bluuebunny/crossref_metadata_2025 huggingface dataset:
0091 Influence of Evening Alcohol Intake on Nocturnal Heart Rate
Authors: Bender Stephen , Bigalke Jennifer , Bigalke Jeremy , Carter Jason
Published: April 2024

Introduction

Binge alcohol consumption has detrimental effects on cardiovascular health and sleep. The simultaneous influence on sleep and cardiovascular measures may lead to an adverse nocturnal cardiac profile. The aim of the present study was to examine the impact of evening alcohol consumption on nocturnal heart rate (HR) patterns. We hypothesized that alcohol intake would result in a sustained increase in HR throughout the night and reduced HR dipping relative to pre-sleep wakefulness.

Methods

In a randomized crossover design, ten participants (5 male, 5 female; 26±2 yrs; 28±1 kg/m2) underwent a night of binge alcohol consumption and a fluid control separated by one month. Sleep and nocturnal HR were measured using continuous overnight polysomnography and electrocardiogram. HR was averaged across 15-minute intervals over the 8-hour sleep period.

Results

Consistent with our initial hypothesis, a condition effect was observed whereby average raw HR was increased following alcohol consumption (Fluid Control: 60±3 vs. Alcohol: 66±3 beats/min, p=0.003). This condition effect was absent when examining average change in HR relative to a 15-minute wakefulness period (Fluid Control: ∆-2.3±0.6 vs. Alcohol: ∆-2.7±1.1 beats/min change, p=0.75). A condition x time effect was present in both average raw HR (p=0.003) and relative HR change from wakefulness (p=0.01). Contrary to our hypothesis, post hoc analyses revealed that the alcohol condition demonstrated augmented relative HR dipping 15 (Fluid Control: ∆-3.2±0.6 vs. Alcohol: ∆-4.8±0.8 beats/min) and 30 minutes (Fluid Control: ∆-3.1±1.1 vs. Alcohol: ∆-6.0±1.0 beats/min) after lights out. However, a substantial increase in relative HR was observed in the alcohol condition when compared to the control 210 (Fluid Control: ∆-3.1±0.8 vs. Alcohol: ∆1.1±1.0 beats/min) and 225 minutes (Fluid Control: ∆-3.6±0.6 vs. Alcohol: ∆1.6±1.5 beats/min) after lights out.

Conclusion

Evening binge alcohol consumption increased HR throughout the sleep period. The overnight profile demonstrated that alcohol elicited a steeper decline in nocturnal HR immediately after lights out, but a significant augmentation of HR during the later portion of the night. The observed elevation in overall HR and further relative increase in the second half of the night may contribute to cardiovascular risk following alcohol intake.

Support (if any)

NIH (AA-024892; U54GM115371; P20GM103474).
0092 Influence of Evening Alcohol Consumption on Nocturnal Cardiac Reactivity During NREM vs REM Sleep
Authors: Beisert Jenna-Marie , Talukdar Ankita , Solis-Montenegro Tatiana , Bigalke Jennifer , Bigalke Jeremy , Carter Jason
Published: April 2024

Introduction

Chronic alcohol consumption disrupts sleep, especially rapid eye movement (REM). However, the impact of alcohol on nocturnal cardiovascular responses to cortical arousal during non-REM (NREM) and REM sleep remains unknown. This present study investigated the impact of evening binge alcohol on heart rate (HR) reactivity following nocturnal cortical arousals in NREM vs. REM sleep. We hypothesized that alcohol intake would lead to increased HR responsiveness following cortical arousals in both sleep stages.

Methods

Fifteen healthy adults (6 male, 9 female; 27±2 yrs.; 28±1 kg/m2) underwent two testing conditions (i.e., alcohol vs fluid control) separated by one month in a randomized cross-over design. In the alcohol condition, a dosage of 4-5 drinks, two hours before bed was given based off the NIAAA definition of binge drinking (i.e., 1g/kg men, 0.85 g/kg women). In the control condition, a volume matched fluid-control was used. Overnight polysomnography with continuous electrocardiogram was used to quantify sleep, arousals, and nocturnal HR following each condition. HR responses were characterized for 20 cardiac cycles following spontaneous cortical arousals.

Results

Absolute HR was elevated following binge alcohol consumption in both REM (Placebo: 65±2 vs. Alcohol: 73±3 beats/min, p< 0.001) and NREM (Placebo: 64±2 vs. Alcohol: 71±3 beats/min, p< 0.001) sleep. In NREM there was a significant condition x time effect in HR reactivity (p< 0.001). NREM early phase HR arousal responsiveness was blunted in cardiac cycles 2,3, and 4 (all p< 0.05) following alcohol consumption, but HR remained elevated in the latter half at cardiac cycle 15 (Placebo: Δ-0.9±1.0 vs. Alcohol: Δ0.9±0.7 beats/min, P=0.038). There was no condition (P=0.916) or condition x time interaction effect (P=0.999) on HR reactivity during REM sleep.

Conclusion

The present study observed an increase in absolute HR in both REM and NREM sleep following evening alcohol intake. However, alcohol has differential effects on HR reactivity to arousal during REM and NREM sleep, whereby the initial HR response to cortical arousals is blunted, but the recovery response is augmented during NREM sleep. These findings point to a stage-specific effect of evening binge alcohol consumption on nocturnal cardiac reactivity to naturally occurring arousals.

