bluuebunny/crossref_metadata_2025 huggingface dataset:
0090 Impact of Evening Binge Alcohol Consumption on Nocturnal Heart Rate Response to Cortical Arousal
Authors: Talukdar Ankita , Solis-Montenegro Tatiana , Beisert Jenna-Marie , Bigalke Jennifer , Bigalke Jeremy , Carter Jason
Published: April 2024

Introduction

Chronic alcohol consumption increases the risk of cardiovascular disease. While acute alcohol intake increases heart rate (HR), the impact of alcohol on HR responses to nocturnal arousals remains unclear. The present study investigated the effect of evening binge alcohol consumption on HR responsiveness to nocturnal cortical arousals. We hypothesized that alcohol intake would lead to an exaggerated HR reactivity to cortical arousals throughout the sleep period.

Methods

Fifteen healthy adults (6 male, 9 female; 27±2 yrs; 28±1 kg/m²) participated in this study. Using a randomized cross-over design, participants underwent two testing conditions (i.e., alcohol vs fluid control) separated by one month. In the alcohol condition, participants consumed the equivalent of 4-5 drinks in the span of two hours prior to sleep. A volume matched fluid-control was utilized for the control condition. The alcohol dose was based on the NIAAA definition of binge drinking (i.e., 1g/kg men, 0.85 g/kg women). Overnight polysomnography (PSG) with continuous electrocardiogram (ECG) was utilized over the course of an 8-hour in laboratory sleep period to quantify sleep, arousals, and nocturnal HR. Arousals were only included if they were not associated with any respiratory events, limb movements, or awakenings. HR responses following spontaneous nocturnal cortical arousals were collected and analyzed across 20 cardiac cycles.

Results

A main effect of experimental condition was observed whereby alcohol consumption resulted in a significantly elevated heart rate (Fluid Control: 64±2 vs. Alcohol: 72±3 beats/min, p< 0.001). There was no main effect of condition on HR reactivity (Placebo: ∆1.7±1, Alcohol: ∆2.1±1 beats/min, p=0.545). A significant condition x time effect was observed when assessing both raw HR (p=0.005) and HR reactivity (p=0.005). In contrast to our initial hypothesis, HR reactivity during the early phase of the arousal response was reduced in the alcohol condition at cardiac cycles 2, 3, and 4 (all p< 0.05) following nocturnal arousal occurrence.

Conclusion

These findings indicate that evening alcohol intake increases nocturnal HR, leading to a blunted HR response to cortical arousals. The sustained effect of alcohol on nocturnal HR may contribute to cardiovascular risks associated with evening binge alcohol consumption.

Support (if any)

Funding: NIH (AA-024892; U54GM115371; P20GM103474).
0095 Fat Intake Modifies the Association Between Sleep Depth and Cardiac Autonomic Modulation in Adolescents
Authors: Rahawi Anthony , Fang Jidong , Calhoun Susan , Liao Jason , Vgontzas Alexandros , Liao Duanping , Bixler Edward , Fernandez-Mendoza Julio
Published: April 2024

Introduction

Prior data shows an association between the odds ratio product (ORP), a continuous EEG measure of sleep depth, with heart rate variability (HRV), a continuous EKG measure of cardiac autonomic modulation. Nutritional lifestyle choices can impact cardiac health, with densely-caloric diets or those with greater percentage of specific macronutrients being associated with adverse cardiac outcomes. Adolescence, a developmental period marked by physical changes, is also marked by changes in sleep depth and dietary intake. We examined whether the association between ORP and HRV is more adverse in adolescents with inadequate nutritional intake.

Methods

We studied 293 adolescents (median 16y) from the Penn State Child Cohort. We extracted ORP during NREM sleep from 9-hour, in-lab polysomnography (PSG), and low-frequency (LF), high-frequency (HF) and time-domain [e.g., root mean square standard deviation (RMSSD)] HRV indices from 24-h Holter EKG monitoring immediately following PSG. Linear regression analyses examined the association between ORP, and its interaction with nutritional intake (total-calories, protein, total-fat, and carbohydrates), with 24-h HRV indices while adjusting for sex, age, race/ethnicity, obesity, metabolic syndrome, PSG-measured sleep apnea, insomnia symptoms, and actigraphy-measured sleep duration.

Results

The interactions between ORP and total-fat intake on LF, HF and RMSSD were statistically significant (p< 0.05), while the interactions between ORP and total-calories (p< 0.10), proteins (p< 0.10) or carbohydrates (p>0.10) on HRV indices were not statistically significant. Among adolescents with high total-fat intake (≥ 60 gm; n=161), each standard deviation increase in ORP was associated with a -0.1 (0.04) log-Hz, -0.2 (0.07) log-Hz, and -4.3 (1.8) ms decrease in LF (p< 0.001), HF (p=0.009) and RMSSD (p=0.02), respectively, while this association was not significant among adolescents with low total-fat intake (< 60 gm; n=162; β=-0.01, SE=0.04, p=0.846; β=0.1, SE=0.07, p=0.348; and β=1.7, SE=2.1, p=0.403, respectively).

Conclusion

Adolescents who follow high-fat diets are more vulnerable to the impact of shallow sleep on impaired cardiac autonomic balance, making them a targeted group for preventative sleep and cardiovascular strategies.

