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.

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

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

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.

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.

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.

Shift Work, Chronotype, and Melatonin Rhythm in Nurses.

BACKGROUND: Previous studies associated night-shift work with melatonin disruption, with mixed evidence regarding the modulating effects of chronotype (i.e., diurnal preference). METHODS: One hundred and thirty active nurses (84 rotating-shift and 46 day-shift workers) in the Nurses' Health Study II wore a head-mounted light meter and collected spontaneous urine voids over 3 days. 6-Sulfatoxymelatonin (aMT6s), the major urinary metabolite of melatonin, was assessed. RESULTS: Rotating-shift workers on night shifts had more light exposure and lower urinary melatonin levels during the night, and urinary melatonin rhythms with smaller peaks [11.81 ng/mg-creatinine/h, 95% confidence interval (CI), 9.49-14.71 vs. 14.83 ng/mg-creatinine/h, 95% CI, 11.72-18.75] and later peak onset (5.71 hours, 95% CI, 4.76-6.85 vs. 4.10 hours, 95% CI, 3.37-4.99), compared with day-shift workers. Furthermore, evening chronotypes' melatonin rhythms had later peak onset compared with morning types (4.90 hours, 95% CI, 3.94-6.09 vs. 3.64 hours, 95% CI, 2.99-4.43). However, among day-shift workers, morning chronotypes had melatonin rhythms with greater mean levels, larger peaks, and earlier peak onset compared with evening chronotypes; patterns were similar comparing evening versus morning chronotypes among rotating-shift workers on night shifts. The interaction of rotating-shift work and chronotype was significant across all parameters (P < 0.05). CONCLUSIONS: As expected, rotating-shift workers on night shifts had greater light exposure and lower urinary melatonin levels during the night compared with day-shift workers. Intriguingly, melatonin rhythms were dependent on both chronotype and rotating-shift work type, and better alignment of rotating-shift work and chronotype appeared to produce less disrupted melatonin rhythms. IMPACT: The joint effects of shift-work type and chronotype require attention in future studies.

Effect of White Light Devoid of "Cyan" Spectrum Radiation on Nighttime Melatonin Suppression Over a 1-h Exposure Duration.

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.

Programmed environmental illumination during autologous stem cell transplantation hospitalization for the treatment of multiple myeloma reduces severity of depression: A preliminary randomized controlled trial.

BACKGROUND: Over a third of multiple myeloma (MM) patients report clinical levels of depression during autologous stem cell transplant (ASCT) hospitalization. We report preliminary results from a randomized clinical trial investigating the effect of Programmed Environmental Illumination (PEI) of hospital rooms on depression. METHODS: Patients (N = 187) scheduled to receive an ASCT were assessed for eligibility. Those who met study eligibility criteria (n = 44) were randomly assigned to one of two PEI conditions involving delivery of either circadian active bright white light (BWL) or circadian inactive dim white light (DWL) throughout the room from 7 to 10 am daily during hospitalization. Patients completed the Center for Epidemiological Studies Depression Scale (CES-D) prior to hospitalization, at days 2 and 7 post-transplant, and on the third day of engraftment. RESULTS: General linear model analyses revealed no difference between the groups in CES-D total score at baseline (P = 0.7859). A longitudinal linear mixed model analysis revealed a significant interaction between time of assessment and light condition [F(3,107) = 2.90; P = 0.0386; ɳ2  = 0.08)], indicating that PEI prevented the development of depression during hospitalization, with effects reaching significance by the third day of engraftment. At the third day of engraftment, 68.4% of the participants in the DWL comparison condition met the criteria for clinically significant depression compared to 42.1% in the BWL condition. CONCLUSION: These findings demonstrate that PEI using BWL during MM ASCT hospitalization is effective in reducing the development of depression. Future studies should examine the mechanisms whereby PEI improves depression.

Disruption of Circadian Rhythms by Light During Day and Night.

PURPOSE OF REVIEW: This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease. RECENT FINDINGS: Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night. SUMMARY: To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.

Measuring Light at Night and Melatonin Levels in Shift Workers: A Review of the Literature.

Shift work, especially that involving rotating and night shifts, is associated with an increased risk of diseases, including cancer. Attempts to explain the association between shift work and cancer in particular have focused on the processes of melatonin production and suppression. One hypothesis postulates that exposure to light at night (LAN) suppresses melatonin, whose production is known to slow the development of cancerous cells, while another proposes that circadian disruption associated with shift work, and not just LAN, increases health risks. This review focuses on six studies that employed quantitative measurement of LAN and melatonin levels to assess cancer risks in shift workers. These studies were identified via searching the PubMed database for peer-reviewed, English-language articles examining the links between shift work, LAN, and disease using the terms light at night, circadian disruption, health, risk, cancer, shift work, or rotating shift. While the results indicate a growing consensus on the relationship between disease risks (particularly cancer) and circadian disruption associated with shift work, the establishment of a direct link between LAN and disease has been impeded by contradictory studies and a lack of consistent, quantitative methods for measuring LAN in the research to date. Better protocols for assessing personal LAN exposure are required, particularly those employing calibrated devices that measure and sample exposure to workplace light conditions, to accurately assess LAN's effects on the circadian system and disease. Other methodologies, such as measuring circadian disruption and melatonin levels in the field, may also help to resolve discrepancies in the findings.