Support (if any)

NIH (AA-024892; U54GM115371; P20GM103474).
0093 Acute Effects of Diaphragmatic Breathing on Circulatory Dynamics and Autonomic Function During Sleep in Young Men
Authors: Kobayashi Ryota , Negoro Hideyuki
Published: April 2024

Introduction

Increased arterial stiffness during rest and blood pressure (BP) during sleep are independent risk factors for cardiovascular disease (Boutouyrie et al.2021, Kario et al.2019). Slow, deep breathing is a useful nonpharmacological intervention to control hypertension (Chang et al.2013). However, the acute effects of diaphragmatic breathing before sleep on arterial stiffness during rest and BP during sleep are unknown. In this study, we investigated the acute effects of diaphragmatic breathing before sleep on arterial stiffness, BP, and cardiac autonomic function in young men.

Methods

Fifteen healthy young men (age: 20.0 ± 0 years, Height: 170 ± 5 cm, Weight: 56 ± 3 kg) participated in this study and underwent two separate sessions in a randomized controlled crossover design: 4-4-8 breathing (BT) protocol (12 consecutive breaths of 4 seconds of inhalation, 4 seconds of pause, and 8 seconds of exhalation through the nose) and control (CON) without 4-4-8 breathing. Brachial-ankle pulse wave velocity (PWV) reflected systemic arterial stiffness and carotid-femoral PWV reflecting central (aortic) arterial stiffness measured using an automated pulse wave testing device. BP was measured simultaneously using an automated oscillometric device. Autonomic function was measured from high-frequency (HF) and low-frequency (LF) components by HR variability spectral analysis. Arterial stiffness, BP, HF, and LF were measured before (baseline) and 30 and 60 min and 24 hours after the 4-4-8 breathing technique. BP, HF, and LF were measured while sleeping.

Results

There was a significant decrease in the baPWV and LF at 30 min after the BT trial compared to baseline values (P< 0.05). cfPWV on both trials was unchanged. There was a significant increase in the HF at 30 min after the BT trial compared to baseline values (P< 0.05). BP and LF during sleep were lower in the BT trial than in the CON trial (P< 0.05). HF during sleep was higher in the BT trial than in the CON trial (P< 0.05).

Conclusion

A novel finding of this study is that practicing slow, diaphragmatic breathing with relatively long exhalation times may reduce arterial stiffness during rest and BP during sleep through activation of the parasympathetic nervous system.

Support (if any)
0094 Habitual Sleep and Autonomic Function in Humans
Authors: Solis-Montenegro Tatiana , Bigalke Jeremy , Bigalke Jennifer , Carter Jason
Published: April 2024

Introduction

Insufficient habitual sleep duration and efficiency are commonly experienced in modern society and are associated with cardiovascular disease development. A potential mediator of this relationship may be impairment in cardiovascular regulation via the autonomic nervous system. The purpose of the present study was to assess the relationships between habitual total sleep time (TST), sleep efficiency (SE), muscle sympathetic nerve activity (MSNA), and heart rate variability (HRV) in a robust sample of healthy adults. We hypothesized that shorter TST would be associated with increased sympathetic and decreased parasympathetic activity.

Methods

A minimum 7 days of at-home, objective actigraphy sleep monitoring was collected in 75 healthy young adults (39 males, 36 females; 24±1 years; 25±1 kg/m2). In each participant, three seated sphygmomanometer recordings were used to determine resting mean arterial blood pressure (MAP). Prior to laboratory testing, participants were asked to refrain from caffeine and exercise for 12 hours, and alcohol for 24 hours. All participants underwent an autonomic function test that simultaneously assessed heart rate (HR, electrocardiogram), beat-to-beat blood pressure (finger plethysmography) and MSNA (microneurography) during 10 minutes of quiet rest. R-R intervals were used to quantify both time (i.e., RMSSD and pNN50) and frequency (high-frequency heart rate variability; HF-HRV) domain HRV parameters. RMSSD and HF-HRV were log-transformed due to non-normal distributions.

Results

Contrary to our hypothesis, habitual TST was not associated with resting MAP (R=0.173, P=0.137), HR (R=-0.137, P=0.241), MSNA (R=-0.186, P = 0.110), RMSSDlog10 (R=0.085, P=0.468), pNN50 (R=0.043, P=0.711), or HF-HRVlog10 (R=0.019, P=0.869). Similarly, SE was not associated with resting MAP (R=0.112, P=0.339), HR (R=-.037, P=0.751), MSNA (R=-0.033, P = 0.778), RMSSDlog10 (R=-0.006, P=0.956), pNN50 (R= -0.003, P=0.983), or HF-HRV (R=-0.028, P=0.810).

Conclusion

Our findings do not support a relationship between habitual TST or SE and measures of autonomic nervous system activity in healthy adults. However, a more pronounced effect may be observed in populations with established sleep disorders such as insomnia and obstructive sleep apnea. Further research is necessary to establish the independent effect of objective sleep quantity and quality on autonomic control in these populations.

Support (if any)

NIH AA-024892
0096 Simulated Night Shift Schedule Alters Endogenous Temporal Regulation of Glucose and Insulin
Authors: Lundholm Kirsie , Skene Debra , McDermott Jason , Liu Peter , Gaddameedhi Shobhan , Van Dongen Hans , Satterfield Brieann
Published: April 2024

Introduction

Shift workers experience misalignment between internally-driven circadian rhythms and externally-driven behavioral schedules. Mounting evidence from hormone-, cytokine-, exosome-, proteome-, and metabolome-based biomarker analyses of blood samples predicts disruption of glucose and insulin regulatory pathways during night shift schedules. Here, we quantified circulating glucose and insulin concentrations in a constant routine (CR) protocol to assess functional metabolic outcomes of prior simulated shift work.

