The higher risk for cancer documented among night-shift nurses compared to the day-shift nurses possibly results from lower melatonin levels associated with exposure to light at night in the work environment. Research demonstrates that eliminating spectral power <530 nm to both eyes prevents light-induced nocturnal melatonin suppression, and complete occlusion of one eye reduces melatonin suppression relative to that when both eyes are open. This study investigated whether filtering short wavelengths from one eye using a blue-blocking filter, rather than occluding one eye, would maintain high melatonin levels, alertness, and visual performance. This crossover, within-subjects study ran for six nights. Subjects experienced one of six light conditions involving combinations of binocular versus monocular and filtered versus unfiltered vision per night. Normalized melatonin concentration area under the curve (AUC(n)) served as the primary outcome and the numerical verification (NVT) and go/no-go (GNG) performance tasks, pupil area, and subjective sleepiness (Karolinska Sleepiness Scale [KSS]) served as secondary outcomes. Both filtered and unfiltered monocular light conditions resulted in significantly greater melatonin AUCn than the unfiltered binocular light condition. Performance at the NVT and at the GNG was not affected by filtering one eye compared to the unfiltered binocular light condition, nor did it affect KSS ratings. Melatonin AUC(n )positively correlated with pupil area for corresponding light conditions. In conclusion, filtering one eye can help preserve melatonin levels in night workers while maintaining alertness and visual performance, which could be a simple and effective solution for improving health in night-shift nurses.

Objectives:Sleep disorders can significantly worsen the quality of life in Parkinson's disease (PD). Variants in LRRK2 and GBA1, the most common genetic contributors to PD, may lead to different clinical features, including more REM sleep behavior disorder (RBD) in PD associated with GBA1 mutations (GBA PD). However, there is a dearth of information about differences in non-RBD sleep disorders among these genetic subgroups. Methods:Seventy-nine participants with PD (18 LRRK2 G2019S carriers with PD [LRRK2 PD], 22 GBA1 [GBA PD], 2 LRRK2 GBA PD and 37 idiopathic PD [iPD]) underwent actigraphy (Actiwatch-2) for 1 week. Subjective sleep quality was assessed using questionnaires. Results:LRRK2 PD participants demonstrated better sleep actigraphy, including reduced wake after sleep onset (-25 minutes; p<0.001) and higher sleep efficiency (6.3%; p=0.015), than iPD and GBA PD in models adjusted for age, age at disease onset, and gender. While sleep onset times did not differ between groups, all groups had mean sleep onset times after 11:00 PM, and did not demonstrate phase advancement. Sleep questionnaires showed only an increased prevalence of RBD in GBA PD and iPD. Conclusions:LRRK2 PD is associated with less fragmented sleep than GBA PD and iPD, suggesting that despite similar objective sleep complaints, genotypic sleep differences extend beyond RBD. These differences support the need for personalized and genotypic approaches to sleep disturbances in PD. The absence of phase advancement in all groups suggests that lighting interventions to improve sleep disorders should be considered for the morning rather than later in the day.

Light at night has been implicated in health risks associated with night-shift work and circadian system disruption, but there are scant data on actual nighttime light exposures experienced by night-shift workers and how they affect melatonin levels. This study analysed salivary melatonin assays and calibrated personal light-exposure measurements obtained from a larger 20-week field study to explore the association between nocturnal melatonin levels and light exposures in 27 nurses working night shifts at four hospitals in southern New York and southern Indiana. Complete time-matched melatonin and light exposure data were available for 20 of the participants, who underwent three 2-week data collection periods (6 weeks total), each separated by six weeks. A mixed-effects model was used to quantify the adjusted association between melatonin levels and light exposures. No significant association was found between the measures after adjusting for age and years working night shifts (β = −6.8, p = 0.26). This study demonstrates that healthcare environments can provide sufficient light for visual tasks without affecting melatonin levels, a marker of the circadian system. Our research also highlights the value of personal light-measurement devices when examining the relationship between exposure to light at night, melatonin levels and the potential for circadian disruption.

