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Glenna S Brewster,1 Melinda Higgins,1 Miranda Varrasse McPhillips,2 Kalisha Bonds Johnson,1 Fayron Epps,1 Katherine A Yeager,1 Donald L Bliwise,3 Kenneth Hepburn1 1Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA; 2University of Pennsylvania, School of Nursing, Philadelphia, PA, USA; 3Division of Sleep Medicine, Emory University School of Medicine, Atlanta, GA, USACorrespondence: Glenna S Brewster, 1520 Clifton Road, NE, Atlanta, GA, 30322-4027, USA, Tel +1 404.712.9164, Email glenna.brewster@emory.eduIntroduction: Sleep disturbance is prevalent in caregivers of persons living with dementia (PLwD). Tele-Savvy, a 7-week virtual psychoeducational intervention, enhances caregivers’ competence and self-care, and reduces depression. While not explicitly designed to do so, Tele-Savvy can potentially improve caregivers’ disturbed sleep. The present study aimed to examine the longitudinal effects of Tele-Savvy on caregivers’ sleep quality and insomnia.Methods: This was a secondary data analysis of a 3-arm randomized control trial [Tele-Savvy (active treatment), Healthy Living (attention control), and usual care (waitlist control)]. Multilevel mixed modeling with intent-to-treat principles tested for group, time, and group-by-time effects. Effect sizes were estimated for all changes from baseline to the initial 6-month post-intervention point. Following completion of the 6-month post-randomization delay, we examined combined outcomes for Tele-Savvy.Results: Participants (n=137; mean age 64.7 years) were predominantly female (68.6%) and White (68.6%). We found no initial group-by-time effects for the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). For the combined Tele-Savvy group, there was a statistically significant improvement in ISI scores across time (p=0.050). The combined Tele-Savvy effect size for PSQI was d=0.126 and ISI was d=0.310.Discussion: Tele-Savvy resulted in a significant long-term reduction in insomnia symptoms in this sample of caregivers of PLwD and demonstrated a positive trend for improvement in their sleep quality. Since sleep disturbance is so prevalent among caregivers of PLwD, the inclusion of sleep health education into psychoeducation caregiver interventions may yield even better outcomes for caregivers.Plain Language Summary: Many caregivers of persons living with dementia have poor sleep. Tele-Savvy is a 7-week intervention that was delivered online to caregivers improved their caregiving skills and self-care and reduced their depressive symptoms; thus, Tele-Savvy may possibly improve their sleep problems. This study aimed to examine the effects of Tele-Savvy on caregivers’ sleep quality and insomnia over 6 months. Caregivers were randomly assigned to Tele-Savvy (intervention), Healthy Living (comparison intervention), and usual care (no initial intervention). One hundred and thirty-seven caregivers, predominantly female, who were on average 64.7 years, participated in this study and completed measures of insomnia and sleep quality. Insomnia symptoms improved and there was a positive trend for improved sleep quality across time for caregivers who received Tele-Savvy. Since so many caregivers have sleep problems, including sleep health education as a part of other caregiver interventions may lead to even better outcomes for caregivers.Keywords: psychoeducational intervention, Alzheimer’s disease, circadian rhythm, cognitive behavioral therapy for insomnia, depression

Background: This study sought to determine the 12-month effects of exercise increases on objective and subjective sleep quality in initially inactive older persons with mild to moderate sleep complaints.Methods: A nonclinical sample of underactive adults 55 years old or older (n=66) with mild to moderate chronic sleep complaints were randomly assigned to a 12-month program of primarily moderate-intensity endurance exercise (n=36) or a health education control program (n=30). The main outcome measure was polysomnographic sleep recordings, with additional measures of subjective sleep quality, physical activity, and physical fitness. Directional hypotheses were tested.Results: Using intent-to-treat methods, at 12 