Circadian rhythm disruption with high-fat diet impairs glycemic control and bone quality.

Biological functions, including glycemic control and bone metabolism, are highly influenced by the body's internal clock. Circadian rhythms are biological rhythms that run with a period close to 24 hours and receive input from environmental stimuli, such as the light/dark cycle. We investigated the effects of circadian rhythm disruption (CRD), through alteration of the light/dark schedule, on glycemic control and bone quality of mice. Ten-week-old male mice (C57/BL6, n = 48) were given a low-fat diet (LFD) or a high-fat diet (HFD) and kept on a dayshift or altered schedule (RSS3) for 22 weeks. Mice were divided into four experimental groups (n = 12/group): Dayshift/LFD, Dayshift/HFD, RSS3/LFD, and RSS3/HFD. CRD in growing mice fed a HFD resulted in a diabetic state, with a 36.2% increase in fasting glucose levels compared to the Dayshift/LFD group. Micro-CT scans of femora revealed a reduction in inner and outer surface expansion for mice on a HFD and altered light schedule. Cancellous bone demonstrated deterioration of bone quality as trabecular number and thickness decreased while trabecular separation increased. While HFD increased cortical bone mineral density, its combination with CRD reduced this phenomenon. The growth of mineral crystals, determined by small angle X-ray scattering, showed HFD led to smaller crystals. Considering modifications of the organic matrix, regardless of diet, CRD exacerbated the accumulation of fluorescent advanced glycation end-products (fAGEs) in collagen. Strength testing of tibiae showed that CRD mitigated the higher strength in the HFD group and increased brittleness indicated by lower post-yield deflection and work-to-fracture. Consistent with accumulation of fAGEs, various measures of toughness were lowered with CRD, but combination of CRD with HFD protected against this decrease. Differences between strength and toughness results represent different contributions of structural and material properties of bone to energy dissipation. Collectively, these results demonstrate that combination of CRD with HFD impairs glycemic control and have complex effects on bone quality.

Lighting and Alzheimer's Disease and Related Dementias: Spotlight on Sleep and Depression.

Alzheimer's disease and related dementias is the collective term for a progressive neurodegenerative disease for which there is presently no cure. This paper focuses on two symptoms of the disease, sleep disturbances and depression, and discusses how light can be used as a non-pharmacological intervention to mitigate their negative effects. Bright days and dark nights are needed for health and well-being, but the present components of the built environment, especially those places where older adults spend most of their days, are too dimly illuminated during the day and too bright at night. To be effective light needs to be correctly specified, implemented, and measured. Yet without the appropriate specification and measurement of the stimulus, researchers will not be able to successfully demonstrate positive results in the field, nor will lighting designers and specifiers have the confidence to implement lighting solutions for promoting better sleep and mood in this population.

Impact of an Individually Tailored Light Mask on Sleep Parameters in Older Adults With Advanced Phase Sleep Disorder.

Objective: This study investigated whether light delivered through the eyelids of sleeping persons might create phase delay in older adults who are adversely affected by advanced sleep phase disorder. Participants: Thirty-two cognitively intact, community-dwelling participants aged ≥ 50 years (20 females, 12 males) with Pittsburgh Sleep Quality Index scores ≥ 5 (poor sleep) completed the study. Methods: This within-subjects, randomized, two-treatment crossover design study exposed participants to an active "blue" (λmax  =  480 nm) lighting intervention or a placebo "red" (λmax = 640 nm) control through closed eyelids during sleep for 8 weeks. Conditions were administered 1 hr after bedtime using custom-built light masks delivering a train of 2-s duration light pulses presented every 30 s for ≤ 2 hr (approximately 240 pulses/night). Dependent variables were subjective measures of sleep and depression (questionnaires) and objective measures of sleep (wrist actigraphy), analyzed using linear mixed models with treatment, period, and carryover as fixed effects. Results: The actigraphy analysis found no effect of the intervention or the control condition on sleep start time, total sleep time, number of sleep bouts, or sleep efficiency, either compared to baseline or to one another. Subjective responses of study participants, however, indicated statistically significant (p < 0.05) improvement in seven of eight reported measures of sleep quality with both the intervention and the control condition, but no difference between the two conditions. Conclusions: The participants reported improvement in sleep quality, but the intervention did not confer additional advantages after adjusting for period and carryover effects.

The NICU Lighted Environment.