Methods

Healthy adults (N=14; aged 22–34; 4 females) completed a 7-day/6-night in-laboratory study, with randomization to either a 3-day simulated day shift (DS) schedule (n=7) with nighttime sleep (22:00–06:00) and 3 daytime meals (07:30, 13:00, 19:30), or a 3-day simulated night shift (NS) schedule (n=7) with daytime sleep (10:00–18:00) and 3 nighttime meals (19:30, 01:00, 07:30). A 24h CR protocol followed, during which participants stayed awake under constant behavioral and environmental conditions, including hourly isocaloric snacks. Serum collected via intravenous catheter every 6h during the CR was assayed using glucose colorimetric detection and human insulin ELISA. Glucose and insulin concentrations were analyzed with mixed-effects ANOVAs with fixed effects of prior simulated shift condition (day, night) and sampling time (01:30, 07:30, 13:30, 19:30) and their interaction, with a random effect over participants on the intercept. Mixed-effects cosinor regression analyses were conducted to compare endogenous circadian rhythms between conditions.

Results

For glucose, there was a significant condition*time interaction (F[3,30]=4.99, P=0.006), with a 9.34±2.42h delay (mean±SE) of the endogenous circadian glucose rhythm after simulated NS compared to DS (t[12]=3.85, P=0.002). For insulin, there were significant effects of condition (F[1,30]=5.93, P=0.021) and time (F[3,30]=3.01, P=0.046), with no significant endogenous rhythmicity after simulated DS, but the appearance of a circadian rhythm with reduced insulin concentrations after simulated NS (t[12]=-3.32, P=0.006).

Conclusion

Under constant routine, we found altered endogenous temporal patterns of glucose and insulin after just 3 days of simulated NS compared to DS. Our results indicate that biomarker and omics-based predictions of disrupted glucose and insulin regulatory pathways have functional significance evident in circulating glucose and insulin concentrations. This may explain the insulin resistance and increased risk of metabolic disorders observed in shift workers.

Support (if any)

Andy Hill CARE Fund FY22-POP-02 and WSU CPPS start-up funds
0097 Cardiovascular Effects of Long-Term Sleep Fragmentation in Mice
Authors: Badran Mohammad , Puech Clementine , Khalyfa Abdelnaby , Gozal David
Published: April 2024

Introduction

Sleep Fragmentation (SF) is a prevalent phenomenon and also a pathognomonic feature of obstructive sleep apnea (OSA). SF is associated with OSA-related morbidities. However, it remains unclear whether prolonged SF exposures contribute to the development of specific cardiovascular morbidities in OSA. In this study, we postulate that chronic SF may induce structural and functional changes in the cardiac and vascular systems.

Methods

Male C57Bl/6J mice (n=8) were housed in custom-designed cages with a near-silent motorized mechanical sweeper crossing the cage in 2-min intervals or sleep control (SC, sweeper inactive) for 12 hours during the light period for 12 weeks. Mean arterial blood pressure (MBP) was assessed using tail-cuff method, while aortic peak velocity (indicator of systolic function), E/A ratio (indicator of diastolic function), coronary flow velocity reserve (CFVR), and pulse wave velocity (PWV) were assessed using Doppler Flow Velocity System. Then, left anterior descending coronary arteries and thoracic aorta were excised, mounted on wire myographs, and used to obtain endothelium-dependent relaxation dose-response curves to acetylcholine (ACh)

Results

MBP was significantly elevated in SF mice (107 ± 7 mmHg) after 12 weeks when compared to SC (89 ± 5 mmHg, p < 0.0001). Systolic and diastolic function, and CFVR were not affected by the 12 weeks of SF exposure. However, SF mice had higher PWV (4.3 ± 0.6 mm/msec) when compared to SC mice (3.1 ± 0.2 mm/msec). Coronary maximal ACh-induced vasodilation was impaired in SF mice (67 ± 9%) when compared to SC (86 ± 5%, p < 0.001). Aortic maximal ACh-induced vasodilation was not affected by 12 weeks of SF.

Conclusion

long-term SF, a hallmark characteristic of OSA, promotes cardiovascular perturbations including coronary artery dysfunction and arterial stiffness, thereby supporting a role for sleep fragmentation in the cardiovascular morbidity of OSA.

Support (if any)

Supported by NIH grant R01-HL166617
0098 Chronic Sleep Restriction Results in Abnormal Bone Development in Adolescent Rats
Authors: Everson Carol , Toth Jeffrey , Wang Mei
Published: April 2024

Introduction

Adolescence is often plagued by years of inadequate sleep at a time when nearly half of the adult skeletal mass is accrued and peak bone mass is attained. Previously we reported that chronic sleep restriction (SR) in adult male rats causes strikingly abnormal bone health. The purpose of this study was to test our hypothesis that SR results in abnormal bone development.

Methods

Chronic SR in juvenile rats from 42–60 d of age was produced by a validated modification of the Bergmann-Rechtschaffen paradigm with ambulation controls (AC). For five-day periods, sleep time was protected for 4 hours/day to model late bedtimes and early awakenings on schooldays, with a 35% sleep reduction for the rest of the time. Between five-day SR periods, sleep was undisturbed for 48 hours to model weekend catch-up sleep. Harvested femurs were studied for bone integrity by biomechanical testing (males and females, SR vs AC, N=3-4/sex/grp) and bone quality by micro-CT (male SR vs AC, N=4/grp). To investigate recovery, other male rats were studied at 90 and 120 d of age (N=5-6/grp) after chronic SR during 42–60 d of age.

