bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; 365 mg (1 mg * 1 yr); 365 mg ≤ group 2 &lt; 1,095 mg (1 mg * 3 yr); 1,095 mg ≤ group 3 &lt; 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.

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1019 Obstructive Sleep Apnea and Cognitive Functioning 2 Years After Injury in Adults with Traumatic Brain Injury
Authors: Sudolcan Benjamin , Babicz-Boston Michelle , Ketchum Jessica , Calero Karel , O’Connor Kristen Dams , Silva Marc 
Published: April 2024

Abstract

Introduction
Obstructive sleep apnea (OSA) is associated with structural and functional brain changes and reduced cognition. Persons with traumatic brain injury (TBI) show disproportionately higher risk of OSA compared to community samples. Moderate-to-severe TBI often results in disabling cognitive sequelae, although the impact of OSA on cognitive outcome after TBI is poorly understood. The purpose of this study was to examine the degree to which OSA features predict cognitive performance during early TBI recovery. We hypothesized that greater obstructions, oxygen saturation, and cortical arousals would predict poorer cognition.

Methods
This was a secondary analysis of participants co-enrolled in the TBI Model Systems (TBIMS) and Comparison of Sleep Apnea Screening and Diagnostic Tools (CSAS) studies. Participants underwent attended PSG while admitted for neurorehabilitation following moderate-to-severe TBI. Telephone follow-up interviews were conducted 2 years ± 3 months from injury date and included the Brief Test of Adult Cognition by Telephone (BTACT). Spearman correlations were calculated between PSG metrics and BTACT performance.

Results
Of 184 participants co-enrolled in the CSAS and TBIMS studies, 123 had valid BTACT data and compromised the analytical sample. There was a negative correlation between the total Apnea-Hypopnea Index (AHI) and the BTACT Executive Function composite (ρ=-0.189, p=0.040), working memory (ρ=-0.199, p=0.029), and reasoning (ρ=-0.192, p=0.035). Cortical arousals was negatively correlated with reasoning (ρ=0.211, p=0.021). Correlations between PSG metrics of oxygen desaturation (nadir, desaturation index, percent sleep time below 90% peripheral oxygen saturation) and BTACT performance were statistically nonsignificant.

Conclusion
This study provides evidence that PSG metrics of OSA are associated with decreased cognitive performance during early recovery from moderate-to-severe TBI. Future studies should examine the degree to which OSA treatment can ameliorate cognitive deficits following TBI.

Support (if any)
PCORI (CER-1511-33005), NIDILRR (90DPTB0007, 90DP0084, 90DPTB0013, 90DPTB0008, 90DPT80004, 90DPTB0001, 90DPTB0024), and DHA Contract HT0014-22-C-0016 (For information, contact dha.TBICOEinfo@health.mil. UNCLASSIFIED). Defined as U.S. Government work under Title 17 U.S.C.§101. Supported with resources and use of facilities at the James A Haley Veterans’ Hospital. Views presented are of the authors and do not necessarily represent official policy or position of any U.S. government agency.
0102 Effects of Daytime Ambient Temperature on Actigraphy-derived Sleep Parameters in Men and Women
Authors: Ishihara Asuka , Brychta Robert , LaMunion Samuel , Chen Kong 
Published: April 2024

Abstract

Introduction
Evening and nocturnal exposure to cold and warm temperature can respectively blunt or enhance vasodilation needed to initiate sleep. However, the effects of temperature exposure several hours prior to bedtime on sleep have not been well studied. We examined the impact of colder and warmer daytime temperatures on nighttime sleep in men and women.

