Dim Light Melatonin Onset Time Research Articles

Does cardiovascular autonomic modulation correspond to the increase in dim-light onset of melatonin? A preliminary analysis

Introduction: The endogenous circadian system promotes the rise in melatonin approximately every 24 hours. In the laboratory, dim light melatonin onset (DLMO) is used as the gold standard method to assess circadian phase. Exogenous melatonin affects cardiac sympathovagal balance and vasomotor sympathetic modulation. Whether or not the endogenous increase in melatonin corresponds to changes in cardiovascular autonomic modulation is unclear. Objective: To evaluate if the timing of DLMO corresponds to the timing of changes in cardiovascular autonomic indices. Methods: Five healthy adults (3 females, age 23.8±SD1.8 y) completed a minimum of four nights of sleep regularization by maintaining a self-selected 8h in bed each night before the experiment. The day after regularization, they reported to the laboratory ~8 hours before bedtime. Measurements for melatonin and cardiovascular autonomic modulation started 6 hours before bedtime and continued 1 hour after. Saliva samples were collected every 30 minutes. At the end of every hour, 10 minutes of continuous R-R intervals (R-R) and systolic blood pressure (SBP) were recorded via electrocardiogram and beat-to-beat finger photoplethysmography, respectively. As currently established, DLMO was defined as the interpolated time for melatonin increase over 3pg/ml. Cardiovascular autonomic indexes were run through CardioSeries v.2 to create a temporal series for R-R interval and systolic blood pressure. Cardiac autonomic modulation was assessed by applying the spectral analysis using the fast Fourier transformation method and time domain analysis of heart rate variability (HRV) and spectral analysis of blood pressure variability (BPV). For each autonomic index, data were plotted and fitted with a segmental linear regression to reveal the intercept of the two segments to define the autonomic onset (AO). A paired t-test compared the difference between DLMO and AO times. Bland-Altman plots with a 95% limit of agreement (LOA) identified the distribution of differences between the methods. Additionally, a one-sample t-test compared the differences between methods to a fixed time clock range. Data are shown as mean ± SD and significance was set as p<0.05. Results: AO time calculated for all indexes from HRV and BPV were not statistically different compared to DLMO time (R-R: +16±86 mins, P=0.70; root mean square of successive differences (RMSSD): -20±91 mins, P=0.67; low frequency (LF) nu: +29±52 mins, P=0.74; high frequency (HF) nu: -43±91 mins, P=0.23; LFHF: -26±73 mins, P=0.47; SBP: -14±104 mins, P=0.78; LFSBP: -6±107 mins, P=0.90). The Bland Altman plots did not identify any systematic difference between AO and DLMO times. The smallest difference was LFnu with a LOA 95% from -73 to +131 minutes, while the largest difference was LFSBP with LOA 95% from -217 to +204 minutes. Additionally, the difference between DLMO and AO LFnu times (LFnu: +29±52) was statistically similar from -36 to +95 minutes. Conclusion: In young healthy adults, our preliminary data shows that AO times of cardiovascular autonomic indexes correspond to salivary DLMO. A larger dataset with more frequent simultaneous measurements of melatonin and cardiovascular autonomic modulation are essential to confirm our preliminary findings. Medical Research Foundation of Oregon, OHSU OFDIR, R01HL163232. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exposure to real-ambient bedroom light at night delayed circadian rhythm in healthy Chinese young adults: A cross-sectional study

BackgroundLight at night (LAN) have attracted increased research attention on account of its widespread health hazards. However, the underlying mechanism remains unknown. The objective of this study was to investigate the effects of real-ambient bedroom LAN exposure on circadian rhythm among young adults and potential sex differences. MethodsBedroom LAN exposure was measured at 60-s intervals for 2 consecutive days using a portable illuminance meter. Circadian phase was determined by the dim light melatonin onset (DLMO) time in 7 time-series saliva samples. ResultsThe mean age of the 142 participants was 20.7 ± 0.8 years, and 59.9% were women. The average DLMO time was 21:00 ± 1:11 h, with men (21:19 ± 1:12 h) later than women (20:48 ± 1:07 h). Higher level of LAN intensity (LANavg ≥ 3lx vs. LANavg < 3lx) was associated with an 81.0-min later in DLMO time (95% CI: 0.99, 1.72), and longer duration of nighttime light intensity ≥ 5lx (LAN5; LAN5 ≥ 45 min vs. LAN5 < 45 min) was associated with a 51.6-min later in DLMO time (95% CI: 0.46, 1.26). In addition, the delayed effect of LAN exposure on circadian phase was more pronounced in men than in women (all P-values <0.05). ConclusionsOverall, bedroom LAN exposure was significantly associated with delayed circadian rhythm. Additionally, the delayed effect is more significant in men. Keeping bedroom dark at night may be a practicable option to prevent circadian disruption and associated health implications. Future studies with more advanced light measurement instrument and consensus methodology for DLMO assessment are warranted.