months exercisers, relative to controls, spent significantly less time in polysomnographically measured Stage 1 sleep (between-arm difference=2.3, 95% confidence interval [CI], 0.7-4.0; p=003), spent more time in Stage 2 sleep (between-arm difference=3.2, 95% CI, 0.6-5.7; p=.04), and had fewer awakenings during the first third of the sleep period (between-arm difference=1.0, 95% CI, 0.39-1.55; p=.03). Exercisers also reported greater 12-month improvements relative to controls in Pittsburgh Sleep Quality Index (PSQI) sleep disturbance subscale score (p=.009), sleep diary-based minutes to fall asleep (p=.01), and feeling more rested in the morning (p=.02).Conclusions: Compared with general health education, a 12-month moderate-intensity exercise program that met current physical activity recommendations for older adults improved some objective and subjective dimensions of sleep to a modest degree. The results suggest additional areas for investigation in this understudied area. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To determine the point prevalence of pulmonary hypertension (PH) and its relationship with respiratory disturbances in obese patients living at moderate altitude. SUBJECTS:: A total of 57 obese patients comprised the final sample and consisted of 34 women and 23 men, with a mean age of 42.7±12.1?ys and a mean body mass index (BMI) 47.1±10.6?kg/m2 (range from 30.1 to 76.1). The mean living altitude was 2248.7?m, range 2100-2400?m above sea level. MEASUREMENTS:: Doppler echocardiography, pulmonary function tests, arterial blood gas analysis, and polysomnography were performed. RESULTS:: Data showed that 96.5% of the studied sample had daytime PH defined as calculated systolic pulmonary artery pressure (PSAP) >30?mmHg (mean PSAP=50, s.d.=13?mmHg). The severity of diurnal PH was found to be related to the presence of alveolar hypoventilation and BMI. The main risk factor for severity of diurnal PH was hypoventilation with a significant odds ratio (OR) 7.96, 95% CI 1.35-46.84, BMI was (OR 1.12, 95% CI 1.02-1.25) and apnea/hypopnea index was not a predictor of pulmonary hypertension severity (OR 0.99, 95% CI 0.97-1.02). CONCLUSION:: We concluded that prevalence of diurnal PH is high in obese patients living at moderate altitude, and that hypoventilation is the main risk factor associated with the severity of pulmonary hypertension.International Journal of Obesity (2004) 28, 1174-1180. doi:10.1038/sj.ijo.0802726 Published online 29 June 2004 [ABSTRACT FROM AUTHOR]

Patients with dementias, such as Alzheimer's disease (AD), often have nocturnally disrupted sleep. Clinically, this may present as agitation during the nighttime hours, which may affect as many as a quarter of AD patients during some stage of their illness. Sleep disturbance in AD may be multifactorial and involve sleep-disordered breathing and disrupted chronobiology, both often characterized by excessive daytime napping. Polysomnographically, AD patients show decreased rapid eye movement (REM) sleep in proportion to the extent of their dementia; some evidence suggests that cholinesterase inhibitors, commonly used pharmacologic agents for cognitive loss in AD, may increase REM sleep measures. Unfortunately, such agents may also induce insomnia and vivid dreams. There have been no randomized clinical trials of sedative-hypnotic medications specifically targeted at AD patients with sleep problems. Evidence suggests that sedative-hypnotics, such as benzodiazepine site-specific agonists, may have a role in some cases, whereas atypical antipsychotics may be necessary in other cases. There are also reports of successful interventions with nonpharmacologic options (eg, exercise, illumination). The utility of melatonin as a hypnotic in this population appears equivocal. [ABSTRACT FROM AUTHOR]

