bluuebunny/crossref_metadata_2025 huggingface dataset:
0684 National RLS Opioid Registry: Four-year Dose Stability, Efficacy and Tolerability
Authors: Winkelman John , Zackon Jordana , Kilty Adysn , Wipper Benjamin
Published: April 2024

Introduction

Refractory or augmented restless legs syndrome (RLS) is often treated with opioids. Despite their short-term efficacy, concerns about long-term efficacy, dose stability, and tolerability persist. The National RLS Opioid Registry is a longitudinal, observational study tracking the long-term efficacy, dose stability, and tolerability of opioids for RLS.

Methods

Extensive interviews were conducted with a baseline population of 500, from 44 US states and 4 countries. All participants have a history of therapeutic response to dopamine agonists–a majority experienced augmentation–and take prescribed opioids for RLS (median duration at BL=2-years). Biannual self-report questionnaires track opioid dosage, side effects, RLS severity, and other relevant factors. No clinical guidance or intervention is provided.

Results

At 4-years, 423 participants continue opioid treatment and study participation (5.8% lost to follow-up or withdrew, 2.4% died, 6.6% stopped opioids). Methadone and oxycodone are the two most common opioids (taken by 54.7% and 21.9% of 4-year participants, respectively). Mean RLS severity (baseline IRLS=13.0; 4-year IRLS=13.3) and sleep disturbance (baseline ISI=10.5, 4-year ISI=9.9) were stable from baseline to 4-years in the Registry. Median daily opioid dose is also unchanged, at 30 MME (equivalent to methadone 7.5 mg or oxycodone 20 mg). Opioid doses were increased by 49.4% of participants (median increase=11.3 MME) and decreased by 19.2% (median decrease=10.5 MME). Large dose increases (25-50 MME or >50 MME) occurred in 5.0% and 5.4% of participants, respectively. Several factors were associated with larger dose increases, including switching opioid medications (OR=3.61, 95% CI [1.80-7.27]), under one year on opioids at baseline (OR=2.03, 95% CI [1.00-4.09]), significant baseline depression (PHQ-9>4) (OR=2.57 95% CI [1.27-5.51]), use of opioids for comorbid pain conditions (OR=3.18, 95% CI [1.21-7.89]), dopamine agonist addition (OR=3.06, 95% CI [0.92-8.77]) or discontinuation (OR=3.16, 95% CI [1.13-8.26]) since baseline, and painful RLS at baseline (OR=3.85, 95% CI [1.26-16.79]). Side effect profiles were unchanged from baseline.

Conclusion

Low-dose opioids effectively control severe RLS symptoms over 4-years of observation. Nearly 50% of participants increased their dose, though most changes were small, with larger dose increases associated with specific risk factors.

Support (if any)

Thank you to the RLS Foundation, Baszucki Group, and Jerry Blakeley.
0687 RLS Treatment Reduces Nighttime Agitation and Increases Sleep Duration in Older Adults with Alzheimer's Disease
Authors: Richards Kathy , Gooneratne Nalaka , Fry Liam , Lozano Alicia , Hanlon Alexandra
Published: April 2024

Introduction

Nighttime agitation is a prevalent, distressing symptom in persons with dementia. We hypothesized that restless legs syndrome (RLS), a sensorimotor disorder of uncomfortable leg sensations that worsen at night, might precipitate nighttime agitation. The purpose of this study was to determine the effect of gabapentin enacarbil (GEn), an FDA approved medication for RLS, versus placebo on nighttime agitation and sleep.

Methods

We conducted an 8-week, double-blind, randomized trial of GEn versus placebo involving 147 older adults with dementia due to Alzheimer's disease, nighttime agitation, and RLS (diagnosed by experts using the Behavioral Indicators Test Restless Legs). The primary endpoint was the Cohen-Mansfield Agitation Inventory, Direct Observation. Multivariable linear mixed effects regression models based on multiply imputed data were estimated on repeated measures of nighttime agitation and sleep, with treatment group, week, the two-way interaction of group x week as predictors, and mean arterial pressure as a covariate based on baseline group imbalances.

Results

Mean age was 83.4 ± 9.1 years. Most were female (72.0%), White (92.3%), non-Hispanic (84.6%), and lived in nursing homes (76.9%). Nighttime agitation by group over time was significant at 2 (Estimate = -2.21, p = 0.002) and 8 weeks (Estimate -2.13, p = 0.004). Total sleep time (actigraphy) by group over time was significant at 8 weeks (Estimate = 48.45, p = 0.026), but not 2 weeks (Estimate = 33.39, p = 0.091). Nighttime wake by group over time was significant at 2 (Estimate = -12.54, p =0.006) and 8 weeks (Estimate = -11.12, p = 0.015). Results were not significantly different by sex, race or ethnicity. The number having one or more adverse events was: GEn 60 (81.1%) and placebo 50 (68.5%). Five events in the GEn group, and 8 in the placebo group were severe. The GEn group had more falls than the placebo group (Mean: 1.3 vs 0.7, p =0.066).

Conclusion

Our results clearly show that RLS is an unrecognized cause for nighttime agitation in older adults with dementia and that treatment of RLS with GEn, compared to placebo, significantly reduced nighttime agitation and improved sleep.

Support (if any)

R01AG051588 UL1TR003015 Arbor - Horizant and placebo
0690 Clinical Outcomes in Adults with Comorbid Restless Legs Syndrome and Obstructive Sleep Apnea (CO-ROSA)
Authors: Bradshaw Samuel , Singh Amitoj , Jain Viraj , DelRosso Lourdes
Published: April 2024

Introduction

Obstructive sleep apnea (OSA) and restless legs syndrome (RLS) both significantly influence important measures of health in adults. The Patient Health Questionnaire (PHQ-9), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Generalized Anxiety Disorder 7 (GAD-7) questionnaires assess depression, sleepiness, insomnia, and anxiety symptoms, respectively. We hypothesized that patients with comorbid RLS and OSA (CO-ROSA) will show worse scores in the above-mentioned questionnaires, than patients with OSA alone.

