bluuebunny/crossref_metadata_2025_split huggingface dataset:
0681 Circadian Rest/activity Rhythms Are Associated with Cognitive Flexibility Among Older Adults with Insomnia
Authors: Pfaeffle Claire , Wilkens Kristine , Zhao Zhiwei , Verceles Avelino , Johnston Christine , Jones Ashley , Chen Shuo , Rogers Valerie , Spira Adam , Buysse Daniel , Wickwire Emerson 
Published: April 2024

Abstract

Introduction
Circadian rest/activity rhythms (RARs) are associated with cognitive function among older adults. Reports of poor cognitive function are common among individuals with insomnia. We examined the association of circadian RARs with performance in multiple cognitive domains among older adults with insomnia.

Methods
Older adults with insomnia were recruited from a tertiary academic medical center. Participants wore an actigraph and completed concurrent sleep diaries for up to 14 days. We derived nonparametric circadian RARs including relative amplitude (RA), interdaily stability (IS), intradaily variability (IV), maximum ten-hour activity (M10) and minimum five-hour activity (L5). Secondary parametric RARs included amplitude, acrophase, and midline statistics of rhythm (MESOR). Cognitive function was measured via the Brief Test of Adult Cognition by Telephone as well as in-home computerized administration of the psychomotor vigilance test, Stroop Test, and a Task-switching test. Cognitive testing results were grouped into eight a priori-defined domains (attention, inhibition, cognitive flexibility, episodic verbal memory, working memory, reasoning, executive function, processing speed). Composite domain scores were calculated by averaging the z-scores for all individual tests within that domain. Finally, a series of 64 linear regression models were tested to determine the association between circadian RAR parameters and cognitive domains. All models were adjusted for age, sex, education, and total sleep time. We used the Benjamini-Hochberg procedure for correcting false discovery rate (BH-FDR) to correct for multiple comparisons.

Results
The final sample included 30 older adults with insomnia (67% women, mean age=68.0 [SD 6.58] years) who self-identified as White (80%), Black (17%) and American Indian (7%) race. Greater IS (t=2.82, p=0.011), RA (t=2.59, p=0.018), and L5 (t = 2.61, p=0.017) were associated with greater cognitive flexibility. Of parametric RARs, greater amplitude (t = 2.53, p=0.020) and acrophase (t=2.67, p=0.015) were also associated with greater cognitive flexibility. No other significant associations were observed for any cognitive domain.

Conclusion
Circadian RARs were associated with cognitive flexibility but not other cognitive domains. These findings highlight the potential importance of circadian RAR parameters among older adults with insomnia and provide further support for cognitive flexibility as a key cognitive outcome among older adults with sleep problems.

Support (if any)
Merck Investigator Studies Program (#59170).
0684 National RLS Opioid Registry: Four-year Dose Stability, Efficacy and Tolerability
Authors: Winkelman John , Zackon Jordana , Kilty Adysn , Wipper Benjamin 
Published: April 2024

Abstract

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 &gt;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&gt;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

Abstract

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

Abstract

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 &lt; 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&lt; 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&lt; 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

Abstract

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&lt; 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

Abstract

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.

Support (if any)
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

Abstract

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 &lt; 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

Abstract

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 (&lt; 15) on both portions of the sleep study, group 2 had elevated periodic limb movement index (PLMI) &gt;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&lt; 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&lt; 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%.

Support (if any)
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

Abstract

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.