Methods
In a 7 to 13-day inpatient study (NCT01568671), the metabolism of twelve men (23.2 ± 4.9 yrs; 23.4 ± 1.6 kg/m2) and fifteen women (25.5 ± 4.0 yrs; 22.1 ± 2.2 kg/m2) was measured in a room calorimeter during exposure to a randomly assigned temperature between 16-31˚C from 0800-1300 each day while wearing standardized clothing. Thereafter, ambient temperature was controlled at a thermal neutral temperature (23-25˚C), including during nighttime sleep. Diet and physical activity each day were also standardized. Sleep parameters were assessed using the wrist actigraphy on the non-dominant hand (ActiGraph wGT3X-BT; 80Hz) and compared amongst thermal neutral (24.3 ± 0.4˚C), coldest (19.1 ± 1.2˚C), and warmest (30.4 ± 0.7˚C) daytime temperatures. Whole-body thermal insulation was calculated as the inverse of the slope of metabolism versus ambient temperature below the thermal neutral zone. Linear mixed effects models were used to predict each sleep parameter with sex and temperature as fixed effects and each subject as a random effect.

Results
Over all temperatures, women spent longer time in bed (460.1 ± 58.6 vs. 405.1 ± 68.9 min, p=0.01) and slept longer (427.3 ± 54.1 vs. 372.3 ± 62.0 min p=0.007). No significant interaction was observed between sex and temperature for the sleep parameters. Sleep efficiency after cold exposure was significantly correlated with insulation (R=0.45, p=0.03), which was greater for women than men (0.38 ± 0.04 vs. 0.34 ± 0.04°C/W/m2, p&lt; 0.04). No differences in sleep parameters were observed after warm exposure.

Conclusion
Our findings suggest that daytime cold exposure may influence nocturnal sleep in a relationship mediated by individual thermal insulation. Future studies will need to assess sleep architecture and skin and core temperature regulations of men and women in response to daytime ambient temperature.

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1020 ◻Rest-activity Rhythm Linked to Parkinsonism in Older Adults: Results from the Rush Memory and Aging Project
Authors: Sugg Elizabeth , Gao Lei , Bennett David , Buchman Aron , Li Peng , Hu Kun , Haghayegh Shahab 
Published: April 2024

Abstract

Introduction
While the inter-relationship between parkinsonism and Parkinson’s disease (PD) in older adults remains unclear, both phenotypes are related to PD pathology. Adults with PD commonly exhibit nonmotor symptoms such as disturbances in sleep-wake cycles or rest-activity rhythm (RAR). In a previous study of older men, RAR disturbances preceded the development of PD. This current study examines whether RAR disturbances are associated with incident parkinsonism in a cohort of older community-dwelling men and women.

Methods
We examined 999 older adults (age=80.1; 76% female) in the Rush Memory and Aging Project who were free from parkinsonian symptoms (i.e., bradykinesia, rigidity, tremor, postural instability) during their baseline actigraphy assessment. Participants completed annual motor tests to identify parkinsonian symptoms during follow-up. Incident parkinsonism was rendered when ≥2 parkinsonian symptoms were present. Parametric and nonparametric RAR measures were derived from actigraphy including amplitude (representing the strength of the ~24-h RAR rhythms); acrophase (representing the peak activity time); the most active 10-hour (M10) and least active 5-hour (L5) period over 24-hours; intradaily stability (IS; estimated regularity of a 24-hour pattern); and interdaily variability (IV; fragmentation across 24-hour patterns). Cox proportional hazards models were performed to examine the associations between RAR measures and incident Parkinsonism. Models were adjusted for age, sex, and education.

Results
Parkinsonism was observed in 448 participants after an average of 6.62 years. Risk for parkinsonism was significantly higher in participants with lower amplitude (Hazard Ratio [HR] per 1-SD decrease: 1.36, 95% CI: 1.21-1.53), lower M10 (HR per 1-SD decrease: 1.33, 95% CI: 1.19-1.48), and higher IV (HR per 1-SD increase: 1.23, 95% CI: 1.13-1.34). The observed associations were similar in men and women. There was no significant association between the risk of parkinsonism and acrophase, L5, or IS.

Conclusion
Perturbed RAR were associated with an increased risk of incident parkinsonism in older men and women, suggesting parkinsonism could be a prodromal manifestation of PD in both genders. Further analysis should explore the underlying mechanisms of this relationship.