Low dose exogenous melatonin plus evening dim light and time in bed scheduling advances circadian phase irrespective of measured or estimated dim light melatonin onset time: preliminary findings.

The purpose of the present study was to preliminarily evaluate whether knowing the dim light melatonin onset (DLMO) time is advantageous when treating delayed sleep-wake phase disorder (DSWPD) with low dose melatonin treatment plus behavioral interventions (i.e., evening dim light and time in bed (TIB) scheduling). In this randomized, controlled, double-blind trial, 40 adults with DSWPD were randomly assigned to 4 weeks of 0.5 mg timed to be administered either 3 hours before the DLMO (measured DLMO group, n = 20) or 5 hours before sleep onset time per actigraphy (estimated DLMO group, n = 20), in conjunction with behavioral interventions. The primary outcome was change in the DLMO (measured in-home). Secondary outcomes included sleep parameters per diary and actigraphy (sleep onset and offset times and total sleep time), Morningness-Eveningness Questionnaire (MEQ), Multidimensional Fatigue Inventory (MFI), PROMIS-Sleep Disturbance (SD), PROMIS-Sleep Related Impairment (SRI), and Pittsburgh Sleep Quality Index (PSQI). Mixed effects models tested for group differences in these outcome. After applying the Bonferroni correction for multiple comparisons (significant p-value set at ˂ .004), there were significant main effects for visit on all outcomes except PSQI and total sleep time per wrist actigraphy and diary. There were no group by visit interactions for any of the outcomes (p > .004). Scheduled low dose melatonin plus behavioral interventions may improve many circadian and sleep parameters regardless of whether melatonin administration is scheduled based on estimated or measured DLMO. A larger-scale trial is needed to confirm these preliminary findings. Clinicaltrials.gov Identifier: NCT03715465; Name: The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder; URL: https://clinicaltrials.gov/study/NCT03715465.

Hippocampal Volume and Circadian Rhythm Characteristics

AbstractBackgroundHippocampal atrophy is one of the prominent neurodegenerative features of Alzheimer’s disease and related dementias. Alterations in circadian rhythms and 24‐hour rest activity rhythms can exacerbate cognitive aging and neurodegeneration. The aim of this study was to examine how 24‐hour rest activity rhythms and circadian rhythms are associated with hippocampal volume.MethodWe studied 61 older adults’ data (mean age±SD = 70.0±7.2). T1‐weighted anatomical images from 3T MRI data were collected and processed using the BRAINSTools toolbox. Hippocampal volume was divided by intracranial volume (ICV). Dim light melatonin onset (DLMO) was used to assess circadian timing. Area under the curve (AUC) was calculated based on melatonin levels 6 hours prior to the bedtime. 10‐day actigraphy data assessed 24‐hour rest activity rhythms. Multiple linear regression was used to develop a model for hippocampal volume, controlling for age and sex. Additional covariates (i.e., depressive symptoms, hypertension, coronary artery disease, handedness, and ICV) and moderating effects of age and sex were examined.ResultAcrophase was positively associated with hippocampal volume (b = 0.12, p = .016). Interaction between mesor and age (b = ‐1.22, p = .006) indicated that positive effect of mesor (b = 8.58, p = .007) on hippocampal volume decreased with age. Advanced DLMO time (b = 0.16, p = .005) and greater AUC/10 (b = 0.05, p = .046) were associated with increased hippocampal volume. Amplitude and Pseudo‐F‐Statistics were not associated with hippocampal volume.ConclusionThe findings indicate delayed peak activity time (acrophase), delayed circadian timing (DLMO), and greater mesor and melatonin (AUC) were associated with increased hippocampal volume. The effect of mesor decreased with age. Future studies using larger sample sizes and prospective designs are needed to better understand the relationships.