Methods

In this observational cross-sectional study, we administered PHQ-9, ESS, ISI, GAD-7 to adult patients with OSA and patients with CO-ROSA, both treated with CPAP, at a single academic sleep center. Inclusion criteria: presence of OSA or CO-ROSA treated with CPAP. Exclusion criteria: diagnosis of narcolepsy, REM behavior disorder, dementia, or unable to communicate (answer the questionnaire). Data collected included demographics (age, sex, self-reported ethnicity), presence of comorbid restless legs syndrome, and polysomnographic data. SPSS was used to obtain descriptive statistics, independent T-Tests, and Pearson correlation. P-values of < 0.05 were significant.

Results

A total of 133 patients were included in the study, 53.4% had OSA alone (OSA) and 46.6% had Co-ROSA. Demographics: White 62.3%, Latino 27.4, Black 5%, and Asian 1.4%. 37% of Latino and 45 % of whites had CO-ROSA. There were no statistically significant differences in age, AHI, polysomnographic parameters, and CPAP adherence between OSA and CO-ROSA groups. Patients with CO-ROSA had higher PHQ-9 scores (8.2±5.1) than patients with OSA alone (5.2±5.6) and higher ESS (9.5 ±5.7) than OSA (5.9±4.5); (p< 0.05); The following did not reach statistical significance: ISI in OSA (14.85±7.9) and CO-ROSA (14.57±6.1); GAD-7 in OSA (4.29±5.1) and CO-ROSA (5.76±4.5). Latino participants had lower PHQ-9 scores (4.71±4.9), p< 0.05. There were no correlations between any of the questionnaire scores with age, severity of OSA, compliance, or polysomnographic parameters.

Conclusion

Patients with CO-ROSA have statistically significant worse measures of depression and sleepiness than those with OSA alone despite equal compliance, age, polysomnographic parameters, and OSA severity. Both groups had elevated ISI scores. As a whole group Latino patients had lower symptoms of depression.

Support (if any)
0692 Medication Use and Restless Legs Syndrome in Pregnancy Among Nulliparous Women
Authors: Kim Minjee , Reid Kathryn , Friedlander Rachel , Wolf Michael , Grobman William , Facco Francesca , Silver Robert , Greenland Philip , Yee Lynn , Zee Phyllis
Published: April 2024

Introduction

Several antiemetics and antidepressants have been associated with the exacerbation of restless legs syndrome (RLS) in non-pregnant adults. Whether this relationship exists among pregnant individuals is uncertain. We investigated whether taking potentially RLS-exacerbating medications during pregnancy is associated with a higher likelihood of RLS symptoms.

Methods

In this prospective study conducted at 8 U.S. sites, structured questions were utilized to capture all medications taken in early (during pregnancy until study visit 1 (6-13 weeks)) and mid-pregnancy (between study visits 2 (16-21 weeks) and 3 (22-29 weeks)). The use (yes/no) of five categories of potentially RLS-exacerbating medications was determined: first-generation antihistamines, serotonergic antidepressants, dopamine antagonists, tricyclic antidepressants, and mirtazapine. Primary outcome variables were the presence of RLS symptoms at study visits 1 and 3, determined by a questionnaire based on International RLS Study Group diagnostic criteria. Poisson regression with robust standard errors estimated the relative risk of RLS symptoms by medication use. Multivariable models included a priori covariates of age, race and ethnicity (as socially constructed variables), and recent tobacco use.

Results

Of 8,057 participants (age 27.2±5.4 years) who completed both medication-use and RLS questionnaires at least once, 12% and 8.7% took potentially RLS-exacerbating medications in early and mid-pregnancy, respectively. The most frequent medications were first-generation antihistamines (early: 6.6%, mid: 5.3%) and serotonergic antidepressants (early: 4.6%, mid: 3.1%), followed by dopamine antagonists (early: 1.7%, mid: 0.9%). Few participants (≤0.2%) used tricyclic antidepressants or mirtazapine. The prevalence of RLS symptoms was 18% in early pregnancy and 31% in mid-pregnancy. After multivariable adjustment, first-generation antihistamine use was associated with a higher prevalence of RLS symptoms in early (adjusted relative risk [aRR], 1.29; 95% confidence interval [CI], 1.08-1.54; p=0.005) and mid-pregnancy (aRR, 1.17; CI, 1.01-1.36; p=0.042). Similarly, serotonergic antidepressant use was associated with a higher prevalence of RLS symptoms in early (aRR, 1.83; CI, 1.55-2.17; p< 0.001) and mid-pregnancy (aRR, 1.25; CI, 1.05-1.50; p=0.013). No association was found between dopamine antagonists, tricyclic antidepressants, or mirtazapine and RLS symptoms.

Conclusion

There was a higher prevalence of RLS symptoms in people taking first-generation antihistamines or serotonergic antidepressants during pregnancy.

Support (if any)

R01HL105549, U10HL119991, U10HL119989, U10HL120034, U10HL119990, U10HL120006, U10HL119992, U10HL120019, U10HL119993, U10HL120018
0693 Polysomnographic Features of Sleep Paralysis
Authors: Heshmati Arezou
Published: April 2024

Introduction

We report the electroencephalography (EEG) changes observed in a case of sleep paralysis.