IMPORTANCE:Sleep disturbances in Parkinson's disease (PD) are common and often adversely affect quality of life. Light therapy has benefited sleep quality and mood outcomes in various populations but results to date with conventional light therapy boxes in PD patients have been mixed. We hypothesized that a passive lighting intervention, applied in the morning and designed to maximally affect the circadian system, would improve measures of sleep and mood in PD patients. METHODS:In this single-arm, within-subjects intervention study, baseline objective sleep (actigraphy), subjective sleep quality (questionnaires), and subjective mood (questionnaires) data were collected for 1 week. Lighting was then administered to participants via table/floor lamps installed in the home or via personal light therapy glasses for 2 h in the morning, 7 days per week, over the following 4-week period. Post-intervention data for the same outcomes were collected during the final week of the intervention period. RESULTS:Among 20 participants (12 women, 8 men; mean [SD] age 72.1 [9.5] years, disease duration 9.0 [5.2] years), objective sleep duration increased significantly by 28.5 min (p = 0.029) and objective sleep time increased significantly by 19.9 min (p = 0.026). CONCLUSION:Passive and easily administered lighting interventions for improving sleep in PD patients hold promise as a treatment for mitigating symptoms and improving quality of life in PD.

Objective: To assess the effects of a short-term tailored lighting intervention therapy (TLI) on sleep disturbances in Parkinson disease (PD). Background: Sleep disturbances are a common non-motor symptom in PD, adversely affecting quality of life, mood and cognition. They suggest underlying disruptions in circadian rhythm. Based on our preliminary studies showing the positive impacts of TLI on sleep, mood and behavior in Alzheimer's disease, we hypothesize that TLI can improve objective sleep measures in PD. Design/Methods: Baseline sleep quality and rest activity were measured with 1-week wrist actigraphy. Light exposure level was measured with a daysimeter. TLI was delivered over a 4-week period, administered for 2 hours every morning via table/floor lamps installed in the home or lighting glasses. Post-intervention actigraph and daysimeter data were collected during the last week of the 4-week intervention. Pre- and post-intervention measures were compared using paired t-tests. Results: In 20 participants (65% women, mean age 73.8 years [SD 8.6], disease duration 9.4 years [7.4]), average time of falling asleep was 19 minutes earlier (p=0.18) with TLI. Sleep time (excluding nocturnal wake after sleep onset) increased significantly by 20 minutes (p=0.049) from 381.11 to 401.36 minutes. Overall sleep duration also increased by 29 minutes but this did not reach significance (p=0.078). Sleep efficiency in this PD cohort was 85% both pre- and post-intervention. Conclusions: This pilot study demonstrates the feasibility of conducting an at home, short-term tailored lighting intervention therapy for participants with PD. In this small group, several sleep measures were improved, despite starting with an overall baseline of good sleep efficiency. Additional analyses are underway to determine effects of TLI on subjective sleep quality, daytime sleepiness, depression, anxiety and fatigue. Follow up studies in a larger cohort are warranted to assess for effects of TLI in participants with poor baseline sleep, as well as longer intervention durations. Disclosure: Dr. Yoo has received research support from Edmond J Safra Foundation. Roberto Ortega has nothing to disclose. The institution of Ms. Raymond has received research support from NIH. Ms. Gerber has nothing to disclose. Ms. Markgraf has nothing to disclose. Ms. Liang has nothing to disclose. Ms. Zians has nothing to disclose. Dr. Wise has nothing to disclose. Ms. Rawal has nothing to disclose. Ms. Plitnick has nothing to disclose. Ms. Brons has nothing to disclose. The institution of Dr. Bressman has received research support from Michael J Fox Foundation . The institution of Dr. Bressman has received research support from NIH . The institution of Dr. Figueiro has received research support from NIH. The institution of Dr. Figueiro has received research support from EU. The institution of Dr. Figueiro has received research support from McClung Foundation. The institution of Dr. Saunders-Pullman has received research support from NIH, Bigglesworth Family Foundation, Empire Clinical Research Investigatory Program.