Circadian timing, melatonin and hippocampal volume in later-life adults.

Hippocampal atrophy is a prominent neurodegenerative feature of Alzheimer's disease and related dementias. Alterations in circadian rhythms can exacerbate cognitive aging and neurodegeneration. This study aimed to examine how dim light melatonin onset and melatonin levels are associated with hippocampal volume in cognitively healthy individuals. We studied data from 52 later-life adults (mean age ± SD = 70.0 ± 6.3 years). T1-weighted anatomical images from 3.0 T magnetic resonance imaging data were collected and processed using the BRAINSTools toolbox. Dim light melatonin onset was used to assess circadian timing. The area under the curve was calculated to quantify melatonin concentration levels 6 hr before bedtime, and 14-day wrist actigraphy data were used to assess habitual bedtime. Multiple linear regression modelling with hippocampal volume as the dependent variable was used to analyse the data adjusting for age and sex. The average dim light melatonin onset was 19:45 hours (SD = 84 min), and area under the curve of melatonin levels 6 hr before habitual bedtime was 38.4 pg ml-1 × hr (SD = 29.3). We found that later dim light melatonin onset time (b = 0.16, p = 0.005) and greater area under the curve of melatonin levels 6 hr before habitual bedtime (b = 0.05, p = 0.046) were associated with greater adjusted hippocampal volume. The time between dim light melatonin onset and the midpoint of sleep timing was not associated with hippocampal volume. The findings suggest that earlier circadian timing (dim light melatonin onset) and reduced melatonin may be associated with reduced hippocampal volume in older adults. Future research will help researchers utilize circadian rhythm information to delay brain aging.

O083 Myopic, or Short-sighted, Children show Delayed Melatonin Circadian Timing, Lower Melatonin Output and Sleep Disruptions

Abstract Introduction Recent studies have reported poor and reduced sleep in myopic, or short-sighted, individuals. Here, we investigated differences in melatonin secretion timing and output and actigraphy-derived sleep in myopic and non-myopic (or emmetropic) children, aged 8-15 years. Methods 26 myopes [refractive error (mean ± standard error mean) -2.06 ± 0.23 dioptres] and 19 emmetropes (-0.06 ± 0.04 dioptres), aged 11.74 ± 2.31 years were recruited. Melatonin timing was assessed using salivary dim light melatonin onset (DLMO), collected half-hourly for 7 hours in a sleep laboratory, beginning 5 hours before and finishing 2 hours after habitual bedtime for the past week. Total melatonin production was assessed via aMT6s levels from urine voids collected from 05:30 pm and until 08:00 am the following morning. Actigraphy-derived sleep was acquired for one week prior to the sleep laboratory visit. Results Myopic children (21:07 ± 0.2 hrs) had a DLMO time 1.1 hrs later compared to emmetropes (19:59 ± 0.2 hrs), p=0.002. aMT6s melatonin levels were significantly lower among myopes (18.70 ± 2.38) than emmetropes (32.35 ± 6.93, p=0.001). Myopes also exhibited significantly delayed sleep onset (21:42 ± 0.2 vs 23:00 ± 0.2 hrs), delayed wake-up time (06:38 ± 0.2 vs 07:29 ± 0.1 hrs), shorter sleep duration (8.1 ± 0.2 vs 7.6 ± 0.1 hrs), and more evening-type diurnal preference than emmetropes (all p&amp;lt;0.05). Discussion These findings suggest a potential association between circadian rhythm dysfunction and myopia in children, supporting towards a shared mechanism of myopia and delayed sleep-wake phased disorder development during adolescence.

Validation of the Self-Rating of Biological Rhythm Disorder for Adolescents (SBRDA) Scale by Dim Light Melatonin Onset in Healthy Young Adults.

