bluuebunny/crossref_metadata_2025 huggingface dataset:
0402 Mediating Effects of Social Support on Associations Between Stress and Insomnia
Authors: Elvariste Stessie , Gallop Erin-Leigh , Blanc Judite , Oliveira Bruno , Casimir Georges , Nunes joao , Seixas Azizi , Jean-Louis Girardin
Published: April 2024

Introduction

Insomnia is a common sleep disorder that is linked to environmental/social factors and medical illnesses. Insomnia is associated with stress, defined as the mental or emotional pressure experienced when an individual is faced with adverse or demanding circumstances that are perceived to or exceed their ability to cope. While stress can lead to insomnia, it is hypothesized that social support could affect the association between stress and insomnia. To understand this mechanism, the presented study examines the relationship between stress and insomnia among blacks, highlighting the role of social support in this demographic.

Methods

Black Participants (N=618; female= 65%, male= 35%), ages 18 and older, from 2 NIH-funded studies, ESSENTIAL and MOSAIC, provided sociodemographic data and completed questionnaires on behavioral and social determinants of sleep and health. Perceived stress, insomnia and social support were evaluated using the perceived stress scale, the insomnia severity index, and the multidimensional scale of perceived social support questionnaire, respectively. Descriptive and linear regression analyses were performed to explore the association between insomnia, stress, and social support. Mediation analysis was conducted to establish and understand the effect of social support on stress score and ISIScore. All analyses were performed using SPSS 29.

Results

Regression analysis revealed stress as the strongest predictor of insomnia in blacks [β= .227; p< .001]. The model adjusted for sex, age, and states (New York vs Florida). Perceived social support was significantly associated with a decrease in stress score and insomnia, [β= -.152; p<.001]. Mediation analysis revealed that the effect between Stress Score and ISIScore via the intermediary variable of Social Support is statistically significant (p=0.0005).

Conclusion

Stress is a robust predictor of insomnia among blacks. However, social support mediates this relationship by decreasing both stress and insomnia. Further research should investigate the importance of social support to promote better overall health and sleep.

Support (if any)

NIH R01AG067523, R01HL142066, K01HL135452
0404 Americas Prevalence of Insomnia Disorder in Adults: Estimation Using Currently Available Data
Authors: Benjafield Adam , Kuniyoshi Fatima Sert , Malhotra Atul , Maurer Leonie , Morin Charles , Martin Jennifer , Wickwire Emerson
Published: April 2024

Introduction

Insomnia disorder is a major clinical issue due to its high prevalence and negative health outcomes. While the prevalence of insomnia in developed countries like the United States and Canada is known, its prevalence across the broader Americas region (Northern America, Latin America and the Caribbean) remains unclear. Limited epidemiological studies have been conducted and the majority of the Americas’ population does not have a reliable estimate for insomnia disorder. The purpose of this analysis was to estimate the Americas’ prevalence of adult insomnia disorder using published data.

Methods

Published nation-specific estimates of the general population prevalence of insomnia disorder were applied to current population estimates for all countries in the Americas. We utilized the following criteria to determine which insomnia prevalence estimates to use: 1) studies that reported prevalence stratified by both age and sex together; 2) studies that reported prevalence by age and sex separately, we used the age-based results; 3) studies that reported prevalence by sex but not age; 4) studies that reported only a single prevalence estimate. Expert opinion was used to select the most methodologically rigorous study when >1 potential reference study existed for a nation. For countries lacking a reference study, we applied the estimates from a large, well-conducted study. Population estimates by sex and age (20yrs+) were sourced from the United Nations World Population Prospects 2022.

Results

There were 55 countries defined by the United Nations comprising the Americas of which 3 (5.5%) had a suitable prevalence estimate of insomnia. We estimated an Americas’ adult insomnia disorder prevalence of approximately 123 million adults (16.8%), comprised of 73 million females (19.5%) and 50 million males (14.0%). The nations with the greatest burden of insomnia disorder are the United States (37 million), Brazil (29 million), and Mexico (16 million).

Conclusion

This large burden of disease, ~17% of adults, highlights the importance of comprehensive sleep health initiatives and the need for promotion of sleep health in public health policy. There is a lack of appropriate prevalence studies especially in low- and middle-income countries within the Americas.

Support (if any)

Study funded by ResMed
0408 Predictors of Responders in Sleep Hygiene Education: A Secondary Analysis of Randomized Controlled Trials
Authors: Yeung Wing Fai , Chak Kin Yeung , Wu Min Ru , Pang Lok Yi , Zhang Xuan , Chen Shu Cheng , Ruan Jia Yin
Published: April 2024

Introduction

Few studies have investigated the predictors of the treatment response after attending sleep hygiene education (SHE). We aimed to explore the patient characteristics associated with a response to SHE for insomnia.

Methods

A secondary analysis was conducted to pool the data of two randomized controlled trials for insomnia (Trial registration number ClinicalTrials.gov: #NCT04227587; NCT03623438), in which the subjects in the comparison group had attended two 2-hour sessions (total 4 hours) of small-group based SHE. We examined the association of sociodemographic variables, clinical characteristics, baseline sleep-wake variables, and Sleep Hygiene Practice Scale (SHPS) items to the treatment response. Subjects with a reduction in insomnia severity index (ISI) scores of ≥ 6 points from baseline to week 8 were classified as responders. Factors were compared between responders and non-responders and by univariate and multivariate logistic regression analysis.