Support (if any)

R01HL136587, R01MH118308, UL1TR000127
1003 Daily Morning Blue Light Exposure for Alertness and Sleep Following Stroke
Authors: Honn Kimberly , Crooks Elena , O'Brien Katie , Sprint Gina , Weeks Douglas , Carter Gregory
Published: April 2024

Introduction

In the acute phase following a stroke, circadian rhythmicity is often disrupted, which undermines sleep, produces fatigue, and impedes recovery. Studies have reported post-stroke sleep architecture abnormalities, as well as acute sleep disorders which can range between extremes of clinically significant insomnia to hypersomnia, with sleep complaints sometimes persisting for months or years. Morning blue light exposure as an early, non-pharmacologic intervention targeted for strengthening circadian rhythmicity could provide acute relief and prevent disordered sleep from becoming chronic following stroke.

Methods

A randomized, single-blind, parallel group, placebo-controlled pilot study compared daily morning exposure to blue light or red light (placebo) for improving daytime sleepiness, fatigue, nocturnal sleep, and cognition in patients receiving inpatient rehabilitation for acute stroke. N=43 patients with disordered sleep secondary to first episode stroke (n=34 ischemic, n=9 hemorrhagic; ages 66.2±14.1y) were randomized to receive 25min of morning blue or red light for 5 or more days depending on inpatient rehabilitation length of stay (blue n=21, red n=22). At baseline and study discharge, daytime sleepiness was measured with the Karolinska Sleepiness Scale and Wits Pictorial Sleepiness Scale, fatigue with a visual analogue scale, and cognitive function with the Rey Auditory Verbal Learning Test and Trail Making Test (TMT). Actigraphy measured sleep continuously throughout participation with nighttime sleep defined as 21:00–05:59. Effect sizes per outcome were used to estimate sample sizes for larger follow-up studies.

Results

Participants with blue light exposure experienced significant improvements in daytime sleepiness, fatigue, and auditory verbal learning (all p<.05) relative to red light exposure. There was a trend toward a greater mean duration of nighttime sleep (p=.076) and fewer awakenings after sleep onset (p=.092) in the blue light compared to red light group. Although change in TMT and nocturnal sleep parameters did not reach statistical significance, effect sizes favored blue-light exposure, ranging from .38–.57.

Conclusion

Morning blue light exposure for 5 or more days led to greater improvements in daytime sleepiness, fatigue, and cognitive outcomes than red light exposure after acute stroke. Effect sizes suggest a larger study is warranted to confirm generalizability of pilot findings.

Support (if any)

Empire Health Foundation
1006 Effect of Obstructive Sleep Apnea on the Longitudinal Change in the Glymphatic System Function
Authors: Park Hyo Jin , Paik Sang Min , Kim Jae Rim , Lee Min-Hee , Lee Woo-Jin , Lee Seung-Ku , Shin Chol , Yun Chang-Ho
Published: April 2024

Introduction

Glymphatic cerebral waste-clearance system is activated during sleep, and obstructive sleep apnea (OSA) might have impact on the long-term disruption of the glymphatic system function and the development of neurodegenerative diseases. This study investigated the longitudinal association of OSA with changes in glymphatic system function and cognitive function domains.

Methods

Based on a community-based prospective cohort, participants who had both baseline and 4-year follow-up polysomnography, brain MRI with diffusion tensor imaging (DTI), and comprehensive cognitive assessment data were included. At both baseline and follow-up, participants were categorized as non-OSA (apnea-hypopnea index, AHI < 5), mild OSA (5≤AHI< 15), and moderate-to-severe OSA (AHI≥15) groups. According to the longitudinal change in the OSA severity, participants were categorized as OSA-free (non-OSA at both baseline and follow-up), improved OSA, stationary OSA, and progressed OSA groups. Glymphatic system function was measured using DTI analysis along the perivascular space (DTI-ALPS) index.

Results

1,110 participants (mean [SD] age, 58.0 [6.0] years; 517 [46.6%] men) were included in the final analysis. At baseline, 621 participants were categorized as non-OSA, 338 participants as mild OSA, and remaining 151 participants as moderate-to-severe OSA. At follow-up, 458 participants were categorized as OSA-free, 114 participants as improved OSA, 303 participants as stationary OSA, and 235 participants as progressed OSA. At baseline, non-OSA group exhibited higher DTI-ALPS index compared to the remaining groups (both, P< 0.001) and AHI was inversely correlated with DTI-ALPS index (R=-0.169, P< 0.001). At follow-up, the change in the DTI-ALPS index (∆DTI-ALPS) was the highest in the improved OSA group, followed by the OSA free, stationary OSA, and progressed OSA groups. ∆DTI-ALPS over 4-year was inversely correlated with ∆AHI (R=-0.171, P< 0.001 for the entire study population and R=-0.218, P< 0.001 for the population excluding OSA-free subgroup). ∆DTI-ALPS over 4-year was correlated with the changes in the visual reproduction–immediate recall (R=0.233), delayed recall (R=0.178), and recognition (R=0.188) scores (all, P< 0.001).

Conclusion

The changes in the OSA status has impact on the longitudinal change in the glymphatic system function and this effect might be reversible. Sustained proper management of OSA might be important in the effective prevention and management of cognitive decline.

Support (if any)
1011 Childhood Predictors and Adult Factors Associated with Long-Term Sleep Disturbance in Tourette’s Disorder
Authors: Tooker Maya , Barber Kathryn , McGuire Joseph , Espil Flint , Stiede Jordan , Schild Jennifer , Bennet Shannon , Specht Matthew , Walkup John , Woods Douglas , Piacentini John , Ricketts Emily
Published: April 2024

Introduction

Tourette’s Disorder (TD) is a childhood-onset neurological disorder characterized by motor and vocal tics present beyond one year. Sleep disturbance presents in 80% of individuals with TD and rises with advancing age. Common clinical correlates are tic severity, functional impairment, female sex, and co-occurring psychiatric symptoms, including attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety and depression. However, we lack understanding of long-term predictors of sleep disturbance in TD. Therefore, this investigation examined childhood predictors and adolescent/adult factors associated with sleep disturbance in a treatment follow-up sample of adolescents/adults with TD.

