: Sleep varies between individuals in response to sleep-wake history and various environmental factors, including light and noise. Here we report on the intranight variation of the ultradian nonrapid eye movement-rapid eye movement (NREM-REM) sleep cycle in 369 participants who have contributed to different laboratory studies from 1994 to 2020 at the Centre for Chronobiology, Basel, Switzerland. RESULTS: We observed a large interindividual variability in sleep cycle duration, including NREM and REM sleep episodes in healthy participants who were given an 8-hour sleep opportunity at habitual bedtime in controlled laboratory settings. The median sleep cycle duration was 96 minutes out of 6064 polysomnographically-recorded cycles. The number and duration of cycles were not normally distributed, and the distribution became narrower for NREM sleep and wider for REM sleep later in the night. The first cycle was consistently shorter than subsequent cycles, and moderate presleep light or nocturnal noise exposure had no significant effects on ultradian sleep cycle duration. Age and sex significantly affected NREM and REM sleep duration, with older individuals having longer NREM and shorter REM sleep particularly in the end of the night, and females having longer NREM sleep episodes. High sleep pressure (ie, sleep deprivation) and low sleep pressure (ie, multiple naps) altered ultradian sleep cycles, with high sleep pressure leading to longer NREM sleep in the first cycle, and low sleep pressure leading to longer REM sleep episodes. Positive correlations were observed between N2 and NREM duration, and between N1 and REM duration. Weak intrasleep REM sleep homeostasis was also evident in our data set. CONCLUSIONS: We conclude that ultradian sleep cycles are endogenous biological rhythms modulated by age, sex, and sleep homeostasis, but not directly responsive to (moderate levels of) environmental cues in healthy good sleepers.

Sleep and sleep disorders during pregnancy and postpartum: The Life-ON study.

OBJECTIVE: to prospectively assess sleep and sleep disorders during pregnancy and postpartum in a large cohort of women. METHODS: multicenter prospective Life-ON study, recruiting consecutive pregnant women at a gestational age between 10 and 15 weeks, from the local gynecological departments. The study included home polysomnography performed between the 23rd and 25th week of pregnancy and sleep-related questionnaires at 9 points in time during pregnancy and 6 months postpartum. RESULTS: 439 pregnant women (mean age 33.7 ± 4.2 yrs) were enrolled. Poor quality of sleep was reported by 34% of women in the first trimester of pregnancy, by 46% of women in the third trimester, and by as many as 71% of women in the first month after delivery. A similar trend was seen for insomnia. Excessive daytime sleepiness peaked in the first trimester (30% of women), and decreased in the third trimester, to 22% of women. Prevalence of restless legs syndrome was 25%, with a peak in the third trimester of pregnancy. Polysomnographic data, available for 353 women, revealed that 24% of women slept less than 6 h, and 30.6% of women had a sleep efficiency below 80%. Sleep-disordered breathing (RDI≥5) had a prevalence of 4.2% and correlated positively with BMI. CONCLUSIONS: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.

Effects of calibrated blue-yellow changes in light on the human circadian clock.

Evening exposure to short-wavelength light can affect the circadian clock, sleep and alertness. Intrinsically photosensitive retinal ganglion cells expressing melanopsin are thought to be the primary drivers of these effects. Whether colour-sensitive cones also contribute is unclear. Here, using calibrated silent-substitution changes in light colour along the blue-yellow axis, we investigated whether mechanisms of colour vision affect the human circadian system and sleep. In a 32.5-h repeated within-subjects protocol, 16 healthy participants were exposed to three different light scenarios for 1 h starting 30 min after habitual bedtime: baseline control condition (93.5 photopic lux), intermittently flickering (1 Hz, 30 s on-off) yellow-bright light (123.5 photopic lux) and intermittently flickering blue-dim light (67.0 photopic lux), all calibrated to have equal melanopsin excitation. We did not find conclusive evidence for differences between the three lighting conditions regarding circadian melatonin phase delays, melatonin suppression, subjective sleepiness, psychomotor vigilance or sleep.The Stage 1 protocol for this Registered Report was accepted in principle on 9 September 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13050215.v1 .

Seasonal Variation in the Responsiveness of the Melanopsin System to Evening Light: Why We Should Report Season When Collecting Data in Human Sleep and Circadian Studies.