Results

Chronic SR resulted in weak femurs, indicated by a 21% decrease in work to failure by three-point bending [N=7-8/grp pooled sexes, SR: 57 (SD 14); AC: 72 (SD 13) mJ, P< 0.02)]. By sex, there was a 23% decreased work to failure in male SR juveniles (P< 0.03) and a nonsignificant 17% decrease in female SR juveniles vs AC, but no differences in fat or lean body mass, leg muscle masses or femoral length. Trabeculae were decreased in number [SR vs AC, 1.9 (SD 0.4) and 2.4 (SD 0.4) /mm, P< 0.05] with increased spacing [SR vs AC, 552 (SD 122) and 419 (SD 66) µm, P=0.05]. In post-SR rats aged to 90 and 120 d, femoral work to failure was decreased by >44% (P< 0.004, P< 0.03 respectively).

Conclusion

Chronic SR during adolescence results in abnormal bone development with deficits that persist into adulthood. Failure to achieve peak bone mass or maintain bone in adolescence is known to significantly affect the progression to osteopenia/osteoporosis in later life.

Support (if any)
0099 Impact of Sleep and Timing of Vaccination on Neutralizing Antibody Responses to the COVID-19 Vaccine
Authors: Prather Aric , Dutcher Ethan , Mason Ashley , Robinson James , Drury Stacy , Hecht Frederick , Epel Elissa
Published: April 2024

Introduction

Vaccines remain the primary mitigating strategy to reduce the burden of disease caused by COVID-19. As such, there is a pressing need to identify factors that promote more robust and durable immune responses to vaccination. Sleep and circadian processes, such as the timing of vaccine administration, have been hypothesized to play a meaningful role in predicting durability of antibody responses; however, empirical data supporting links between sleep and timing on COVID-19 vaccine response is limited.

Methods

We recruited 428 adults (aged 18-88 years old) naive to the COVID-19 vaccination series and SARS-CoV-2 infection who received the mRNA COVID-19 vaccine series (% Pfizer; % Moderna) and underwent blood draws to quantify neutralizing antibody responses (nAB) 1 and 6 months post vaccination series. They completed sleep questionnaires (Pittsburgh Sleep Quality Index) and a week of sleep diaries at three time points. In addition, 198 participants wore a wearable device (Oura Ring) for 2 months to capture behavioral sleep metrics. Time of day of vaccine was obtained by self-report as part of the daily diaries.

Results

Analyses revealed that independent of age, sex, BMI, smoking status, and vaccine type, poorer global sleep quality was associated with lower nABs 6-months post vaccination (F(1, 424.3)=5.30, p=0.02). We also did detected a trend-level 3-way interaction between vaccine type, time point, and OURA based sleep duration indicating that shorter sleep duration was associated with lower 6-month nAB in those who received the Pfizer vaccine (b=0.17, SE=0.07, p=0.009). In analyses examining the impact of time of day of vaccine administration on nABs, we failed to find any evidence that timing of vaccine administration was associated with nABs at 1 or 6 months post vaccination (Dose 1: F(1, 330.1)=0.01, p=0.91; Dose 2: F(1, 344.5)=0.46, p=0.50).

Conclusion

Findings suggest that better global sleep quality is associated with greater nAB durability to the COVID-19 vaccine, and among those who received the Pfizer vaccine, longer average sleep duration promoted higher nAB 6-months post-vaccination. However, there was no clear evidence indicating that timing of vaccination administration was relevant to nAB responses. Further research is warranted including investigations into whether sleep interventions can enhance vaccine efficacy.

Support (if any)

R24AG048024
0100 Excretion of the Dual Orexin Receptor Antagonist Daridorexant into Breast Milk of Healthy Lactating Women
Authors: Kaufmann Priska , Anliker-Ort Marion , Siebers Nicholas , Muehlan Clemens , Dingemanse Jasper
Published: April 2024

Introduction

Daridorexant is a dual orexin receptor antagonist approved for the treatment of adult patients with insomnia. Following single-dose administration to healthy lactating female subjects, pharmacokinetics (PK) of daridorexant and its major metabolites were assessed in breast milk and plasma.

Methods

A single oral dose of 50 mg daridorexant was administered in the morning to 10 healthy lactating subjects (fasted state). To evaluate the transfer of daridorexant and its major metabolites into breast milk, all secreted breast milk over 72 h post dose as well as several plasma samples were collected. The PK of daridorexant in milk and plasma were assessed including the cumulative amount and fraction of dose excreted, estimation of the daily infant dose, and the relative, i.e., weight-adjusted infant dose that would be consumed by the breastfed child. Safety and tolerability were also investigated.

Results

All 10 subjects completed the study and were evaluable for PK and safety. Daridorexant was rapidly absorbed and distributed from plasma. Parent daridorexant and its major metabolites could be quantified in breast milk of all subjects. The shape of the individual milk concentration-time profiles of daridorexant closely followed the corresponding plasma profiles, and area under the curve and peak concentrations in breast milk were approximately 45- and 50-fold lower than in plasma. The cumulative total amount of daridorexant excreted over 72 h was 0.010 mg, which corresponds to 0.02% of the maternal dose. Overall, a mean daily infant dose of 0.009 mg/day and a relative infant dose of less than 0.22% over 24 h were determined. The known safety profile of daridorexant was confirmed. Headache was the most frequently reported adverse event (4 subjects).

Conclusion

Daridorexant was safe and well tolerated in healthy lactating women and presence of daridorexant and its major metabolites in breast milk is very low. However, despite the minimal excretion of daridorexant into breastmilk, a risk of somnolence to the breastfed infant cannot be excluded.