Support (if any)
5T32HL007901-25, NIH RF1AG064312, and BrightFocus A2020886S.
1021 Samelisant: Clinician and Patient Global Impression from a Double-Blind, Phase-2 Study in Patients with Narcolepsy
Authors: Nirogi Ramakrishna , Jayarajan Pradeep , Goyal Vinod Kumar , Ravula Jyothsna , Jetta Satish , Shinde Anil , Benade Vijay , Abraham Renny , Palacharla Veera Raghava Chowdary , Pandey Santosh Kumar , Mohammed Abdul Rasheed , Jasti Venkat 
Published: April 2024

Abstract

Introduction
Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor (H3R) inverse agonist. Samelisant exhibited desired pharmacokinetic properties in rodents and healthy human volunteers. Preclinical studies in orexin knockout mice demonstrated wake promoting and anticataplectic effects of samelisant. To confirm the preclinical findings, Samelisant was evaluated as monotherapy for the treatment of excessive daytime sleepiness (EDS) in patients with narcolepsy with or without cataplexy. The primary endpoint was changes in the Epworth Sleepiness Scale (ESS) scores. Clinician and Patient Global Impression for EDS were assessed as secondary and exploratory endpoints.

Methods
Two doses of samelisant (2 and 4 mg) were evaluated as a monotherapy in a Phase-2 study for the treatment of EDS in subjects with narcolepsy (ClinicalTrials.gov Identifier: NCT04072380). Subjects diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an ESS score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of &lt; 12 min were recruited in the study. A total of 190 subjects were randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio and received either placebo or samelisant once daily for 2 weeks. The primary efficacy endpoint was the change in ESS score from baseline to week 2. Clinical Global Impression – Severity (CGI-S) was a secondary endpoint, whereas change in Patient Global Impression – Change (PGI-C) and Clinical Global Impression of Change (CGI-C) scores related to EDS were exploratory endpoints.

Results
At the end of the double-blind period, the samelisant treated groups demonstrated clinically and statistically significant improvements in CGI-S (p&lt; 0.01), PGI-C (p&lt; 0.001) and CGI-C (p&lt; 0.0001) with regards to EDS. The proportion of patients reporting improvement in EDS was significantly higher in the samelisant treatment arms compared to placebo arm.

Conclusion
Treatment with samelisant as monotherapy resulted in significant improvement in excessive day time sleepiness as assessed by both clinicians and patients. These outcomes support the efficacy of samelisant observed in the primary endpoint, ESS, in patients with narcolepsy with or without cataplexy.

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1022 Sleep in Duchenne Muscular Dystrophy
Authors: Low Dominique , MD Partha Ghosh 
Published: April 2024

Abstract

Introduction
Duchenne Muscular Dystrophy (DMD), the prevalent childhood-onset muscular dystrophy, affects 1 in 3500 males due to a mutation in the DMD gene, leading to compromised dystrophin production and resultant muscle weakness. Steroid therapies, including prednisolone and deflazacort, commonly used in DMD treatment, may contribute to weight gain. Patients with DMD frequently experience sleep symptoms or disorders, particularly sleep-disordered breathing, impacting their quality of life.

Methods
The objective of this chart review of DMD patients in a multi-disciplinary DMD clinic at a tertiary referral center over a 3-month period is to estimate from the most recent notes, particularly the neurology and pulmonary notes, the prevalence of sleep symptoms and disorders in our multidisciplinary clinic. Clinical observations were also made and recorded by the investigators in the neuromuscular division of the DMD multidisciplinary clinic.

Results
Of the 29 patients reviewed, the average age was 13.3 (SD 3.8) years. All of the patients were male. The racial groups the patients identified as were: 11 (37.9%) “White,” 3 (10.3%) “Black or African American,” 2 (6.9%) “Asian,” 8 (27.6%) “Other,” and 5 (17.2%) “Declined to Answer.” The average BMI was 24.7 (SD 5.3). Of the 29 patients reviewed, 18 (62.1%) exhibited sleep symptoms or disorders. Of these 18 patients, 6 (33.3%) were treated with CPAP or BiPAP.