Objectives: Restless legs syndrome (RLS), a common, treatable, sensorimotor disorder of nighttime uncomfortable leg sensations that interfere with sleep, may prompt nighttime agitation in persons with dementia., Design: This randomized trial was double-blind and placebo-controlled. Participants received a Food and Drug Administration-approved drug for RLS, gabapentin enacarbil (GEn) (Horizant) or placebo., Setting and Participants: Older adults (N = 147) with dementia due to Alzheimer's disease, nighttime agitation, and RLS, residing in long-term care or at home, participated., Methods: The primary outcome was change from baseline to 8 weeks in nighttime agitation between 5 pm and 7 am on the Cohen-Mansfield Agitation Inventory Index, Direct Observation. Multivariable linear mixed effects regression models based on multiply imputed data were estimated on nighttime agitation and sleep, with treatment group, week, the 2-way interaction of group and week as predictors, and mean arterial pressure as a covariate based on baseline group imbalances., Results: Mean age ± SD 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 8 weeks (estimate, -1.67; P = .003) and 2 weeks. Total sleep time (actigraphy) by group over time was significant at 8 weeks (estimate, 48.45; P = .026). Observed nighttime wake by group over time was significant at 2 (estimate, -12.54; P = .006) and 8 weeks (estimate, -11.12; P = .015). The number having ≥1 adverse events was 60 in the GEn group (81.1%) and 50 in the placebo group (68.5%); with 12 serious adverse events in placebo and 10 in the GEn group. The GEn group had a trend toward more falls (P = .066)., Conclusions and Implications: Our findings suggest a novel approach for nighttime agitation in persons with dementia: assessing for RLS and initiating interventions. Larger and longer trials are needed., Competing Interests: Disclosure D.L.B. has consulted for Ferring, Idorsia, and Merck. K.C.R. has consulted for Merck and Woolsey. These are not actual conflicts but could be construed as such. The other authors declare no conflicts of interest., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Nocturia (waking from sleep at night to void) and chronic insomnia frequently co-exist in older adults, contributing synergistically to sleep disturbance. Treatments typically target either nocturia or insomnia rather than simultaneously addressing shared mechanisms for these disorders., Methods: We conducted a multisite feasibility study to: (1) test and refine a protocol for recruitment, randomization, and assessment of older adults with co-existing nocturia and insomnia; and (2) examine preliminary changes in outcome measures to inform a future larger, multisite clinical trial. Participants were men and women aged 60 years and older recruited from outpatient clinics, reporting an average of two or more nocturia episodes per night over the past 4 weeks and meeting diagnostic criteria for chronic insomnia disorder. Participants were randomized to receive either integrated cognitive-behavioral therapy for insomnia and nocturia or a health education control program involving five weekly visits with a trained nurse practitioner interventionist. Outcomes (e.g., nocturia episodes) were measured 1-week post-treatment and 4-month post-randomization. Descriptive statistics examined the feasibility of outcomes to guide preparations for a future efficacy trial., Results: Of 245 adults screened, 55% were ineligible and 25% declined to participate. Sixty-one percent of 49 participants who provided informed consent were randomized. Of the 30 participants randomized (mean age = 70.6 years, 60% White), 14 were assigned to integrated cognitive-behavioral treatment and 16 to the control group. All randomized participants provided 4-month follow-up data. At 4 months, mean nightly nocturia episodes decreased by 0.9 (SD 1.0) in the integrated treatment group and by 0.2 (SD 1.2) in the control group compared with baseline., Discussion: Findings demonstrate the feasibility of recruiting, randomizing, and collecting outcome data from older adults (predominantly male) assigned to an integrated cognitive-behavioral therapy for coexisting insomnia and nocturia or a health education control program., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background and Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD., Methods: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5., Results: Of 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease., Discussion: Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings., Trial Registration Information: NCT03623672.