Methods

We present the case of a 15-year-old boy with recurrent isolated sleep paralysis. As part of the diagnostic evaluation, the patient underwent overnight polysomnography (PSG) and subsequently, a multiple sleep latency test (MSLT). During the MSLT, the patient experienced sleep paralysis, which was captured on the EEG and is detailed in this report.

Results

In Epoch 27 (30-second segments), the patient exhibited rapid eye movement (REM) sleep. In Epoch 28, while maintaining REM atonia (observed on the chin EMG channel), faster EEG frequencies intruded in the middle of the epoch. In Epoch 29, rapid eye movements and REM atonia persisted, accompanied by EEG patterns displaying faster frequencies and alpha waves consistent with a wakeful state. Sleep paralysis, lasting approximately 48 seconds, was documented from the middle of Epoch 28 to the end of Epoch 29. In Epoch 30, the patient transitioned to wakefulness, reporting the occurrence of sleep paralysis. The EEG during this epoch demonstrated the return of normal awake brainwave patterns.

Conclusion

REM sleep is often associated with vivid dreaming and muscle atonia. During episodes of sleep paralysis, an overlap of characteristics of REM sleep, including theta waves typically seen during REM sleep, and the presence of alpha brain waves indicative of relaxed wakefulness. The convergence of REM features and alpha waves underscores the mixed state of consciousness experienced during sleep paralysis episodes. These findings contribute to a better understanding of the complex neurophysiological changes associated with sleep paralysis.

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0694 REM Density in Patients with Idiopathic Parkinson’s Disease with and Without REM Sleep Behavior Disorder
Authors: Prier Jillian , Nelson Michele , Phipps Kristin , Barrett Matthew , Berman Brian , Alattar Maha , Rath Subhendu
Published: April 2024

Introduction

Previous studies have reported reduced rapid eye movement density (REM density) in idiopathic Parkinson's disease (PD). It remains unclear how REM density in PD differs between those who have or do not have REM Sleep Behavior Disorder (RBD). The objective of this study was to investigate whether REM density differs in patients with PD with and without RBD.

Methods

A sample of fourteen patients with PD were enrolled in a cross-sectional study at Virginia Commonwealth University and underwent one-night polysomnography (PSG). Five of fourteen patients had dream enactment behavior and REM sleep without atonia on PSG and were diagnosed with RBD. REM eye movements were visually inspected by two sleep medicine specialists. REM density was defined as the number of rapid eye movements per minute of REM sleep. Mean and standard deviation for the REM density, total sleep time (TST), stage REM (R) percentage and total apnea-hypopneas indices (AHI) were calculated. Two-tailed T-tests were used to compare the means between the two groups.

Results

For PD without RBD, the mean REM density was 2.3±1.6, mean stage R percentage was 20.1% ±5.5, mean TST was 351.3±72.1 minutes, and mean AHI was 4.1± 4.0. For PD plus RBD, mean REM density was 6.8±1.9 minutes, mean stage R percentage was 20.9% ±9.6, mean TST was 307.6±72.3 minutes, and mean AHI was 1.5 ±3.3. The mean REM density was significantly greater in PD with RBD compared to PD without RBD (P < 0.001). There was no statistical significance of the means of TST, R percentage, and AHI across the two groups.

Conclusion

Our results show that PD patients with RBD have increased REM density compared to PD patients without RBD, a similar finding to prior studies. Future evaluations and further research open the possibility for REM density as a potential diagnostic biomarker.

Support (if any)
0695 Residual Periodic Limb Movement Index After CPAP Titration Is Correlated with Hypoxemia
Authors: Vazquez Itzel , Meghpara Sanket , Modi Harshil , Jain Viraj , DelRosso Lourdes
Published: April 2024

Introduction

Periodic limb movement of sleep (PLMS) are commonly seen in patients with obstructive sleep apnea (OSA) . There are few studies that have assessed the persistence of PLMS in patients with OSA, treated with continuous positive airway pressure (CPAP). In the current study we analyzed PLMS outcomes in split studies and found correlates.

Methods

Retrospective chart review of adult patients undergoing split studies. Demographics, diagnostic and titration polysomnographic data was collected. Groups were divided in four: group 1 had normal index of PLMS (< 15) on both portions of the sleep study, group 2 had elevated periodic limb movement index (PLMI) >15, but did not change with treatment, group 3 had worse PLMI on titration, group 4 had resolution of PLMI during titration portion.

Results

A total of 138 patients were included (62.8% male, 37.2% female). age±SD was not statistically significant between groups, Group 1 (40.6% of patients) with mean age 56.4±14.5, group 2 (17.9%) mean age 51.3±15.6, group 3 (13.1%) mean age 65.1±12.1 and group 4 (28.3%) mean age 60.4±9.8. PLMI was different among groups (p< 0.001) both during diagnostic and titration. During diagnostic PLMI Group 1 was 3.8±4.7, group 2 was 56.8±29.7, group 3 was 11.9±9.9 and group 4 was 55.5±36.8. During treatment portion PLMI group 1 was 2.6±4, Group 2 was 64.9±35.7, group 3 was 55±31.9 and group 4 was 8.9±9. None of the sleep parameters were statistically significant between groups except the time spent with saturation below 88% (p< 0.05) With the normal group (1) and group 4 having the least time below 88%. Group 1: 11.5±18 minutes, group 4 spent 11.5±18 minutes. While group 2 spent 36.6±41.2 and group 3 spent 26.3±25.7 minutes. There was a moderate Pearson correlation of 0.384 (CI 0.206-0.538) between saturation time below 88% and PLMI in the titration portion.