Introduction: Sleep disturbance is a hallmark of Alzheimer’s disease and related dementias, and caregiver stress caused by patients’ nighttime wandering, injuries, and agitation are frequently at the root of decisions to move them to assisted living facilities, where typically dim institutional lighting can further exacerbate their sleep problems. This study explored the effects of a circadian-effective lighting intervention on actigraphic sleep measures and subjective assessments of sleep disturbance, depression, and sleep-disturbed behaviors.Methods: Fourteen older adult (≥60 years) participants (11 females, mean age = 84.1 [SD 8.9]), all diagnosed with moderate to severe dementia and sleep disturbance, were recruited from 3 assisted living and memory care facilities. Following a crossover, placebo-controlled design, 3 different lighting modes were used to deliver high levels of circadian stimulus to the participants’ eyes for two 8-week intervention periods in a counter balanced order with a 4-week washout between the study’s 2 conditions (dim light control vs. active intervention). Actigraphy and questionnaire data were collected over 7-day assessment periods that preceded (baseline weeks 1 and 9) and concluded (post-intervention week 9 and 22) the intervention periods. Actigraphic outcomes included sleep duration, sleep time, sleep efficiency, sleep start time, and sleep end time. Subjective assessments included the Cornell Scale for Depression in Dementia (CSDD), Pittsburgh Sleep Quality Index (PSQI), and Sleep Disorders Inventory (SDI) instruments.Results: Under the active condition, sleep duration significantly (p = 0.018) increased and sleep start time significantly (p = 0.012) advanced after the intervention compared to baseline. Also under the active condition, PSQI (p = 0.012), CSDD (p = 0.007), Sleep Disorders Inventory frequency (p = 0.015), and SDI severity (p = 0.015) scores were significantly lower after the intervention compared to baseline.Discussion: This study demonstrates that a circadian-effective lighting intervention delivering bright days and dark nights improves measures of sleep and mood in dementia patients living in controlled environments.

Background Despite compelling epidemiological evidence that circadian disruption inherent to long‐term shift work enhances atherosclerosis progression and vascular events, the underlying mechanisms remain poorly understood. A challenge to the use of mouse models for mechanistic and interventional studies involving light‐dark patterns is that the spectral and absolute sensitivities of the murine and human circadian systems are very different, and light stimuli in nocturnal mice should be scaled to represent the sensitivities of the human circadian system. Methods and Results We used calibrated devices to deliver to low‐density lipoprotein receptor knockout mice light‐dark patterns representative of that experienced by humans working day shifts or rotating shift schedules. Mice under day shifts were maintained under regular 12 hours of light and 12 hours of dark cycles. Mice under rotating shift schedules were subjected for 11 weeks to reversed light‐dark patterns 4 days in a row per week, followed by 3 days of regular light‐dark patterns. In both protocols the light phases consisted of monochromatic green light at an irradiance of 4 µW/cm2. We found that the shift work paradigm disrupts the foam cell's molecular clock and increases endoplasmic reticulum stress and apoptosis. Lesions of mice under rotating shift schedules were larger and contained less prostabilizing fibrillar collagen and significantly increased areas of necrosis. Conclusions Low‐density lipoprotein receptor knockout mice under light‐dark patterns analogous to that experienced by rotating shift workers develop larger and more vulnerable plaques and may represent a valuable model for further mechanistic and/or interventional studies against the deleterious vascular effects of rotating shift work.

As the primary environmental cue for the body’s master biological clock, light–dark patterns are key for circadian alignment and are ultimately fundamental to multiple dimensions of health including sleep and mental health. Although daylight provides the proper qualities of light for promoting circadian alignment, our modern indoor lifestyles offer fewer opportunities for adequate daylight exposure. This field study explores how increasing circadian-effective light in residences affects circadian phase, sleep, vitality, and mental health. In this crossover study, 20 residents spent one week in their apartments with electrochromic glass windows and another week with functionally standard windows with blinds. Calibrated light sensors revealed higher daytime circadian-effective light levels with the electrochromic glass windows, and participants exhibited consistent melatonin onset, a 22-min earlier sleep onset, and higher sleep regularity. In the blinds condition, participants exhibited a 15-min delay in dim light melatonin onset, a delay in subjective vitality throughout the day, and an overall lower positive affect. This study demonstrates the impact of daytime lighting on the physiological, behavioral, and subjective measures of circadian health in a real-world environment and stresses the importance of designing buildings that optimize daylight for human health and wellbeing.