Results

A total of 170 subjects with insomnia disorder who had received the SHE program were included and 42 (24.7%) of them were classified as responders. At 8 weeks after baseline, the subjects showed a 2.88 points reduction in ISI total score, 11.5 minutes reduction in sleep onset latency, 10.4 minutes reduction in waketime after sleep onset, 20.3 minutes increase in total sleep time, and 4.42% increase in sleep efficiency. Univariate logistic regression analysis has identified 12 potential predictors for SHE responders, including age, gender, baseline sleep parameters, and SHPS items. In the multivariate logistic regression analysis, age, ever tried exercise for improving sleep, and baseline ISI score remained significant predictors of SHE treatment response (age, adjusted OR 0.88, 95%CI 0.79, 0.97, p = 0.011; ever tried exercise for improving sleep, adjusted OR 11.0, 95%CI 1.16, 104.9, p = 0.037; baseline ISI score, adjusted OR 1.59, 95%CI 1.15, 2.19, p = 0.005).

Conclusion

Lower age, higher baseline ISI score, and ever-tried exercise for improving sleep were shown to predict the response of SHE. Our findings inform individuals who have insomnia to select the treatment for chronic insomnia in the future.

Support (if any)

The RCTs were supported by the Research Grants Council, General Research Fund (NCT04227587, Project no.: 15100419), and Health and Medical Research Fund (NCT03623438, Project no.: 19200171).
0409 The Impact of Fragrance on the Quality of Sleep
Authors: Seiger Anja , Spahn Lukas , Rosenblum Lisa , Penzel Thomas , Lederer Katharina , Salanitro Matthew , Fietze Ingo
Published: April 2024

Introduction

The utilization of scents in sleep medicine is gaining increased attention due to their demonstrated ability to enhance sleep quality. This study employed a randomized double-blinded crossover trial to investigate the effects of continuous nightly exposure to a synthetic jasmine scent, combined with lavender oil and passionflower herb, on both subjective and objective measures of sleep quality. With a focus on individuals characterized by delayed sleep onset and frequent disturbances, this research aimed to assess the potential benefits of aromatherapy in addressing sleep-related issues.

Methods

Thirty sensitive sleepers, falling within the Insomnia Severity Index (ISI) range of 7-14 and experiencing 2-3 sleep disturbances per week, participated in the study. The experiment was conducted over four nights in a sleep laboratory, with the initial night serving as an acclimation (baseline) period. The subsequent nights involved randomized exposure to different conditions: a placebo rose scent, a high-dose of jasmine scent, or a low-dose relative to essential oils. Participants were monitored, and standardized questionnaires were administered in both morning and evening sessions. The scent application, specifically on T-shirts, was assessed for tolerance.

Results

Comparisons to baseline revealed a significant improvement in both sleep quality and total sleep time when using scents. Notably, both high and low doses of jasmine demonstrated a reduction in wake after sleep onset. The application of scent on T-shirts was well-tolerated by all participants. These results collectively suggest a positive impact of jasmine scent on sleep parameters.

Conclusion

In conclusion, the findings of this study highlight the potential of aromatherapy, particularly the use of synthetic jasmine scent, in positively influencing sleep quality. The reduction in wake after sleep onset indicates a promising avenue for addressing sleep disturbances. Further exploration into factors such as dosage, application method, and duration of scent exposure is warranted to refine our understanding and optimize the therapeutic use of scents in sleep medicine.

Support (if any)

This study received support from Marome GmbH, which supplied the scents.
0413 Exploring the Efficacy of Cannabinol in Sleep Enhancement: A Breakthrough in Non-Intoxicating Solutions
Authors: Lindquist Alleh
Published: April 2024

Introduction

Sixty percent of Americans report getting less than the recommended seven hours of nightly sleep. Poor sleep is a public health concern linked to many health issues, including inflammatory conditions, obesity, heart disease and reduced quality of life. As consumers seek natural, safe alternatives for better sleep, the introduction of a non-intoxicating hemp-derived cannabinoid solution presents an attractive option.

Methods

Conducting the first-ever double-blind, randomized, placebo-controlled trial, an independent clinical research company examined the effects of TruCBN, FloraWorks proprietary ultra pure CBN on sleep patterns. The trial involved over 1,000 participants at least 21 years old from across the US, comparing the outcomes of CBN to melatonin and a placebo. There were three CBN groups, one melatonin group and one placebo group, as follows: CBN groups: 25 mg, 50 mg, 100 mg Melatonin: 4 mg Control: placebo

Results

- The group taking 50 mg of CBN showed significant sleep improvements compared to placebo, and most of the group experienced a clinically important improvement. - The group taking 4 mg melatonin also showed significant sleep improvements compared to the placebo. - The group taking 50 mg of CBN had slightly better sleep improvements compared to 4 mg of melatonin. - The groups taking 25 mg and 100 mg of CBN had marginally significantly better sleep improvements compared to placebo. - All three tested doses of CBN are statistically equivalent to one another, and statistically equivalent to 4 mg melatonin, for improving sleep quality. All three doses of CBN show a Minimal Clinically Important Difference (MCID) with respect to placebo. - All side effects were mild or moderate. There were no significant differences in the frequency of reported side effects between any dose of CBN or melatonin compared to placebo.