Conclusion

An elevated PLMI was present in 59.4% of patients with OSA undergoing split studies. Resolved in 28.3% and worsened in 13.1%. The group with no change in PLMI (group 2) had that worse PLMI and worse hypoxemia. PLMI was moderately correlated with time spent with saturation below 88%.

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0697 DIAGNOSIS DELAY and FAILED RECOGNITION of RBD: FROM “FITS to PARKINSON’S DISEASE”
Authors: Murray Benjamin , Molina Courtney , Rivera Adreanne , Avidan Alon
Published: April 2024

Introduction

The diagnosis of REM sleep behavior disorder (RBD) requires the presence of dream enactment behaviors (DEB) and polysomnographic confirmation of REM sleep without atonia (RWA). Recent data illustrates a significant diagnostic delay from the onset of DEB until the formal diagnosis of RBD. The North American Prodromal Synucleinopathy (NAPS) Consortium was established to prospectively follow a clinic-based cohort to better understand baseline characteristics of patient with RBD at diagnosis, help uncover predictors of phenoconversion, and enable early-stage clinical trial enrollment. We sought to measure the extent of diagnostic delay within our UCLA NAPS cohort and identify common misdiagnoses on initial presentation to confirmation of diagnosis.

Methods

Retrospective review of patients in the UCLA NAPS Cohort. Results are reported as mean ± standard deviation.

Results

We identified 32 patients, 24 (75%) male and 8 (25%) female, with an age range of 32 to 85 in a cohort of patients who were diagnosed with RBD between 2012 and 2023. Mean age of DEB onset was 52.2 ± 15 years. Mean age of RBD diagnosis was 60.2 ± 13 years. Average time from DEB presentation to RBD confirmation by PSG was 8 ± 9 years. There was no significant difference in diagnostic delay between male and female (8.9 ± 9 v. 8.9 ± 9 years, respectively; p=0.89). Diagnoses given at time of presentation included sleep (night) terrors (n=12), nightmares (n=7), anxiety/panic (n=4), severe obstructive sleep apnea (n=2), RBD (n=2), Parkinson’s disease (n=1), and foodborne illness (n=1).

Conclusion

Our data reveals pervasive and significant delay in time from initial presentation of dream enactment to the formal diagnosis of RBD. Enhancing primary clinicians’ education and competency in recognition of RBD and knowing when to refer patients suspected of having RBD is a critical step to address this gap.

Support (if any)

This work was funded by NIH-NIA National Institute on Aging, U19 AG071754 and the Karen Toffler Charitable Trust.
0707 Erectile Dysfunction in Restless Legs Syndrome
Authors: Kim Geun Yeong , Bang Sung Jo , Kim Keun Tae , Cho Yong Won
Published: April 2024

Introduction

Restless Legs Syndrome (RLS) is a sleep disorder characterized by uncomfortable dysesthesia and the urge to move the legs, particularly during sleep. Erectile dysfunction (ED) is a condition of inability to get or maintain sufficient firmness to have satisfactory sexual intercourse. This study aims to investigate the ED using the International Index of Erectile Function (IIEF) in RLS patients.

Methods

This is a prospective study at a university hospital in South Korea. From May 2021 to August 2023, all male subjects who underwent overnight polysomnography were asked to complete a series of sleep questionnaires including Insomnia severity index (ISI), Beck's depression inventory (BDI), Beck's anxiety inventory (BAI), Epworth sleepiness scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Short-form 36 (SF-36), and IIEF.

Results

A total of 74 and 107 subjects of RLS and controls were included in this study, respectively. Excluding 29 who haven't had sex in the past month, 58 RLS and 94 controls were analyzed. There was no difference in mean age between RLS (52.38±14.39) and controls (53.21±15.07) (p=0.767). The total score of IIEF was 15.31±5.73 in RLS and 17.77±6.26 in control (p=0.010). RLS had lower body mass index than controls (25.39±3.41 vs. 27.54±4.23, p=0.010); however, no difference in BDI (14.22±7.71 vs.13.80±11.96, p=0.391), BAI (10.90±8.29 vs. 9.50±12.53, p=0.267), and apnea-hypopnea index (16.39±24.95 vs. 13.63±16.01, p=0.523). RLS had a higher score in insomnia (ISI: 15.62±6.79 vs. 5.70±5.04, p< 0.001), more daytime somnolence (ESS: 7.97±4.33 vs. 4.58±2.71, p< 0.001), lower quality of sleep (PSQI: 12.59±4.22 vs. 6.81±3.53, p< 0.001). RLS showed lower mental health (SF-36 mental health: 62.91±17.75 vs. 73.75±11.05, p=0.014), although there was no difference in SF-36 total score.

Conclusion

This is the first study that evaluated ED in patients with RLS. The subjects with RLS showed poorer sleep quality and lower IIEF scores than the controls. This study suggests an association between RLS and erectile dysfunction.

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0708 Exploratory Cost-Effectiveness Analysis of TOMAC for Medication-Refractory RLS, Based on Longer-term Clinical Data
Authors: Ryschon Anne , Roy Asim , Pietzsch Jan
Published: April 2024

Introduction

Tonic motor activation (TOMAC) is a non-invasive neuromodulation therapy that provides a non-pharmacologic treatment alternative for patients suffering from medication-refractory restless legs syndrome (RLS). In the current analysis, recently reported longer-term clinical data were used to update prior exploratory cost-effectiveness work.