Understanding the biological rhythms that influence young adult health is vital because the combination of biological changes and a circadian phase delay lead to young adults being at high risk of circadian misalignment. We have previously established a self-rating of biological rhythm disorder for adolescents (SBRDA). However, we did not externally validate the SBRDA against objective measures of biological rhythms such as dim light melatonin onset (DLMO)-the gold standard of the endogenous circadian phase. The purpose of this study was to verify the effectiveness of SBRDA in identifying individuals with biological rhythm disorders. Our participants were 42 (47.2%) boys and 47 (52.8%) girls with an average age of 18.5 ± 1.2 years. Saliva samples were collected from 4 h before bed time to 2 h after sleep every 60 min in a dim-light (<50 lx) laboratory environment. Biological rhythm parameters were assessed using questionnaires, including SBRDA, MEQ, and MCTQ. The mean DLMO time (h) was 22.2 ± 1.9. The DLMO correlated significantly with the SBRDA score (r = 0.33, p < 0.001), MEQ score (r = -0.24, p < 0.05), and MSFsc (r = 0.26, p < 0.05). ROC curve analysis showed that SBRDA was of diagnostic value for biological rhythm disorder (p < 0.05). Our observations demonstrate that SBRDA, which is consistent with MEQ and MCTQ, can be used to reflect endogenous circadian rhythm disorders in young adults. Exposure to dim light may activate melatonin secretion and lead to an earlier peak in young adults with biological rhythm disorder.

Actigraphic and melatonin alignment in older adults with varying dementia risk

ABSTRACT Circadian rhythms alter with ageing and may be aetiologically linked to neurodegeneration. This study explored the association between clinical markers and 1) dim light melatonin onset (DLMO) time and 2) phase angle derived from sleep midpoint, in older adults with varying dementia risks. Participants completed 14 days of actigraphy followed by in-lab measurement of salivary melatonin, from which DLMO time and phase angle were computed. Eighty participants (age = 65.5, SD = 9.6), 44 males (55%), MMSE (28.6, SD = 1.5) were included in the analysis. Sex (t = 2.15, p = .04), sleep onset (r = 0.49, p < .001) and midpoint (r = 0.44, p < .001) also correlated with DLMO time. Multiple linear regression showed chronotype, average actigraphy-derived light exposure during the DLMO window (window 2 h prior to DLMO to 2 h post), early biological day (6–10 h post DLMO time) and late biological day (10–14 h post DLMO time) were predictive of DLMO time (adjusted R2 = 0.75). Sleep offset, depression severity, average light exposure during the early biological night and early and late biological day were shown to be predictive variables in the estimation of phase angle (adjusted R2 = 0.78). The current study highlights the potential use of clinical variables, such as actigraphy-derived light, as circadian markers in ageing which could be easily implemented into existing clinical practice and could yield potential targets focusing on chronotherapeutic interventions.

O023 Predicting Dim Light Melatonin Onset in elite athletes without actigraphy

Abstract Introduction Elite athletes are exposed to irregular schedules, jetlag and intensive physical activity that is sometimes completed late at night, all of which can misalign circadian rhythms and therefore negatively affect recovery and performance. The aim of this study was to predict circadian phase in athletes without actigraphy. Methods A regularised random forest model comprising of 17 questionnaire and sleep diary measures was used to predict dim light melatonin onset (DLMO) times from 128 DLMO times collected from 98 (age = 24.3 ± 3.7 years) Australian Football League and National Rugby League male (n = 72, age = 24.6 ± 3.4 years) and female (n = 26, age = 23.3 ± 4.3 years) athletes. Results DLMO time was predicted with an out-of-sample root mean square error of 52 minutes, capturing 75% with ± 1 hour of actual DLMO time. Actual DLMO time (20.65 ± 1.00) was significantly correlated with predicted DLMO time (20.69 ± 0.29; r2 = 0.36, p &amp;lt; 0.001). Discussion DLMO time can be predicted without actigraphy in elite athletes. This approach enables the possibility of immediate circadian phase and sleep insights, and the development of interventions necessary for the fast-paced environment of elite sport where optimising athlete recovery and performance is critical.

Delayed circadian rhythms in older Africans living with human immunodeficiency virus (HIV).

