INTRODUCTION Obstructive sleep apnea (OSA) is associated with cognitive decline, but short-term studies show limited cognitive benefits of its treatment with continuous positive airway pressure (CPAP). We examined whether longer follow-up exhibits greater cognitive differences associated with CPAP use.METHODS We analyzed 777 participants from the 2011 National Health and Aging Trends Study (NHATS) with linked Medicare claims, with one or more claims for OSA and no baseline cognitive impairment. CPAP treatment was defined by one or more CPAP claims. Cognitive trajectories from 2011 to 2021 were estimated using a factor score derived from annual cognitive performance assessments and compared by CPAP treatment status using adjusted generalized linear mixed models.RESULTS Cognitive performance declined over follow-up. CPAP-treated participants declined by -0.03 standard deviation (SD) units per year (95% confidence interval [CI]: -0.04, -0.02). Untreated participants experienced a 69% faster decline (CPAP-by-time interaction: -0.02; 95% CI: -0.04, -0.001).DISCUSSION CPAP therapy may slow cognitive decline in older adults with OSA.

Older adults experience the highest rates of traumatic brain injury (TBI) related hospitalizations and deaths of any age group, yet TBI remains understudied in this population. To improve understanding of recovery over the year following TBI among older adults, we designed the RETRO-TBI study. This manuscript reports the protocol for RETRO-TBI, a prospective cohort study of older adults (65 years and older) with mild TBI (mTBI) with planned enrollment of 250 participants. The study is designed to evaluate recovery across four key domains: physical function, cognitive function, psychological function, and sleep quality. Participants are followed for 12 months after injury, with in-home study visits conducted at approximately 2 weeks and 3, 6, and 12 months post-injury. Blood samples are collected at all visits. The specific aims are to: (1) identify trajectories of recovery in physical function and predictors of poorer physical recovery; (2) identify trajectories of recovery in cognitive function, psychological function, and sleep quality and predictors of poorer recovery in these domains; and (3) examine associations among recovery trajectories across domains. The RETRO-TBI study represents an important step in addressing the knowledge gap on recovery following TBI among older adults and is expected to result in identification of sub-groups of individuals more likely to have poor recovery, informing individualized treatment plans and development of future domain-based rehabilitation strategies. The study has several strengths including its focus on older adults, evaluation of recovery across four domains of function, and longitudinal assessments will permit evaluation of heterogeneity in recovery trajectories.

Importance:Daytime symptoms, including negative mood, fatigue, and cognitive impairment, are core features and diagnostic criteria for insomnia disorder. Historically, assessment of these daytime insomnia symptoms has relied on retrospective questionnaires with varying recall periods and that may lack sensitivity to detect subtle change attributable to insomnia treatment. Objective:To use smartphone-based ecological momentary assessment (EMA) to determine the effect of insomnia pharmacotherapy on daytime insomnia symptoms. Design, Setting, and Participants:This was a double-blind, placebo-controlled randomized clinical trial. All procedures were conducted remotely between October 9, 2023, and August 8, 2024. Following baseline assessment, participants were randomized to suvorexant or placebo, including 2 nights at 10 mg then 14 nights at 20 mg. Participants completed the Daytime Insomnia Symptoms Scale (DISS) 4 times per day (ie, 64 administrations over 16 days) and a posttreatment assessment. Participants were recruited from an academic center. Inclusion criteria were individuals aged 60 to 85 years, diagnosed with chronic insomnia per clinical interview, with moderate to severe insomnia symptoms (Insomnia Severity Index [ISI] ≥15), and owning a smartphone. Exclusion criteria were major untreated medical or psychiatric condition, contraindications for a dual-orexin receptor antagonist, refusal to discontinue other insomnia medications, or severe obstructive sleep apnea. Data were analyzed between September 6, 2024, and October 28, 2025. Intervention:Suvorexant 20 mg nightly vs placebo. Main Outcomes and Measures:The primary EMA measure was the DISS. During baseline and posttreatment assessments, participants also completed questionnaires assessing insomnia severity, sleepiness, fatigue, anxiety, and depression. Results:Participants included 40 older adults (mean [SD] age, 67.9 [5.4] years; 36 [90%] women), with 20 participants randomized to suvorexant and 20 to placebo. There were no dropouts. The overall completion rate for EMA surveys was 93.3%. Relative to placebo, suvorexant reduced insomnia severity (mean [SD] change in ISI, -9.6 [5.4] vs -5.5 [6.8]; estimate [SE], 4.1 [1.9]; t = 2.1; df = 36; P = .04, effect size, 0.66 [95% CI, 0.02 to 1.30]). Based on retrospective questionnaires, no statistically significant between-group differences in daytime insomnia symptoms were detected. Based on EMA, significant between-group differences were detected in subjective cognition (χ24 = 11.12; P = .03) and fatigue (χ24 = 21.43; P = .003) at 1 or more times of day. Conclusions and Relevance:In this randomized clinical trial of older adults with insomnia, although traditional outcomes assessments detected no between-group differences, EMA was sensitive to detect effects of insomnia pharmacotherapy on daytime insomnia symptoms at various times of day, a critical gap in the literature. Trial Registration:ClinicalTrials.gov Identifier: NCT05908526.