Methods

A previously published decision-analytic Markov model was utilized to project outcomes over a lifetime horizon. The cohort and treatment effects modeled were sourced from the extension cohort of the RESTFUL study (mean age 57.6, 43.8% male). Health-related quality of life (EQ-5D utilities) and symptom severity were derived from International RLS Study Group (IRLS) scores reported at baseline and 32-weeks after RESTFUL study entry and compared between the TOMAC (continued TOMAC for 24-weeks following RESTFUL study completion) and control arms. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), measured as the difference in quality-adjusted life years (QALY) gained divided by difference in costs, with costs and resource utilization derived from fee schedules and published data. Cost-effectiveness was evaluated against thresholds of $50,000/$150,000 per QALY, and extensive scenario analyses were performed.

Results

Study-observed IRLS scores were reduced by -11.3 from baseline to 32 weeks for TOMAC and -5.4 for control. The resulting treatment effect of -5.9 corresponded to a change in utility from 0.82 to 0.87 (0.77 to 0.87 vs. baseline). Over lifetime, TOMAC added 0.73 and 1.44 QALYs (12.98 vs. 12.25 and 12.91 vs.11.47) at incremental costs of $28,066 and $19,072 ($211,704 vs. $183,638 and $212,644 vs. $193,572), resulting in ICERs of $38,685 and $13,251 per QALY gained vs. control and baseline, respectively. TOMAC was found cost-effective or dominant across all tested scenarios, with ICERs ranging from -$29,558 to $48,266 and -$40,684 to $19,564, vs. control and baseline, respectively.

Conclusion

This updated analysis based on longer-term data confirms earlier findings and suggests TOMAC therapy can provide a high value treatment alternative for patients suffering from medication-refractory RLS. Further increased effect sizes in the longer-term data support assumptions about maintained effect size over time.

Support (if any)

Wing Tech Inc. received consulting fees from Noctrix Health. AR is an investigator in the RESTFUL study.
0714 Weight Loss in Patients Prescribed Methadone for Restless Legs Syndrome
Authors: Winkelman John , Kilty Adysn
Published: April 2024

Introduction

Weight loss is an underexplored side effect of methadone. While methadone is associated with weight gain when used to treat opioid use disorder, its impact on patients with restless legs syndrome (RLS) remains unclear. This study aims to assess the prevalence of significant weight loss in RLS patients prescribed methadone.

Methods

73 consecutive patients for whom at least 6 months of follow-up was available following initiation of methadone for RLS and who were not undergoing weight loss interventions were assessed. Clinical information was extracted from the initial visit and all subsequent visits conducted throughout the course of methadone treatment (mean duration=2.9 years). Examination of associations with weight loss >10% and >20% of body weight within the first 6 months of methadone initiation was performed.

Results

In the 73 patients, the mean age was 67.6, mean BMI=29.3 and 51.4% were female. At methadone initiation, 18.1% were taking dopamine agonists (DA), 30.6% alpha-2-delta calcium channel ligands (A2D), and 38.9% both DAs and A2Ds. Notably, 19.4% of patients experienced weight loss >10%, and 6.9% lost >20% of their body weight. Those who lost >10% had higher rates of reducing or discontinuing DAs (71.4% vs 49.2%) and higher average BMI (31.9 vs 28.6) than those who did not, but had similar prevalence of reducing or discontinuing A2Ds (35.7% vs 42.4%). Other factors, such as 6-month methadone dose, use of antidepressants, diagnoses of obstructive sleep apnea, and prior opioid use were balanced between the two groups. 80% of those with >20% weight loss (vs 11.8% with < 20% weight loss) had nighttime eating diagnoses. Patients with substantial weight loss described a dramatic reduction in appetite with loss of interest and pleasure from normally desirable foods.

Conclusion

This study reveals significant weight loss in a subset of RLS patients prescribed methadone. Changes in A2Ds, an RLS medication known to increase weight, were not different in those with weight loss. Other opioid-related side effects, such as nausea or constipation, could impact appetite and also contribute to weight loss. Clinicians should monitor patient weight during methadone treatment to prevent potential health risks.

Support (if any)

Baszucki Brain Research Fund
0716 Longitudinal Associations of Weekend Catch-up Sleep and Sleep Ability with Mortality in Middle-aged Adults
Authors: Yoshiike Takuya , Kawamuraa Aoi , Utusumi Tomohiro , Matsui Kentaro , Kuriyama Kenichi
Published: April 2024

Introduction

The question remains as to whether and in which individuals weekend catch-up sleep (CUS) promotes health. The health effects of weekend CUS could differ depending on both the ability to obtain sufficient sleep during weekdays and the amount of weekend CUS required to compensate for sleep lost during the week. We examined the longitudinal association of these two aspects of sleep with all-cause mortality.

Methods

We used data from 3,128 middle-aged (40–64 years) participants of the Sleep Heart Health Study. We defined one’s weekend CUS as no, short (1 h), and long (2 h or more) according to self-reported sleep durations on weekdays and weekends. Polysomnography-measured total sleep time, representing the ability to obtain sufficient sleep, was classified into short (< 360 min) or normal (≥ 360 min) sleep durations. We estimated multivariable-adjusted mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for six groups divided by the extent of CUS and sleep duration.

Results

A total of 232 deaths (7.4%) were reported over a median (interquartile range) follow-up time of 12.3 (11.3–13.5) years. Short weekend CUS with normal sleep duration (≥ 360 min) was associated with lower mortality compared to no CUS with normal sleep duration after adjustment for established risk factors for survival including self-reported habitual sleep duration and social jetlag (adjusted HR, 0.48; 95% CI 0.27–0.83). When stricter cutoffs were applied for short and normal sleep durations, while the protective effect of short CUS with normal sleep duration (≥ 390 min) was strengthened (adjusted HR, 0.36; 95% CI 0.17–0.78), the harmful effect of short CUS with short sleep duration (< 330 min) emerged (adjusted HR, 1.84; 95% CI 1.08–3.14).