Conclusion

Beyond illuminating CBN's efficacy in enhancing sleep, this research positions it as a formidable player in the pursuit of superior sleep aids, disrupting the conventional over-the-counter sleep aid market. The discovery that CBN is at least as effective as melatonin for improving sleep is particularly promising, especially given the side effects of melatonin and the growing concerns surrounding children consuming melatonin beyond recommended limits.

Support (if any)
0416 The Effect of Doxepin 3 Mg on Sleep Latency: Results from a Meta-analysis of Two Phase 3 Trials
Authors: Fisher Matt , Franks Billy , Araga Mako , Rawal Kapil , Kyle Michael , Krystal Andrew
Published: April 2024

Introduction

Doxepin 3 and 6 mg are FDA-approved treatments for insomnia characterized by sleep maintenance symptoms. A large, randomized, placebo-controlled trial has confirmed the sleep latency effects of doxepin 6 mg in a phase advance model of healthy adults. The antihistaminic effects of doxepin 3 mg may also lead to sleep latency benefits in adults with insomnia symptoms.

Methods

Two randomized, double-blind, parallel group, placebo-controlled phase 3 trials involving doxepin 3 mg in subjects with chronic insomnia were used to assess the sleep latency effects on night 1/day 2. Meta-analysis methods were used to assess latency to sleep onset (LSO) and latency to persistent sleep (LPS), each on a log scale, for subjects with evaluable data in the intent to treat analysis set. Subgroup analyses were performed for both LSO and LPS for subjects above and at or below the median baseline values. Fixed and random effects models were performed using generic inverse variance methods.

Results

The analysis included a total of 460 subjects. Among these subjects, 68.5% were female, 65.2% were White and 20.0% were African American. The mean age was 58.5 years (median 65 years). The baseline median LSO was 55 minutes and median LPS was 35 minutes. We observed limited evidence for heterogeneity (all p-values > 0.2) and therefore present fixed effects estimates only. Doxepin 3 mg improved LSO by 12% (RR=0.88; 95% CI [0.73 to 1.05]) and LPS by 22% (RR=0.78; 95% CI [0.64 to 0.94]) when compared to placebo. There was a non-statistically significant 6% improvement in LSO observed among subjects above the median (RR=0.94) and a 15% non-statistically significant improvement among subjects below the median (RR=0.85). A statistically significant 29% improvement in LPS was observed for subjects above the median (RR=0.71; 95% CI [0.56 to 0.91]) and a non-statistically significant 6% improvement for those below the median (RR=0.94). All subgroup data reflect results compared to placebo.

Conclusion

Doxepin 3 mg may be an effective option to treat sleep latency in adults with insomnia symptoms, especially those with a long latency to persistent sleep.

Support (if any)

This work was supported by Haleon and Currax.
0417 The Effect of CBT-I Combines with Craving Management Strategies on Hypnotic Discontinuation
Authors: Yu Tsai-Ching , Yang Chien-Ming , Huang Ya-Chuan , Wu Yu-Ting , Huang Chih-Shan , Sung Jia-Ying
Published: April 2024

Introduction

Although the use of hypnotics is recommended for short-term management, long-term use is quite common in clinical practice. Gradual tapering, either alone or in combination with cognitive-behavioral therapy for insomnia (CBT-I), has been shown to facilitate the discontinuation of hypnotics. However, some patients are unsuccessful with these strategies. Previous studies suggest that individuals having difficulty discontinuing hypnotic use may develop a craving for these drugs, and such craving is a significant barrier in discontinuing substances like alcohol or drugs. The present study aims to examine whether combining CBT-I with craving management strategies can enhance the success rate of discontinuing hypnotics.

Methods

Twenty-one patients with insomnia disorder, who had been taking hypnotics for over three months, were randomly assigned to a CBT-I group (N=11) or a CBT-I+CM (craving management) group (N=10). Participants in both groups received eight sessions of CBT-I along with a progressive tapering plan. Those in the CBT-I+CM group received additional craving management strategies. Outcome variables included the average number of pills taken per day, the Insomnia Severity Index (ISI), and the Hypnotic Urge Scale (HUS), assessed at baseline and at the end of the program.

Results

ANOVA results indicated a significant reduction in the number of pills taken daily at the end of the program for both groups (CBT-I: 1.96 to 0.24; CBT-I+CM: 1.17 to 0.03; F=61.59, p<.001) and in the HUS scores (CBT-I: 97.00 to 72.55; CBT-I+CM: 105.89 to 63.67; F=25.73, p<.001). Unexpectedly, in the ISI scores, only the CBT-I+CM group showed significant improvement at the end of the program (17.5 to 7.2; t=6.46, p<.001), while the CBT-I group did not show significant improvement (13.36 to 11.55; t=1.20, p=0.25). No significant differences were found between the CBT-I and the CBT-I+CM group in all outcome variables.