BACKGROUND:Prior research indicates a connection between obstructive sleep apnea (OSA) and cognitive deficits, prompting interest in whether OSA treatment can prevent or slow cognitive decline. Past clinical trials on OSA treatment and cognitive impairment have shown inconsistent results. However, observational data might help by examining more diverse populations and larger sample sizes, increasing the ability to detect subtle effects. Therefore, we reviewed literature to characterize studies evaluating cognitive outcomes from OSA treatment using observational study data. METHODS:We conducted a scoping review of studies retrieved on PubMed and Embase. Studies were screened by title/abstract, and then full text, for inclusion. We extracted data characterizing data source, study design, population, sample size, follow-up time, treatments assessed, cognitive outcome variables, and key associations. RESULTS:Of 3655 unique articles obtained from PubMed and Embase, 13 met eligibility criteria. All were retrospective cohort studies. Ten studies evaluated positive airway pressure (PAP) therapies, one examined uvulopalatopharyngoplasty, and 2 evaluated any type of OSA treatment. No studies evaluated mandibular advancement devices. Cognitive outcomes assessed included dementia diagnosis (8 studies), and changes in cognitive performance (5 studies). Results from studies for the most part found OSA treatment was associated with better cognitive outcomes, although effects varied in magnitude and statistical significance based on the data source, outcomes, and sample size. CONCLUSIONS:Observational data has the potential to help evaluate cognitive outcomes from OSA treatment, but more studies are needed, especially for OSA therapies beyond PAP alone.

BACKGROUND:Whether daytime napping may be a risk factor for dementia, in addition to nighttime sleep disturbances, remains unclear. This study investigated longitudinal associations of napping characteristics with incident dementia among U.S. older adults. METHODS:Data came from the National Health and Aging Trends Study (NHATS). Napping characteristics were self-reported in a sleep module at round 3 (2013), including (1) frequency (non-napper, infrequent, frequent); (2) intention (non-napper, intentional, unintentional); (3) duration (non-napper, ≤30 minutes, >30 minutes). Dementia classification was established at each round using a validated algorithm and possible/probable dementia served as our outcome. We included 995 participants free of possible/probable dementia at round 3 who were followed up to round 13 (2023). Discrete-time complementary log-log models were used for hazard ratio (HR) of incident possible/probable dementia associated with napping characteristics, adjusting for demographic, health, and sleep variables (duration, daytime sleepiness, obstructive sleep apnea risk). RESULTS:When compared to non-nappers, frequent nappers had 1.48 times the hazard of developing incident possible/probable dementia (95% confidence interval [CI]: 1.14, 1.94). Unintentional napping was associated with incident possible/probable dementia (HR = 1.39, 95% CI: 1.06, 1.81). No associations were found for infrequent or intentional napping. Napping ≤30 minutes was associated with possible/probable dementia (HR = 1.40, 95% CI: 1.06, 1.85), but the association of napping >30 minutes was attenuated with additional adjustment for sleep variables (HR = 1.28, 95% CI: 0.96, 1.69). CONCLUSIONS:Daytime napping may be a modifiable risk factor for dementia if supported by further evidence. Future studies with detailed napping characteristics and longer follow-up are needed.

PURPOSE:Tirzepatide, a GLP-1 receptor agonist (GLP-1RA), is the first approved medication for the treatment of moderate to severe OSA and has previously been found to reduce cardiovascular risks in patients with type 2 diabetes mellitus (T2DM). Our study analyzed the effects of GLP-1RA in preventing cardiovascular and pulmonary complications in patients with OSA and T2DM during a 5-year follow-up period. METHODS:Through the TriNetX database, patients with OSA and T2DM from 2010-2022 were included. We compared patients receiving GLP-1RA versus other diabetic medications including metformin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylurea, and thiazolidinedione. Using a propensity score model, participants were matched on a range of demographic and clinical factors. Patients were evaluated for cardiovascular and pulmonary outcomes using a Kaplan-Meier survival analysis. We additionally analyzed the incidence rate of ED visits and inpatient admissions. RESULTS:After matching, 5,750 to 21,065 patients were included in the GLP-1RA versus other diabetes medication groups. GLP-1RA showed a lower risk of acute respiratory failure compared to metformin (HR 0.89; 95%CI 0.80-0.98), DPP-4 inhibitors (HR 0.78; 95%CI 0.71-0.85), sulfonylureas (HR 0.70; 95%CI 0.64-0.76) and TZD (HR 0.76; 95%CI 0.65-0.89). GLP-1RA group demonstrated significantly lower risk of pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and heart failure when compared to DPP-4 inhibitors, sulfonylureas, and TZD. CONCLUSION:GLP-1RA use was associated with a lower risk of pulmonary complications including acute respiratory failure, pulmonary hypertension, and COPD as well as lower ED visits and inpatient admissions compared to other diabetes medications. Further prospective studies are needed to evaluate the benefits of GLP-1RA.