Background and Objective: Although there are several treatments for narcolepsy type 2 and idiopathic hypersomnia, studies that assess amphetamines, symptoms beyond sleepiness, and comparative effectiveness are needed. We performed a randomized, fully blinded, noninferiority trial of modafinil versus amphetamine-dextroamphetamine in these disorders., Methods: Forty-four adults were randomized to modafinil or amphetamine-dextroamphetamine, individually titrated to a maximum of modafinil 200 mg twice daily or amphetamine-dextroamphetamine 20 mg twice daily, for 12 weeks. Primary outcome was change in Epworth from baseline to week 12, with a noninferiority threshold of 2 points. Secondary outcomes were (1) patient global impression of change measures of disease severity, sleepiness, sleep inertia, and cognition; (2) change from baseline in Hypersomnia Severity Index; and (3) change from baseline in Sleep Inertia Questionnaire. Adverse events were compared between groups., Results: Epworth improved 5.0 [± standard deviation (SD) 2.7] points with modafinil and 4.4 (± SD 4.7) with amphetamine-dextroamphetamine; noninferiority of amphetamine-dextroamphetamine was not demonstrated (P = 0.11). Noninferiority of amphetamine-dextroamphetamine was demonstrated for change scores of severity, sleepiness, sleep inertia, Hypersomnia Severity Index, and Sleep Inertia Questionnaire. Dropouts due to adverse events were 31.8% for modafinil (including two severe events) and 9.1% for amphetamine-dextroamphetamine, P = 0.13. Anxiety was more common with modafinil and appetite suppression with amphetamine-dextroamphetamine., Conclusion: Noninferiority of amphetamine-dextroamphetamine to modafinil was not demonstrated for the primary outcome. However, amphetamine-dextroamphetamine was noninferior on multiple secondary measures of disease severity and symptomatology. These data may inform shared decision-making regarding treatment for idiopathic hypersomnia and narcolepsy type 2., Registration: Clinicaltrials.gov Registration (NCT03772314) 12/10/18. ., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Study Objectives: Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinson's disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)-henceforth "neurotrauma" (NT)-increase the odds of RBD by ~2.5-fold and are associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD., Methods: Participants ≥18 years with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal Synucleinopathy Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory, and autonomic function, were completed. This cross-sectional analysis compared cases (n = 24; RBD + NT) to controls (n = 96; RBD), matched for age (~60 years), sex (15% female), and years of education (~15 years)., Results: RBD + NT reported earlier RBD symptom onset (37.5 ± 11.9 vs. 52.2 ± 15.1 years of age) and a more severe RBD phenotype. Similarly, RBD + NT reported more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to RBD. No differences in olfaction or color vision were observed., Conclusions: This cross-sectional, matched case:control study shows individuals with RBD + NT have significantly worse neurological measures related to common features of an overt synucleinopathy. Confirmatory longitudinal studies are ongoing; however, these results suggest RBD + NT may be associated with more advanced neurological symptoms related to an evolving neurodegenerative process., (Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2024.)

Importance: Obstructive sleep apnea (OSA) is a common condition in older adult (aged >65 years) populations, but more mechanistic research is needed to individualize treatments. Previous evidence has suggested an association between OSA and posttraumatic stress disorder (PTSD) but is limited by possible selection bias. High-quality research on this association with a careful evaluation of possible confounders may yield important mechanistic insight into both conditions and improve treatment efforts., Objective: To investigate the association of current PTSD symptoms and PTSD diagnosis with OSA., Design, Setting, and Participants: This cross-sectional study of twin pairs discordant for PTSD, which allows for adjustment for familial factors, was conducted using in-laboratory polysomnography from March 20, 2017, to June 3, 2019. The study sample comprised male veteran twins recruited from the Vietnam Era Twin Registry. The data analysis was performed between June 11, 2022, and January 30, 2023., Exposure: Symptoms of PTSD in twins who served in the Vietnam War. Diagnosis of PTSD was a secondary exposure., Main Outcomes and Measures: Obstructive sleep apnea was assessed using the apnea-hypopnea index (AHI) (≥4% oxygen saturation criterion as measured by events per hour) with overnight polysomnography. Symptoms of PTSD were assessed using the PTSD Checklist (PCL) and structured clinical interview for PTSD diagnosis., Results: A total of 181 male twins (mean [SD] age, 68.4 [2.0] years) including 66 pairs discordant for PTSD symptoms and 15 pairs discordant for a current PTSD diagnosis were evaluated. In models examining the PCL and OSA within pairs and adjusted for body mass index (BMI) and other sociodemographic, cardiovascular, and psychiatric risk factors (including depression), each 15-point increase in PCL was associated with a 4.6 (95% CI, 0.1-9.1) events-per-hour higher AHI. Current PTSD diagnosis was associated with an adjusted 10.5 (95% CI, 5.7-15.3) events-per-hour higher AHI per sleep-hour. Comparable standardized estimates of the association of PTSD symptoms and BMI with AHI per SD increase (1.9 events per hour; 95% CI, 0.5-3.3 events per hour) were found., Conclusions and Relevance: This cross-sectional study found an association between PTSD and sleep-disordered breathing. The findings have important public health implications and may also enhance understanding of the many factors that potentially affect OSA pathophysiology.