Methods

Eighty participants of a randomized-placebo controlled trial of behavior therapy for tics in childhood (M = 11.47, SD = 2.42 years) received follow-up evaluation 11.7 (SD = 1.25) years later in adolescence/adulthood (M = 22.87, SD = 2.70 years). At baseline and long-term follow-up, an independent evaluator assessed tic severity tic-related impairment and psychiatric diagnosis via interviews. At baseline, children rated anxiety and depression, and parents rated ADHD, and provided demographic and psychiatric history (e.g., tic and stimulant medication status). At follow-up, adolescents/adults rated anxiety, depression, and ADHD severity, and reported tic medication and stimulant medication status since trial termination. Multiple linear regression analysis was performed without and with backward elimination to examine childhood predictors and adult factors (sex, tic and stimulant medication status, tic severity and impairment, anxiety, depression, and ADHD severity, OCD diagnosis) sleep disturbance (Pittsburgh Sleep Quality Index) at long-term follow-up.

Results

Childhood tic-related impairment significantly predicted sleep disturbance (β = 0.35, t = 2.66, p = .010). However, with backward elimination both childhood tic-related impairment (β = 0.32, t = 2.81, p = .007) and depression (β = 0.33, t = 2.92, p = .005) significantly predicted sleep disturbance. There were no significant adolescent/adult factors associated with sleep disturbance. However, backward elimination showed depression was associated with sleep disturbance (β = 0.46, t = 3.95, p < .001).

Conclusion

Findings highlight the role of tic-related impairment in childhood and depression in childhood and adulthood in sleep disturbance in adolescents/adults with TD. Findings suggest the utility of targeted intervention for tic-related impairment and depression to minimize their long-term influence on sleep in TD.

Support (if any)
1012 Concordance and Test-Retest Consistency of Sleep Biomarker Based Phenotyping of Neurodegenerative Disorders
Authors: Levendowski Daniel , Walsh Christine , Cho Yeilim , Yack Leslie , Tsuang Debby , Lee-Iannotti Joyce , Berka Chris , Mazeika Gandis , Boeve Bradley , Neylan Thomas , Louis Erik St
Published: April 2024

Introduction

In this pilot study, the diagnostic agreement for sleep biomarker-based neurodegenerative disorder (NDD) risk probabilities was evaluated in patients with Alzheimer’s disease dementia (AD), Lewy Body disease (LBD), and isolated REM sleep behavior disorder (iRBD) and controls with a Mini-Mental State Exam scores>28.

Methods

Sleep biomarkers recorded with the Sleep Profiler (Advanced Brain Monitoring, Inc) were used as inputs to a 4-class machine learning algorithm trained to assign NDD risk probabilities to AD=27, LBD=19, iRBD=15 and controls (CG=58). Input variables included age, time-REM, non-REM hypertonia, autonomic-activation index, spindle-duration, atypical-N3, time-supine, sleep-efficiency, relative-theta, and theta/alpha. Records with CG output probabilities >70% were labeled Probably-normal, and from 45-70% Likely-normal with indications of a NDD added when the LBD, AD or prodromal synucleinopathy (pSYN) risks exceeded approximately 25%. Similar thresholds were used to assign Likely- or Probable- LBD, AD, or pSYN based each of the group probabilities. Classification accuracies were evaluated in AD=37, LBD=19, iRBD=19 and CG=61 records. Longitudinal test-retest reliabilities were assessed for CG (n=45, range 8-56 months), and after six-months for LBD (n=10) and AD (n=9).

Results

In the AD group, NDD risk assignments were consistent with diagnoses=85%, with Probable-NDD=59%, Likely-NDD=11%, Normal plus AD/Mixed indications=15%, but with 5%=Probably-normal. In the LBD group, assigned risks were consistent with the diagnosis=79%, with Probable-NDD=74%, Normal with pSYN indications=5%, but with 11%=Probably-normal. In the iRBD group, Probable-NDD=42%, Normal plus pSYN indications=26% and Probably-normal=32%. In the CG group, 89% were assigned minimal NDD risks with Probably-normal=67%, Normal plus indications=22%, but with Likely NDD=8% and Probable NDD=3%. The AD test-retest reliability showed the same NDD classifications=78%, with slightly increasing=11% and decreased=11%. In the LBD group, the same NDD classifications were achieved=80%, with trending equivalence=10%, and decreasing severity=20%. The CG test-retest reliability showed the same NDD classifications=76%, with trending equivalence=22%, and increased severity=2%.

Conclusion

Consistencies between the diagnoses and assigned NDD risks and test-retest classification agreements were approximately 80% in the AD, LBD, and CG groups. In the iRBD group, the NDD risks were disbursed consistent with the range of expected severities. These results needed to be cross-validated in independent NDD datasets.

Support (if any)

NIH grants R44AG050326, R44AG054256, RO1AG060477, R33AG064271, ULRR024150, R34AG056639.
1014 Effects of Sleep on Real-World Daily Decisions to Drive in Older Adults with Neurodegeneration
Authors: Chang Jun Ha , Chen Su , Zhang Ying , Murman Daniel , Rizzo Matthew
Published: April 2024

Introduction

Sleep dysfunction increases the risk of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). Emerging sensor technologies can index real world (RW) sleep and instrumental activities of daily living affected by neurodegeneration, as outlined below.