Background: Persons with Alzheimer’s disease and related dementias (ADRD) frequently experience sleep–wake (circadian) cycle disturbances that lead them to remain awake at night, causing stress and fatigue for families and caregivers. Light therapy shows promise as a nonpharmacological treatment for regulating sleep in this population. Objective: We investigated the long-term impact of a circadian-effective lighting intervention on sleep, mood, and behavior problems in persons with ADRD. Methods: This 25-week clinical trial administered an all-day lighting intervention to 47 patients with ADRD in 9 senior-care facilities, employing wrist-worn actigraphy measures and standardized measures of sleep quality, mood, and behavior. Results: The intervention significantly improved Pittsburgh Sleep Quality Index scores, from an estimated mean±SEM of 11.89±0.53 at baseline to 5.36±0.63 at the end of the intervention. Additional improvements were noted for sleep efficiency data from actigraph measurements. The intervention significantly reduced Cornell Scale for Depression in Dementia scores (mean±SEM of 11.36±0.74 at baseline and 4.18±0.88 at the end of the intervention) and Cohen-Mansfield Agitation Inventory scores (mean±SEM of 47.10±1.98 at baseline and 35.33±2.23 at the end of the intervention). Conclusion: A regular circadian-effective daytime lighting intervention can improve sleep at night and reduce depression and agitation in patients with dementia living in controlled environments. More importantly, the positive effects of the tailored lighting intervention on these outcomes appear to be cumulative over time.

The human circadian system is primarily regulated by the 24-h LD cycle incident on the retina, and nocturnal melatonin suppression is a primary outcome measure for characterizing the biological clock's response to those light exposures. A limited amount of data related to the combined effects of light level, spectrum, and exposure duration on nocturnal melatonin suppression has impeded the development of circadian-effective lighting recommendations and light-treatment methods. The study's primary goal was to measure nocturnal melatonin suppression for a wide range of light levels (40 to 1000 lux), 2 white light spectra (2700 K and 6500 K), and an extended range of nighttime light exposure durations (0.5 to 3.0 h). The study's second purpose was to examine whether differences existed between adolescents' and adults' circadian sensitivity to these lighting characteristics. The third purpose was to provide an estimate of the absolute threshold for the impact of light on acute melatonin suppression. Eighteen adolescents (age range, 13 to 18 years) and 23 adults (age range, 24 to 55 years) participated in the study. Results showed significant main effects of light level, spectrum, and exposure duration on melatonin suppression. Moreover, the data also showed that the relative suppressing effect of light on melatonin diminishes with increasing exposure duration for both age groups and both spectra. The present results do not corroborate our hypothesis that adolescents exhibit greater circadian sensitivity to short-wavelength radiation compared with adults. As for threshold, it takes longer to observe significant melatonin suppression at lower CS levels than at higher CS levels. Dose-response curves (amount and duration) for both white-light spectra and both age groups can guide lighting recommendations when considering circadian-effective light in applications such as offices, schools, residences, and healthcare facilities.