Conclusion

The results suggest that CBT-I, whether alone or combined with craving management strategies, can facilitate the tapering of hypnotics and the reduction of craving for them. The inclusion of craving management strategies proved beneficial in improving symptoms of insomnia and, thus, could be integrated into clinical practice. Future research should investigate the long-term outcomes of these strategies in managing hypnotic discontinuation, with follow-up evaluations.

Support (if any)
0418 A Day-by-Day Prospective Analysis of Stress and Hypnotic Craving During Hypnotic Tapering in Insomnia
Authors: Wu Yu-Ting , Yang Chien-Ming , Huang Ya-Chuan , Yu Tsai-Ching , Huang Chih-Shan , Sung Jia-Ying
Published: April 2024

Introduction

Craving plays a crucial role in the persistence and relapse of substance use. While hypnotic usage may differ from that of addictive substances, previous research has indicated that long-term use of hypnotics is associated with a craving for hypnotics among patients with insomnia. Stress, which is commonly linked to sleep disturbances, has also been shown to enhance cravings for substance use. The current study aims to investigate the relationship between stress and craving for hypnotics using day-to-day assessments.

Methods

Twenty-seven participants with insomnia disorder (age = 41.66 ± 12.88; Male:Female = 14:13), who had been taking hypnotics for more than three months, were recruited for a two-week study. During the first week, they were permitted to take their usual dosage of hypnotics, while in the second week, their dosage was reduced by 25%. Each night before bed, participants recorded the level of stress they experienced and their craving for hypnotics, both on a scale of 1 to 9. Data were collected through responses to questions delivered via a social media app (Line). Mixed Effects Models were utilized to examine the relationship between stress and craving, separating out between-subject and within-subject associations.

Results

The findings revealed no significant associations between stress and craving at the between-subject level for either week (β = -0.08, p = 0.77; β = 0.07, p = 0.80). However, at the within-subject level, there was a significant association between stress and craving during the usual dosage week (β = 0.22, p < .05), but not during the reduced dosage week (β = 0.14, p = 0.17).

Conclusion

Our study indicates that there is no significant correlation between stress and craving across the participants. Conversely, within individuals, heightened stress was correlated with increased craving when participants were allowed to take their usual hypnotic dosage. These results underscore the importance of taking stress into consideration when assisting insomnia patients in managing their cravings for hypnotics.

Support (if any)

National Science and Technology Council
0425 Detecting Insomnia and Predicting Difficulty Falling Asleep: Machine Learning of Heart Rate Data During Sleep Onset
Authors: Ma Yan , Wayne Peter , Yu Chen-Hsiang , Yeh Gloria
Published: April 2024

Introduction

Insomnia is highly prevalent and difficulty falling asleep is the most common complaint. The transition from wakefulness to sleep is characterized by a shift from sympathetic to parasympathetic regulation, which can be assessed by heart rate dynamics. Using a machine learning approach, we aimed to explore whether heart rate dynamics during sleep onset can indicate the presence of insomnia.

Methods

We used data from a multi-center cohort study (Sleep Heart Health Study) and included 1835 subjects (age 40-90 years, mean age 62.2±11.2 years, 50.8% male) with overnight polysomnography-based sleep studies and validated sleep scorings. Heart rate data during sleep onset was analyzed using heart rate variability time domain measures (NN, SDNN, RMSSD, pNN20) and a nonlinear measure (multiscale entropy). These measures along with basic demographic features (age, sex and BMI) were used as features in machine learning. We ran four commonly used machine learning approaches, including support vector machines (SVMs), decision tree, random forest, and K-nearest neighbors (KNN), with 80% data for training and 20% for testing.

Results

Based on the mean of test accuracy of five iterations for each model, the highest accuracy for detecting insomnia was achieved by random forest (mean accuracy of 0.902), followed by SVM (mean accuracy 0.894), decision tree (mean accuracy 0.892), and KNN (mean accuracy 0.891). When using the same features to predict self-reported difficulty falling asleep during the study night, SVM achieved the highest accuracy (0.68) while the accuracy of the other approaches were slightly lower.

Conclusion

Machine learning models may effectively predict insomnia using demographic features and heart rate data during sleep onset, but unbiased analysis is needed for the next step. With wearable technology, easily accessible heart/pulse rate data may provide valuable detection of physiological alteration during sleep onset and offer an evaluation approach for the efficacy of interventions targeting sleep onset difficulties.

Support (if any)

This research project was made possible by a grant from the American Academy of Sleep Medicine Foundation (PI: Yan Ma). We acknowledge the National Sleep Research Resource as the resource through which the Data/Datasets were obtained. PW and GY were supported by NIH K24 AT009282 and K24 AT009465 respectively.
0426 Graph Convolutional Network (GCN)-Based Prediction of Brain Age in Individuals with Insomnia
Authors: Bae Heewon , Jo Hyunjin , Joo Eun Yeon , Kim Hosung , Park Gilsoon
Published: April 2024

Introduction

The impact of insomnia on brain aging and cognitive function remain undisclosed. The Brain Age Index has arisen as a robust biomarker for assessing an individual’s brain health, quantifying the deviations from normative aging trajectories. This study investigates accelerated brain aging in insomnia suffers compared to non-suffers using the Brain Age Index, exploring its correlation with the neurocognitive function.