Light, sleep and circadian rhythms in older adults with Alzheimer's disease and related dementias.

Alzheimer's disease and related dementias (ADRD) can cause sleep and behavioral problems that are problematic for ADRD patients and their family caregivers. Light therapy has shown promise as a nonpharmacological treatment, and preliminary studies demonstrate that timed light exposure can consolidate and improve nighttime sleep efficiency, increase daytime wakefulness and reduce evening agitation without the adverse effects of pharmacological solutions. Compliance with light treatment and the accurate measurement of light exposures during treatment, however, have presented barriers for the adoption of light therapy for ADRD. Recent research showing that the circadian system is maximally sensitive to short-wavelength light opens the way for the potential application of lower, more-targeted light intensities to maximize compliance and individualize light dose/timing in therapeutic settings.

Field measurements of light exposures and circadian disruption in two populations of older adults.

The absence of daily robust light-dark exposure patterns may contribute to sleep disturbances in persons with Alzheimer's disease and related dementias (ADRD). Personal light-dark and activity-rest patterns were measured for healthy older adults and for persons with ADRD. Persons with ADRD experienced lower light levels, exhibited lower activity levels, and had greater levels of circadian disruption than healthy older adults during winter. Seasonal differences were observed for persons with ADRD; lower levels of light exposure and greater levels of circadian disruption were seen during the winter than during the summer, although activity levels did not differ for the two seasons.

Measurements of light at night (LAN) for a sample of female school teachers.

Epidemiological studies have shown an association between rotating shiftwork and breast cancer (BC) risk. Recently, light at night (LAN) measured by satellite photometry and by self-reports of bedroom brightness has been shown to be associated with BC risk, irrespective of shiftwork history. Importance has been placed on these associations because retinal light exposures at night can suppress the hormone melatonin and/or disrupt circadian entrainment to the local 24-h light-dark cycle. The present study examined whether it was valid to use satellite photometry and self-reports of brightness to characterize light, as it might stimulate the circadian system and thereby affect BC incidence. Calibrated photometric measurements were made at the bedroom windows and in the bedrooms of a sample of female school teachers, who worked regular dayshifts and lived in a variety of satellite-measured sky brightness categories. The light levels at both locations were usually very low and were independent of the amount of satellite-measured light. Calibrated photometric measurements were also obtained at the corneas of these female school teachers together with calibrated accelerometer measurements for seven consecutive days and evenings. Based upon these personal light exposure and activity measurements, the female teachers who participated in this study did not have disrupted light-dark cycles like those associated with rotating shiftworkers who do exhibit a higher risk for BC. Rather, this sample of female school teachers had 24-h light-dark and activity-rest patterns very much like those experienced by dayshift nurses examined in an earlier study who are not at an elevated risk of BC. No relationship was found between the amount of satellite-measured light levels and the 24-h light-dark patterns these women experienced. It was concluded from the present study that satellite photometry is unrelated to personal light exposures as they might affect melatonin suppression and/or circadian disruption. More generally, photometric devices calibrated in terms of the operational characteristics of the human circadian system must be used to meaningfully link LAN and BC incidence.

Effects of an advanced sleep schedule and morning short wavelength light exposure on circadian phase in young adults with late sleep schedules.

OBJECTIVE: We examined the effects of an advanced sleep/wake schedule and morning short wavelength (blue) light in 25 adults (mean age±SD=21.8±3 years; 13 women) with late sleep schedules and subclinical features of delayed sleep phase disorder (DSPD). METHODS: After a baseline week, participants kept individualized, fixed, advanced 7.5-h sleep schedules for 6days. Participants were randomly assigned to groups to receive "blue" (470nm, ∼225lux, n=12) or "dim" (<1lux, n=13) light for 1h after waking each day. Head-worn "Daysimeters" measured light exposure; actigraphs and sleep diaries confirmed schedule compliance. Salivary dim light melatonin onset (DLMO), self-reported sleep, and mood were examined with 2×2 ANOVA. RESULTS: After 6days, both groups showed significant circadian phase advances, but morning blue light was not associated with larger phase shifts than dim-light exposure. The average DLMO advances (mean±SD) were 1.5±1.1h in the dim light group and 1.4±0.7h in the blue light group. CONCLUSIONS: Adherence to a fixed advanced sleep/wake schedule resulted in significant circadian phase shifts in young adults with subclinical DSPD with or without morning blue light exposure. Light/dark exposures associated with fixed early sleep schedules are sufficient to advance circadian phase in young adults.

Lack of short-wavelength light during the school day delays dim light melatonin onset (DLMO) in middle school students.