Conclusion

Our results emphasize the importance of balancing between the extent of weekend CUS required to compensate for sleep debt that accumulates during weekdays and one’s ability to obtain sufficient sleep that could minimize the accumulation of nightly sleep loss among middle-aged adults. Weekend CUS may substantially benefit individuals who maintain their sleep ability and thus require a small amount of CUS.

Support (if any)

This work was supported by the Ministry of Health, Labor and Welfare, Government of Japan (Grant numbers #21FA1002 and #22FA2001).
0718 Latent Classes of Sleep Problems and Subjective Cognitive Decline Among U.S. Middle-Aged and Older Adults
Authors: Huang Jing , Spira Adam , Perrin Nancy , Ellis Aisha , Hsu Erh-Chi , Li Junxin
Published: April 2024

Introduction

Subjective Cognitive Decline (SCD) can be an early sign of Alzheimer’s disease. Previous studies have linked sleep problems to a higher risk of SCD using a variable-centered approach (e.g., adding sleep symptoms to form a score); however, sleep problems may cluster differently among people. Thus, we employed a person-centered approach to understand sleep problems and their association with SCD. We aimed to: 1) identify latent classes (profiles) of self-reported sleep problems among U.S. middle-aged and older adults; 2) investigate the cross-sectional association between the classes and SCD; and 3) investigate whether this association differs by age group.

Methods

For Aim 1, we studied 33,922 adults aged 45+ years from the 2017 U.S. Behavioral Risk Factor Surveillance System (BRFSS) with data on sleep problems, including short or long sleep duration, trouble falling or staying asleep, unintentionally falling asleep, snoring loudly, and observed breathing stopped. Latent class analysis classified participants based on their responses to sleep problems. For Aim 2, we studied a subsample from Oregon, the only state that administered both sleep and SCD modules (n=2,747). SCD was assessed by an item regarding worsened confusion or memory loss in the past 12 months. Logistic regression examined the association between class membership and SCD, adjusting for demographics, socioeconomics, health behaviors, and chronic conditions. For Aim 3, we added a class membership × age group (45-65 years; >65 years) interaction term to the model.

Results

Among all participants, 51.5% were aged 45-65 years, 56.7% were females, and 85.1% were White. We identified and labeled four classes: “Combined Insomnia and Apnea” (8.6%); “Primarily Insomnia ” (17.6%); “Primarily Apnea ” (25.8%); and “Healthy” (48.0%). In adjusted models, compared to the Healthy class, participants in the Combined Insomnia and Apnea class had higher odds of SCD (OR=1.91, 95% CI =1.15-3.15). There was no significant age × class membership interaction.

Conclusion

U.S. adults aged 45+ years in the “Combined Insomnia and Apnea” latent class of sleep problems showed a higher risk for cognitive decline, compared to the “Healthy” class. The finding may help to facilitate more targeted and tailored sleep interventions to prevent cognitive decline in middle-aged and older adults.

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0719 How Weekly Sleep Fluctuations Affect Pain Perception: An Experimental Study in Healthy Females
Authors: Rouhi Shima , Brumley Natalia , Jordan Amy
Published: April 2024

Introduction

Acute experimental sleep deprivation is known to induce pain hypersensitivity, with a more pronounced impact on females than males. Sleep restriction or fragmented sleep result in distinct pain hypersensitivity profiles. However, the influence of weekly sleep fluctuations, particularly between working days and weekends, on pain perception remains unclear. This experimental study investigates how weekly sleep variations affect pain perception in healthy women recruited from a university community.

Methods

A DREEM headband was used to monitor sleep, and pain sensitivity was measured using quantitative sensory testing, including heat, cold, and pressure thresholds, as well as temporal summation and conditioned pain modulation on both Monday and Friday.

Results

26 healthy females with an average age of 25.53 (CI: 22.95 to 28.11) participated. A distinct sleep pattern was observed, with a shorter sleep onset latency (t = -1.58, df = 25, p = .033), a higher number of awakenings (t = 1.98, df = 24, p = .03), and a higher N1 sleep percentage (t = 1.72, df = 25, p = .049) on Sunday night compared to Thursday night. Sleep patterns throughout the week indicated a one-hour shift later in bedtime (F=2.45, p =.06, Observed power=.69) and wake-up time (F=4.48, p=.007, Observed power= .92), more awakenings (X2 (2) = 12.17, p = 0.05), and less N3 sleep duration (F=3.29, p = .022, Observed power=.82) over weekends than weekdays, highlighting more fragmented sleep during weekends. Paired-sample t-tests revealed pain hypersensitivity with increased heat pain summation (t= 3.353, CI: .57 to 2.39, p = .003) and a trend toward decreased pain inhibition (t=-.56, CI: -45.28 to 26.28, p>.05) on Monday compared to Friday. No changes in pain thresholds were observed.

Conclusion

Although the sleep changes were somewhat unexpected, with poorer sleep observed over the weekend, the study underscores the potential role of weekly sleep fluctuations in modulating pain sensitivity,

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0722 Clinical, Demographic, Functional, and Symptom Correlates of COMISA in Stable Heart Failure
Authors: LaFleur Kelley , Jeon Sangchoon , Wang Zequan , Conley Samantha , Redeker Nancy
Published: April 2024

Introduction

Sleep disordered breathing (SDB: obstructive & central sleep apnea) and insomnia are common in heart failure (HF). However, most studies have not addressed the presence of combined SDB and insomnia (COMISA). The purposes of this study were to (1) describe COMISA among adults with stable chronic HF; (2) compare the clinical and demographic characteristics between groups with COMISA, insomnia, SDB, and normal sleep; and (3) examine the risk of COMISA in the presence of normal sleep, insomnia, SDB and other clinical and demographic characteristics.