Background: Autonomic function can be measured noninvasively using heart rate variability (HRV), which indexes overall sympathovagal balance. Deceleration capacity (DC) of heart rate is a more specific metric of vagal modulation. Higher values of these measures have been associated with reduced mortality risk primarily in patients with cardiovascular disease, but their significance in community samples is less clear., Methods and Results: This prospective twin study followed 501 members from the VET (Vietnam Era Twin) registry. At baseline, frequency domain HRV and DC were measured from 24-hour Holter ECGs. During an average 12-year follow-up, all-cause death was assessed via the National Death Index. Multivariable Cox frailty models with random effect for twin pair were used to examine the hazard ratios of death per 1-SD increase in log-transformed autonomic metrics. Both in the overall sample and comparing twins within pairs, higher values of low-frequency HRV and DC were significantly associated with lower hazards of all-cause death. In within-pair analysis, after adjusting for baseline factors, there was a 22% and 27% lower hazard of death per 1-SD increment in low-frequency HRV and DC, respectively. Higher low-frequency HRV and DC, measured during both daytime and nighttime, were associated with decreased hazard of death, but daytime measures showed numerically stronger associations. Results did not substantially vary by zygosity., Conclusions: Autonomic inflexibility, and especially vagal withdrawal, are important mechanistic pathways of general mortality risk, independent of familial and genetic factors.

Background and Objectives: REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment. The International RBD Study Group developed the RBD Symptom Severity Scale (RBDSSS) to assess symptom severity for clinical or research use. We assessed the psychometric and clinimetric properties of the RBDSSS in participants enrolled in the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD., Methods: NAPS participants, who have polysomnogram-confirmed RBD, and their bedpartners completed the RBDSSS (participant and bedpartner versions). The RBDSSS contains 8 questions to assess the frequency and severity/impact of (1) dream content, (2) vocalizations, (3) movements, and (4) injuries associated with RBD. Total scores for participant (maximum score = 54) and bedpartner (maximum score = 38) questionnaires were derived by multiplying frequency and severity scores for each question. The Clinical Global Impression Scale of Severity (CGI-S) and RBD symptom frequency were assessed by a physician during a semistructured clinical interview with participants and, if available, bedpartners. Descriptive analyses, correlations between overall scores, and subitems were assessed, and item response analysis was performed to determine the scale's validity., Results: Among 261 study participants, the median (interquartile range) score for the RBDSSS-PT (participant) was 10 (4-18) and that for the RBDSSS-BP (bedpartner) was 8 (4-15). The median CGI-S was 3 (3-4), indicating moderate severity. RBDSSS-BP scores were significantly lower in women with RBD (6 vs 9, p = 0.02), while there were no sex differences in RBDSSS-PT scores (8 vs 10.5, p = 0.615). Positive correlations were found between RBDSSS-PT vs RBDSSS-BP (Spearman r s = 0.561), RBDSSS-PT vs CGI-S ( r s = 0.556), and RBDSSS-BP vs CGI-S ( r s = 0.491, all p < 0.0001). Item response analysis showed a high discriminatory value (range 1.40-2.12) for the RBDSSS-PT and RBDSSS-BP (1.29-3.47)., Discussion: We describe the RBDSSS with adequate psychometric and clinimetric properties to quantify RBD symptom severity and good concordance between participant and bedpartner questionnaires and between RBDSSS scores and clinician-assessed global severity.