Support (if any)

At time of study conduct, Priska Kaufmann, Marion Anliker-Ort, Clemens Muehlan, and Jasper Dingemanse were employees of Idorsia Pharmaceuticals Ltd (sponsor). Nicholas Siebers was the Principal Investigator at Labcorp.
1000 The Association Between Sleep Problems and Self-Rated Psychotic Experiences
Authors: Grabner Palmer , Huskey Alisa , Hildebrand Lindsey , Grandner Michael , Killgore William
Published: April 2024

Introduction

Schizophrenia spectrum and other psychotic disorders are associated with a wide variety of functional impairments that interfere with daily functioning. Sleep is one domain that is disturbed in almost 80% of people experiencing schizophrenia and similar symptoms. We hypothesized that self-reported sleep disturbances would significantly predict tendencies consistent with schizophrenia and its associated subdomains—psychotic experiences, social detachment, and thought disorder symptoms. Social detachment and thought disorder symptoms are transdiagnostic traits that span many psychopathologies. We further hypothesized that each subdomain may be differentially associated with unique types of sleep disturbances.

Methods

Our sample comprised 190 participants with a mean age of 25 years old (SD=6.81) and a sex ratio of 71 males to 119 females. Each participant completed the Personality Assessment Inventory (PAI) to assess aspects of mental health consistent with schizophrenia spectrum disorders and the Pittsburgh Sleep Quality Index (PSQI) to assess sleep disturbances according to seven facets: subjective sleep quality, latency, duration, efficiency, disturbance, sleep medication use, and daytime dysfunction (DD). We used a stepwise linear regression to predict schizophrenia domain severity from sleep problems. Bivariate correlations were run to clarify the associations between schizophrenia and sleep disturbance subdomains.

Results

When considered in combination, self-reported DD was the only significant predictor of schizophrenic domain severity (β=.489, p<.001; R^2=.239: F(1)=54.874, p<.001). Individually, the psychotic experiences domain was correlated with DD (r=.230, p=.002) and sleep disturbances (r=.201, p=.007). Self-reported thought disorder traits were significantly related to sleep disturbances (r=.254, p<.001), DD (r=.491, p<.001), sleep medication use (r=.178, p=.016), and subjective sleep quality (r=.312, p<.001). Social detachment was correlated with DD (r=.322, p<.001) and sleep efficiency (r=-.162, p=.030).

Conclusion

Sleep-related daytime impairment predicted greater severity on the schizophrenia scale of the PAI and was associated with all related subdomains. Additionally, each of the subdomains were correlated with sleep disturbances, which could reflect the hyperarousal found with positive symptoms disturbing sleep maintenance. Sleep related interventions could contribute to reducing schizophrenia symptom severity. As hypothesized, specific sleep disturbance facets were differentially associated with schizophrenia subdomains. Each of these sleep facets may serve as important therapeutic targets in minimizing symptom severity in schizophrenia spectrum disorders.

Support (if any)

USAMRAA: W81XWH1210386
1002 Heart Rate Variability During Sleep and Future Risk of Parkinson’s Disease in Community-dwelling Older Men
Authors: Milton Sasha , Sun Haoqi , Kaffashi Farhad , Loparo Kenneth , Stone Katie , Yaffe Kristine , Westover M Brandon , Leng Yue
Published: April 2024

Introduction

Autonomic dysfunction is common in early stages of Parkinson’s disease (PD), providing an opportunity for early diagnosis and disease prediction. However, little is known about the longitudinal association between overnight—and sleep stage specific—heart rate variability (HRV), a marker of autonomic function, and incident PD.

Methods

Our sample consisted of 2470 older men (mean [SD] age = 76.1 [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. HRV was calculated from the electrocardiogram in 5-minute epochs across the whole night and during rapid eye movement (REM) sleep and non-REM stages N2 and N3 (N2N3) alone. HRV metrics included measures of overall HRV (SDNN, standard deviation of NN intervals), short-term HRV/parasympathetic influence (RMSSD, root mean square of successive NN interval differences; HF, high frequency power), long-term HRV/sympathetic, parasympathetic, and baroreflex influence (LF, low frequency power), and long-term to short-term HRV balance (LF/HF; LFnu, normalized LF power, LF/[HF+LF]), which may represent sympatho-vagal balance. Associations between tertiles of HRV metrics and incident PD were assessed using multivariable logistic regression.

Results

During 11 years of follow-up, 60 incident PD cases were identified. After adjustment for covariates including age and comorbidities, men in the lowest tertile of LFnu measured across the whole night [OR (95% CI) = 2.13 (1.09,4.35)] and during REM alone [OR (95% CI) = 2.44 (1.23,5.55)] had approximately twice the odds of developing PD compared to those in the highest tertile. Results were similar for LF/HF, though the association was only significant during REM [OR (95% CI) = 2.33 (1.08,5.55)]. Further adjustment for apnea-hypopnea index did not attenuate these associations. HRV metrics assessed during N2N3 were not associated with incident PD, nor were SDNN, RMSSD, HF, and LF.

Conclusion

Individuals with decreased long-term to short-term HRV balance (possibly representing low sympatho-vagal balance) had higher risk of developing PD. REM may be a particularly important sleep stage for measurement of autonomic dysfunction in early PD and assessment of future PD risk.

Support (if any)

Support comes from the National Institute on Aging (R21AG085495).
1004 Predicting Incident Parkinson’s Disease and Dementia with Lewy Bodies from Nocturnal Wrist Actigraphy
Authors: Wickramaratne Sajila , Brink-Kjaer Andreas , Marwaha Salonee , Parekh Ankit , During Emmanuel
Published: April 2024

Introduction

“Isolated” REM sleep behavior disorder (iRBD) is an early marker of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) that affects 1-2% of individuals after 60 years of age. We published on a classifier using nocturnal wrist actigraphy data which achieved >90% accuracy for iRBD detection. Here, we applied the same iRBD classifier in a population sample, the UK Biobank data to predict risk of incident PD or DLB.