Methods

Secondary analysis of an observational study of sleep among adults with stable HF. COMISA was defined as an apnea hypopnea index (AHI) > 15 with difficulty initiating or maintaining sleep or waking too early in the morning (Insomnia). We measured self-reported (Pittsburgh Sleep Quality Index) and objective sleep characteristics (polysomnography – PSG), symptoms (depression, sleepiness); used chi-square and ANOVA; and calculated the risks of COMISA for normal sleepers and with insomnia or SDB under different conditions (depression, poor sleep quality, left ventricular ejection fraction, age, race, and sex).

Results

The sample included 170 [(M age = 60.3 ± 16.8 years; n = 60 (35%] female. They had normal sleep (n = 37/22%); insomnia only (n = 48/28%): SDB only (n = 46/27%); and COMISA (n = 39/23%). Those with COMISA were significantly more likely to be obese (32.1%) compared to others [13.6% -29.6%, p = 0.0128]. They had the shortest total sleep time (TST) (mean = 291 ± 109 mins) and poorest sleep efficiency (M = 65.8 ± 20.5%) (p = .05). Women with insomnia were less likely to have COMISA than men (36% vs. 51%), while 74% of adults with SDB who were depressed had COMISA, compared with 41% of those with insomnia.

Conclusion

Risk of COMISA is associated with depression and poor sleep among adults with stable HF and SDB. Future study is needed to better understand the risks of COMISA among adults with chronic HF outcomes and to address the need for intervention that addresses it beyond a focus on only SDB or insomnia.

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0723 Multidimensional Sleep and Mental and Physical Health Among Retired Workers: A Sex-stratified Analysis
Authors: tracy Eunjin , Lehrer Matthew , So Christine , Hasler Brant , Kanaley Jill , Manrique-Acevedo Camila , Chin Brian , Buysse Daniel
Published: April 2024

Introduction

Although individual sleep characteristics relate to mental and physical health among older adults, such sleep characteristics do not exist in isolation. Multidimensional sleep measures may better capture the comprehensive impact of sleep on health. However, few studies have examined multidimensional sleep health in relation to mental and physical health outcomes among retired older adults. Likewise, few studies have examined sex differences in these relationships. This study examined associations between multidimensional sleep and health outcomes (i.e., depressive symptoms, mental health, physical health, and overall perceived health) among retired older adults in models stratified by sex.

Methods

Older adults (n = 154; Mage = 68.4, 55.2 % assigned female at birth) reported depressive symptoms (CES-D), and perceived mental, physical, and overall health (RAND-12). The measurement of multidimensional sleep health involved utilizing wrist actigraphy to assess sleep efficiency, timing, duration, and regularity, alongside diary measures to evaluate alertness and satisfaction. Each component was dichotomized and summed to create a composite score (0-6); higher values indicated better sleep health. Hierarchical linear regressions were used to examine relationships between multidimensional sleep health and health outcomes. Covariates include race, age, years of education, subjective social status, and shiftwork exposure history.

Results

Compared to men, women had poorer multidimensional sleep health (t(135)=2.38, p=.028). In the full sample, poorer multidimensional sleep was associated with greater depressive symptoms (b = -.70, se = .31, p =.024, r2 = .39) as well as poorer physical (b = 1.03, se = .37, p = .006, r2 = .45), mental (b = 1.37, se = .40, p < .001, r2 = .44), and overall perceived health (b = 1.42, se = .35, p <.001, r2 = .52). Sex-stratified analyses showed that significant findings were exclusively evident in women and not in men.

Conclusion

Multidimensional sleep health influences the physical and mental health among older retired women. Future studies should identify the mechanisms underlying sex differences in multidimensional sleep and the links between multidimensional and health outcomes. Such information could provide valuable insights leading to tailored therapeutics that benefit each sex.

Support (if any)

This research was supported by the National Institute of Aging (R01AG047139; K01AG0751).
0724 Wake Intrusion Index During NREM Sleep Is Associated with Comorbid Insomnia and Sleep Apnea Exclusively in Men
Authors: Gratton Matthew , Younes Magdy , Hamilton Nancy , Gerardy Bethany , Mazzotti Diego
Published: April 2024

Introduction

Sex differences in the clinical presentation of obstructive sleep apnea (OSA) comorbid with insomnia (COMISA) exist. Men typically exhibit more severe OSA during NREM sleep, while women are more prone to insomnia. Yet, little is know about the physiological correlates likely explaining these differences. This study evaluated the association between sleep stage-specific wake intrusions, a measure of 3-second perturbations in the odds ratio product (ORP) during sleep, and insomnia, OSA, and COMISA, and assessed whether sex differences in these associations are observed.

Methods

Data from the Sleep Heart Health Study (SHHS1; N=5,771) was accessed via the National Sleep Research Resource. Stage-specific wake intrusions were defined as ORP spikes above 2.0, from within N1, N2, N3, and REM. Wake intrusion index (WII) for each sleep stage was calculated as the number of intrusions divided by total sleep time from each stage. Insomnia was determined based on self-report of insomnia symptoms (>15 times/month) including delayed sleep onset, maintenance difficulty, or early morning awakenings (N=617). Obstructive sleep apnea (OSA) was defined by an apnea-hypopnea index (AHI) of ≥15 (N=1,225), and COMISA was defined as having both OSA and insomnia (N=147). Linear regression was used to assess the relationship between sleep disorders and stage-specific WII, adjusted for age and AHI, separately for men and women.