Study Objectives: Accurate diagnosis of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is crucial due to its injury potential and neurological prognosis. We aimed to analyze visual and automated REM sleep without atonia (RSWA) diagnostic thresholds applicable in varying clinical presentations in a contemporary cohort of patients with iRBD using submentalis (SM) and individual bilateral flexor digitorum superficialis (FDS) and anterior tibialis electromyography limb recordings during polysomnography., Methods: We analyzed RSWA in 20 patients with iRBD and 20 age-, REM-, apnea-hypopnea index-matched controls between 2017 and 2022 for phasic burst durations, density of phasic, tonic, and "any" muscle activity (number of 3-second mini-epochs containing phasic or tonic muscle activity divided by the total number of REM sleep 3-second mini-epochs), and automated Ferri REM atonia index (RAI). Group RSWA metrics were comparatively analyzed. Receiver operating characteristic curves determined optimized area under the curve (AUC) and maximized specificity and sensitivity diagnostic iRBD RSWA thresholds., Results: All mean RSWA metrics were higher in patients with iRBD than in controls ( P < .05), except for selected anterior tibialis measures. Optimized, maximal specificity AUC diagnostic cutoffs for coprimary outcomes were: SM "any" 6.5%, 14.0% (AUC = 92.5%) and combined SM+FDS "any" 15.1%, 27.4% (AUC = 95.8%), while SM burst durations were 0.72, and 0.72 seconds (AUC 90.2%) and FDS RAI = 0.930, 0.888 (AUC 92.8%)., Conclusions: This study provides evidence for current quantitative RSWA diagnostic thresholds in chin and individual 4 limb muscles applicable in different iRBD clinical settings and confirms the key value of SM or SM+FDS to assure accurate iRBD diagnosis. Evolving iRBD recognition underscores the necessity of continuous assessment with future large, prospective, well-harmonized, multicenter polysomnographic analyses., Citation: Leclair-Visonneau L, Feemster JC, Bibi N, et al. Contemporary diagnostic visual and automated polysomnographic REM sleep without atonia thresholds in isolated REM sleep behavior disorder. J Clin Sleep Med . 2024;20(2):279-291., (© 2024 American Academy of Sleep Medicine.)

Importance: Sham-controlled trials are needed to characterize the effect of hypoglossal nerve stimulation (HGNS) therapy on cardiovascular end points in patients with moderate-severe obstructive sleep apnea (OSA)., Objective: To determine the effect of therapeutic levels of HGNS, compared to sham levels, on blood pressure, sympathetic activity, and vascular function., Design, Setting, and Participants: This double-blind, sham-controlled, randomized crossover therapy trial was conducted from 2018 to 2022 at 3 separate academic medical centers. Adult patients with OSA who already had an HGNS device implanted and were adherent and clinically optimized to HGNS therapy were included. Participants who had fallen asleep while driving within 1 year prior to HGNS implantation were excluded from the trial. Data analysis was performed from January to September 2022., Interventions: Participants underwent a 4-week period of active HGNS therapy and a 4-week period of sham HGNS therapy in a randomized order. Each 4-week period concluded with collection of 24-hour ambulatory blood pressure monitoring (ABPM), pre-ejection period (PEP), and flow-mediated dilation (FMD) values., Main Outcomes and Measures: The change in mean 24-hour systolic blood pressure was the primary outcome, with other ABPM end points exploratory, and PEP and FMD were cosecondary end points., Results: Participants (n = 60) were older (mean [SD] age, 67.3 [9.9] years), overweight (mean [SD] body mass index, calculated as weight in kilograms divided by height in meters squared, 28.7 [4.6]), predominantly male (38 [63%]), and had severe OSA at baseline (mean [SD] apnea-hypopnea index, 33.1 [14.9] events/h). There were no differences observed between active and sham therapy in 24-hour systolic blood pressure (mean change on active therapy, -0.18 [95% CI, -2.21 to 1.84] mm Hg), PEP (mean change on active therapy, 0.11 [95% CI, -5.43 to 5.66] milliseconds), or FMD (mean change on active therapy, -0.17% [95% CI, -1.88% to 1.54%]). Larger differences between active and sham therapy were observed in a per-protocol analysis set (n = 20) defined as experiencing at least a 50% reduction in apnea-hypopnea index between sham and active treatment., Conclusions and Relevance: In this sham-controlled HGNS randomized clinical trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different between sham and active HGNS therapy. Several methodologic lessons can be gleaned to inform future HGNS randomized clinical trials., Trial Registration: ClinicalTrials.gov Identifier: NCT03359096.