STUDY OBJECTIVES:We investigated the effectiveness of a lighting intervention tailored to maximally affect the circadian system as a nonpharmacological therapy for treating problems with sleep, mood, and behavior in persons with Alzheimer disease and related dementias (ADRD).METHODS:This 14-week randomized, placebo-controlled, crossover design clinical trial administered an all-day active or control lighting intervention to 46 patients with ADRD in 8 long-term care facilities for two 4-week periods (separated by a 4-week washout). The study employed wrist-worn actigraphy measures and standardized measures of sleep quality, mood, and behavior.RESULTS:The active intervention significantly improved Pittsburgh Sleep Quality Index scores compared to the active baseline and control intervention (mean ± SEM: 6.67 ± 0.48 after active intervention, 10.30 ± 0.40 at active baseline, 8.41 ± 0.47 after control intervention). The active intervention also resulted in significantly greater active versus control differences in intradaily variability. As for secondary outcomes, the active intervention resulted in significant improvements in Cornell Scale for Depression in Dementia scores (mean ± SEM: 10.30 ± 1.02 at baseline, 7.05 ± 0.67 after active intervention) and significantly greater active versus control differences in Cohen-Mansfield Agitation Inventory scores (mean ± SEM: -5.51 ± 1.03 for the active intervention, -1.50 ± 1.24 for the control intervention).CONCLUSIONS:A lighting intervention tailored to maximally entrain the circadian system can improve sleep, mood, and behavior in patients with dementia living in controlled environments.CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov, title: Methodology Issues in a Tailored Light Treatment for Persons With Dementia, URL: https://clinicaltrials.gov/ct2/show/NCT01816152, identifier: NCT01816152.

Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n = 37) treated with methadone (n = 15) or buprenorphine (n = 22). For 16 weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00-09:00) vs. Late hours (12:00-13:00) for 4 weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00-11:30) for 8 weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.

Introduction: Sleep inertia, broadly defined as decrements in performance and lowering of alertness following waking, lasts for durations ranging between 1 min and 3 hrs. This study investigated whether, compared to a dim light condition (the control), exposure to long-wavelength (red) light delivered to closed eyelids during sleep (red light mask) and to eyes open upon waking (red light goggles) reduced sleep inertia. Methods: Thirty participants (18 females, 12 males; mean age=30.4 years [SD 13.7]) completed this crossover, within-subjects, counterbalanced design study. Self-reported measures of sleepiness and objective measures of auditory performance and cortisol levels were collected on 3 Friday nights over the course of 3 consecutive weeks. Results: Performance improved significantly during the 30-min data collection period in all experimental conditions. Subjective sleepiness also decreased significantly with time awake in all experimental conditions. As hypothesized, performance of some tasks was significantly better in the red light mask condition than in the dim light condition. Performance scores in the red light goggles condition improved significantly after a few minutes of wearing the light goggles. Discussion: The results show that saturated red light delivered through closed eyelids at levels that do not suppress melatonin can be used to mitigate sleep inertia upon waking.

This study investigated how light exposure duration affects melatonin suppression, a well-established marker of circadian phase, and whether adolescents (13-18 years) are more sensitive to short-wavelength (blue) light than adults (32-51 years). Twenty-four participants (12 adolescents, 12 adults) were exposed to three lighting conditions during successive 4-h study nights that were separated by at least one week. In addition to a dim light (<5lux) control, participants were exposed to two light spectra (warm (2700K) and cool (5600K)) delivering a circadian stimulus of 0.25 at eye level. Repeated measures analysis of variance revealed a significant main effect of exposure duration, indicating that a longer duration exposure suppressed melatonin to a greater degree. The analysis further revealed a significant main effect of spectrum and a significant interaction between spectrum and participant age. For the adolescents, but not the adults, melatonin suppression was significantly greater after exposure to the 5600K intervention (43%) compared to the 2700K intervention (29%), suggesting an increased sensitivity to short-wavelength radiation. These results will be used to extend the model of human circadian phototransduction to incorporate factors such as exposure duration and participant age to better predict effective circadian stimulus.