Results

Among men, adjusted analyses showed that WII during NREM was significantly higher in those with COMISA as compared to those with OSA (β[SE]=73.3[27.3] intrusions/h, p=0.008), with effects likely being driven by higher WII during stage N1 (β[SE]=126.4[39.7] intrusions/h, p=0.008). These associations were not observed among women. No other significant differences were found in WII during N2, N3, or REM sleep.

Conclusion

Our findings show a sleep stage and sex-specific association between wake intrusion and COMISA. We speculate that men with COMISA may experience more unstable N1 stage, when compared to those with only OSA. These findings suggest the need for sex-specific approaches to characterization and treatment of COMISA.

Support (if any)

NHLBI (U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL64360, U01HL53938, U01HL53940, U01HL53941, U01HL63463, R24HL114473, 75N92019R002).
0732 Poor Perinatal Sleep Quality Is Associated with an Elevated Cortisol Awakening Response
Authors: Okun Michele , Segerstrom Suzanne , Ross Kharah , Schetter Chris Dunkel , Coussons-Read Mary
Published: April 2024

Introduction

The perinatal period is a time of disrupted sleep. Sleep quality progressively worsens across gestation and into the postpartum. A mechanism linking poor sleep with certain adverse pregnancy outcomes is dysregulation of the HPA axis resulting in atypically elevated cortisol production. Although total cortisol output normally increases across pregnancy, the cortisol awakening response (CAR) attenuates as pregnancy progresses, with normalization in the first couple of weeks after delivery. The objective of this study was to evaluate longitudinal associations between maternal sleep quality and indices of cortisol across the perinatal period.

Methods

Data were collected as part of the HB3 study. PSQI and saliva were collected at four time-points (8-16 weeks, 30-36 weeks, 6 months postpartum, and 1-year postpartum). Participants (N = 230) who had sleep and cortisol data from at least 1 of 4 time-points were included in analyses. Multi-level models were run to predict cortisol parameters based on deviations in average maternal sleep quality at each wave. Values below the detectable limit were imputed and samples taken < 20 minutes or > 60 minutes were excluded.

Results

Multilevel (time, wave, and person) modeling indicated an average positive CAR slope (g=0.29, p=.02) that was affected by whether sleep quality was better or worse at that wave (p=.04). When PSQI scores were higher than the woman's own average, the CAR slope was steeper (+1 point in PSQI, g=0.32), and when scores were lower than average, the CAR slope was flatter (-1 point, g=0.25). CAR slope was not affected by average sleep quality across waves (p=.21). Diurnal slope was not affected by sleep quality being better or worse at that wave (p = .82) or by average sleep quality across waves (p=.61).

Conclusion

Women with poorer sleep quality than their average had a larger CAR than women with better sleep quality than their average. There was no association between sleep quality and the diurnal slope. These data suggest that greater variability in sleep quality significantly increases the amount of cortisol secreted upon awakening. Further examination is needed to determine if sleep quality is associated with adverse pregnancy/delivery outcomes via HPA axis dysregulation.

Support (if any)

NICHD R01HD073491-01
0733 Associations Between Multiple Dimensions of Sleep and Cognition by Race/Ethnicity and Gender
Authors: Zendels Philip , Gaston Symielle , Payne Christopher , Jackson W Braxton , Jackson Chandra
Published: April 2024

Introduction

Sleep disturbances (including unhealthy duration, insomnia symptoms, and poor sleep quality) have been associated with impairments to memory and concentration. Although racially minoritized groups and women generally have poorer sleep quality and faster cognitive decline, few studies have investigated associations between multiple sleep dimensions and cognition by race/ethnicity and gender.

Methods

To investigate multiple sleep dimensions in relation to cognitive impairment, overall and by race/ethnicity and gender among US adults aged ≥40 years, cross-sectional data were pooled from the 2011-2018 National Health Interview Survey. Participants self-reported short (< 7 hours) and long (>9 hours) sleep duration and sleep disturbances (i.e., insomnia symptoms: trouble falling asleep and/or staying asleep 3+ nights/week; non-restorative sleep: waking up not feeling rested 4+ nights/week). Cognitive impairment (yes vs. no) was self-reported in one item of the Washington Group Short Set on Functioning and defined as either not being able to or having a lot of difficulty remembering and concentrating. Using Poisson regression with robust variance and adjusting for sociodemographic, health behavior, and clinical characteristics, we estimated prevalence ratios for associations between sleep dimensions and cognitive impairment, overall and by race/ethnicity and gender.

Results

Among, 73,477 participants, mean age was 58.3±0.7 years, and most (86.7%) attained high school or higher education. Overall, 2.2% had cognitive impairment (by race/ethnicity: Latinx (2.5%), Asian (1.6%), Black/African American (2.5%), and White (2.1%); by gender: women (2.4%), men (1.9%)). Short sleep was associated with higher prevalence of cognitive impairment only among White adults (PR=1.30 [95% CI:1.10-1.55] vs. range: PR-Asian=0.69 [95% CI:0.33-1.45] to PR-Latinx=1.14 [95% CI:0.75-1.73];p-interaction< 0.05) Although long sleep duration was associated with a higher prevalence of cognitive impairment among the overall population (PR=4.10 [95% CI:3.48-4.83]), associations were strongest among Asian adults (PR=5.27 [95% CI:2.84-9.80]; p-interaction< 0.05). Both insomnia symptoms (PR=1.40 [95% CI:1.40-1.87) and non-restorative sleep (PR=1.67 [95% CI:1.44-1.94) were associated with a higher prevalence of cognitive impairment across racial/ethnic groups. No associations varied by gender.

Conclusion

Short and long sleep, insomnia symptoms, and non-restorative sleep were associated with cognitive impairment with potential differences by race/ethnicity for sleep duration. Future studies identifying factors driving observed disparities by race/ethnicity and gender are warranted.

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