It is well known that variations in light exposure during the day affect light sensitivity in the evening. More daylight reduces sensitivity, and less daylight increases it. On average days, we spend less time outdoors in winter and receive far less light than in summer. Therefore, it could be relevant when collecting research data on the non-image forming (NIF) effects of light on circadian rhythms and sleep. In fact, studies conducted only in winter may result in more pronounced NIF effects than in summer. Here, we systematically collected information on the extent to which studies on the NIF effects of evening light include information on season and/or light history. We found that more studies were conducted in winter than in summer and that reporting when a study was conducted or measuring individual light history is not currently a standard in sleep and circadian research. In addition, we sought to evaluate seasonal variations in a previously published dataset of 72 participants investigating circadian and sleep effects of evening light exposure in a laboratory protocol where daytime light history was not controlled. In this study, we selectively modulated melanopic irradiance at four different light levels (<90 lx). Here, we aimed to retrospectively evaluate seasonal variations in the responsiveness of the melanopsin system by combining all data sets in an exploratory manner. Our analyses suggest that light sensitivity is indeed reduced in summer compared to winter. Thus, to increase the reproducibility of NIF effects on sleep and circadian measures, we recommend an assessment of the light history and encourage standardization of reporting guidelines on the seasonal distribution of measurements.

34th Annual Meeting of the Society for Light Treatment and Biological Rhythms (SLTBR), 30 May-1 June, Lausanne, Switzerland.

The Society for Light Treatment and Biological Rhythms (SLTBR) held this year's annual meeting at the Ecole Polytechnique Fédérale (EPFL) in Lausanne, Switzerland from 30 May to 1 June in conjunction with the Day Light Academy (DLA) [...].

Effects of nature-adapted lighting solutions ("Virtual Sky") on subjective and objective correlates of sleepiness, well-being, visual and cognitive performance at the workplace.

Exposure to natural daylight benefits human well-being, alertness, circadian rhythms and sleep. Many workplaces have limited or no access to daylight. Thus, we implemented a light-panel ("Virtual Sky"), which reproduced nature-adapted light scenarios. In a laboratory office environment, three lighting scenarios were presented during the day: two lighting conditions with nature-adapted spectral light distributions, one with static and one with dynamic clouds, and a standard office lighting condition. We compared the impact of the three lighting scenarios on subjective and objective measures of alertness, cognitive performance, wellbeing, visual comfort, contrast sensitivity, and cortisol levels in 18 healthy young male volunteers in a within-participant cross-over study design. We found no evidence that an 8-h lighting scenario with static or dynamic clouds during the waking day (9am-5pm) was associated with any significant effect on objective and/or subjective alertness, cognitive performance and morning cortisol concentrations compared to standard workplace lighting. However, the dynamic light scenario was accompanied with lower levels of perceived tensionafter completing cognitive tasks and less effort to concentrate compared to the static lighting scenarios. Our findings suggest that apart from smaller effects on tension and concentration effort, nature-adapted lighting conditions did not improve daytime alertness and cognitive performance in healthy well-rested young participants, as compared to standard office lighting.

Sleep disturbance, but not depression severity, is associated with inflammation in children and adolescents.

STUDY OBJECTIVES: We aimed to examine the association between self-rated and clinician-rated sleep disturbances and C-reactive protein (CRP), an objective marker of inflammation, in pediatric depression. METHODS: Two hundred fifty-six children and adolescents (15.2 ± 1.6 y, 72.3% female) with moderate to severe symptoms of depression participated in the study. Sleep disturbances were assessed by self-reports (Insomnia Severity Index) and clinician ratings (Kiddie-Schedule for Affective Disorder and Schizophrenia), inflammation by plasma CRP levels. RESULTS: Higher levels of CRP correlated positively with clinician-rated middle insomnia and hypersomnia. After adjusting for control variables (body mass index, tobacco, alcohol, stress, age, sex, antidepressants, sleep medication, depression severity), regression models confirmed the significant association of clinician-rated hypersomnia and middle insomnia symptoms with elevated CRP levels. In the adjusted regression models, other clinician-rated manifestations of sleep disturbance (eg, initial insomnia) and insomnia self-ratings were not significantly associated with CRP. Body mass index correlated positively with CRP, but body mass index had no mediating effect on the associations between sleep disturbances and CRP. We did not find an association between depression severity, assessed by the Children's Depression Rating Scale-Revised, and CRP. CONCLUSIONS: Results of the present study indicate a significant association of hypersomnia and middle insomnia symptoms with CRP in pediatric depression, not linked to alterations in the body mass index. CITATION: Strumberger MA, Häberling I, Emery S, et al. Sleep disturbance, but not depression severity, is associated with inflammation in children and adolescents. J Clin Sleep Med. 2023;19(10):1775-1784.

Association between circadian sleep regulation and cortical gyrification in young and older adults.

The circadian system orchestrates sleep timing and structure and is altered with increasing age. Sleep propensity, and particularly REM sleep is under strong circadian control and has been suggested to play an important role in brain plasticity. In this exploratory study, we assessed whether surface-based brain morphometry indices are associated with circadian sleep regulation and whether this link changes with age. Twenty-nine healthy older (55-82 years; 16 men) and 28 young participants (20-32 years; 13 men) underwent both structural magnetic resonance imaging and a 40-h multiple nap protocol to extract sleep parameters over day and night time. Cortical thickness and gyrification indices were estimated from T1-weighted images acquired during a classical waking day. We observed that REM sleep was significantly modulated over the 24-h cycle in both age groups, with older adults exhibiting an overall reduction in REM sleep modulation compared to young individuals. Interestingly, when taking into account the observed overall age-related reduction in REM sleep throughout the circadian cycle, higher day-night differences in REM sleep were associated with increased cortical gyrification in the right inferior frontal and paracentral regions in older adults. Our results suggest that a more distinctive allocation of REM sleep over the 24-h cycle is associated with regional cortical gyrification in aging, and thereby point towards a protective role of circadian REM sleep regulation for age-related changes in brain organization.