Methods

85 legally licensed active drivers with cognitive decline (76 MCI, 9 mild AD) (mean age = 75.6 years; 37 females) and 54 age and education-matched controls (mean age= 74.7 years; 36 females) participated. Cognitive status was assessed using standardized neuropsychological tests according to NIA-AA guidelines. Sensor systems installed in participants’ own vehicles recorded driving incidence (driving or not each day). Sleep was recorded using wrist-worn actigraphy, and verified with self-reported sleep diaries over three continuous months. A mixed-effect logistic regression analyzed daily driving incidence with predictors including z-scores of total sleep time (TST) and sleep efficiency (SE) in previous night, and cognitive status (MCI or AD v. controls), adjusted for age, gender, employment status, and driving season.

Results

From 9,214 days of data on nightly sleep and next day driving, increase in TST significantly reduced driving incidence (21% per standard deviation [SD]; Odds Ratio [OR] = 0.79, 95% Confidence Interval [CI] = 0.74 – 0.84, p < 0.001). Increase in SE was associated with increased driving incidence among those with cognitive decline, compared to controls (15% per SD; OR = 1.14, 95% CI = 1.03 – 1.27, p = 0.01).

Conclusion

Findings underscore the value of RW digital biomarkers to track the effects of neurodegeneration on sleep and instrumental activities of daily living. Deciding to drive increased with greater sleep efficiency, particularly for those with cognitive decline. Quantitative profiles of sleep and driving behavior offer novel opportunities for early detection of the effects of AD.

Support (if any)

The present study is supported by the National Institute on Aging at the National Institutes of Health (5R01AG17177-18).
1023 Solriamfetol and Maintenance of Wakefulness Outcomes in Patients with Narcolepsy and Obstructive Sleep Apnea
Authors: Thorpy Michael , Eglit Graham , Floam Samantha , Parks Gregory , Krahn Lois
Published: April 2024

Introduction

Patients with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) struggle to maintain wakefulness. Solriamfetol (Sunosi®) is a dopamine/norepinephrine reuptake inhibitor with agonistic properties at TAAR1 and serotonin 1A receptors; it is approved to treat EDS associated with narcolepsy (75–150 mg/day) or OSA (37.5–150 mg/day). This post-hoc analysis characterized the effects of solriamfetol on the propensity of participants with EDS associated with narcolepsy or OSA to maintain wakefulness.

Methods

The safety and efficacy of solriamfetol has been evaluated in participants with EDS and narcolepsy or OSA in the phase 3 trials, TONES 2 and TONES 3. Participants were randomized to placebo or solriamfetol (37.5 mg [OSA only], 75 mg, 150 mg, or 300 mg) once daily for 12 weeks. This post-hoc analysis evaluated the proportion of participants who achieved improvement from baseline on various 40-minute Maintenance of Wakefulness Test (MWT) thresholds (≥5, ≥10, ≥15, and ≥20 minutes) and mean sleep latencies ≥30 and ≥40 minutes at weeks 1, 4, and 12. Comparisons between solriamfetol and placebo were evaluated using Fisher’s exact test.

Results

A greater proportion of participants with narcolepsy achieved improvement from baseline of ≥15 and ≥20 minutes on the MWT with solriamfetol 150 mg (36% and 18%, respectively) and 300 mg (38% and 28%) compared with placebo (4% and 4%) at week 12 (P≤0.028); findings were similar at week 12 in participants with OSA with solriamfetol 75 mg (28% and 13%), 150 mg (37% and 25%), and 300 mg (44% and 28%) compared with placebo (8% and 3%; P≤0.034). A greater proportion of participants with narcolepsy achieved MWT sleep latency ≥30 minutes at week 12 with solriamfetol 150 mg (24%) and 300 mg (30%) compared with placebo (2%; P≤0.002); results were similar in participants with OSA for MWT sleep latency ≥30 minutes at week 12 with solriamfetol 75 mg (28%), 150 mg (34%), and 300 mg (44%) compared with placebo (11%; P≤0.012).

Conclusion

These findings suggest solriamfetol leads to substantial improvements on objective propensity to stay awake in a large proportion of patients with narcolepsy or OSA when compared with placebo.

Support (if any)

Axsome Therapeutics, Jazz Pharmaceuticals
1028 Wake Time After Morning Awakening as a Predictive Factor for Seizures in Juvenile Myoclonic Epilepsy
Authors: Villalobos Rafael , Villalobos Sarah , JR Rafael Villalobos , Diaz Saulo
Published: April 2024

Introduction

Seizure recurrence in the early morning is well known in Juvenile Myoclonic Epilepsy, the presence of seizures happens usually after waking up and there is a clear relationship with sleep as most of the seizures happen in a time frame that involves the next 30 to 120 minutes of wake time after sleep. We wanted to analyze the time frame that is most associated with seizure recurrence as that can have serious implications for safety, not to exclude driving in the morning hours.

Methods

We investigated on a sample of 20 patients with JME and the pattern on seizure recurrence in the morning. A time frame of wake after sleep was established as follows; the first 30 minutes, 30 to 60 minutes, 60 to 90 minutes and more than 90 minutes. Seizure diaries were given to patients and the seizure recurrence was evaluated. A variable that included earlier waking time in the morning was also taken into account. A follow up of 6 months was given in a retrospective manner. All patients were seen in an outpatient epilepsy clinic.

Results

All patients were into the JME spectrum, all patients were seen at least 3 times in the follow up time, 70 percent of all cases had at least one event of seizure recurrence, 10 percent had more than 3 events. The majority of the seizures were strongly associated with a wake after sleep time of 60 to 90 minutes. The patients that had an earlier wake time that was out of the usual sleep schedule had increased chances of seizure recurrence.