Methods

Forty chronic insomnia patients (31 females, mean age 51.2 years) and 80 healthy controls (57 females, mean age 52.0 years) were analyzed. Graphical convolutional networks (GCNs) constructed regional brain age prediction models, integrating cortical morphology and topology data for comprehensive graph structure. Cortical thickness and gray-/white matter intensity ratio mapped on the cortical surface mesh were input to the GCNs. Ten brain network regions (sensorimotor, frontoparietal, dorsal attention, ventral attention, default mode, salience, language, auditory, visual, and limbic) were employed in the analysis of regional brain ages, utilizing automated anatomical labeling. Each model was trained on data from 6,563 healthy controls, with five-fold cross-validation indicating approximately three years of mean absolute error. These models computed the Brain Age Index for 80 healthy sleepers and 40 insomnia individuals. Linear regression models, adjusted for age, sex, and Beck Depression Inventory, scrutinized group disparities in regional Brain Age Indices. An additional analysis explored the association Brain Age Index and neuropsychological test utilizing linear regression analysis.

Results

While the global Brain Age Index revealed no significant group differences, notable regional Brain Age Index distinctions emerged in insomnia subjects. The regional Brain Age Index were significantly elevated in three distinct brain network regions—limbic, frontoparietal, and language (in descending significance order)—compared to normal subjects. The Brain Age Index within the language network exhibited a discernible negative correlation with neuropsychological deficits in attention and visuospatial domains.

Conclusion

This pioneering study validates neuroimaging-driven brain age in chronic insomnia, unveiling accelerated brain aging in distinct regions. Such revelations signify the potential impact of insomnia on the brain aging trajectory independently of chronological age. The potential association between accelerated brain aging in the language network and cognitive impairments has the potential to elucidate the intricate interplay between brain aging patterns and cognitive performance.

Support (if any)
0431 Transcranial Electrical Stimulation with a Wearable Device Dramatically Reduces Sleep Onset Latency in Insomnia
Authors: Simons Stephen , Provo Maria , Shimizu Renee
Published: April 2024

Introduction

The normal transition to sleep is characterized by a reduction in higher frequency activity and an increase in lower frequency activity in frontal brain regions. In sleep onset insomnia these changes in activity are weaker and may prolong the transition to sleep. We performed a translational study to investigate the impact of a new wearable neurotechnology using 0.75 Hz transcranial electrical stimulation (tES) to improve sleep outcomes in a population displaying symptoms of sleep onset insomnia.

Methods

Participants were enrolled based on a qualifying insomnia severity index score of greater than 7 and an average sleep onset latency of greater than 30 minutes during baseline monitoring. Using a wearable device we compared 30 minutes of 0.75 Hz tES prior to going to bed with an active control at 25 Hz in the same individuals. Sleep behaviors were tracked in the home using a FitBit inspire wrist worn actigraphy device. Sleep onset latency (SOL), time asleep, and wake after sleep onset were measured during one-week baselines and then again over the two, one-week periods of use with the wearable device. Neurophysiological responses to both stimulation frequencies were observed using electroencephalography within the wearable device and correlated with observed differences in sleep behaviors. All outcome measures were compared against pre-stimulation baselines within subjects and then averaged across subjects.

Results

Treatment with 0.75 Hz consistently reduced SOL by 54% when compared with pre-treatment baselines (p<< 0.001). Stimulation with 25 Hz reduced SOL by 28% (p< 0.05) but displayed order effects suggesting the possibility of placebo. The reduction in SOL with 0.75 Hz treatment was linearly proportional to an individual’s baseline with those individuals with the greatest severity realizing the greatest benefit (r^2 = 0.62, p<< 0.001). Changes in SOL were correlated with left/right coherence around the stimulation frequency of 0.75 Hz (r^2 = 0.33, p< 0.01) providing a possible mechanism. Time asleep was increased by 20 minutes with 0.75 Hz treatment (p< 0.05), and -1 minute with 25 Hz (N.S.).

Conclusion

Our study provides translational evidence for an exciting new treatment for sleep onset insomnia that is safe, effective and can be delivered in the home.

Support (if any)
0432 Neuromodulation of REM Sleep: Age-Associated Effects of Transcranial Magnetic Stimulation
Authors: Yakpogoro Nekabari , Desai Shivani , Huskey Alisa , Henderson-Arredondo Kymberly , Jankowski Samantha , Patel Salma , Hildebrand Lindsey , Trapani Christopher , Franca Gabriela , Reich-Fuehrer Melissa Melissa , Grandner Michael A , Chen Yu-Chin (Allison) , Chou Ying-Hui , Dailey Natalie , Killgore William
Published: April 2024

Introduction

We recently reported findings from a project that used a form of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS) to modulate connectivity within the brain’s Default Mode Network (DMN) as a potential treatment for insomnia. Continuous theta-burst stimulation(cTBS) was used to reduce cortical excitability within the DMN. Our prior analyses showed that the approach significantly improved total sleep time, sleep efficiency, N3 latency, and the arousal index, but rapid eye-movement (REM) did not appear affected. Based on growing evidence that REM sleep may show changes in the third decade and beyond, and that the effects of rTMS may be, at least partially, influenced by age, we further explored the potential effect of age in this dataset.

