Citations

Abstract Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia strongly associated with α-synucleinopathies, most commonly Parkinson’s disease (PD). Among Veterans, posttraumatic stress disorder (PTSD) is common and may influence RBD presentation and outcomes. The extent to which PTSD modifies demographic, medical, and mortality profiles in Veterans with RBD, and how these differ from those with RBD and Parkinson’s disease (PD), remains poorly characterized. Methods We conducted a retrospective cohort study using the Veterans Health Administration Corporate Data Warehouse. Veterans with at least one ICD-9 or ICD-10 diagnostic code for RBD were identified between 1999 - 2020 and categorized into three, mutually-exclusive groups based on the presence or absence of co-occurring ICD codes: RBD-only, RBD+PTSD, or RBD+PD. Demographics, comorbidities (Charlson Comorbidity Index [CCI]), and mortality outcomes were compared using logistic regression models adjusted for age, sex, race/ethnicity, BMI, and CCI. Results The cohort included 11,283 Veterans with RBD only, 17,527 with RBD+PTSD, and 5,675 with RBD+PD. Veterans with RBD+PTSD were younger (mean 58.9 ± 14.9 y) and had higher psychiatric comorbidity (94.2%) compared to RBD only (54.2%) or RBD+PD (46.5%). Those with RBD+PD were older (73.6 ± 8.1 y), predominantly male (98.9%), and had the highest neurological comorbidity (92.6%). Unadjusted mortality was lowest in RBD+PTSD (15.3%) and highest in RBD+PD (53.6%). Adjusted models showed reduced mortality risk for RBD+PTSD (aOR 0.73, 95% CI 0.70–0.80, p < 0.001) and increased risk for RBD+PD (aOR 2.43, 95% CI 2.3–2.6, p < 0.001) vs. RBD alone. Higher age, male sex, and greater comorbidity independently predicted mortality. Conclusion In this large national VA cohort, comorbid PTSD and Parkinson’s disease were associated with distinct demographic and clinical profiles among Veterans with RBD. RBD+PTSD was linked to younger age, greater psychiatric burden, and lower mortality. These findings underscore the heterogeneity of RBD in Veterans and support stratified approaches to surveillance for synucleinopathy and trauma-related sleep disturbances. Support (if any) VA CDA # IK2CX002363-01A1 (MJ); NHLBI K25 #1K25HL152006-01 (JR)

Abstract Introduction Once-nightly sodium oxybate (ON-SXB) is approved to treat cataplexy or excessive daytime sleepiness (EDS) in patients ≥7 years of age with narcolepsy. ON-SXB demonstrated significant improvements in both objective (Maintenance of Wakefulness Test) and subjective (Epworth Sleepiness Scale [ESS] score) measurements of sleepiness in the REST-ON trial and via the ESS in the real-world REFRESH study. Assessing ON-SXB ESS data from a specialty pharmacy and outside of clinical studies further informs the generalizability of effectiveness. Methods Demographic and clinical data were collected from Optum Frontier Therapies pharmacy for patients with ≥1 filled ON-SXB prescription, ≥1 ON-SXB-related clinical assessment, and ≥1 follow-up ESS score (6/1/2023-9/30/2024). Participation in ESS assessment was voluntary. ESS scores were assessed for patients who switched from twice-nightly oxybate (TN-OXB) treatment (first ON-SXB prescription filled ≤30 days of last TN-OXB prescription [switch]) and those new to oxybate or with >30 days between TN-OXB and ON-SXB prescription fills (not-on-oxybate) who had ESS data at initial ON-SXB prescription and at each follow-up assessment. Results Of 452 identified patients, 215 had ≥1 follow-up ESS score (switch, n=82 [mean age, 38.4 years; female, 71%]; not-on-oxybate, n=133 [mean age, 40.0 years; female, 71%]). Of patients who had any prior oxybate use (switch, 100%; not-on-oxybate, 46%), the most common prior oxybate was mixed-salt oxybates (switch, 59%; not-on-oxybate, 70%). Stimulants/wake-promoting agents were taken by 51% of switch and 65% of not-on-oxybate patients. Baseline mean (SD) ESS scores were 11.3 (5.5) for switch and 12.5 (5.6) for not-on-oxybate patients; 23% of switch and 38% of not-on-oxybate patients experienced severe EDS. By the first follow-up (median [IQR], 49 [28-94] days), mean (SD) ESS scores were within the normal EDS range with ON-SXB for both subgroups (ie, ESS < 10; switch, 9.7 [5.5]; not-on-oxybate, 9.5 [5.2]); the majority reported normal levels of daytime sleepiness (switch, 56%; not-on-oxybate, 57%). Mean (SD) change in ESS score from baseline to follow-up was -1.6 [4.5] for switch and -3.1 [5.0] for not-on-oxybate groups. Conclusion Patients who initiated ON-SXB experienced improvements in daytime sleepiness regardless of prior TN-OXB use, and many achieved normal levels of daytime sleepiness in ≤2 months of starting ON-SXB. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Zolpidem is a commonly prescribed FDA- approved hypnotic. In 2013, the FDA recommended reducing maximum dosing of zolpidem in female patients due to concern for slower elimination time as compared to their male counterparts. Despite this, none of the FDA warnings or communications cited published studies that support the claim that women are at increased risk of adverse events. Subsequent prescribing data has shifted to reflect FDA recommendations. In this study we examined risks of using above FDA recommended doses in female patients. Methods This is a retrospective chart review including all adult female patients (> 18 years old) evaluated and managed at the Mayo Clinic Center for Sleep Medicine between 1/1/2024 to 12/31/2024. Detailed review of Mayo Clinic’s EMR was accomplished with subjects on zolpidem split into supratherapeutic and non-supratherapeutic dosing groups. Subjects were relegated to the above maximum dose group if they were ever prescribed FDA-defined supratherapeutic dosing (>5 mg IR formulation or >6.25 mg ER formulation) for a >1 week period. Adverse events were defined as: falls, parasomnias, and cognitive impairment determined via ICD-10-CM codes that occurred at any period following zolpidem initiation. We analyzed rates of adverse effects using chi-square test of independence and Fischer’s exact test in patients with or without supratherapeutic dosing. Results 435 female patients met inclusion criteria. Among the demographic characteristics, only weight was associated with receiving a higher dose of zolpidem (P< 0.001). There were similar rates of adverse effects in both dosing groups with 11.4% of female patients on supratherapeutic dosing as compared to 10.9% of female patients on non-supratherapeutic dosing reporting adverse effects (chi-square test of independence (X2=6.5, N=435, p=0.99) or Fischer’s exact test (OR=1.05, p=0.87). Conclusion Overall, there was not a significant difference in rates of adverse events in female patients receiving supratherapeutic vs non-supratherapeutic doses of zolpidem during the time frame described. Further studies are warranted to better elucidate longitudinal risk of adverse effects related to gender-related differences with zolpidem dosing. Support (if any)

Abstract Introduction Hypoglossal nerve stimulation (HGNS) is an effective therapy for moderate-to-severe obstructive sleep apnea (OSA) in patients intolerant of positive airway pressure. Comorbid insomnia (COMISA) is common and may shape their engagement. Despite reports of improved insomnia symptoms, real-world data suggest reduced adherence and increased support needs. This study evaluated the impact of COMISA on HGNS therapy patterns and outcomes. Methods We conducted a retrospective cohort study of 46 adults with OSA who underwent HGNS implantation at Mayo Clinic Rochester between July 2020 and August 2025. Patients were categorized as OSA alone or COMISA based on pre-implantation data, including documented insomnia diagnosis, insomnia severity index score ≥15, sleep initiation or maintenance complaints, hypnotic or melatonin use, participation in cognitive behavioral therapy for insomnia, or an insomnia care plan within one year prior to activation. We collected HGNS adherence metrics (30-day average nightly use, nightly pauses, percent nights used) at 1, 3, 6, and 12 months; non-visit HGNS-related clinical encounters at 6 and 12 months; and pre- and post-activation AHI from polysomnography or home sleep apnea testing. Longitudinal outcomes were analyzed using mixed-effects models with fixed effects for time and COMISA status and a random intercept for patient. Results The cohort was 54% male and 98% White, with median age 66 years and BMI 31 kg/m2 (24–34). Median pre-implant AHI was 27 (19–40), and 30 patients (65%) had COMISA. Median nightly HGNS use declined from 7.8 to 6.6 hours from 1 to 12 months; mixed-effects modeling confirmed significant decreases over time (p≤0.03). Median nightly therapy pauses increased from 0.1 to 0.5, and median non-visit clinical encounters increased cumulatively from 2.5 at 6 months to 3.0 by 12 months (both p≤0.01). Median AHI reduction was 18.5 (2–27) (p=0.047). There were no statistically significant differences between OSA-alone and COMISA groups in HGNS adherence trajectories, therapy pauses, support needs, or AHI improvement (all p>0.05). Conclusion Although HGNS use declined modestly over time, COMISA was not statistically associated with differences in adherence, clinical support needs, or treatment response. Directional trends suggest greater adaptation challenges among patients with COMISA, warranting evaluation in larger prospective studies. Support (if any)