OBJECTIVE: Circadian timing affects sleep onset. Delayed sleep onset can reduce sleep duration in adolescents required to awake early for a fixed school schedule. The absence of short-wavelength ("blue") morning light, which helps entrain the circadian system, can hypothetically delay sleep onset and decrease sleep duration in adolescents. The goal of this study was to investigate whether removal of short-wavelength light during the morning hours delayed the onset of melatonin in young adults. METHODS: Dim light melatonin onset (DLMO) was measured in eleven 8th-grade students before and after wearing orange glasses, which removed short-wavelength light, for a five-day school week. RESULTS: DLMO was significantly delayed (30 minutes) after the five-day intervention, demonstrating that short-wavelength light exposure during the day can be important for advancing circadian rhythms in students. CONCLUSIONS: Lack of short-wavelength light in the morning has been shown to delay the circadian clock in controlled laboratory conditions. The results presented here are the first to show, outside laboratory conditions, that removal of short-wavelength light in the morning hours can delay DLMO in 8th-grade students. These field data, consistent with results from controlled laboratory studies, are directly relevant to lighting practice in schools.

A personal light-treatment device for improving sleep quality in the elderly: dynamics of nocturnal melatonin suppression at two exposure levels.

Light treatment has been used as a non-pharmacological tool to help mitigate poor sleep quality frequently found in older people. In order to increase compliance to non-pharmacological light treatments, new, more efficacious light-delivery systems need to be developed. A prototype personal light-treatment device equipped with low brightness blue light-emitting diodes (LEDs) (peak wavelength near 470 nm) was tested for its effectiveness in suppressing nocturnal melatonin, a measure of circadian stimulation. Two levels of corneal irradiance were set to deliver two prescribed doses of circadian light exposure. Eleven older subjects, between 51 and 80 yrs of age who met the selection criteria, were exposed to a high and a low level of light for 90 min on separate nights from the personal light-treatment device. Blood and saliva samples were collected at prescribed times for subsequent melatonin assay. After 1 h of light exposure, the light-induced nocturnal melatonin suppression level was about 35% for the low-light level and about 60% for the high-light level. The higher level of blue light suppressed melatonin more quickly, to a greater extent over the course of the 90 min exposure period, and maintained suppression after 60 min. The constant exposure of the low-light level resulted in a decrease in nocturnal melatonin suppression for the last sampling time, whereas for the high-light level, suppression continued throughout the entire exposure period. The present study performed with healthy adults suggests that the tested personal light-treatment device might be a practical, comfortable, and effective way to deliver light treatment to those suffering from circadian sleep disorders; however, the acceptance and effectiveness of personal light-treatment devices by older people and by other segments of the population suffering from sleep disorders in a real-life situation need to be directly tested.

Does architectural lighting contribute to breast cancer?

OBJECTIVES: There is a growing interest in the role that light plays on nocturnal melatonin production and, perhaps thereby, the incidence of breast cancer in modern societies. The direct causal relationships in this logical chain have not, however, been fully established and the weakest link is an inability to quantitatively specify architectural lighting as a stimulus for the circadian system. The purpose of the present paper is to draw attention to this weakness. DATA SOURCES AND EXTRACTION: We reviewed the literature on the relationship between melatonin, light at night, and cancer risk in humans and tumor growth in animals. More specifically, we focused on the impact of light on nocturnal melatonin suppression in humans and on the applicability of these data to women in real-life situations. Photometric measurement data from the lighted environment of women at work and at home is also reported. DATA SYNTHESIS: The literature review and measurement data demonstrate that more quantitative knowledge is needed about circadian light exposures actually experienced by women and girls in modern societies. CONCLUSION: Without such quantitative knowledge, limited insights can be gained about the causal relationship between melatonin and the etiology of breast cancer from epidemiological studies and from parametric studies using animal models.

Of mice and women: light as a circadian stimulus in breast cancer research.

OBJECTIVE: Nocturnal rodents are frequently used as models in human breast cancer research, but these species have very different visual and circadian systems and, therefore, very different responses to optical radiation or, informally, light. Because of the impact of light on the circadian system and because recent evidence suggests that cancer risk might be related to circadian disruption, it is becoming increasingly clear that optical radiation must be properly characterized for both nocturnal rodents and diurnal humans to make significant progress in unraveling links between circadian disruption and breast cancer. In this paper, we propose a quantitative framework for comparing radiometric and photometric quantities in human and rodent studies. METHODS: We reviewed published research on light as a circadian stimulus for humans and rodents. Both suppression of nocturnal melatonin and phase shifting were examined as outcome measures for the circadian system. RESULTS: The data were used to develop quantitative comparisons regarding the absolute and spectral sensitivity for the circadian systems of humans and nocturnal rodents. CONCLUSIONS: Two models of circadian phototransduction, for mouse and humans, have been published providing spectral sensitivities for these two species. Despite some methodological variations among the studies reviewed, the circadian systems of nocturnal rodents are approximately 10,000 times more sensitive to optical radiation than that of humans. Circadian effectiveness of different sources for both humans and nocturnal rodents are offered together with a scale relating their absolute sensitivities. Instruments calibrated in terms of conventional photometric units (e.g., lux) will not accurately characterize the circadian stimulus for either humans or rodents.