Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Upsetting the Balance: How Modifiable Risk Factors Contribute to the Progression of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder affecting nearly one in nine older adults in the US. This number is expected to grow exponentially, thereby increasing stress on caregivers and health systems. While some risk factors for developing AD are genetic, an estimated 1/3 of AD cases are attributed to lifestyle. Many of these risk factors emerge decades before clinical symptoms of AD are detected, and targeting them may offer more efficacious strategies for slowing or preventing disease progression. This review will focus on two common risk factors for AD, metabolic dysfunction and sleep impairments, and discuss potential mechanisms underlying their relationship to AD pathophysiology. Both sleep and metabolism can alter AD-related protein production and clearance, contributing to an imbalance that drives AD progression. Additionally, these risk factors have bidirectional relationships with AD, where the presence of AD-related pathology can further disrupt sleep and worsen metabolic functioning. Sleep and metabolism also appear to have a bidirectional relationship with each other, indirectly exacerbating AD pathophysiology. Understanding the mechanisms involved in these relationships is critical for identifying new strategies to slow the AD cascade.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults.

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study.

Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males; Mage = 14.6 ± 2.3 yr) completed two study visits on weekdays bracketing an ambulatory assessment during summer vacation. Visit 1 included in-laboratory CRF assessment (peak V̇o2) using a ramp-type progressive cycle ergometry protocol and gas exchange measurement, which was followed by 7-14 days of actigraphy to assess sleep/wake patterns and 24-h activity rhythms. During Visit 2, chronotype, social jetlag (i.e., the difference in midsleep time between weekdays and weekends), and phase preference were assessed using a questionnaire, and hourly saliva samples were collected to determine the dim light melatonin onset (DLMO) phase. All analyses were adjusted for sex, pubertal status, and physical activity. Greater peak V̇o2 was associated with earlier sleep/wake times and circadian phase measures, including acrophase, UP time, DOWN time, last activity peak (LAP) time, and chronotype (all P < 0.05). Peak V̇o2 was negatively associated with social jetlag (P = 0.02). In addition, the mixed-model analysis revealed a significant interaction effect between peak V̇o2 and actigraphy-estimated hour-by-hour activity patterns (P < 0.001), with the strongest effects observed at around the time of waking (0600-1000). In healthy adolescents, better CRF was associated with an earlier circadian phase and increased activity levels notably during the morning. Future studies are needed to investigate the longitudinal effects of the interactions between CRF and advanced rhythms on health outcomes.NEW & NOTEWORTHY In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity and verbal memory.

Background: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. Methods: Eighty-one adults (mean age:61.7±6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. Results: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60+ years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. Conclusion: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults.

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality-graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes-map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

The effect of zolpidem-CR on the suicide item of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia and suicidal ideation: Lessons learned.

The REST-IT study found the addition of zolpidem-controlled release (CR) provided a significant reduction in observer-rated measurement of suicidal ideation (the Columbia Suicide Severity Rating Scale) in 103 depressed outpatients with insomnia and suicidal ideation, but without significant change in a self-report measure of suicidal ideation (the Scale for Suicide Ideation). This secondary analysis of the REST-IT data examined the suicide item of another observer-rated scale, the Hamilton Rating Scale for Depression (HRSD), further clarifying the impact of insomnia-focused treatment on suicidal ideation. This analysis established a significant advantage for zolpidem-CR compared with placebo on the HRSD suicide item.

Sleep and Women's Mental Health.

Women have increased risks for both sleep disturbances and disorders and for mental health issues throughout their lives, starting in adolescence. Women have a higher prevalence of insomnia disorder and restless legs syndrome (RLS) versus men, and obstructive sleep apnea (OSA) is more likely as women age. Hormonal transitions are important to consider in women's sleep. For women, insomnia, OSA, and RLS are predictive of depression, and insomnia and sleep-disordered breathing are predictive of Alzheimer disease. These findings underscore the importance of assessment, treatment, and future research examining sleep and mental health in women, given their unique and increased vulnerability.

Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia.

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1-2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.

Wake Up America: National Survey of Patients' and Physicians' Views and Attitudes on Insomnia Care.