Methods

cTBS was administered to a total of 20 participants with self-reported insomnia symptoms (Mage=26.90, SD=6.56). Each participant underwent one round of sham stimulation and one round of active cTBS in a randomized order with one week in between. Participants were monitored with polysomnography (PSG) during a 7-hour sleep window. We first examined the association between age and REM sleep at each visit. A repeated measures ANOVA was employed, incorporating age as a covariate to assess potential age-dependent effects on cTBS effects.

Results

REM duration was positively correlated with age for the active cTBS visits (r=0.506, p=0.023) but not for the sham (r=-0.059, p= .806). With age as a covariate, the ANOVA revealed a significant effect of TMS treatment on REM sleep duration, F(1,18)=7.507, p=0.013. Participants in the TMS treatment group experienced an increase in REM sleep duration compared to the sham group when age was controlled in the analysis.

Conclusion

Age significantly influenced the effect of cTBS on REM sleep outcomes. The finding that older individuals demonstrated a greater effect of stimulation on REM duration suggests potential implications for clinical application in individuals with insomnia. Future work may focus on refining therapeutic strategies for sleep modulation, advocating for a personalized and age-aware approach.

Support (if any)

US Army Medical Research Acquisition Activity Grant: W81XWH2010173
0433 Suppression of the Default Mode Network Affects the Arousal and Reduces Time in Non-Restorative Sleep
Authors: Franca Gabriela , Negelspach David , Reich-Fuehrer Melissa Melissa , Franz Daniel , Wellman Camryn , Grabner Palmer , Huskey Alisa , Henderson-Arredondo Kymberly , Jankowski Samantha , Patel Salma , Trapani Christopher , Chen Yu-Chin (Allison) , Chou Ying-Hui , Dailey Natalie , Killgore William
Published: April 2024

Introduction

We recently demonstrated that continuous theta burst stimulation (cTBS), a form of suppressive transcranial magnetic stimulation (TMS), was effective at improving total sleep time, sleep efficiency and arousal index scores in people with symptoms of insomnia (Killgore, 2023, zsad077.0332). We now present additional analyses on the effects of this stimulation on functional brain activation during a complex cognitive task (multi-source interference task; MSIT) that targets the cingulo-frontal-parietal cognitive/attention network and its correlations with overnight polysomnography (PSG).

Methods

Nineteen people (11 females) with moderately severe symptoms of insomnia (age=27.2 SD=6.6), underwent active or sham cTBS followed by an overnight PSG monitored sleep study on two counterbalanced occasions separated by at least a week. Immediately before and after each cTBS/sham stimulation, participants completed functional MRI scans that included the MSIT. Contrasts were created between the more difficult interference condition and the simple control condition and task activation changes were compared across time and treatment condition using paired t-tests, repeated measures ANOVA, and within-condition Pearson’s correlations.

Results

A paired t-test of the primary task contrast (interference>control) maps showed a significant decline from pre- to post-treatment in a region of the supplementary motor area (SMA) for the active cTBS (p< 0.001, FWE corrected), but no change for the sham condition, as evidenced by a significant time x treatment interaction (p=.004). Moreover, for the sham condition, activation of this region was correlated with more time in wake/non-restorative sleep (i.e., wake, N1, N2, awakenings, and arousal index, all p-values<.05), while for the active cTBS, changes in activation within this region were no longer associated with indices of poor sleep.

Conclusion

Building on our previously reported finding that cTBS reduced arousal and improved sleep time, this analysis suggests that activity within the SMA may play a role in mediating the insomnia-related symptoms with respect to arousal. Under sham conditions, increased activity of the SMA was associated with increased awakenings and arousal index. This disruptive effect appears to be eliminated by cTBS to the DMN. This result raises the possibility that insomnia symptoms may be partially mediated through the interactions between DMN and cognitive-attention networks.

Support (if any)

USAMRAA: W81XWH2010173
0437 The Effects of a 6-week Single-blind Online CBT-I Program on Daily Subjective and Objective Sleep Parameters
Authors: Topalidis Pavlos , Eigl Esther-Sevil , Hinterberger Alexandra , Schabus Manuel
Published: April 2024

Introduction

Insomnia exerts a substantial impact on a considerable portion of the population, resulting in significant detriments to health, workplace safety, and overall quality of life. Digital treatment programs have currently made effective and easily accessible treatment options possible. In our current study, we examine the impact of a 6-week single-blind digital CBT-I program by daily tracking sleep quality, duration, and fragmentation, subjectively and objectively. Tracking sleep objectively was made possible using an innovative sleep staging method founded on heartbeat variability and machine learning, enabling access to daily sleep macrostructure (i.e., a hypnogram).

Methods

Fifty-six participants with self-reported sleep problems were randomly assigned to either a control or an experimental group. Both groups used a mobile smartphone application daily to provide subjective reports and track their sleep using a heart-rate wearable (H10, POLAR®) over the course of 6 consecutive weeks. Only the experimental group completed the sleep training program (e.g., included educational videos, relaxation exercises, and cognitive training). We examined changes in subjective and objective sleep parameters using mixed Analysis of Variance with the factors Group (Control, Experimental) and Time (Beginning, End). We also analysed significant interactions with paired samples t-tests. Spearman correlations were used to examine the changes in daily sleep parameters over time.