Lighting technologies are rapidly evolving, creating many opportunities for good lighting within the NICU. With the widespread adoption of advanced solid-state lighting technologies, lighting no longer needs to be static. Rather, lighting systems can be more easily adjusted to the different and changing visual and non-visual needs of the professional staff, infants and family members throughout the 24-hour day. This paper provides a conceptual framework for defining good lighting in the NICU, recognizing the needs of various constituent groups, each with very different needs from the lighting. Several other papers on the topic of lighting for various constituent groups at different times of the day in the NICU are summarized. Attention is given specifically to the Recommended Standards for Newborn ICU Design, a consensus standard developed by a wide range of experts, to help the reader translate this conceptual framework to practice.

Understanding Rotating Shift Workers' Health Risks.

Until we know more, it is recommended that lighting in health care facilities should be designed to minimize acute melatonin suppression in night shift workers.

Daily activity and light exposure levels for five species of lemurs at the Duke Lemur Center.

Light is the primary synchronizer of all biological rhythms, yet little is known about the role of the 24-hour luminous environment on nonhuman primate circadian patterns, making it difficult to understand the photic niche of the ancestral primate. Here we present the first data on proximate light-dark exposure and activity-rest patterns in free-ranging nonhuman primates. Four individuals each of five species of lemurs at the Duke Lemur Center (Eulemur mongoz, Lemur catta, Propithecus coquereli, Varecia rubra, and Varecia variegata variegata) were fitted with a Daysimeter-D pendant that contained light and accelerometer sensors. Our results reveal common as well as species-specific light exposure and behavior patterns. As expected, all five species were more active between sunrise and sunset. All five species demonstrated an anticipatory increase in their pre-sunrise activity that peaked at sunrise with all but V. rubra showing a reduction within an hour. All five species reduced activity during mid-day. Four of the five stayed active after sunset, but P. coquereli began reducing their activity about 2 hours before sunset. Other subtle differences in the recorded light exposure and activity patterns suggest species-specific photic niches and behaviors. The eventual application of the Daysimeter-D in the wild may help to better understand the adaptive evolution of ancestral primates.

Corrigendum: Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep.

[This corrects the article DOI: 10.3389/fnins.2024.1390216.].

Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep.

Postoperative cognitive dysfunction (POCD) is a neurological disorder characterized by the emergence of cognitive impairment after surgery. A growing body of literature suggests that the onset of POCD is closely tied to circadian rhythm disruption (CRD). Circadian rhythms are patterns of behavioral and physiological change that repeat themselves at approximately, but not exactly, every 24 h. They are entrained to the 24 h day by the daily light-dark cycle. Postoperative CRD affects cognitive function likely by disrupting sleep architecture, which in turn provokes a host of pathological processes including neuroinflammation, blood-brain barrier disturbances, and glymphatic pathway dysfunction. Therefore, to address the pathogenesis of POCD it is first necessary to correct the dysregulated circadian rhythms that often occur in surgical patients. This narrative review summarizes the evidence for CRD as a key contributor to POCD and concludes with a brief discussion of how circadian-effective hospital lighting can be employed to re-entrain stable and robust circadian rhythms in surgical patients.

Associations between circadian alignment and cognitive functioning in a nationally representative sample of older adults.

Proper alignment of activity-rest and light-dark patterns allows for healthy bodily functions to occur at optimal times of the day. Disruptions to this alignment may cause poor sleep as well as physical, mental, and cognitive problems. The purpose of this cross-sectional study was to determine if poorer circadian alignment was associated with decreased cognitive functioning among older (> 60 years) participants in the National Health and Nutrition Examination Survey. We utilized actigraphy-based rest-activity and dark-light measurements to calculate phasor magnitude (strength of circadian alignment coupling) and phasor angle (phase difference between activity-rest and light-dark cycles). Multiple linear regression models were used to determine associations of phasor magnitude and angle with performance in various cognitive tests, including Digit Symbol Substitution Test score (DSSS), CERAD Savings Percentage (CSP), and Animal Fluency Test (AFT) score. The results showed that a lower phasor magnitude (which indicates decreased strength of alignment coupling between rest-activity and dark-light cycles) was significantly associated with decreased DSSS (indicating slower processing speed and poorer working memory) when controlling for many important sociodemographic factors. However, this association became non-significant when accounting for sleep duration and total physical activity. Phasor angle did not have a significant association with any of the cognitive scores. Overall, we provided evidence indicating that circadian alignment may be a predictor of cognitive performance. Future studies should investigate whether improving circadian alignment may improve cognitive function and prevent cognitive decline.

Cardiovascular disease and lifestyle choices: Spotlight on circadian rhythms and sleep.