Methods

30,000 records were randomly selected from the United Kingdom Biobank (UKBB) cohort dataset and were included based on age>60 years, no neurological diagnosis and >3-day valid nocturnal actigraphy data. Our published models were used to generate an iRBD score through automated detection of sleep periods and movement features from the accelerometer data. The iRBD score was generated for all the subjects and divided into: top 1%tile (predicted iRBD) and bottom 90%tile (predicted no-iRBD). The outcomes of interest were: 1) PD; 2) possible DLB. Odds ratio were then calculated using the iRBD scores (predictor) and the outcomes of interest (1 or 2).

Results

In the 10,087 records that met inclusion criteria, mean age was 63.8±2.8 years and subjects had on average 6.4±0.9 nights of valid actigraphy data. 109 subjects developed PD, and 67 DLB after 5.1±2.1 years. In the top 1%tile (n=101), 10 of 109 incident PD, and 18 of 67 DLB were accurately predicted by the calculated iRBD scores (sensitivity 9.2% and 26.8%, respectively). In the bottom 90%tile (n=9,078), 8,952 were accurately predicted to not develop PD or DLB (specificity 98.6%). Odds ratio were 9.1 [4.0 – 20.1] for PD, 40.2 [21.3 – 75.7] for DLB, and 19.8 [11.9 – 32.76] for either PD or DLB.

Conclusion

These results provide proof of concept that the existing iRBD detection model can be used to predict neurodegenerative outcomes in the community setting using ≥3 nights of actigraphy data. Future studies may assess additional actigraphy features related to 24h rest-activity rhythms (RAR) and gait patterns.

Support (if any)

Michael J Fox Foundation
1005 Improved Sleep Apnea Screening After Stroke Using Multimodal Wearable Sensors and Machine Learning
Authors: Sindorf Jacob , O’Brien Megan , Sunderrajan Aashna , Knutson Kristen , Zee Phyllis , Wolfe Lisa , Fiala Justin , Arora Vineet , Jayaraman Arun
Published: April 2024

Introduction

Sleep apnea affects over half of stroke survivors, impacting post-stroke recovery and outcomes. Early intervention through continuous positive airway pressure (CPAP) can reduce the impact of sleep apnea, motivating the need for accurate sleep apnea screening tools. Current screening tools such as home sleep apnea tests (HSATs) are difficult to use and uncomfortable due to bulky acquisition systems, electrodes, straps, and/or nasal cannulas, whereas questionnaires (i.e., STOP, STOP-BANG, Berlin OSA) suffer from lack of reliability and low sensitivity. Wireless, multimodal wearable sensors are promising tools to address these gaps; however, stroke-specific algorithms are essential to account for post-stroke physiological changes. The objective of this study was to develop and validate an apnea screening system using wearable sensors and machine learning during early stroke recovery.

Methods

Patients wore an HSAT (ApneaLink Air) and the Advanced NeoNatal Epidermal (ANNE) Chest and Limb sensors for one night within a week of admission to an acute rehabilitation facility. ANNE sensors are flexible, light-weight (< 17 grams), adhesive based sensors capable of continuous monitoring (up to 7 days). Sleep-based features derived from physiological signals were extracted from ANNE sensors and paired with the ground truth apnea indication from the ApneaLink Air. A logistic regression machine learning model was trained to classify no apnea (normal, AHI< 5) from apnea (mild, moderate, severe, AHI≥5).

Results

Forty-seven patients were screened with ApneaLink; over 60% had sleep apnea. Models using data from the ANNE Limb sensor performed best, with an F1 score (F1=0.75) outperforming the STOP (F1=0.62), STOP-BANG (F1=0.63), Berlin-OSA (F1=0.62) and a naive classifier (F1=0.38). Model performance increased when distinguishing between AHI< 5 versus AHI≥15 (F1=0.94), whereas the surveys and naive classifier (F1=0.67, F1=0.58, F1=0.58, F1=0.33, respectively) saw a decline in performance.

Conclusion

Wearable sensors and stroke-specific machine learning models outperformed traditional questionnaires for sleep apnea screening, approaching HSAT-level accuracy (ApneaLink Air). The accessibility, comfort, and ease of use of sensors are well-suited for early application and continuous sleep monitoring compared to commercial HSAT devices.

Support (if any)

NIH R01HD097786-01A1.
1008 Daytime Sleepiness Is Associated with Increased Cerebrospinal Fluid Tau Proteins in Alzheimer’s Disease
Authors: Okamoto Cynthia , Sordo Lorena , Neikrug Ariel , Grill Joshua , Head Elizabeth , Benca Ruth , Sultzer David , Mander Bryce
Published: April 2024

Introduction

Sleep disturbance increases Alzheimer’s disease (AD) biomarkers, but it remains unclear whether the magnitiude of this effect differs by cognitive status. Addressing this unknown will elucidate when it is most critical to intervene to moderate AD pathophysiology and slow or arrest clinical progression.

Methods

A total of 155 participants, enrolled in Alzheimer Disease Research Center studies at University of California, Irvine (mean age 72.34 ± 7.07 years, 60.0% female) completed subjective assessment of sleep and cerebrospinal fluid (CSF) collection. Participants were divided into four cognitive status groups (Cognitively Normal, n=89; Questionable Cognitive Impairment, n=19; Mild Cognitive Impairment, n=33; and mild to moderately severe AD dementia, n=14). The Medical Outcomes Study Sleep Scale (MOS-SS) subscales assessed multiple sleep domains: Sleep Disturbance, Sleep Adequacy, Sleep Somnolence, Sleep Problems Index I, and Sleep Problems Index II. CSF biomarkers included β-amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181). Moderation by cognitive status on the relationships among sleep scores and CSF biomarkers was assessed using the PROCESS macro in SPSS, adjusting for age and sex. Moderation by sleep scores in the cognitive status-CSF biomarkers relationship was also tested.