The intrinsically photosensitive retinal ganglion cells are the main conduit of the light signal emanating from the retina to the biological clock located in the suprachiasmatic nuclei of the hypothalamus. Lighting manufacturers are developing white light sources that are devoid of wavelengths around 480 nm ("cyan gap") to reduce their impact on the circadian system. The present study was designed to investigate whether exposure to a "cyan-gap," 3000 K white light source, spectrally tuned to reduce radiant power between 475 and 495 nm (reducing stimulation of the melanopsin-containing photoreceptor), would suppress melatonin less than a conventional 3000 K light source. The study's 2 phases employed a within-subjects experimental design involving the same 16 adult participants. In Phase 1, participants were exposed for 1 h to 3 experimental conditions over the course of 3 consecutive weeks: 1) dim light control (<5 lux at the eyes); 2) 800 lux at the eyes of a 3000 K light source; and 3) 800 lux at the eyes of a 3000 K, "cyan-gap" modified (3000 K mod) light source. The same protocol was repeated in Phase 2, but light levels were reduced to 400 lux at the eyes. As hypothesized, there were significant main effects of light level ( F1,12 = 9.1, p < 0.05, ηp² = 0.43) and exposure duration ( F1,12 = 47.7, p < 0.05, ηp² = 0.80) but there was no significant main effect of spectrum ( F1,12 = 0.16, p > 0.05, ηp² = 0.01). There were no significant interactions with spectrum. Contrary to our model predictions, our results showed that short-term exposures (≤ 1 h) to "cyan-gap" light sources suppressed melatonin similarly to conventional light sources of the same CCT and photopic illuminance at the eyes.

The increased use of self-luminous displays, especially in the evening prior to bedtime, has been associated with melatonin suppression, delayed sleep and sleep curtailment. The present study set out to investigate whether the Night Shift application provided by Apple Inc. for use on its portable electronic devices is effective for reducing acute melatonin suppression, a well-established marker of circadian phase. Participants experienced four experimental conditions: a dim light control, a high circadian stimulus true positive intervention and two Night Shift interventions delivering low and high correlated colour temperature light from the devices. Melatonin suppression did not significantly differ between the two Night Shift interventions, which indicates that changing the spectral composition of self-luminous displays without changing their brightness settings may be insufficient for preventing impacts on melatonin suppression.

Persons with Alzheimer’s disease and related dementias (ADRD) are difficult for caregivers to manage because of sleep problems, wandering, and associated daytime irritability. Light exposure during the day helps consolidate sleep and improve behavior ADRD patients, but the light levels required are high and lighting fixtures that are currently available cannot deliver the level and spectrum of lighting that maximally affects the circadian system. This study tested whether a tailored lighting intervention could improve sleep and behavior in ADRD patients living in long-term care facilities. In the context of a crossover, repeated-measures design, we exposed 42 subjects diagnosed with ADRD (Mini mental scale below 24) to an active (circadian stimulus, CS=0.3) and inactive (CS=0.1) tailored lighting intervention for successive 4-week periods, spaced by a 4-week washout period. The lighting intervention was added to spaces in which patients spent most of their waking hours and was energized from wake time until 6:00 pm. Calibrated personal light meters monitored exposures. Measures of sleep disturbances (Pittsburgh Sleep Quality Index, PSQI), mood (Cornell Scale for Depression in Dementia, CSDD) and agitation (Cohen-Mansfield Agitation Index, CMAI) were collected at baseline and during the last week of the intervention. Compared to baseline and to the inactive lighting condition, the lighting intervention significantly decreased sleep disturbances, depression and agitation. The mean ± SEM PSQI scores was 10.4 ± 0.4 and 6.4 ± 0.5 at baseline and after active intervention and 9.7 ± 0.5 and 8.0 ± 0.4 at baseline and after the inactive intervention. The mean ± SEM CSDD scores was 10.9 ± 1.1 and 7.3 ± 0.7 at baseline and after active intervention and 10.6 ± 0.9 and 9.1 ± 0.9 at baseline and after the inactive intervention. The mean ± SEM CMAI scores was 43.6 ± 2.5 and 37.5 ± 1.9 at baseline and after active intervention and 41.5 ± 1.8 and 40.4 ± 1.9 at baseline and after the inactive intervention. When carefully delivered to patients’ eye and monitored with calibrated instrument, daytime light can improve sleep, mood and behavior in nursing home residents with ADRD. The NIA provided funding under grant number R01 AG034157.