Results

Only the experimental group showed higher subjective sleep quality (t=-3.8, p<.001) and shorter sleep onset latency (t=3.1, p=.006) at the end of the program. Among the objective sleep parameters, we found a small but statistically significant increase in the amount of deep sleep (t(25)=-2.93, p=.007), while the number of awakenings (t(25)=2.21, p=.03) and the number of sleep stages (t(25)=2.17, p=.04) showed a significant decrease from the beginning to the end of the sleep training.

Conclusion

The results reported in the current study indicate significant improvements in subjective sleep parameters and objective sleep parameters throughout a digital CBT-I sleep training program. When assessing the effects of digital interventions, it is important to consider daily and long-term objective sleep-related parameters.

Support (if any)

We would like to express our gratitude to the Doctoral College 'Imaging the Mind' for their financial support (FWF, Austrian Science Fund: W 1233-B).
0442 A Qualitative Assessment of Digital Cognitive Behavioral Therapy for Insomnia in Heavy Drinkers with Insomnia
Authors: Moloney Mairead , Verlinden Justin , Weafer Jessica
Published: April 2024

Introduction

Insomnia, a public health problem impacting approximately 10-30% of the population, is both a risk factor for Alcohol Use Disorder and a common comorbid condition. Evidence suggests that intervening on sleep problems could serve as a novel and efficacious means of simultaneously improving sleep and problematic drinking. This study qualitatively and quantitatively assessed a well-validated, interactive version of digital cognitive behavioral therapy for insomnia (dCBTI) in heavy drinkers with insomnia. We report on qualitative themes related to beliefs about alcohol’s impact on sleep, self-reported positive outcomes of the dCBTI program, and aspects of the program that participants found most helpful.

Methods

Heavy drinking men (n = 28) and women (n = 42) with insomnia were randomly assigned to complete either the dCBTI program or a control patient education program. Semi-structured qualitative interviews were conducted at baseline and after program completion. Interviews were digitally recorded, professionally transcribed, and lasted approximately 45 minutes on average. The first and second authors conducted and coded the interviews using a multi-stage, inductive process aided by NVIVO software. Here we report on data from pre-intervention interviews with all 70 subjects and post-intervention interviews with the dCBTI subjects (n=40).

Results

At baseline most participants did not associate their heavy drinking habits with their difficulties in falling or staying asleep. Some participants reported using alcohol to help them fall asleep more quickly or “pass out.” Participants who participated in the dCBTI program reported improved ease in falling asleep, fewer nighttime awakenings, and the ability to fall more readily back asleep if they experienced early or nighttime awakenings. These participants also reported a new or increased understanding of the ways in which alcohol use impacted their sleep. Participants reported that having to track their daily number of drinks, and learning to stop drinking several hours before bedtime were the most helpful components of the dCBTI program.

Conclusion

Heavy drinkers with insomnia may lack awareness of how alcohol use impacts their sleep or believe that alcohol helps them sleep. Using a well-validated version of dCBTI may be an accessible, efficacious means of improving two burgeoning public health problems.

Support (if any)

NIAAA R21 AA029201, T32 AA027488
0443 Change in Sleep-Cognitions After Digital or Therapist-Led Cognitive Behavioral Therapy for Insomnia in Older Adults
Authors: Burda Kristen , Gumport Nicole , Tully Isabelle , Simpson Norah , Manber Rachel
Published: April 2024

Introduction

Traditional therapist-led cognitive behavioral therapy for insomnia (CBTI) is associated with a shift to more adaptive cognitions about sleep, as measured by the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS). To address unhelpful beliefs about sleep, CBTI uses cognitive therapy strategies. This study sought to assess the degree to which changes in DBAS differ between patients receiving digital CBTI (dCBTI) and those receiving therapist-led CBTI after two months of treatment access.

Methods

The RCT of the Effectiveness of Stepped-Care Sleep Therapy in General Practice (RESTING) study evaluated a triaged stepped-care framework for delivering dCBTI and therapist-led CBTI. Based on a study-developed checklist, 137 (M age=63.26 years [SD=7.79], 69% female) participants were identified as candidates who would likely benefit from higher intensity CBTI. However, these candidates were randomly assigned to one of two study arms: online only (n=68) or stepped care (n=69). Those in the online only arm received dCBTI, and those in the stepped care arm received therapist-led CBTI. Both arms included the same CBTI components, but therapist-led CBTI additionally included a module on supporting reduction in sleep medications. Participants completed the 16-item DBAS at baseline and two months post randomization. Multilevel modeling was used to examine changes in DBAS scores and subscale scores, including Expectations, Worry/Helplessness, Consequences, and Medication subscales.

Results

There were no significant differences in DBAS scores between participants receiving dCBTI and those receiving therapist-led CBTI (Beta=-0.05, SE=0.21, p=.82). At the level of subscale scores, compared to dCBTI, therapist-led CBTI was associated with greater reduction in dysfunctional beliefs in the 3-item Medication subscale (Beta=-1.10, SE=0.34, p=.001).