Results

After adjusting for age and sex, moderation analyses revealed significant interactions between sleep somnolence and cognitive status on CSF t-tau (F=3.3, p=0.023) and p-tau181 (F=2.9, p=0.035) but not Aβ42 (F=0.057, p=0.98) protein levels. The associations between sleep somnolence and t-tau (B = 4.18, SE = 1.51, t = 2.76, p = 0.01) and p-tau181 (B = 0.50, SE = 0.18, t = 2.69, p = 0.01) were positive and stronger in the AD group in comparison to all other cognitive status groups (all p>0.35).

Conclusion

These findings indicate that in AD patients, greater subjective daytime sleepiness is associated with higher levels of t-tau and p-tau181 protein levels. As tau proteins are associated with neurodegeneration and cognitive decline, daytime sleepiness, whether or not due to the presence of sleep disorders such as sleep apnea, may be a risk factor or indicator of symptomatic progression of dementia in AD. Future studies should explore the efficacy of sleep-based interventions in slowing AD dementia progression.

Support (if any)

NIH K01AG068353, NIH T35AG076424, ADRC P30AG066519
1009 Association of Circadian Rhythm with 27-Hydroxycholesterol in Amnestic Mild Cognitive Impairment (aMCI) Patients
Authors: Kim Seong Jae , Lee Jung Hie , Jang Jae-Won , Choi Min Seo , Suh In Bum
Published: April 2024

Introduction

The 27-hydroxycholesterol(27-OH) has been proposed as a factor mediating the risk of Alzheimer's disease(AD) through oxidative cholesterol metabolism associated with cognitive impairment. Meanwhile, circadian disturbance has been implicated in accelerated aging and incident dementia, mediating metabolic dysregulation, which may lead to neurodegenerative diseases like AD. However, the relationship between circadian rhythm and cholesterol metabolism in MCI is poorly understood. We aimed to compare circadian parameters between amnestic MCI(aMCI) patients and normal controls(NC), and to examine whether changes in circadian parameters can be related with 27-OH levels.

Methods

Participants over 50 years were recruited from the Memory Clinic at Kangwon National University Hospital, and two public Dementia Care Centers. The diagnosis of aMCI was made according to Petersen’s criteria. Actigraphy monitoring was conducted at home for five days. Nonparametric variables including the inter-daily stability(IS), intra-daily variability(IV) and relative amplitude(RA) were calculated for rest-activity rhythm(RAR) and light exposure rhythm(LER), respectively. DLMO was determined from five hourly saliva samples obtained before sleep onset. The 27-OH levels were measured using high performance liquid chromatography/mass spectrometry(HPLC/MS). Eighteen aMCI patients(76.6 ±6.1 years) and 21 NCs(70.4±6.7years) were finally analyzed. Generalized linear models(GLMs) were used to assess the main effects of circadian parameters on 27-OH levels and their interactions with group.

Results

There were no significant differences in the RAR and LER variables(IV, IS and RA), and the DLMO between the aMCI and NC groups. In GLMs, significant main effects of RA in RAR and IV in LER on 27-OH levels were shown (β = -461.43, p=.036; β = -149.35, p=.001, respectively). There was no difference in the effects of circadian parameters on 27-OH levels between the aMCI and NC groups (p>.05).

Conclusion

In our study, a strong 24-hour activity rhythm was associated with lower 27-OH levels, indicating less cholesterol metabolic dysfunction. It suggests that changes in circadian rhythm may affect cholesterol metabolism in preclinical AD patients.

Support (if any)

Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science and ICT(2020R1F1A1050416);Learning & Academic research institution for Master’s·PhD students, and Postdocs(LAMP) Program of the National Research Foundation of Korea(NRF) grant funded by the Ministry of Education(No. RS-2023-00285353).
1010 Bruxism and Non-functional Jaw Muscular Activity in the Disorders of Consciusness
Authors: Marelli Sara , Sattin Davide , Castelnuovo Alessandra , Barbadoro Filippo , Ippoliti Camilla , Magnani Francesca Giulia , Cacciatore Martina , Leonardi Matilde , Sebastiano Davide Rossi , Strambi Luigi Ferini
Published: April 2024

Introduction

In the last decades, the role of the neurophysiological techniques in the assessment of Disorders of Consciousness (DOCs) after severe acquired brain injuries has been enhanced, leading to a growing interest in this challenging field. However, only few works focused on the presence of bruxism or non-functional jaw muscular activity (NFJMA) in these patients. Here we present our experience in 32 patients assessed with a long lasting polygraphy (PG).

Methods

Thirty-two patients (14 females and 18 males, mean age 55.3 + 11.7 years) with prolonged or chronic DOC were consecutively enrolled as part of a national, multicentric clinical trial aimed at evaluating the tolerance and the efficacy of treatments for sleep disorders in DOC patients. All the patients underwent to a 24h PG visually inspected in order to determine the periods of wakefulness or sleep on the basis of PG pattern(s), as well as the occurrence of bruxism or NFJMA.