The increasing number of people living with human immunodeficiency virus,HIV, (PLWH) have an elevated incidence of risk for noncommunicable comorbidities, the aetiology of which remains incompletely understood. While sleep disturbances are often reported in PLWH, it is unknown to what extent they relate to changes in the circadian and/or sleep homeostatic processes. We studied the relationship between sleep characteristics, circadian phase,and HIV status in older adults from the HAALSI (Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa) subsample of the Agincourt Health and Demographic Surveillance System in South Africa (n = 187, 36 human immunodeficiency virus positive[HIV+], age: 66.7 ± 11.5years, range 45-93years), where HIV prevalence is high and (in contrast to the global north) does not associate significantly with potentially confounding behavioural differences. In participants with valid actigraphy data (n = 172), regression analyses adjusted for age and sex indicated that HIV+ participants had slightly later sleep onset (β = .16, p = .039), earlier sleep offset times (β = -.16, p = .049) and shorter total sleep times (β = -.20, p = .009) compared to the HIV negative (HIV-) participants. In a subset of participants (n = 51, 11 HIV+), we observed a later dim light melatonin onset (DLMO) in HIV+ (21:16 ± 01:47) than in HIV- (20:06 ± 00:58) participants (p = .006). This substantial difference remained when adjusted for age and sex (β = 1.21; p = .006). In 36 participants (6 HIV+) with DLMO and actigraphy data, median phase angle of entrainment was -6 min in the HIV+ group and +1 h 25 min in the HIV- group. DLMO time correlated with sleep offset (ρ = 0.47, p = .005) but not sleep onset (ρ = -0.086, p = .623). Collectively, our data suggest that the sleep phase occurred earlier than what would be biologically optimal among the HIV+ participants. This is the first report of a mistimed circadian phase in PLWH, which has important potential implications for their health and well-being, especially given the well-established relationships between circadian asynchrony and sleep deprivation with poorer health outcomes.

Dim light melatonin onset following simulated eastward travel is earlier in young males genotyped as PER35/5 than PER34/4

ABSTRACT Inter-individual variability exists in recovery from jetlag following travel across time zones. Part of this variation may be due to genetic differences at the variable number tandem repeat (VNTR) polymorphism of the PERIOD3 (PER3) gene as this polymorphism has been associated with chronotype and sleep, as well as sensitivity to blue light on melatonin suppression. To test this hypothesis we conducted a laboratory-based study to compare re-entrainment in males genotyped as PER34/4 (n = 8) and PER35/5 (n = 8) following simulated eastward travel across six time zones. The recovery strategy included morning blue-enriched light exposure and appropriately-timed meals during the first 24 h after simulated travel. Dim light melatonin onset (DLMO), sleep characteristics, perceived sleepiness levels (Stanford Sleepiness Scale), and resting metabolic parameters were measured during constant routine periods before and after simulated travel. While DLMO time was similar between the two groups prior to simulated eastward travel (p = .223), it was earlier in the PER35/5 group (17h23 (17h15; 17h37)) than the PER34/4 group (18h05 (17h53; 18h12)) afterwards (p = .046). During resynchronisation, perceived sleepiness and metabolic parameters were similar to pre-travel in both groups but sleep was more disturbed in the PER35/5 group (total sleep time: p = .008, sleep efficiency: p = .008, wake after sleep onset: p = .023). The PER3 VNTR genotype may influence the efficacy of re-entrainment following trans-meridian travel when blue-enriched light exposure is incorporated into the recovery strategy on the first day following travel.

A classification approach to estimating human circadian phase under circadian alignment from actigraphy and photometry data.

The time of dim light melatonin onset (DLMO) is the gold standard for circadian phase assessment in humans, but collection of samples for DLMO is time and resource-intensive. Numerous studies have attempted to estimate circadian phase from actigraphy data, but most of these studies have involved individuals on controlled and stable sleep-wake schedules, with mean errors reported between 0.5 and 1hour. We found that such algorithms are less successful in estimating DLMO in a population of college students with more irregular schedules: Mean errors in estimating the time of DLMO are approximately 1.5-1.6hours. We reframed the problem as a classification problem and estimated whether an individual's current phase was before or after DLMO. Using a neural network, we found high classification accuracy of about 90%, which decreased the mean error in DLMO estimation-identifying the time at which the switch in classification occurs-to approximately 1.3hours. To test whether this classification approach was valid when activity and circadian rhythms are decoupled, we applied the same neural network to data from inpatient forced desynchrony studies in which participants are scheduled to sleep and wake at all circadian phases (rather than their habitual schedules). In participants on forced desynchrony protocols, overall classification accuracy dropped to 55%-65% with a range of 20%-80% for a given day; this accuracy was highly dependent upon the phase angle (ie, time) between DLMO and sleep onset, with the highest accuracy at phase angles associated with nighttime sleep. Circadian patterns in activity, therefore, should be included when developing and testing actigraphy-based approaches to circadian phase estimation. Our novel algorithm may be a promising approach for estimating the onset of melatonin in some conditions and could be generalized to other hormones.