While both patients and physicians consider sleep to be important, sleep health may not receive appropriate consideration during patient visits with health care professionals (HCPs). We completed the first large-scale survey of people with trouble sleeping (PWTS) and physicians who treat insomnia to understand their perspectives and potential discrepancies between them. The Harris Poll conducted online surveys of adult PWTS and HCPs (primary care physicians [PCPs] and psychiatrists) in the United States from September to October 2021. Respondents included 1001 PWTS, 300 PCPs, and 152 psychiatrists. Most HCPs agreed that sleep is critical to good health, yet very few reported routinely conducting full sleep histories on their patients. Approximately 30% of PWTS reported that their PCP never asks about sleep; zero HCPs in this survey reported "never" inquiring. Few HCPs reported being "very satisfied" with current treatment options; 50% of PCPs reported their patients being satisfied. Two-thirds of PWTS did not believe current treatment options adequately improved their sleep. This survey provides evidence that both PWTS and physicians agreed on the importance of sleep, but that treatment is often perceived as ineffective. This survey identifies a need for HCPs to address insomnia management and treatment gaps.

Recognition and Management of Obstructive Sleep Apnea in Psychiatric Practice.

Objective: The aims of this review were to describe the relationship between obstructive sleep apnea (OSA) and psychiatric disorders and provide an overview of how to recognize/manage OSA in psychiatric practice.Data Sources: A literature search of PubMed was conducted (in adults, English language, no limitation on year). Among others, main keywords included "obstructive sleep apnea" AND "psychiatric."Study Selection: Articles relevant to the treatment of OSA in psychiatric populations were selected manually.Data Extraction: No formal data charting was conducted.Results: A total of 141 articles were included from the literature search. Comorbid OSA is common among patients with psychiatric disorders, particularly depression and posttraumatic stress disorder. Evidence suggests that OSA may be an independent risk factor for the development of psychiatric conditions, as well as for suicidal ideation and attempts in psychiatric populations. Recognizing OSA in patients with psychiatric disorders can be challenging due to the overlap of symptoms (eg, sleep issues, mood changes, and vegetative symptoms) between OSA, psychiatric disorders, and side effects of psychiatric medications. Inadequately treated OSA can affect the severity of psychiatric symptoms and impair response to psychiatric treatment.Conclusions: Clinicians should not assume that all sleep-related symptoms are consequences of psychiatric illness or medication but should instead be cognizant of the potential for coexisting OSA that requires treatment. Recognizing and managing OSA in patients with psychiatric disorders are critical to improve response to treatment, quality of life, and overall health.

A 2023 Update on Managing Insomnia in Primary Care: Insights From an Expert Consensus Group.

Objective: To evaluate the status of management of insomnia disorder, describe gaps in current recognition and treatment, identify current guidance for optimal management, and develop up-to-date educational recommendations for primary care providers.Participants: Four insomnia experts representing primary care, psychiatry, and clinical research were selected based on clinical expertise, educational qualifications, and research experience. A patient with insomnia was also included.Consensus Process: The Insomnia Working Group met in March 2022 to review data on available therapies (including medications approved since publication of current guidelines) and share current best practices for evidence-based multimodal treatment of insomnia disorder.Conclusions: Insomnia is highly prevalent but underdiagnosed and undertreated. It is increasingly recognized as a distinct disorder, not merely a symptom arising secondary to another medical or psychiatric illness. The subtypes of sleep disturbance-reports of difficulty falling or staying asleep, insufficient sleep duration, early waking-and the presence of next-day impairment and common comorbid conditions require a targeted, individualized approach to therapy. Challenges exist in treating insomnia with commonly used on- and off-label drugs, including low-dose antidepressants, benzodiazepines, and benzodiazepine receptor agonists because of the risk of adverse effects, including impaired next-day functioning. The dual orexin receptor antagonists have a novel mechanistic target and offer an alternative pharmacologic choice. Optimal outcomes for insomnia require a comprehensive approach that includes lifestyle and behavioral strategies to mitigate maladaptive thoughts and behaviors related to sleep and selection of pharmacotherapy based on individual patient complaints and characteristics.

Solriamfetol treatment of excessive daytime sleepiness in participants with narcolepsy or obstructive sleep apnea with a history of depression.

Given the high rate of depression associated with narcolepsy or obstructive sleep apnea (OSA), this analysis compared effects of solriamfetol treatment of excessive daytime sleepiness (EDS) in participants with/without a history of depression (DHx+/DHx-). This secondary analysis included data from two randomized, controlled trials in which participants were randomized to 12 weeks placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day. Efficacy/safety (combined solriamfetol doses) was summarized for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and 23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean sleep latency increased (5.4 and 7.0 min), Epworth Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points), and percentage of participants improved on Patient Global Impression of Change (PGI-C) was higher (31.7% and 39.4%) relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean sleep latency increased (7.7 and 10.7 min), ESS decreased (3.5 and 3.7 points), and percentage of participants improved on PGI-C was higher (41.1% and 29.4%) relative to placebo. Common treatment-emergent adverse events (headache, decreased appetite, nausea, anxiety) were similar in DHx+/DHx-. This study suggests that safety and efficacy of solriamfetol for treating EDS in narcolepsy and OSA are not affected by depression history. Moreover, the findings emphasize the high prevalence of depression in people with sleep disorders and suggest that increased awareness of this association may have clinical significance.

Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to ß-amyloid positivity.

STUDY OBJECTIVES: Fast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD. METHODS: Fifty-eight cognitively unimpaired, ß-amyloid-negative, older adults (mean ±â€…SD; 61.4 ±â€…6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) ε4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, ß-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to <16Hz) sleep spindle measures through these AD biomarkers. RESULTS: Glial activation was associated with prefrontal fast frequency sleep spindle expression deficits. While adjusting for sex, APOE ε4 genotype, apnea-hypopnea index, and time between CSF sampling and sleep study, serial mediation models detected indirect effects of age on fast sleep spindle expression through microglial activation markers and then tau phosphorylation and synaptic degeneration markers. Sleep spindle expression at these electrodes was also associated with overnight memory retention in multiple regression models adjusting for covariates. CONCLUSIONS: These findings point toward microglia dysfunction as associated with tau phosphorylation, synaptic loss, sleep spindle deficits, and memory impairment even prior to ß-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD.

Latent anxiety in clinical depression is associated with worse recognition of emotional stimuli.

BACKGROUND: Major Depressive Disorder, characterized by cognitive affective biases, is a considerable public health challenge. Past work has shown that higher depressive symptoms are associated with augmented memory of negative stimuli. In contrast, anxiety symptoms have been associated with overgeneralization of emotional memories. Given the high comorbidity of depression and anxiety, it is critical to understand how cognitive affective biases are differentially associated with clinical symptoms. METHOD: We used continuous measures of depression (Beck Depression Inventory [BDI-II]) and anxiety (Beck Anxiety Inventory [BAI]) to evaluate an adult sample (N = 79; 18-41 years old, 58 female). Emotional memory discrimination and recognition memory were tested using an emotional discrimination task. We applied exploratory factor analysis to questions from the BAI and BDI-II to uncover latent constructs consisting of negative affect, anhedonia, somatic anxiety, and cognitive anxiety. RESULTS: We report evidence that anxious symptoms were associated with impaired recognition of negative items after accounting for age and sex. Our exploratory factor analysis revealed that impaired negative item recognition is largely associated with somatic and cognitive anxiety factors. LIMITATIONS: Interpretations in a mixed pathology sample, especially given collinearity among factors, may be difficult. CONCLUSIONS: We provide evidence that somatic and cognitive anxiety are related to impaired recognition memory for negative stimuli. Future clinical investigations should uncover the neurobiological basis supporting the link between recognition of negative stimuli and somatic/cognitive symptoms of anxiety.

Burden of Insomnia and Sleep Disturbances and the Impact of Sleep Treatments in Patients with Probable or Possible Alzheimer's Disease: A Structured Literature Review.

BACKGROUND: Sleep disturbances are frequent in Alzheimer's disease (AD). OBJECTIVE: To summarize the impact of sleep disturbances on AD patients and their caregivers and the effects of currently available sleep therapies. METHODS: Published studies (January 1985-March 2020) assessing the burden associated with insomnia/sleep disturbances in the AD population and insomnia treatment effects were identified by searching PubMed, Embase, and Cochrane Library and screened against inclusion criteria. RESULTS: 58 studies assessing patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances were identified. Sleep disturbances were associated with worse cognition, functional ability, and behavioral and neuropsychological functioning. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances. Sleep disturbances were also associated with institutionalization. Although significant associations between sleep problems and clinical outcomes were apparent, there was generally no control for other influencing factors (e.g., cognitive status). Bright light and behavioral therapies as well as drugs showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to the effect on associated clinical burden. CONCLUSION: Sleep disturbances are a significant problem for AD patients and caregivers, associated with behavioral and psychological problems and cognitive decline. However, they remain poorly characterized and under-researched. As the global population is aging and AD is on thes rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact insomnia treatments can have.

Symptoms of obstructive sleep apnea are associated with less frequent exercise and worse subjective cognitive function across adulthood.