The advent of electric lighting in the built environment has radically transformed the human experience of light and darkness, which is often insufficient to stimulate and synchronize the circadian system to the day-night cycle. The lack of circadian system entrainment leads to poor sleep and could be an important biophysical mechanism underlying increased incidence of certain types of diseases, including cardiovascular (CV) disease (CVD). This contribution proposes to carve out a niche for including daily exposures to light and darkness among lifestyle factors for reducing the risk and progression of CVD. The fundamental workings of the human circadian system and its primary outputs are described. The discussion then progresses to light's effects on the circadian system and its outputs, and how threats to circadian health pose risks for CV health. The contribution concludes with simple recommendations for incorporating regular, robust daily exposures in lifestyle adjustments to combat CVD risks and progression.

Tailored lighting intervention (TLI) for improving sleep-wake cycles in older adults living with dementia.

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.

Alignment Between 24-h Light-Dark and Activity-Rest Rhythms Is Associated With Diabetes and Glucose Metabolism in a Nationally Representative Sample of American Adults.

OBJECTIVE: The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations. RESEARCH DESIGN AND METHODS: The analysis included ∼7,000 adults (aged 20-80 years) from the National Health and Nutrition Examination Survey (NHANES) (2011-2014) with actigraphy-measured, multiday, 24-h activity and light data. We used phasor analysis to derive phasor magnitude and phasor angle, which measures coupling strength and phase difference between the activity-rest and light-dark cycles, respectively. We used multinomial logistic regression and multiple linear regression to study phasor magnitude and phasor angle in relation to diabetes (primary outcome) and multiple secondary biomarkers of glycemic control. RESULTS: Lower alignment strength (i.e., a shorter phasor magnitude) and more delayed activity relative to the light cycle (i.e., a larger phasor angle) were both associated with diabetes. Specifically, compared with individuals in the quintiles indicating the most proper alignment (Q5 for phasor magnitude and Q1 for phasor angle), those in the quintiles with the most impaired alignment had a >70% increase in the odds of diabetes for phasor magnitude (odds ratio 1.76 [95% CI 1.39, 2.24]) and for phasor angle (1.73 [1.34, 2.25]). Similar associations were observed for biomarkers for glucose metabolism. The results were generally consistent across diverse sociodemographic and obesity groups. CONCLUSIONS: The alignment pattern between 24-h activity-rest and light-dark cycles may be a critical factor in metabolic health.

Evaluation of a Novel Ambient Light Survey Question in the Cancer Prevention Study-3.

Nighttime light exposure may increase cancer risk by disrupting the circadian system. However, there is no well-established survey method for measuring ambient light. In the Cancer Prevention Study-3, 732 men and women answered a light survey based on seven environments. The light environment in the past year was assessed twice, one year apart, and four one-week diaries were collected between the annual surveys. A total of 170 participants wore a meter to measure photopic illuminance and circadian stimulus (CS). Illuminance and CS values were estimated for lighting environments from measured values and evaluated with a cross validation approach. The kappas for self-reported light environment comparing the two annual surveys were 0.61 on workdays and 0.49 on non-workdays. Kappas comparing the annual survey to weekly diaries were 0.71 and 0.57 for work and non-workdays, respectively. Agreement was highest for reporting of darkness (95.3%), non-residential light (86.5%), and household light (75.6%) on workdays. Measured illuminance and CS identified three peaks of light (darkness, indoor lighting, and outdoor daytime light). Estimated illuminance and CS were correlated with the measured values overall (r = 0.77 and r = 0.67, respectively) but were less correlated within each light environment (r = 0.23-0.43). The survey has good validity to assess ambient light for studies of human health.

Associations of 24-Hour Light Exposure and Activity Patterns and Risk of Cognitive Impairment and Decline in Older Men: The MrOS Sleep Study.

BACKGROUND: Older men with the worse alignment of activity and light may have lower levels of cognition and increased rates of cognitive decline. METHODS: This cohort consisted of 1 036 older men (81.1 ± 4.6 years) from the MrOS Sleep Study (2009-2012). Light and activity levels were gathered by wrist actigraphy. Phasor analysis was used to quantify the alignment of light-dark and rest-activity patterns (magnitude) and their temporal relationship (angle). Global cognitive function (Modified Mini-Mental State examination [3MS]) and executive function (Trails B test) were measured, then repeated 4.2 ± 0.8 years later. Linear regression models examined the associations of phasor magnitude and angle with cognition and cognitive decline. Models were adjusted for age, clinic, race, education, and season. RESULTS: Smaller phasor magnitude (worse aligned light and activity patterns) was associated with lower initial level and increased decline in executive function. Compared to those with higher phasor magnitude, those with lower magnitude took an average of 11.1 seconds longer to complete the Trails B test (quartile 1 vs quartile 4, p = .02). After follow-up, Trails B completion time increased an average of 5.5 seconds per standard deviation decrease in phasor magnitude (95% confidence interval [CI] 0.7-10.4, p = .03). There were no associations with phasor angle, and none with magnitude and global cognition (3MS). CONCLUSION: Among older men, worse alignment of light and activity patterns was associated with worse initial performance and increased decline in executive function, but not related to global cognition. Interventions that improve the alignment of light and activity may slow cognitive decline in older adults.