Effect of Light Emitted by Smartphones at Bedtime on Circadian Rhythm and Sleep: Is It Different between Day Worker and Shift Worker?

Objectives Light at night (LAN) can suppress melatonin secretion and thus disturb normal sleep. The aim of this study was to investigate how the illumination of a smartphone at bedtime affects the circadian rhythm and sleep in patients with insomnia. Methods We recruited two middle-aged patients (one day worker and one shift worker) with insomnia. They used a smartphone more than 12 hours a day, particularly at bedtime. This was a crossover design study, and each patient spent a night at the light control unit twice at a one-week interval, with or without smartphone use. Patients were instructed to look at a smartphone (5–10 lux) under 150 lux of ceiling illumination from 18:00 until lights-off. During the night, without a smartphone, they read a book or newspaper. Saliva was collected every 30 minutes and analyzed for melatonin. Sleep was monitored by polysomnography. Results The day worker showed a delayed dim light melatonin onset time (DLMO) (21:30 vs. 22:00) and a 38.7% decrease in melatonin levels with smartphone use. For the shift worker, both melatonin and cortisol showed abnormal patterns, and thus DLMO was not determined in either condition. In the day worker, shorter rapid eye movement (REM) latency and increased REM were observed with smartphone use. Conclusions This study demonstrates that the use of smartphones at bedtime acutely suppresses melatonin secretion and delays the sleep-wake cycle. However, the effect of LAN on melatonin secretion was not apparent in the shift worker with already misaligned circadian rhythm. Keywords: Circadian rhythm, Light, Shift work schedule, Smartphone, Melatonin

The Role of Light Sensitivity and Intrinsic Circadian Period in Predicting Individual Circadian Timing.

There is large interindividual variability in circadian timing, which is underestimated by mathematical models of the circadian clock. Interindividual differences in timing have traditionally been modeled by changing the intrinsic circadian period, but recent findings reveal an additional potential source of variability: large interindividual differences in light sensitivity. Using an established model of the human circadian clock with real-world light recordings, we investigated whether changes in light sensitivity parameters or intrinsic circadian period could capture variability in circadian timing between and within individuals. Healthy participants (n = 12, aged 18-26 years) underwent continuous light monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim-light melatonin onset (DLMO) was measured each week. Using the recorded light patterns, a sensitivity analysis for predicted DLMO times was performed, varying 3 model parameters within physiological ranges: (1) a parameter determining the steepness of the dose-response curve to light (p), (2) a parameter determining the shape of the phase-response curve to light (K), and (3) the intrinsic circadian period (tau). These parameters were then fitted to obtain optimal predictions of the three DLMO times for each individual. The sensitivity analysis showed that the range of variation in the average predicted DLMO times across participants was 0.65 h for p, 4.28 h for K, and 3.26 h for tau. The default model predicted the DLMO times with a mean absolute error of 1.02 h, whereas fitting all 3 parameters reduced the mean absolute error to 0.28 h. Fitting the parameters independently, we found mean absolute errors of 0.83 h for p, 0.53 h for K, and 0.42 h for tau. Fitting p and K together reduced the mean absolute error to 0.44 h. Light sensitivity parameters captured similar variability in phase compared with intrinsic circadian period, indicating they are viable targets for individualizing circadian phase predictions. Future prospective work is needed that uses measures of light sensitivity to validate this approach.

0433 Targeting Light Sensitivity Parameters to Optimize Circadian Phase Predictions

Abstract Introduction Existing models of the human circadian clock accurately predict phase at group-level but not at individual-level. Interindividual variability in light sensitivity is not currently accounted for in these models and may be a practical approach to improving individual-level predictions. Using the gold-standard predictive model, we (i) identified whether varying light sensitivity parameters produces meaningful changes in predicted phase in field conditions; and (ii) tested whether optimizing parameters can significantly improve accuracy of circadian phase prediction. Methods Healthy participants (n=12, 7 women, aged 18-26) underwent continuous light and activity monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim light melatonin onset (DLMO) was measured each week. A model of the human circadian clock and its response to light was used to predict the three weekly DLMO times using the individual’s light data. A sensitivity analysis was performed varying three model parameters within physiological ranges: (i) amplitude of the light response [p]; (ii) advance vs. delay bias of the light response [K]; and (iii) intrinsic circadian period [tau]. These parameters were then fitted using least squares estimation to obtain optimal predictions of DLMO for each individual. Accuracy was compared between optimized parameters and default parameters. Results The default model predicted DLMO with mean absolute error of 1.02h. Sensitivity analysis showed the average range of variation in predicted DLMOs across participants was 0.65h for p, 4.28h for K and 3.26h for tau. Fitting parameters independently, we found mean absolute error of 0.85h for p, 0.71h for K and 0.75h for tau. Fitting p and K together reduced mean absolute error to 0.57h. Conclusion Light sensitivity parameters capture similar or greater variability in phase as intrinsic circadian period, indicating they are a viable option for individualising circadian phase predictions. Future prospective work is needed using measures of light sensitivity to validate this approach. Support N/A