Conclusion

Patient with JME have a very close relationship of seizure recurrence with the sleep-wake cycle. The seizure recurrence is strongly associated with a time frame of 90 minutes after waking up. We conclude that the chance of seizure recurrence is less after the 90 minute mark, and that can reasonably be a potential target as far as allowing to drive a motor vehicle passed that time for safety issues. Earlier than usual morning awakenings can precipitate seizures in a greater degree.

Support (if any)
0103 Daily Associations Between Relationship Stress and Sleep Health in Young Adults
Authors: Jakubowski Karen , Tapia Amanda , Guzman Maria , Oryshkewych Nina , Wallace Meredith , Pedersen Sarah , Hasler Brant
Published: April 2024

Introduction

Stress in interpersonal relationships has been related to adverse mental health outcomes, however, fewer studies have examined associations with physical health, particularly sleep. To date, most studies rely on retrospective reports of stress and sleep measured at a single timepoint, and do not examine multiple types of relationship stress. We tested whether daily stress with family, partner/spouse, and/or friends predicted shorter total sleep time (TST), lower sleep efficiency (SE), and/or later sleep midpoint via ecological momentary assessment (EMA) among young adults.

Methods

Participants were 293 young adults (21-30 y/o; 64% female; 5% Asian, 25% Black, 5% Biracial or Multiracial, 1% Other race, 64% White) reporting regular alcohol use from two studies with a shared assessment battery and up to 18-day EMA protocol. Participants reported daily sleep (TST [hours], SE, and midpoint, calculated from sleep diary reports), cannabis use (yes/no), alcohol use (total number of drinks), and stress with family, spouse/partner, and friends (coded as: 0=not at all, 1=somewhat, 2=moderately/very much). We fit generalized linear mixed effects models and estimated within-subject and between-subject associations between each stress variable and sleep outcome, respectively, adjusting for time-invariant (age, past-year household income, assigned sex) and time-variant covariates (weekend, cannabis use, alcohol use, pre- vs. post-COVID-19 pandemic).

Results

Participants completed a median of 17 EMA daily records (range: 1-18). Considering between-person effects, participants who reported feeling somewhat stressed with family [B(SE)=-.66(.32), p=0.04] or partner/spouse [B(SE)=-.63(.35), p=0.07] reported lower average TST over the EMA protocol. No associations emerged with experiencing moderately/very much stress in any relationship, nor for SE or midpoint outcomes. Results did not suggest a within-person effect of any type of daily relationship stress on sleep that night.

Conclusion

Among a well-characterized sample with up to 18 days of EMA data, reporting some stress in family and partner/spouse relationships predicted lower TST, relative to peers without stress in these relationships. Results may suggest that cumulative stress over time may be more detrimental for sleep than acute day-to-day stressors. When intervening on sleep, clinicians should also consider relationship stress, which is amenable to evidence-based interventions such as cognitive behavioral therapy.

Support (if any)

R01AA025617 (SLP), R01AA026249 (BPH/SLP), K23HL159293 (KJ)
1031 Association Between Objective Sleep Architecture and Biomarkers of Alzheimer's Disease
Authors: Chen Jiong , Cavailles Clemence , Jin Jiangli , Stankeviciute Laura , Gao Song , Peng Dantao , Leng Yue
Published: April 2024

Introduction

Growing evidence suggests a bi-directional association between sleep and Alzheimer’s disease (AD), with several studies showing an association between self-reported sleep disturbances and AD biomarkers. However, the association between polysomnography (PSG)-assessed sleep architecture and AD biomarkers remains unknown. We aim to investigate the associations between sleep architecture features and AD biomarkers in a clinical population with and without cognitive impairment.

Methods

We examined 128 participants [mean age of 70.9 years (±9.7), 43.8% of men] from an outpatient memory clinic, of whom 23 were healthy controls, 41 patients with mild cognitive impairment, and 64 patients with AD. Sleep architecture features were derived from PSG data and categorized by tertiles. Four AD biomarkers were measured, including tau-181, Brain-Derived Neurotrophic Factor (BDNF), and neurofilament light (NFL) obtained from blood samples, along with Aβ levels measured from amyloid positron emission tomography scans. Multivariable linear regressions models were performed to assess the associations between sleep architecture features and AD biomarkers.

Results

After adjustment for age, gender, APOE4 status, diabetes mellitus, smoking habits, and body mass index, participants in the highest REM latency tertile (i.e., with longer REM latency; >192.7 minutes) were associated with increased levels of tau-181 (β= 0.25, 95% confidence interval (CI)= 0.01;0.55) and Aβ (β= 0.15, 95% CI= 0.06;0.26), and with decreased level of BDNF (β= -0.51, 95% CI= -0.70;-0.20) compared to participants in the lowest tertile (i.e., with shorter REM latency; < 98.2 minutes). Moreover, being in the middle SWS percentage tertile (i.e., SWS percentage between 2.5 and 10.2) was associated with a lower level of tau-181 (β= -0.18, 95% CI= -0.34;-0.02) compared to being in the lowest tertile (i.e., shorter SWS percentage; < 2.5)). We did not find any association between AD biomarkers and sleep duration, efficiency, latency, or other sleep architecture features.

Conclusion

In this cross-sectional study of a clinical population, we highlight the importance of REM latency, and to a lesser extent, SWS percentage, in relation to AD biomarkers. Future research is needed to examine the longitudinal association between sleep architecture and AD biomarkers and clarify underlying mechanisms.