STUDY OBJECTIVES: To determine whether subjective measures of exercise and sleep are associated with cognitive complaints and whether exercise effects are mediated by sleep. METHODS: This study analyzed questionnaire data from adults (18-89) enrolled in a recruitment registry. The Cognitive Function Instrument (CFI) assessed cognitive complaints. Medical Outcomes Study Sleep Scale (MOS-SS) subscales and factor scores assessed sleep quality, daytime sleepiness, nighttime disturbance, and insomnia and obstructive sleep apnea (OSA)-like symptoms. Exercise frequency was defined as the weekly number of exercise sessions. Exercise frequency, MOS-SS subscales, and factor scores were examined as predictors of CFI score, adjusting for age, body mass index, education, sex, cancer diagnosis, antidepressant usage, psychiatric conditions, and medical comorbidities. Analyses of covariance examined the relationship between sleep duration groups (short, mid-range, and long) and CFI score, adjusting for covariates. Mediation by sleep in the exercise-CFI score relationship was tested. RESULTS: Data from 2106 adults were analyzed. Exercise and MOS-SS subscales and factor scores were associated with CFI score. Higher Sleep Adequacy scores were associated with fewer cognitive complaints, whereas higher Sleep Somnolence, Sleep Disturbance, Sleep Problems Index I, Sleep Problems Index II, and factor scores were associated with more cognitive complaints. MOS-SS subscales and factor scores, except Sleep Disturbance and the insomnia factor score, mediated the association between exercise and cognitive complaints. CONCLUSIONS: The relationship between exercise frequency and subjective cognitive performance is mediated by sleep. In particular, the mediation effect appears to be driven by symptoms possibly suggestive of OSA which are negatively associated with exercise engagement, sleep quality, daytime sleepiness, and subjective cognitive performance.

Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study.

STUDY OBJECTIVES: The clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial. METHODS: Participants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10). RESULTS: In 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73). CONCLUSIONS: Although subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP); URL: https://clinicaltrials.gov/ct2/show/NCT00642486; Identifier: NCT00642486. CITATION: Pascoe M, Bena J, Andrews ND, et al. Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study. J Clin Sleep Med. 2022;18(4):1027-1034.

Changes in Healthcare Resource Use and Costs in Commercially Insured Insomnia Patients Initiating Suvorexant.

INTRODUCTION: Insomnia diagnosis has been associated with a significant clinical and economic burden on patients and healthcare systems. This study examined changes in healthcare resource use (HCRU) and costs in insomnia patients before and after initiation of suvorexant treatment. METHODS: This retrospective cohort study analyzed Optum Clinformatics Data Mart claims data (Jan 2010-Dec 2018). Patients with ≥ 2 insomnia diagnosis claims and ≥ 1 prescription for suvorexant were included. Prevalent and incident insomnia patients were analyzed separately. The change in the trends of HCRU and costs were examined for 12 months before and 12 months after suvorexant initiation. An interrupted time series (ITS) analysis was conducted to assess the level and slope changes. Subgroups of patients with mental health comorbidities were examined. RESULTS: The study included 18,919 and 5939 patients in the prevalent and incident insomnia cohorts, respectively. For the prevalent cohort, mean (SD) age was 64.5 (14.1) years, 65% were female, 74% had Medicare Advantage coverage, and 61% had a Charlson comorbidity index score ≥ 1. Characteristics for the incident cohort were similar. The ITS results suggested that the trend for monthly total healthcare cost (THC) was increasing before suvorexant initiation (US$52.51 in the prevalent cohort, $74.93 in incident insomnia cohort), but, after suvorexant initiation, the monthly total cost showed a decreasing trend in both cohorts. The decrease in slope for THC after suvorexant initiation were $72.66 and $112.07 per month in the prevalent and incident cohorts, respectively. The monthly trends in HCRU rates also decreased. The subgroup analysis showed that decreases were 1.5-3 times greater for patients with mental health comorbidities. CONCLUSIONS: In this real-world study, suvorexant initiation was associated with immediate and continued decreases in HCRU and costs in insomnia patients. Further research is needed to understand the effect of suvorexant initiation on direct medical costs as well as costs associated with lost productivity in other real-world settings.

Examining suicide assessment measures for research use: Using item response theory to optimize psychometric assessment for research on suicidal ideation in major depressive disorder.

INTRODUCTION: Progress reducing suicide death will require randomized clinical trials (RCTs) specifically targeting suicide risk. Even large RCTs may not stipulate suicide death as the primary outcome, as suicide death is relatively uncommon. Therefore, RCTs may need to specify suicidal ideation as a proxy indicator of risk. There is no consensus on the best tool for measuring suicidal ideation within RCTs. We contrasted the psychometric performance of three suicidal ideation measures to address this need. METHODS: We applied item response theory to the Beck Scale for Suicide Ideation (BSSI), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the suicide item of the Hamilton Rating Scale for Depression (HRSD) for 101 outpatients with depression and suicidal ideation participating in a RCT with suicidal ideation as the primary outcome. RESULTS: All measures of suicidal ideation were equally able to detect low and very high levels of suicidal ideation. CONCLUSIONS: The choice of the specific measure of suicidal ideation in a clinical trial may be dictated by time and financial resources versus the need for granularity in the interpretation of the scores.