Conclusion
Our findings align with existing literature, emphasizing the prevalence of sleep-related symptoms and disorders in DMD patients. As DMD management progresses and treatment options expand, resulting in increased life expectancy, addressing sleep-related challenges becomes imperative to enhance the overall quality of life for these individuals. Further research is essential to delve into the intricate relationship between DMD and potential sleep co-morbidities, guiding interventions that can positively influence clinical trajectories and improve overall quality of life.

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1024 SURWEY: Treatment of Excessive Daytime Sleepiness with Solriamfetol: Initiation, Titration, and Outcomes
Authors: Parks Gregory , Burghaus Lothar , Eglit Graham , Abeynayake Iresha , Floam Samantha , Winter Yaroslav 
Published: April 2024

Abstract

Introduction
Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor with agonistic properties at TAAR1 and 5HT1A receptors, is a wake-promoting agent approved to treat excessive daytime sleepiness (EDS) associated with narcolepsy (75–150 mg/day) or obstructive sleep apnea (OSA; 37.5–150 mg/day). Real world data on solriamfetol safety and efficacy remains limited. Here we review real-world survey results to evaluate dosing/titration strategies and outcomes on EDS in patients with OSA, narcolepsy, and the pooled (OSA + narcolepsy) population.

Methods
Data from a retrospective chart review (SURWEY) by German physicians who prescribed solriamfetol for EDS associated with narcolepsy or OSA were analyzed. Inclusion criteria have been previously reported. Initiation and titration strategies (new-to-therapy, changeover, add-on) and Epworth Sleepiness Scale (ESS) scores are reported for each diagnosis and the pooled population to examine EDS as a symptom independent of etiology.

Results
Differences in baseline age, sex, and body mass index were observed for OSA (n=83) and narcolepsy (n=71) patients. Most common initiation strategy was new-to-therapy (n=63/83; 74.7%) for OSA and changeover (n=44/71; 62.0%) for narcolepsy. Patients with a final dose ≥150 mg/day were n=16 (19.5%), n=31 (45.6%), and n=47 (26.1%) for OSA, narcolepsy, and pooled, respectively. At initiation, mean±SD ESS scores were similar: 16.0±3.2 (OSA), 17.6±3.1 (narcolepsy), 16.7±3.2 (pooled). Mean±SD change from baseline in ESS scores at final follow-up were –5.4±3.6 (OSA), –4.5±3.2 (narcolepsy), –5.0±3. 5 (pooled). In the pooled analysis, ESS scores improved by 5.5, 4.7, and 4.4 in new-to-therapy, changeover, and add-on groups, respectively. In the changeover group, ESS scores improved by 5.7, 4.7, 4.6, and 4.0 points in patients who switched to solriamfetol from modafinil (n=13), stimulants (n=3), pitolisant (n=16), or unknown medication (n=21), respectively, while patients who added solriamfetol to pitolisant (n=13) or modafinil (n=3) improved by 4.4 and 3.3 points, respectively. Common adverse effects were headache, insomnia, and decreased appetite.

Conclusion
These real-world data describe the use of solriamfetol in patients with EDS in OSA or narcolepsy. Titration strategies differed by primary etiology but changes in ESS scores were similar. Although sample size was limited, clinically meaningful improvements in ESS scores were observed with solriamfetol regardless of switch/add-on medication.

Support (if any)
Axsome Therapeutics, Jazz Pharmaceuticals, Pharmanovia
1027 Valproic Acid and Central Sleep Apnea: A Retrospective Study
Authors: Martin Kari , Ruoff Chad , Carvalho Diego , Goswami Umesh , Ashley Garrett , Louis Erik St 
Published: April 2024