Corrigendum: Modeling Circadian Phototransduction: Quantitative Predictions of Psychophysical Data.

[This corrects the article DOI: 10.3389/fnins.2021.615322.].

The circadian stimulus-oscillator model: Improvements to Kronauer's model of the human circadian pacemaker.

Modeling how patterns of light and dark affect circadian phase is important clinically and organizationally (e.g., the military) because circadian disruption can compromise health and performance. Limit-cycle oscillator models in various forms have been used to characterize phase changes to a limited set of light interventions. We approached the analysis of the van der Pol oscillator-based model proposed by Kronauer and colleagues in 1999 and 2000 (Kronauer99) using a well-established framework from experimental psychology whereby the stimulus (S) acts on the organism (O) to produce a response (R). Within that framework, using four independent data sets utilizing calibrated personal light measurements, we conducted a serial analysis of the factors in the Kronauer99 model that could affect prediction accuracy characterized by changes in dim-light melatonin onset. Prediction uncertainty was slightly greater than 1 h for the new data sets using the original Kronauer99 model. The revised model described here reduced prediction uncertainty for these same data sets by roughly half.

Impact of Circadian Rhythms on the Development and Clinical Management of Genitourinary Cancers.

The circadian system is an innate clock mechanism that governs biological processes on a near 24-hour cycle. Circadian rhythm disruption (i.e., misalignment of circadian rhythms), which results from the lack of synchrony between the master circadian clock located in the suprachiasmatic nuclei (SCN) and the environment (i.e., exposure to day light) or the master clock and the peripheral clocks, has been associated with increased risk of and unfavorable cancer outcomes. Growing evidence supports the link between circadian disruption and increased prevalence and mortality of genitourinary cancers (GU) including prostate, bladder, and renal cancer. The circadian system also plays an essential role on the timely implementation of chronopharmacological treatments, such as melatonin and chronotherapy, to reduce tumor progression, improve therapeutic response and reduce negative therapy side effects. The potential benefits of the manipulating circadian rhythms in the clinical setting of GU cancer detection and treatment remain to be exploited. In this review, we discuss the current evidence on the influence of circadian rhythms on (disease) cancer development and hope to elucidate the unmet clinical need of defining the extensive involvement of the circadian system in predicting risk for GU cancer development and alleviating the burden of implementing anti-cancer therapies.

Circadian Rhythm Disruption as a Contributor to Racial Disparities in Prostate Cancer.

In the United States, African American (AA) men have a 2.4 times higher mortality rate due to prostate cancer than White men. The multifactorial causes of the racial disparities in prostate cancer involve various social determinants of health, socioeconomic status, and access to healthcare. However, emerging evidence also suggests that circadian rhythm disruption (CRD) contributes to prostate cancer, and AA men may be more susceptible to developing CRDs. Circadian rhythms play a significant role in metabolism, hormone secretion, and sleep/wake cycles. Disruption in these circadian rhythms can be caused by airplane travel/jetlag, night shift work, exposure to light, and neighborhood noise levels, which can contribute to sleep disorders and chronic conditions such as obesity, diabetes, cardiovascular disease, and depression. The drivers of the racial disparities in CRD include night shift work, racial discrimination, elevated stress, and residing in poor neighborhoods characterized by high noise pollution. Given the increased vulnerability of AA men to CRDs, and the role that CRDs play in prostate cancer, elucidating the clock-related prostate cancer pathways and their behavior and environmental covariates may be critical to better understanding and reducing the racial disparities in prostate cancer.

Lighting and perceptual cues: effects on gait measures of older adults at high and low risk for falls.

BACKGROUND: The visual system plays an important role in maintaining balance. As a person ages, gait becomes slower and stride becomes shorter, especially in dimly lighted environments. Falls risk has been associated with reduced speed and increased gait variability. METHODS: Twenty-four older adults (half identified at risk for falls) experienced three lighting conditions: pathway illuminated by 1) general ceiling-mounted fixtures, 2) conventional plug-in night lights and 3) plug-in night lights supplemented by laser lines outlining the pathway. Gait measures were collected using the GAITRite© walkway system. RESULTS: Participants performed best under the general ceiling-mounted light system and worst under the night light alone. The pathway plus night lights increased gait velocity and reduced step length variability compared to the night lights alone in those at greater risk of falling. CONCLUSIONS: Practically, when navigating in more challenging environments, such as in low-level ambient illumination, the addition of perceptual cues that define the horizontal walking plane can potentially reduce falls risks in older adults.