Results

Bruxism or NFJMA were found in 9 out of 31 patients, during periods of sleep (3 patients), awake (3 patients) or both (3 patients). We detected two forms of NFJMA in our case-series: a) a sustained (tonic) contraction of masseter and mylohyoid progressively weaker until returning to previous muscle tone in 2-10 seconds; b) phasic contractions of masseter and mylohyoid, detectable as a biphasic, waxes and wanes activity, typically lasting 0.25-0.5 seconds and usually repeated with pseudo-rhythmic intervals of 0.5-1.5 seconds and often limited to 4-15 events. In 3 patients muscular activity was continuous or subcontinuous for a very long time (up to 1.5 hours), always maintaining 0.75-1.5 Hz frequency.

Conclusion

Although much is unknown about the non-functional jaw muscular activity, our work demonstrated that the bruxism and NFJMA are very frequent in DOC patients.

Support (if any)

This research was funded by the Italian Ministry of Health GR-2016-02365049—Pilot Study on sleep pathologies treatments in patients with Vegetative and Minimally Conscious State diagnosis for improving Consciousness level: the STRIVE project.
1013 Cross Validation of Sleep Biomarker Based Phenotyping of Neurodegenerative Disorders
Authors: Levendowski Daniel , Neylan Thomas , Walsh Christine , Yack Leslie , Tsuang Debby , Lee-Iannotti Joyce , Berka Chris , Mazeika Gandis , Boeve Bradley , Louis Erik St
Published: April 2024

Introduction

n this cross-validation study, the distributions of sleep biomarker-based neurodegenerative disorder (NDD) risk were evaluated across a spectrum of NDD patients and presumed controls which were independent of the model development dataset.

Methods

Variables that included age, time-REM, non-REM hypertonia, autonomic-activation index, spindle-duration, atypical-N3, time-supine, sleep-efficiency, relative-theta, and theta/alpha obtained with Sleep Profiler were used to train a 4-class machine learning algorithm that generated probabilities of NDD risk for the groups: Alzheimer’s dementia (AD), Lewy body disorder (LBD), prodromal synucleinopathy (pSYN based on REM sleep behavior disorder patients), and controls (CG). 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 pSYN risks exceeded approximately 25%. Similar thresholds were used to assign Likely- or Probable- LBD, AD, pSYN or Mixed based on the group probabilities. This cross-validation study was designed to use datasets that were independent of those used to train the classification algorithm. Thus, NDD risk distributions were evaluated in patients with mild cognitive impairment (MCI=71), Parkinson’s disease (PD=16), progressive supranuclear palsy (PSP=21) and control subjects (NC=41) with Mini-Mental State Exam scores>28 and/or normal for MCI by Petersen criteria.

Results

In the MCI group, NDD risk assignments were Probable-AD=26%, -Mixed=10%, -LBD=1%, Likely-AD= 7%, -Mixed=6%, -LBD=3%, -pSYN=1%, Likely-Normal indications-AD=9%, -pSYN=7%, -Mixed=4%, and Probably-Normal=26% In the PSP group, Probable-LBD=43%, -Mixed=29% and -pSYN=4%, Likely-Mixed=10%, Likely-Normal indications AD=10%, and Probably-Normal=4%. In the PD group, Probable-LBD=13%, -pSYN=13%, -AD=6%, Likely-Mixed=19%, -pSYN=6%, Likely-Normal Indications-pSYN=19%, -AD=12%, Likely-Normal=6% and Probably-Normal=6% In the NC group, 83% were assigned minimal NDD risk with Probably-Normal=70%, Likely-Normal plus indications=13%, but with Likely NDD=13% and Probable NDD=4%.

Conclusion

NDD risks were disbursed in a manner consistent with the range of severities expected In MCI and PD groups, with 25% exhibiting relatively normal sleep patterns. Over 70% of the PSP patients exhibited probable NDD risk, with patterns similar to those with LBD. The NC NDD risk distributions were consistent with those assigned to the CG used for model development.

Support (if any)

NIH grants R44AG050326, R44AG054256, RO1AG060477, R33AG064271, ULRR024150, R34AG056639.
1018 Minimal Effect of Long-Term Clonazepam on Cognitive Function in Patients with Isolated RBD
Authors: Yoon In-Young , Lee Minji , Hong Jung Kyung , Kim Tong Keon , Han Sojung , Park Chae Rin
Published: April 2024

Introduction

Despite its widespread use in patients with isolated rapid eye movement sleep behavior disorder (iRBD), the cognitive effect of clonazepam is uncertain. This study aimed to investigate effect of cumulative clonazepam on cognitive function in iRBD patients.

Methods

Demographic characteristics, baseline cognitive test, and most recent cognitive test information were collected retrospectively. Based on cumulative clonazepam doses, patients were classified into four subgroups: group 1 < 365 mg (1 mg * 1 yr); 365 mg ≤ group 2 < 1,095 mg (1 mg * 3 yr); 1,095 mg ≤ group 3 < 2,190 mg (1 mg * 6 yr); and group 4 ≥ 2,190 mg. Cognitive test scores were calculated as z-scores adjusted for age, education, and gender.

Results

This study included 101 iRBD patients (63 males). Groups 1, 2, 3, and 4 had 14, 20, 32, and 35 patients, respectively. In within-group comparisons, follow-up Digit Span Backward test and the Trail Making Test A (TMT-A) scores decreased in group 3, and follow-up TMT-A and the Trail Making Test B scores decreased significantly in group 4. In the multiple regression analysis to determine influential factors on cognitive decline, cumulative clonazepam dose did not show a significant correlation with any cognitive domain. Follow-up cognitive function showed significant correlation only with baseline cognitive function.

Conclusion

Memory and executive functions tended to decline in iRBD patients. However, there was no significant effect of cumulative clonazepam. There was no evidence that long-term use of clonazepam was related to cognitive decline in iRBD patients.

Support (if any)