Background and Objectives: Although orthostatic hypotension (OH) can be an early feature of autonomic dysfunction in isolated REM sleep behavior disorder (iRBD), no large-scale studies have examined the frequency of OH in iRBD. In this study, we prospectively evaluated the frequency of OH in a large multicenter iRBD cohort., Methods: Participants 18 years or older with video polysomnogram-confirmed iRBD were enrolled through the North American Prodromal Synucleinopathy consortium. All participants underwent 3-minute orthostatic stand testing to assess the frequency of OH, and a Δ heart rate/Δ systolic blood pressure (ΔHR/ΔSBP) ratio <0.5 was used to define reduced HR augmentation, suggestive of neurogenic OH. All participants completed a battery of assessments, including the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction (SCOPA-AUT) and others assessing cognitive, motor, psychiatric, and sensory domains., Results: Of 340 iRBD participants (65 ± 10 years, 82% male), 93 (27%) met criteria for OH (ΔHR/ΔSBP 0.37 ± 0.28; range 0.0-1.57), and of these, 72 (77%) met criteria for OH with reduced HR augmentation (ΔHR/ΔSBP 0.28 ± 0.21; range 0.0-0.5). Supine hypertension (sHTN) was present in 72% of those with OH. Compared with iRBD participants without OH, those with OH were older, reported older age of RBD symptom onset, and had worse olfaction. There was no difference in autonomic symptom scores as measured by SCOPA-AUT., Discussion: OH and sHTN are common in iRBD. However, as patients may have reduced autonomic symptom awareness, orthostatic stand testing should be considered in clinical evaluations. Longitudinal studies are needed to clarify the relationship between OH and phenoconversion risk in iRBD., Trial Registration Information: ClinicalTrials.gov: NCT03623672; North American Prodromal Synucleinopathy Consortium.

Competing Interests: Competing interests: None declared.

Study Objectives: Social support (SS) is associated with better health outcomes, including sleep health. However, the specific sources of SS that benefit sleep are unclear, and whether these associations vary by race/ethnicity or age is unknown. The aim of this study was to examine cross-sectional associations between sources of SS (number of friends, financial, church attendance, and emotional support) and self-reported short sleep duration (< 7 hours) overall and by race/ethnic groups and age among a representative sample., Methods: Using National Health and Nutrition Examination Survey (NHANES) data, logistic regression (marginal standardization) and linear regression models were fit accounting for survey design and weights to test associations between sources of SS (number of friends, financial, church attendance, emotional support) and self-reported short sleep duration (< 7 hours) overall and by race/ethnic groups (Black, Hispanic, and White) and age (< 65 vs ≥ 65 years)., Results: Among 3,711 participants, the mean (standard error) age was 57 (0.3) years and 37% slept < 7 hours. Black adults had the highest prevalence of short sleep (55%). Overall, participants with financial support compared with those without financial support had a lower prevalence of short sleep: 23% (confidence interval [CI]: 0.68, 0.87). As the number of SS sources increased, the prevalence of short sleep duration decreased and the racial disparity in sleep duration narrowed. Associations between financial support and sleep were most pronounced among Hispanic and White adults and adults < 65 years., Conclusions: In general, financial support was associated with a healthier sleep duration, particularly among those < 65 years of age. Individuals with numerous sources of SS were less likely to be short sleepers. The benefits of SS on sleep duration varied by race. Targeting specific sources of SS may help to improve sleep duration among those most at risk., Citation: Johnson DA, Prakash-Asrani R, Lewis BD, Bliwise DL, Lewis TT. Racial/ethnic differences in the beneficial effect of social support on sleep duration. J Clin Sleep Med . 2023;19(7):1231-1238., (© 2023 American Academy of Sleep Medicine.)