0047 The Change in Melatonin Rhythm Depending on Dementia Severity in Alzheimer’s Disease (AD) Patients

Abstract Introduction In Alzheimer’s disease (AD), both sleep and circadian dysfunctions are commonly reported and these are associated with neurodegenerative change. Actually, it has been reported that changes in circadian rhythms in AD were apparently discrete from those seen in normal aging. Previous studies reported the delayed phase in the activity or core body temperature rhythms in severe AD patients compared to normal controls. However, it is unknown whether similar changes in melatonin rhythms occur in AD patients who were not severely demented. We aimed to compare melatonin rhythms depending on dementia severity in mild and moderate AD patients. Methods We recruited AD patients of mild or moderate degree who had the Pittsburgh Sleep Quality Index (PSQI) score of 5 or greater and/or complained insomnia symptoms more than 3 times a week for a month. The patients were classified according to their Clinical Dementia Rating (CDR) score into 3 groups (CDR=0.5, 1, 2). The dim light melatonin onset (DLMO) was determined from seven hourly saliva samples obtained in the laboratory prior to sleep onset measured by actigraphy. The phase angle between the DLMO and sleep onset (PA-SO), and that between the DLMO and midsleep time (PA-MST) were calculated. Each group included 13, 13 and 6 AD patients with the CDR score of 0.5, 1 and 2, respectively. The DLMO and PA were compared among the 3 groups, and correlation analyses of the DLMO and PA with the MMSE in the Korean version of CERAD Packet (MMSE-KC) scores were done in total patients. Results There was no significant difference in the DLMO and PA between the 3 groups. The MMSE-KC score was positively correlated with the DLMO and negatively correlated with the PA-MST. Conclusion There were no changes in melatonin rhythms according to dementia severity in mild and moderate AD patients with sleep complaints. However, our study showed that earlier melatonin phase was associated with more impaired cognitive function. Support Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT &amp; Future Planning (2017R1A2B4003493)

Circadian rhythm and sleep alterations in older people with lifetime depression: a case-control study

BackgroundDepression is common in older people and is associated with underlying brain change increasing the risk of dementia. Sleep disturbance is frequently reported by those with lifetime depression, however whether circadian misalignment also exists is unclear. We aimed to examine circadian rhythms and sleep associations in older patients with and without lifetime depression.MethodsThirty-four older people meeting DSM-IV criteria for lifetime major depression (mean age = 63.9 years), and 30 healthy controls (mean age = 65.7 years) were recruited. Participants underwent 2-weeks of actigraphy followed by a 3-night protocol including dim light melatonin onset (DLMO) assessment and overnight polysomnography (PSG) for sleep architecture. DLMO and phase angle of entrainment were computed.ResultsCompared to controls, participants with depression had a significantly longer phase angle of entrainment (6.82 h ± 1.45 vs. 5.87 h ± 1.60, p = 0.02, Cohens-d = 0.62). A small to moderate yet non-significant difference in DLMO times, with earlier DLMO (34 ± 27 min) observed in depression (20:36 ± 1:48 vs. 21:10 ± 1:48, p = 0.22, Cohens-d = 0.32). Individuals with depression had longer sleep latency and latency to rapid eye movement sleep than controls (all p < 0.05).ConclusionCircadian advancement and alterations to the timing of sleep and REM onset are evident in older people with lifetime major depression, despite having only mild residual symptoms. Further research examining the prognostic significance of these changes is warranted as well as chronotherapeutic treatment studies.

Chronotype-Dependent Changes in Sleep Habits Associated with Dim Light Melatonin Onset in the Antarctic Summer.