Support (if any)
1033 Association of the Cardiopulmonary Coupling Sleep Spectrogram with Incident Parkinson’s Disease in Older Men
Authors: Milton Sasha , Sun Haoqi , Stone Katie , Yaffe Kristine , Westover M Brandon , Thomas Robert , Leng Yue
Published: April 2024

Introduction

The cardiopulmonary coupling (CPC) sleep spectrogram is an increasingly recognized measure of sleep quality which integrates sleep, autonomic drive, and respiration. Specifically, CPC is an estimate of the sleep state modulated synchronization and coupling between heart rate variability and respiration. Those with Parkinson’s disease (PD) have been shown to exhibit alterations in CPC and have higher rates of sleep disturbances, respiratory abnormalities, and autonomic dysfunction. However, little is known about the longitudinal association of CPC with incident PD in community-dwelling older men.

Methods

We studied 2859 men (mean [SD] age = 76.2 [5.4] years) without PD who underwent polysomnography between 2003 and 2005 and were followed until 2016 for incident self-reported PD as part of the Osteoporotic Fractures in Men (MrOS) prospective study. CPC was calculated from the electrocardiogram (ECG) during rapid eye movement (REM) sleep, N2 and N3 (N2N3) stages of non-REM sleep, and across the whole night. CPC metrics included high, low, and very low frequency coupling (HFC, LFC, and VLFC, respectively). Ratios of the 3 power bands were computed to assess deviation from or concordance with typical stage specific CPC patterns. Associations between tertiles of CPC metrics and incident PD were assessed using multivariable logistic regression.

Results

During 11 years of follow-up, 64 incident PD cases were identified. After adjustment for covariates including age, comorbidities, and apnea-hypopnea index (AHI), men in the lowest tertile of VLFC/(LFC+HFC) during REM sleep had approximately twice the risk of developing PD [OR (95% CI) = 2.22 (1.20,4.35)] relative to men in the highest tertile. Whole-night and N2N3 CPC metrics were not associated with incident PD.

Conclusion

Disruption of the typical CPC pattern during REM, representing potential altered interactions between brain (sleep electrocortical activity), cardiac (heart rate variability) and respiratory output mechanisms, was associated with an increased risk of incident PD. Our findings may reflect a prodromal alteration of interactions between sleep subsystems, though future studies are needed to understand potential mechanisms linking CPC to incident PD.

Support (if any)

Support comes from the National Institute on Aging (R21AG085495) and the Institute for Personalized Sleep Health (Beth Israel Deaconess Medical Center).
1035 Automated Analysis of REM Sleep Without Atonia in the Lewy Body Disease Spectrum
Authors: Jagielski Jack , Kelleher Makayla , Finstuen Thomas , LeClair-Visonneau Laurene , Kejal Kantarci , McCarter Stuart , Boeve Bradley , Michael Silber , Dredla Brynn , Louis Erik St
Published: April 2024

Introduction

Quantitative rapid eye movement (REM) sleep without atonia (RSWA) recorded during polysomnography (PSG) represents loss of normal REM sleep atonia. RSWA is the neurophysiologic signature of REM sleep behavior disorder (RBD). Visually scored RSWA is a candidate biomarker for synucleinopathies. However, visual RSWA scoring requires expert scoring, limiting widespread application. We comparatively analyzed RSWA in DLB and iRBD using the automated Ferri REM Atonia Index (RAI).

Methods

We quantitatively analyzed the RAI in 17 DLB and 20 iRBD patients, compared to 20 controls using Hypnolab Software for Sleep Analysis (SWS Soft, Colognola ai Colli, Italy). PSG data were converted to European Data Format (.EDF), and the submentalis surface electromyogram (EMG) signal was notch-filtered at 60 Hertz and rectified. Automatically calculated RAI scores were comparatively analyzed across groups (DLB, iRBD, controls) using Kruskal Wallis H tests for group comparisons, and regression analyses determined relationships between diagnosis, age, and sex. Logistic regression ROC determined optimal RAI for distinguishing iRBD from DLB. When interpreting RAI, lower values represent greater amounts of RSWA, and higher values represent more normal REM atonia.

Results

Median age was no different between DLB (72.6 years), iRBD (69.4 years), and controls (68.0 years). The DLB group consisted of 16 men and one woman, the iRBD group had 18 men and 2 women, and controls were comprised of 16 men and 4 women. Median RAI was lowest in DLB (0.32), intermediate in iRBD (0.84) and highest in controls (0.96), indicating a gradient in RSWA amounts from DLB patients (highest) to controls (lowest). Regression demonstrated diagnosis independently predicted RAI, controlling for age and sex (adjusted R2=0.64, p=0.0001). The RAI that optimally distinguished iRBD from DLB was 0.48 (specificity 85%, sensitivity 76%, AUC=0.88).

Conclusion

The RAI demonstrated a clear gradient throughout the Lewy body spectrum; highest (indicating lowest RSWA amounts) in controls, intermediate in iRBD, and lowest (indicating greatest RSWA) in DLB. The RAI is a promising, time efficient and broadly applicable candidate biomarker for DLB and iRBD. Automated quantitative RSWA could be a valuable tool for deep phenotyping throughout the Lewy body disease spectrum.

Support (if any)

This study was supported by: U01NS100620, R34AG056639, U19AG071754, and P30AG62677.
1038 C-reactive Protein as a Risk Predictive Marker for Sleep-Related Alzheimer’s Disease in Blacks
Authors: Scott Sadeaqua , Blanc Judite , Gallop Erin-Leigh , Moise Rhoda , Chung Debbie , Thompson Michelle , Oliveira Bruno , Seixas Azizi , Rundek Tatjana , Jean-Louis Girardin
Published: April 2024

Introduction

Sleep is regulated by the microbiota-gut-brain axis, which plays a critical role in amyloid beta (Aβ) production and clearance; two key processes in the progression of sleep-related Alzheimer’s disease (SRAD). C-reactive protein (CRP) is an inflammatory biomarker correlated with Aβ levels in SRAD. Although Blacks are disproportionately affected by SRAD, a paucity of knowledge exists regarding effective early detection and prevention of this disease in this population. This study investigated the levels of CRP in Black participants with subjective Sleep apnea (SA) to determine what indicators or thresholds may serve as a risk predictive marker for Aβ blood biomarker screening for SRAD.