Abstract Introduction Isolated REM sleep behavior disorder (iRBD) is characterized by loss of normal REM sleep atonia and dream enactment behavior. iRBD is strongly associated with α-synucleinopathies and risk for developing Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), yet phenoconversion risk for long-term outcomes of younger women and men remains undefined. We aimed to ascertain longitudinal outcomes and phenoconversion risk in the Mayo Clinic iRBD cohort. Methods Eighty-nine of 165 registry participants with at least one-year follow-up were included. Retrospective chart review attained baseline demographics, age at presentation, baseline Timed Up and Go (TUG) and Montreal Cognitive Assessment (MoCA) scores, and phenoconversion status (iRBD, PD, DLB, mild cognitive impairment [MCI], MSA, or other). Kaplan–Meier survival analysis and Cox proportional hazards modeling were analyzed with alpha at p < 0.05. Results 68 men and 21 women had a mean age of 63 years at polysomnographic diagnosis. At follow-up, 64 (71.9%) remained iRBD; 7 (7.9%) developed PD, 11 (12.4%) developed DLB, 3 (3.4%) developed MCI, 1 (1.1%) developed MSA, and 3 (3.4%) developed another dementia. Abnormal TUG (>12 seconds) occurred in 5.9% and abnormal MoCA (< 24) in 23.3%. Phenoconversion rates were similar in women and men (p = 0.44). Older age at PSG predicted phenoconversion, corresponding to a two-fold increase in risk with each 10-year increase (HR 2.00, 95% CI 1.15–3.52). Neither abnormal TUG nor MoCA predicted conversion. Cumulative phenoconversion was approximately 1% at 1 year, 7% at 3 years, 10% at 5 years, 30% at 10 years, 34% at 12 years, and 49% at 15 years. Mean and median time to phenoconversion was 7 years (range, 1-18 years). Conclusion We found that iRBD phenoconversion rates were lower than historically reported. Only age at presentation predicted phenoconversion, with risk doubling per decade. At 12 years, cumulative phenoconversion rate was approximately 34%. Support (if any)

Abstract Introduction Adherence to continuous positive airway pressure (CPAP) therapy is difficult for many patients with obstructive sleep apnea. Clinical outcomes are improved with CPAP adherence ≥6 hr/night, yet scalable approaches to personalized support are limited. We developed a theory-based, clinic experience–driven conceptual dynamical model for optimizing CPAP use and applied it to a ‘just-in-time’ adaptive version of SleepWell24, a smartphone application integrating near–real-time wearable data, CPAP use, and patient-reported symptoms and CPAP-related problems with evidence-based behavior change interventions. In this feasibility optimization trial, we examined patient acceptability and initial outcomes of the adaptive SleepWell24 platform, and guided by the conceptual model, evaluated a control systems engineering approach to demonstrate, in simulation, improved CPAP adherence. Methods Aim 1: Naïve CPAP users (N=10; M age=61.7, 60% female) participated in this 60-day ongoing trial. Patients were encouraged to interact daily with SleepWell24 to report symptoms, receive personalized troubleshooting recommendations, set goals, and receive feedback on CPAP use (via Wi-Fi-enabled smart plug assessing CPAP ‘on/off state’) and sleep/activity (Fitbit). We assessed SleepWell24 use, post-intervention acceptability, and consistent CPAP use defined as ≥6hr, for ≥6nights/week for ≥2 consecutive weeks. Aim 2: The conceptual model of CPAP adherence produced a dynamical system, informed by Model Predictive Control (MPC) as a decision-making algorithm to optimize CPAP use to ≥6hr/night by tailoring actionable behavioral recommendations using patient data integrated in real-time. Results Aim 1: Across the 60-day trial, average daily SleepWell24 engagement was 72.7%. Median CPAP adherence of ≥6hr/night was 65.8%. All participants (100%) rated SleepWell24 as moderately-to-totally acceptable and would recommend it; perceived helpfulness averaged 7.0 (of 10). Eighty percent achieved consistent CPAP use. Aim 2: In simulation, the MPC framework managed CPAP-associated symptoms (e.g., nasal, anxiety, leak) and adjusted CPAP use goals, improving predicted CPAP adherence and sleep duration and quality. Conclusion SleepWell24 was engaging, acceptable, and helpful, with most users reaching optimal CPAP use. We will next estimate dynamical models using data from trial patients, a necessary step towards full automation of SleepWell24. Support (if any) AASMF #285-SR-22