Abstract

Introduction
Central sleep apnea (CSA) is associated with several medical conditions (e.g., heart failure, atrial fibrillation) and medications (e.g., opioids, ticagrelor, sodium oxybate and valproic acid). We report a case of a 31-year-old female with bipolar disorder treated with valproic acid diagnosed with central sleep apnea on polysomnography, which revealed an apnea-hypopnea index of 150/hour, central apnea index of 112/hour, nadir oxygen saturation of 78%, and 38.6 minutes with oxygen saturation ≤ 88%. Echocardiogram, electrocardiogram, brain magnetic resonance imaging, serum acylcarnitine and serum ammonia levels were unremarkable. Total and free serum valproic acid level was 33 and &lt; 3 mcg/mL, respectively. Two cases of central sleep apnea associated with valproic acid use, both of which improved upon discontinuation of valproic acid, have been reported in the literature. We started the patient on positive airway pressure and suggested she taper off valproic acid and then repeat polysomnography. Given the possible association between central sleep apnea and valproic acid use, we retrospectively analyzed patients receiving valproic acid at time of polysomnography.

Methods
We retrospectively identified patients between 2005-2017 who were prescribed valproic acid (n=6,169), and of these 72 received valproic acid within 90 days of polysomnography. After chart review, we were able to confirm that 29 received valproic acid at time of polysomnography via blood levels or clear chart documentation.

Results
Four patients (13.8 %) demonstrated a central apnea index ≥ 5 per hour (mean apnea-hypopnea index 39.2/hour +/- 32.2/ hour including a central apnea index 11.7 +/- 6.6/hour) during polysomnography. Although one patient (3.4 %), a 2-year-old child with Dravet syndrome and refractory/drug resistant generalized epilepsy, was diagnosed clinically with central sleep apnea, the other three patients were diagnosed with obstructive sleep apnea and had other potential reason(s) for the elevated central apnea index (e.g., opioid use as needed for migraines).

Conclusion
Our case describes a third report of central sleep apnea possibly associated with valproic acid, and our retrospective study indicates that this association is rare. Prospective sleep studies on patients before and after receiving valproic acid are warranted to determine if valproic acid causes central sleep apnea.

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1029 Actigraphy-informed Poor Sleep Health Is Associated with Worse Cognitive Performance Among Older Adults
Authors: Blankenship Anneka , Bock Karen , Watts Amber , Mahnken Jonathan , Hunt Suzanne , Siengsukon Catherine , Mazzotti Diego 
Published: April 2024

Abstract

Introduction
Sleep quality is a modifiable risk factor for Alzheimer’s Disease and other dementias due to the role it plays in removal of beta-amyloid and tau from the brain during sleep. The aim of this retrospective observational study was to examine the association between cognition and domains of sleep health in older adults at baseline and over time.

Methods
Older adults (≥60 years) underwent comprehensive sleep and cognition assessments as part of annual evaluations for a longitudinal cohort study about dementia risk factors. Participants completed self-reported (Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index) and objective (wrist-worn actigraphy) sleep assessments. Definitions for poor, moderate, and good sleep health were established based on composite scores derived from self-report only and from self-report plus actigraphy data using the RuSATED model. Verbal memory, attention, and executive function factors were measured annually. The relationship between composite sleep health scores and cognition factors at baseline and follow-up visits were assessed using linear mixed models adjusted for age, sex, and education.

Results
Among participants with available self-reported sleep health at baseline (N=174), 44.3% and 6.9% had moderate and poor sleep health, respectively. For those with actigraphy-informed sleep health at baseline (N=177), 56.5% and 11.9% had moderate and poor sleep health, respectively. Cross-sectional analyses revealed that participants with actigraphy-informed poor sleep health had lower performance on verbal memory (β [SE] = -0.58 [0.29], p = 0.045) and on executive function (β [SE] = -0.48 [0.18], p = 0.009). No significant relationships between self-reported or actigraphy-informed sleep health and cognition factors were found in longitudinal analyses.

Conclusion
Participants with actigraphy-informed poor sleep health exhibited worse verbal memory and executive function at baseline. These findings underscore the potential influence of sleep health on specific cognitive functions, offering valuable insights for future research and clinical implications in the intersection of sleep health and prevention of Alzheimer's disease and other dementias.

Support (if any)
NIA P30AG035982; General Faculty Research Fund (University of Kansas)