Conclusion

Whereas there was no differential impact of delivery mode on overall DBAS scores, therapist-led treatment resulted in greater change in DBAS Medication subscale scores for participants pre-identified as those who would benefit from higher intensity treatment. Specifically, therapist-led interventions might be especially effective for changing beliefs that insomnia has a biochemical etiology and that sleep medications are necessary for better sleep. Changing such beliefs may be an important element in supporting sustained improvement and potentially reducing sleep medication use.

Support (if any)

R01AG057500
0448 Upper Airway Collapsibility Is Associated with Fluid Shifts in Patients with Sleep Apnea and Diastolic Dysfunction
Authors: Tolbert Thomas , Lerakis Stamatios , Zhao Wenli , Valencia Daphne , Licona Diego Quintana , Hadley Michael , Correa Ashish , Parekh Ankit , Ayappa Indu , Rapoport David
Published: April 2024

Introduction

Left ventricular systolic dysfunction contributes to sleep-disordered breathing (SDB) pathophysiology through overnight rostral fluid shifts leading to fluid accumulation in the neck (increasing upper airway collapsibility) and pulmonary vasculature (increasing ventilatory control instability). In contrast to systolic dysfunction, the relationship of left ventricular diastolic dysfunction (LVDD) to overnight fluid shifts and SDB pathophysiology is less well characterized. In an ongoing prospective clinical study of patients with risk factors for or established LVDD and untreated SDB, we are using Phenotyping Using Polysomnography (PUP) analysis to investigate the relationship of overnight fluid shifts to upper airway collapsibility and ventilatory control instability.

Methods

Patients are enrolled in the presence of known LVDD or ≥1 risk factor (age ≥55 years, hypertension, diabetes, coronary artery disease, or amyloidosis) and known or suspected SDB with an apnea-hypopnea index (AHI3A) of ≥15 events/hr. Exclusion criteria include ejection fraction (EF) < 40% or factors suspected to interfere with LVDD indices or PUP estimates (e.g. ventricular dyssynchrony, severe lung disease). LVDD is confirmed on transthoracic echocardiography. Patients undergo in-lab polysomnography (PSG) with pre- and post-sleep circumference measurements of the neck and calves (averaged from both calves). PUP estimates of upper airway collapsibility (Vpassive) and ventilatory control instability (loop gain, LG1) are determined for the first and second half of sleep.

Results

14 patients have been enrolled. Complete PSG data is available for 8 patients (age 52.6±10.7 years, 50% female, BMI 36.2±5.0 kg/m^2, AHI3A 28.7±18.4 events/hr, EF 63.0±7.0%). While neck circumference did not significantly change, calf circumference significantly decreased overnight (pre- vs post-sleep median [IQR] 39.4 [37.3-40.5] cm vs 38.6 [25.8-40.2] cm, p = 0.047). Overnight change in Vpassive was inversely correlated with overnight change in neck circumference (R = -0.82, p = 0.023) and positively correlated with overnight change in calf circumference (R = 0.76, p = 0.049). Correlations of overnight changes in LG1 with neck and calf circumferences were not significant.

Conclusion

PUP analysis suggests overnight rostral fluid shift in patients with LVDD contributes to upper airway collapsibility. This preliminary trend will be more fully investigated on reaching the enrollment goal of 30 patients.

Support (if any)

AASM PSTA. NIH T32HL160511.
0451 Different Roles of Homocysteine Metabolism in Hypertension Among Normal-weight and Obese Patients with OSA
Authors: Chen Baixin , Chen Le , Dai Yanyuan , Vgontzas Alexandros , Li Yun
Published: April 2024

Introduction

Obstructive sleep apnea (OSA) is causally associated with hypertension. However, the differential mechanisms underlying OSA related hypertension between normal-weight vs. obese patients is limited.

Methods

We studied 92 consecutive patients with OSA. Blood pressure (BP) was measured twice during awake and continuously monitored during nighttime sleep. Obesity and normal weight were defined as body mass index ≥ and < 28 kg/m2. Serum metabolite levels were assessed by metabolomics.

Results

Among 59 normal-weight and 33 obese patients, 639 and 174 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling for confounders. These metabolites were significantly involved in 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients, whereas 6 pathways overlapped between these two phenotypes. Among these 6 overlapping pathways, 4 pathways were related to homocysteine metabolism and the other two were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified by metabolomics. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.081) and 8 metabolites associated with DBP (all interaction-p≤0.034) were opposite between normal-weight and obese patients. Specifically, in normal-weight patients increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration whereas in obese patients increased BP was associated with enhanced betaine-dependent remethylation and reduced transsulfuration. Similar findings were observed in ambulatory BP during sleep.

Conclusion

Mechanisms in OSA related hypertension differ between normal-weight and obese patients, which can be primarily explained by the different systematic changes in homocysteine metabolism. Assessing the metabolites in homocysteine metabolism pathway may benefit personalized treatments for hypertension in these two OSA phenotypes.

Support (if any)

This study was supported by the National Natural Science Foundation of China (81970087, 82270105, 82300117), 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (2020LKSFG05B) and China Postdoctoral Science Foundation (2022M712010).