Abstract Introduction Hypoglossal nerve stimulators (HGNS) are used in patients with moderate-to-severe obstructive sleep apnea (OSA) who are unable to tolerate or do not respond to continuous positive airway pressure (CPAP) therapy. However, a subgroup of patients fail to achieve resolution of OSA with HGNS alone. Previous studies have shown that lower BMI, lower nadir oxygenation, decreased sleep latency, and higher VOTE score on drug-induced sleep endoscopy (DISE) predict better treatment outcome. We hypothesize that baseline diagnostic polysomnography (PSG) may further predict which patients will achieve successful therapeutic outcome with HGNS therapy. Methods We conducted a retrospective analysis of all adult patients who underwent HGNS implantation at Mayo Clinic Arizona between 2019-2025 and had a pre-implantation diagnostic PSG available for review. Treatment success was defined by Sher Criteria: >50% reduction in post-treatment apnea hypopnea index (AHI) to a final AHI of < 20/hr. Responders met Sher criteria and non-responders did not meet Sher criteria. Demographics, sleep questionnaire results, PSG variables, and VOTE score on DISE were collected and analyzed using Spearman’s rank correlation of reduction in AHI. Results Twenty-three patients (11M/12F, median age: 69[IQR:64,75] years) met inclusion criteria. Median baseline AHI was 24[IQR:19,37]/hr. Median post-implant AHI was 8 [IQR:3, 14]/hr. Responders (n=15, 65%) and non-responders (n=8, 35%) demonstrated median post-implant AHI of 4.5[IQR:2.3,7.3]/hr and 15.7[IQR:12.3,28.5]/hr, respectively. Treatment response was associated with less time with SpO2 < 88% (T88%) (21min [IQR:3,64] vs. 73[IQR:36,105mins]; p=0.023) and higher central apnea index (CAI) (1[IQR:0.1,3] vs. 0[IQR:0,1], p=0.03) on pre-implantation PSG. Conclusion In this small cohort of OSA patients, less nocturnal hypoxemia as defined by T88% and higher baseline central apnea index were predictors of better treatment response to HGNS therapy as measured by Sher criteria. We hypothesize that greater nocturnal hypoxemia likely reflects more severe airway obstruction during sleep. Our analysis also showed that responders had higher baseline CAI than non-responders, however we believe this association is not clinically significant and likely driven by one outlier (CAI 13/hr). Further analysis in a larger HGNS cohort is needed to confirm these findings. Data enrichment efforts and more sophisticated analyses are underway. Support (if any)

Abstract Introduction Sodium oxybate is strongly recommended by the American Academy of Sleep Medicine for the treatment of narcolepsy, a chronic sleep disorder characterized by excessive daytime sleepiness (EDS). This study was conducted to characterize demographic characteristics and concomitant medication use of patients with narcolepsy treated or not treated with oxybates (OXB). Methods An electronic health record–based search identified first-time patients from Mayo Clinic and Duke Health between 2002-2024 and 2012-2024, respectively. Patients had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (via natural language processing algorithm). Patients from both Mayo Clinic and Duke Health who were or were not treated with OXB were identified. Data were analyzed descriptively. Results Of 4722 patients, 654 (Mayo Clinic, n=378; Duke Health, n=276) received OXB, and 4068 (Mayo Clinic, n=2800; Duke Health, n=1268) received non-OXB treatments. The majority of patients were white (OXB-treated: 92.1%, 73.6%; non–OXB-treated: 91.1%, 69.2%) and female (OXB-treated: 68.3%, 76.8%; non–OXB-treated: 61.7%, 68.1%). Most OXB-treated patients (65.3%; 63.4%) had narcolepsy type 1 (NT1); the majority of non–OXB-treated patients (78.1%; 64.0%) had narcolepsy type 2 (NT2). The mean (SD) age of the OXB-treated cohort was younger than the non–OXB-treated cohort at the time of diagnosis (OXB-treated: 33.9 [15.3] years, 35.7 [13.2] years; non–OXB-treated: 45.5 [19.2] years, 42.5 [17.8] years). For both cohorts, the most common concomitant medications were stimulants (OXB-treated: 50.3%, 42.8%; non–OXB-treated: 41.8%, 35.2%). Conclusion In this retrospective analysis of nearly 5000 patients from Mayo Clinic and Duke Health, approximately 1 in 8 received OXB. While sodium oxybate has been approved for >2 decades and is strongly recommended for treatment of both EDS and cataplexy in narcolepsy, substantially greater OXB utilization was observed in patients with NT1. As both patients with NT1 and NT2 can experience other narcolepsy symptoms, further OXB-related education remains critical—particularly on the efficacy of sodium oxybate in the treatment of NT2. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) was the first study to evaluate effectiveness/safety of low-sodium oxybate (LXB; Xywav®) >9 g/night (outside the recommended range: 6–9 g/night). This analysis evaluated changes in patient-reported hypersomnolence measures in participants with narcolepsy taking LXB >9 g/night compared with LXB 9 g/night. Methods DUET was a phase 4, prospective, open-label study with screening, 8-day LXB 9 g/night (9g-baseline), titration/optimization, stable-dose, and 8-day end-of-treatment (EOT) optimized LXB >9 g/night (up to 12g; >9g-EOT) periods. Patient-reported measures included Epworth Sleepiness Scale (ESS), electronic sleep diaries (completed daily during 9g-baseline and >9g-EOT; subjective total sleep time [TST], number of awakenings, sleep efficiency [TST divided by time in bed], sleep quality [5-point scale; “very good” to “very poor”], and how rested/refreshed the participant felt upon awakening [5-point scale; “very well” to “not at all”]), Karolinska Sleepiness Scale (KSS; administered 90 minutes post-polysomnography awakening at 9g-baseline and >9g-EOT), and Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10). LSM differences (95% CI) from 9g-baseline to >9g-EOT (nominal P-values) were 9g-baseline-adjusted. Results Forty-eight participants took LXB >9g (mean±SD age: 39.2±10.9 years; 62.5% female). Total stable-dose LXB (mean±SD) was 11.1±1.0 g/night (n=45). From 9g-baseline to >9g-EOT, ESS scores improved (LSM [95% CI]: –3.1 [–4.2, –1.9]; P< 0.0001; n=44), nocturnal TST increased (0.3h [0.1, 0.4]; P=0.0163; n=26), sleep efficiency increased (3.8% [1.7, 5.9]; P=0.0011; n=26), and number of awakenings remained stable (–0.2 [–0.7, 0.3]; P=0.3959; n=26). Percentage of participants rating sleep quality as “very good”/”good” increased from 26.9% (9g-baseline) to 61.5% (>9g-EOT), as did rested sleep (“very well”/”well”/”somewhat” rested) from 57.7% to 69.2%, respectively. From 9g-baseline to >9g-EOT, KSS scores decreased (–0.9 [–1.4, –0.4]; P=0.0004; n=39); FOSQ-10 scores also increased (1.3 [0.5, 2.0]; P=0.0014; n=40). Of 48 participants, 36 (75.0%) experienced ≥1 TEAE (mostly mild/moderate and 1 serious [syncope, unrelated to treatment]). No changes in respiratory polysomnography measures were observed. Conclusion Participants with narcolepsy who optimized to LXB >9 g/night, relative to 9 g/night, reported increased sleep quality and restfulness that paralleled improvements in daytime sleepiness and daytime functioning. TEAEs were consistent with those at lower dosages. Support (if any) Jazz Pharmaceuticals

Abstract Introduction Obstructive sleep apnea is an increasingly common condition seen in sleep medicine with prevalence estimates of up to 1 billion patients globally. Treatment with CPAP machines is the mainstay of therapy for patients with moderate-severe OSA, but is resource intensive due to the need for complex electronic equipment and frequent supply refills. The United States healthcare system is estimated to produce.9 million tons of solid waste annually; however, it has not been determined how sleep medicine clinical practices contribute to this total. The purpose of this study was to estimate the total solid waste produced by the treatment of moderate-severe OSA with CPAP in the U.S. over a 10 year period. Methods We modeled waste generation under a steady-state CPAP-treated population (4.8 or 24 million patients), assuming an annual 15% exit/entry rate. Each new patient was assigned a CPAP machine at initiation; existing users contributed waste from ongoing consumable use. Waste calculations included machine and accessory weight (masks, tubing, filters). We evaluated scenarios by varying mask type distribution, tubing type (heated; non-heated), and machine/supply replacement schedules to create total waste estimates. Results The solid waste associated with treating 4.8 million U.S. patients with moderate-severe OSA over ten years ranged from 88.7 to 104.4 kilotons. Maximum waste occurred with heated tubing use, CMS replacement schedules, 5-year device replacement, regardless of mask mix (104.4-104.5 kilotons). Waste was reduced by 15% using lightweight tubing and extending device life to 7 years, and by 45% using a reduced replacement schedule modeled on French practice (2–4 masks/year, 1 tubing/filter/year, 1 water reservoir/year). Conclusion Treatment with CPAP is a resource intensive therapy that produces a significant amount of plastic and electronic waste annually, likely contributing to ongoing environmental and climate degradation. Extending CPAP machine and supply lifespan and selecting for lighter PAP supplies, such as non-heated tubing, can significantly reduce the waste associated with U.S. CPAP use. Support (if any)