Dim light melatonin onset (DLMO) is the most reliable measure of human central circadian timing. Its modulation by light exposure and chronotype has been scarcely approached. We evaluated the impact of light changes on the interaction between melatonin, sleep, and chronotype in university students (n = 12) between the Antarctic summer (10 days) and the autumn equinox in Montevideo, Uruguay (10 days). Circadian preferences were tested by validated questionnaires. A Morningness–Eveningness Questionnaire average value (47 ± 8.01) was used to separate late and early participants. Daylight exposure (measured by actimetry) was significantly higher in Antarctica versus Montevideo in both sensitive time windows (the morning phase-advancing and the evening phase-delaying). Melatonin was measured in hourly saliva samples (18–24 h) collected in dim light conditions (<30 lx) during the last night of each study period. Early and late participants were exposed to similar amounts of light in both sites and time windows, but only early participants were significantly more exposed during the late evening in Antarctica. Late participants advanced their DLMO with no changes in sleep onset time in Antarctica, while early participants delayed their DLMO and sleep onset time. This different susceptibility to respond to light may be explained by a subtle difference in evening light exposure between chronotypes.

Caloric and Macronutrient Intake Differ with Circadian Phase and between Lean and Overweight Young Adults.

The timing of caloric intake is a risk factor for excess weight and disease. Growing evidence suggests, however, that the impact of caloric consumption on metabolic health depends on its circadian phase, not clock hour. The objective of the current study was to identify how individuals consume calories and macronutrients relative to circadian phase in real-world settings. Young adults (n = 106; aged 19 ± 1 years; 45 females) photographically recorded the timing and content of all calories for seven consecutive days using a smartphone application during a 30-day study. Circadian phase was determined from in-laboratory assessment of dim-light melatonin onset (DLMO). Meals were assigned a circadian phase relative to each participant’s DLMO (0°, ~23:17 h) and binned into 60° bins. Lean (n = 68; 15 females) and non-lean (n = 38, 30 females) body composition was determined via bioelectrical impedance. The DLMO time range was ~10 h, allowing separation of clock time and circadian phase. Eating occurred at all circadian phases, with significant circadian rhythmicity (p < 0.0001) and highest caloric intake at ~300° (~1900 h). The non-lean group ate 8% more of their daily calories at an evening circadian phase (300°) than the lean group (p = 0.007). Consumption of carbohydrates and proteins followed circadian patterns (p < 0.0001) and non-lean participants ate 13% more carbohydrates at 240° (~1500 h) than the lean group (p = 0.004). There were no significant differences when caloric intake was referenced to local clock time or sleep onset time (p > 0.05). Interventions targeting the circadian timing of calories and macronutrients for weight management should be tested.

Randomized trial of polychromatic blue-enriched light for circadian phase shifting, melatonin suppression, and alerting responses

Wavelength comparisons have indicated that circadian phase-shifting and enhancement of subjective and EEG-correlates of alertness have a higher sensitivity to short wavelength visible light. The aim of the current study was to test whether polychromatic light enriched in the blue portion of the spectrum (17,000 K) has increased efficacy for melatonin suppression, circadian phase-shifting, and alertness as compared to an equal photon density exposure to a standard white polychromatic light (4000 K). Twenty healthy participants were studied in a time-free environment for 7 days. The protocol included two baseline days followed by a 26-h constant routine (CR1) to assess initial circadian phase. Following CR1, participants were exposed to a full-field fluorescent light (1 × 1014 photons/cm2/s, 4000 K or 17,000 K, n = 10/condition) for 6.5 h during the biological night. Following an 8 h recovery sleep, a second 30-h CR was performed. Melatonin suppression was assessed from the difference during the light exposure and the corresponding clock time 24 h earlier during CR1. Phase-shifts were calculated from the clock time difference in dim light melatonin onset time (DLMO) between CR1 and CR2. Blue-enriched light caused significantly greater suppression of melatonin than standard light ((mean ± SD) 70.9 ± 19.6% and 42.8 ± 29.1%, respectively, p < 0.05). There was no significant difference in the magnitude of phase delay shifts. Blue-enriched light significantly improved subjective alertness (p < 0.05) but no differences were found for objective alertness. These data contribute to the optimization of the short wavelength-enriched spectra and intensities needed for circadian, neuroendocrine and neurobehavioral regulation.