Methods

Blood from a total of 104 Blacks enrolled in two NIH-funded community-based sleep studies, ESSENTIAL and MOSAIC, was collected from January 2020 until October 2023. CRP levels were accessed according to clinical standards in ranges of normal or minor elevation, moderate elevation, marked elevation, and severe elevation. Frequency distributions and analyses were performed using SPSS29.

Results

Twenty-one participants self-reported an existing SA diagnosis; of which 19% had CRP levels at 0.3 - 1.0 mg/dL, 62% at 1.0 - 10.0 mg/dL, 19% at >10.0 mg/dL, and none at >50.0 mg/dL. Of the 83 participants without SA, 31% had CRP levels at 0.3 - 1.0 mg/dL, 61% at 1.0 - 10.0 mg/dL, 7% at >10.0 mg/dL, and 1% at >50.0 mg/dL. In total, 81% of participants with subjective SA had CRP levels above minor elevation, while 69% of participants without subjective SA had levels above minor elevation, showing a 10% difference in elevated CRP levels between both groups. These results suggest that SA can lead to greater levels of inflammation among Blacks.

Conclusion

A 10% difference in elevated CRP levels of participants with and without SA diagnosis may suggest that undiagnosed participants could be at risk for SA. Identifying factors that predict blood Aβ levels such as CRP may lead to a cost-effective, SRAD specific prescreening panel to identify patients at higher risk of SRAD, and aid risk stratification in Blacks. Future research is needed to further explore this area.

Support (if any)

R01AG067523, R01HL142066, and T32HL166609-02
0104 Biological Embedding and Sleep Quality in Adulthood: Evidence from a 30-year Prospective Longitudinal Cohort Study
Authors: Omisakin Olusola , Felt John M , Noll Jennie , Buxton Orfeu
Published: April 2024

Introduction

Attenuation over the life course of hypothalamic-pituitary-adrenal (HPA) axis activity, such as reduced cortisol secretion, represents biological embedding of early-life stress. Biological embedding is implicated in myriad health concerns including disruptive sleep patterns. We hypothesized that attenuation of cortisol over the first half of the life-course will be negatively correlated with objectively indicated sleep quality in adulthood.

Methods

Cohort participants included females referred by child welfare agencies for having experienced intra-family childhood sexual abuse (CSA) at mean age 10.5 years. A counterfactual group of non-abused females from the same zip codes were demographically matched. The cohort was assessed at 7 timepoints across development longitudinally from 1987-2019. Resting cortisol was obtained through blood (waves 1-3) and saliva (waves 4-6). A formula approved by the US FDA was employed to convert salivary cortisol concentrations to blood-based equivalents: (serum µg/dL) = 5.177 + 15.132*(saliva µg/dL). Using a bilinear spline model – a model for tracking trajectories at different phases of development – pre-knot slopes (rates of change during childhood of cortisol, indicative of HPA attenuation and biological embedding) from waves 1 to 6 (or ages 6-32) were extracted. Wave 7 (mean age 36.1 years) included wrist actigraphy for a week. Ordinary Least Squares (OLS) regression examined whether cortisol slope from ages 6 to 32 predicted adult sleep.

Results

We found no group differences in sleep between participants exposed to CSA and demographically similar non-abused participants. Using individual slopes from T1-T6 models of cortisol levels, we observed a positive correlation between cortisol slope and sleep maintenance efficiency (r = 0.22; p < 0.05); sleep duration was not significant at Time 7. OLS regression showed that each additional year of increase in cortisol slope (µg/dL) was associated with 21.4% increase (p < 0.05) in mean sleep efficiency.

Conclusion

Findings suggest that sleep quality in middle adulthood was better when participants did not experience attenuation of cortisol (biological embedding of stress) earlier in the life course. Our study provides evidence of effects of biomarker-based biological embedding on sleep quality in middle adulthood among a sample of women maltreated as children and a matched control group.

Support (if any)

T32HD101390, R01AG059682, R01HD072468, R01AG04879
1041 Increased Delta-Gamma Coupling During Phasic REM Sleep in Isolated RBD
Authors: Tea-Gon Noh , Yoonkyung Lee , Young Kim Eun , Jun-Sang Sunwoo , Ki-Young Jung
Published: April 2024

Introduction

This study examines the phasic and tonic states of REM sleep with a focus on idiopathic rapid eye movement sleep behavior disorder (iRBD), which is characterized by REM sleep without atonia and is thought to be a precursor to alpha-synucleinopathies. By examining specific EEG dynamics associated with dreaming, specifically delta and gamma power during phasic REM sleep states and their correlation with iRBD characteristics, we aim to develop a comprehensive understanding of dream enactment.

Methods

In-depth analysis was performed using polysomnography (PSG) and 21-channel EEG data from 13 iRBD patients and 10 controls who had been drug-free for six months and had not progressed to alpha-synucleinopathy. REM sleep states were categorized into phasic and tonic states based on eye movements, and the Kullback-Leibler modulation index was used to assess phase-amplitude coupling (PAC) and calculated phase-locked amplitudes (PLA) to determine interphase coupling. Gini coefficients were calculated to identify within- and between-component imbalances, and extensive statistical analysis was performed using permutation cluster analysis, repeated measures analysis of variance, Mann-Whitney U tests, and correlation assessments to identify differences and relationships.