Melanopic irradiance defines the impact of evening display light on sleep latency, melatonin and alertness.

Evening light-emitting visual displays may disrupt sleep, suppress melatonin and increase alertness. Here, we control melanopic irradiance independent of display luminance and colour, in 72 healthy males 4 h before habitual bedtime and expose each of them to one of four luminance levels (i.e., dim light, smartphone, tablet or computer screen illuminance) at a low and a high melanopic irradiance setting. Low melanopic light shortens the time to fall asleep, attenuates evening melatonin suppression, reduces morning melatonin, advances evening melatonin onset and decreases alertness compared to high melanopic light. In addition, we observe dose-dependent increases in sleep latency, reductions in melatonin concentration and delays in melatonin onset as a function of melanopic irradiance-not so for subjective alertness. We identify melanopic irradiance as an appropriate parameter to mitigate the unwanted effects of screen use at night. Our results may help the many people who sit in front of screens in the evening or at night to fall asleep faster, feel sleepier, and have a more stable melatonin phase by spectrally tuning the visual display light without compromising the visual appearance.

Brain activity during a working memory task after daily caffeine intake and caffeine withdrawal: a randomized double-blind placebo-controlled trial.

Acute caffeine intake has been found to increase working memory (WM)-related brain activity in healthy adults without improving behavioral performances. The impact of daily caffeine intake-a ritual shared by 80% of the population worldwide-and of its discontinuation on working memory and its neural correlates remained unknown. In this double-blind, randomized, crossover study, we examined working memory functions in 20 young healthy non-smokers (age: 26.4 ± 4.0 years; body mass index: 22.7 ± 1.4 kg/m2; and habitual caffeine intake: 474.1 ± 107.5 mg/day) in a 10-day caffeine (150 mg × 3 times/day), a 10-day placebo (3 times/day), and a withdrawal condition (9-day caffeine followed by 1-day placebo). Throughout the 10th day of each condition, participants performed four times a working memory task (N-Back, comprising 3- and 0-back), and task-related blood-oxygen-level-dependent (BOLD) activity was measured in the last session with functional magnetic resonance imaging. Compared to placebo, participants showed a higher error rate and a longer reaction time in 3- against 0-back trials in the caffeine condition; also, in the withdrawal condition we observed a higher error rate compared to placebo. However, task-related BOLD activity, i.e., an increased attention network and decreased default mode network activity in 3- versus 0-back, did not show significant differences among three conditions. Interestingly, irrespective of 3- or 0-back, BOLD activity was reduced in the right hippocampus in the caffeine condition compared to placebo. Adding to the earlier evidence showing increasing cerebral metabolic demands for WM function after acute caffeine intake, our data suggest that such demands might be impeded over daily intake and therefore result in a worse performance. Finally, the reduced hippocampal activity may reflect caffeine-associated hippocampal grey matter plasticity reported in the previous analysis. The findings of this study reveal an adapted neurocognitive response to daily caffeine exposure and highlight the importance of classifying impacts of caffeine on clinical and healthy populations.

How to deal with sleep problems during heatwaves: practical recommendations from the European Insomnia Network.

Heatwaves are occurring more frequently and are known to affect particularly night-time temperatures. We review here literature on how night-time ambient temperature changes affect body temperature and sleep quality. We then discuss how these temperature effects impact particularly vulnerable populations such as older adults, children, pregnant women, and those with psychiatric conditions. Several ways of dealing with sleep problems in the context of heatwaves are then suggested, adapted from elements of cognitive behavioural therapy for insomnia, with more specific advice for vulnerable populations. By better dealing with sleep problems during heatwaves, general health effects of heatwaves may be more limited. However, given the sparse literature, many links addressed in this review on sleep problems affected by temperature changes should be the focus of future research.

Preliminary evidence that daily light exposure enhances the antibody response to influenza vaccination in patients with dementia.

Enhancing lighting conditions in institutions for individuals with dementia improves their sleep, circadian rhythms and well-being. Here, we report first findings that exposure to brighter light during daytime may support 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. We analysed the patients' immune response from two blood samples taken before and 4 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 preliminary evidence for a potentially enhanced immune response in patients with dementia when they received more daily light. Future studies are needed to determine whether regular daily light exposure may have beneficial effects on the human immune system, either directly or via a stabilising circadian sleep-wake rhythms.