Objective: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment., Methods: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were enrolled from nine sites across North America (8/2018 to 4/2021). Data collection included family/personal history of RBD and standardized assessments of cognitive, motor, sensory, and autonomic function., Results: Outcomes are primarily reported based on sex (361 total: n = 295 male, n = 66 female), and secondarily based on history of antidepressant use (n = 200 with, n = 154 without; with correction for sex differences) and based on extent of synucleinopathy burden (n = 56 defined as isolated RBD, n = 305 defined as RBD+ [i.e., exhibiting ≥1 abnormality]). Overall, these participants commonly demonstrated abnormalities in global cognition (MoCA; 38%), motor function (alternate tap test; 48%), sensory (BSIT; 57%), autonomic function (orthostatic hypotension, 38.8%), and anxiety/depression (BAI and PHQ-9; 39.3% and 31%, respectively)., Interpretation: These RBD participants, assessed with extensive history, demographic, cognitive, motor, sensory, and autonomic function demonstrated a lack of sex differences and high frequency of concomitant neurological abnormalities. These participants will be valuable for future longitudinal study and neuroprotective clinical trials., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: "Sleep CALM"-Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications., Methods: Narrative review of current evidence regarding the relevance of each "Sleep CALM" factor to nocturia pathogenesis, evaluation, and management., Results: Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment., Conclusion: "Sleep CALM" provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best-practice guidelines for nocturia. Although not intended as an all-encompassing diagnostic tool, the "Sleep CALM" schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first-line treatment targets., (© 2023 Wiley Periodicals LLC.)

Introduction: Aging is associated with a combination of several lower urinary tract (LUT) signs and symptoms, including residual urine, overactive bladder and nocturia. One of the mechanisms of this LUT dysfunction that has not been discussed in dept so far is the role of dopamine (DA)., Methods: In this narrative review, we explore the dopaminergic hypothesis in the development of this combination of LUT signs and symptoms in older adults., Results: DA is one of the neurotransmitters whose regulation and production is disrupted in aging. In synucleinopathies, altered DAergic activity is associated with the occurrence of LUTS and sleep disorders. Projections of DAergic neurons are involved in the regulation of sleep, diuresis, and bladder activity. The low dopamine hypothesis could explain the genesis of a set of LUT signs and symptoms commonly seen in this population, including elevated residual urine, Overactive bladder syndrome and Nocturia (discussed as the RON syndrome). This presentation is however also common in older patients without synucleinopathies or neurological disorders and therefore we hypothesise that altered DAergic activity because of pathological aging, and selective destruction of DAergic neurons, could underpin the presentation of this triad of LUT dysfunction in the older population., Conclusion: The concept of RON syndrome helps to better understand this common phenotypic presentation in clinical practice, and therefore serves as a useful platform to diagnose and treat LUTS in older adults. Besides recognizing the synucleinopathy "red flag" symptoms, this set of multi-causal LUT signs and symptoms highlights the inevitable need for combination therapy, a challenge in older people with their comorbidities and concomitant medications., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)