Results

The results showed a significant increase in delta-gamma coupling during phasic REM sleep in RBD compared to controls (FDR p < 0.0001). A detailed comparison of the delta signal component, the component in which the imbalance was found (FDR p < 0.0001), at different spatial locations revealed distinct patterns of delta-gamma coupling, with significant phase-amplitude coupling (PAC) observed in frontal and parietal cortex. These results showed a clear linear relationship (FDR p < 0.0001), with notable correlations with the RBDQ-KR (FDR p < 0.0001) and the REM atonia index (FDR p=0.0003). The average area under the ROC-AUC curve for separating the RBD group from the control group based on PAC values was 0.88.

Conclusion

The study significantly highlights the role of EEG metrics, especially the coupling of delta and gamma oscillation during REM sleep, as key indicators of dream-related enactment in iRBD. The strong correlations with clinical indices not only underscore the diagnostic value of these EEG measures but also suggest their potential to revolutionize the diagnosis and understanding of iRBD.

Support (if any)
1045 Sleep Disorders in Pediatric Patients with Agenesis of the Corpus Callosum
Authors: Kwon Ashley , Gu Payal , Zhang Christina , Ward Sally , Perez Iris
Published: April 2024

Introduction

Agenesis of the corpus callosum (ACC) is a complete or partial absence of the corpus callosum arising from disruption of brain development. There is limited information about sleep in children with ACC. We aim to describe the sleep architecture and respiratory parameters of children with ACC.

Methods

Retrospective study of 20 patients with ACC who had polysomnography (PSG) between 2000-2023. Demographic data, BMI or weight for length (percentile), associated conditions, and PSG findings were collected. Sleep quality was compared to the National Sleep Foundation’s guidelines. Poor sleep quality indicators were sleep latency >45 min, sleep efficiency (SE) < 75%, N1 ≥20%, N2 >81%, N3 ≤5% for 14-17 years, N3 ≤10% for < 14 years, REM ≤10% excluding 6-13 year-olds, or arousal index >10/h. Fisher’s exact test or unpaired t-test was used to compare groups.

Results

Average age was 5.9 ± 5.4 years old, and 12/20 patients were male. 6/20 were overweight/obese. 14/20 had complete ACC, and 6/20 had partial ACC. 8/20 had seizures. 15/20 had ≥1 poor sleep quality indicator, notably decreased SE (45%) , decreased REM (53%), and increased arousals (45%). Between complete and partial ACC, there was no difference in presence of ≥1 poor sleep quality indicator (p= 0.61), SE (p=0.34), REM (p=0.28), and arousals (p=1). Sleep quality was similar between seizure and no seizure groups (p=0.60). 11/18 had obstructive sleep apnea (OSA); 5/11 also had central sleep apnea (CSA). 1/20 had CSA alone. Only 1 with OSA was overweight. Excluding patients with tracheostomies, there was no difference in OSA between those with complete and partial ACC (p=1) or those with and without seizures (p=0.16). SpO2 baseline was 95 ± 2%; SpO2 nadir was 85 ± 0.1%. 4/20 had ≥5 minutes of total sleep time (TST) with SpO2 < 90%. PETCO2 maximum was 48 ± 5 mmHg; none had PETCO2 >50mmHg for >25% of TST.

Conclusion

Children with ACC have poor sleep quality, and many have OSA. There was no difference in sleep quality or presence of OSA between those with complete and partial ACC. Our study supports the need for screening of sleep-related disorders in patients with ACC.

Support (if any)
1048 Ambulatory Sleep EEG in Post-Stroke Hospitalization
Authors: Lott Morgan , Romanowski Alan , Soto Valentine , Banik Nandita , Lynn Alexia , Sokoloff Greta , Blumberg Mark , Boes Aaron , Baran Bengi
Published: April 2024

Introduction

An important function of sleep is neuroplasticity, which is essential to functional recovery after stroke. However, inpatient acute care settings may not be conducive to restful and consolidated sleep. The goals of the present study were to test the feasibility of using wearable technology to objectively quantify sleep during inpatient stay in the first few days of hospitalization post stroke and examine relations of sleep quality and architecture with stroke severity.

Methods

Data collection is ongoing, preliminary analyses are based on 8 patients (5F/3M, 41-78 yrs, mean age=61.7 yrs). A headband style EEG acquisition device (Sleep Profiler) was used for one night (0-8 days following a first-ever stroke, mean=3 days) either in ICU or neurology inpatient floors. Sleep was scored based on standard AASM criteria. The National Institute of Health Stroke Scale (NIHSS) was administered to assess stroke/disability severity.

Results

We observed great variability in sleep duration (2.1-6.2 hrs, mean=4.1 hrs), sleep efficiency (29-81%, mean=51%) and increased time spent in N3 (compared to standard sleep architecture; 21.2-72.8%, mean=41.7% of total sleep time). Stroke severity correlated with WASO (r=.82, p=.02) and time spent in supine position after sleep onset (r=.83, p=.02).

Conclusion

While preliminary, these findings identify profound sleep restriction and fragmentation experienced by stroke survivors during the first few days of hospitalization. Further, stroke severity predicts increased sleep fragmentation, possibly due to more intensive medical care required. Future plans involve examining long-term cognitive and functional outcomes in patients to test the hypothesis that better sleep during the acute phase of stroke enhances recovery.

Support (if any)

Iowa Neuroscience Institute Research Program of Excellence