QuestionWhat is the effect of insomnia suvorexant pharmacotherapy on daytime insomnia symptoms as assessed via smartphone ecological momentary assessment (EMA)?FindingsIn this randomized clinical trial that included 40 older adults with insomnia, traditional outcomes assessments detected differences between suvorexant and placebo groups in daytime insomnia symptoms; however, EMA was sensitive to detect effects of insomnia pharmacotherapy at various times of day.MeaningThese findings suggest that EMA warrants further refinement in sleep and psychiatric research and clinical care. This randomized clinical trial explores the use of smartphone-based ecological momentary assessment to determine the effect of suvorexant on daytime insomnia symptoms. ImportanceDaytime symptoms, including negative mood, fatigue, and cognitive impairment, are core features and diagnostic criteria for insomnia disorder. Historically, assessment of these daytime insomnia symptoms has relied on retrospective questionnaires with varying recall periods and that may lack sensitivity to detect subtle change attributable to insomnia treatment.ObjectiveTo use smartphone-based ecological momentary assessment (EMA) to determine the effect of insomnia pharmacotherapy on daytime insomnia symptoms.Design, Setting, and ParticipantsThis was a double-blind, placebo-controlled randomized clinical trial. All procedures were conducted remotely between October 9, 2023, and August 8, 2024. Following baseline assessment, participants were randomized to suvorexant or placebo, including 2 nights at 10 mg then 14 nights at 20 mg. Participants completed the Daytime Insomnia Symptoms Scale (DISS) 4 times per day (ie, 64 administrations over 16 days) and a posttreatment assessment. Participants were recruited from an academic center. Inclusion criteria were individuals aged 60 to 85 years, diagnosed with chronic insomnia per clinical interview, with moderate to severe insomnia symptoms (Insomnia Severity Index [ISI] >= 15), and owning a smartphone. Exclusion criteria were major untreated medical or psychiatric condition, contraindications for a dual-orexin receptor antagonist, refusal to discontinue other insomnia medications, or severe obstructive sleep apnea. Data were analyzed between September 6, 2024, and October 28, 2025.InterventionSuvorexant 20 mg nightly vs placebo.Main Outcomes and MeasuresThe primary EMA measure was the DISS. During baseline and posttreatment assessments, participants also completed questionnaires assessing insomnia severity, sleepiness, fatigue, anxiety, and depression.ResultsParticipants included 40 older adults (mean [SD] age, 67.9 [5.4] years; 36 [90%] women), with 20 participants randomized to suvorexant and 20 to placebo. There were no dropouts. The overall completion rate for EMA surveys was 93.3%. Relative to placebo, suvorexant reduced insomnia severity (mean [SD] change in ISI, -9.6 [5.4] vs -5.5 [6.8]; estimate [SE], 4.1 [1.9]; t = 2.1; df = 36; P = .04, effect size, 0.66 [95% CI, 0.02 to 1.30]). Based on retrospective questionnaires, no statistically significant between-group differences in daytime insomnia symptoms were detected. Based on EMA, significant between-group differences were detected in subjective cognition (chi 24 = 11.12; P = .03) and fatigue (chi 24 = 21.43; P = .003) at 1 or more times of day.Conclusions and RelevanceIn this randomized clinical trial of older adults with insomnia, although traditional outcomes assessments detected no between-group differences, EMA was sensitive to detect effects of insomnia pharmacotherapy on daytime insomnia symptoms at various times of day, a critical gap in the literature.Trial RegistrationClinicalTrials.gov Identifier: NCT05908526

Insomnia disorder is common among U.S. military personnel and negatively impacts health and military readiness. Among civilians, insomnia is associated with substantial economic burden; yet, little is known about the burden of insomnia within the US Military Health System (MHS). The MHS is a large, integrated healthcare delivery system with worldwide operations and thus ideal for health services research. This study aimed to determine the association between insomnia disorder and healthcare resource utilization (HCRU) in the MHS. Our data source was the Military Data Repository (MDR) between years 2016-2021. This large data repository includes encounter, procedure, medication, and durable medical equipment information for active-duty military personnel, military dependents, National Guard, and Reserves. Demographic and military information was obtained from the MDR. Inclusion criteria were age < 65 years, active-duty military personnel, 12 months of continuous enrollment before and after first insomnia diagnosis (i.e., the index date), and no evidence of insomnia during the 12 months prior to first diagnosis. Insomnia and comorbid medical and psychiatric conditions were defined based on International Classification of Disease-10th Edition codes. Beneficiaries with insomnia were matched 1:1 with non-insomnia controls on >20 demographic, military, and medical and psychiatric comorbidity variables. Mixed effects models were used to compare non-insomnia related HCRU between groups across multiple points of service: outpatient, inpatient, and emergency department (ED). We identified 40,978 MHS beneficiaries with insomnia and 40,978 matched non-insomnia controls. Most (35.9%) beneficiaries with insomnia were between ages 25-34 years, and 20.7% were women. 4.2% of beneficiaries with insomnia had one comorbid medical or psychiatric condition, and 1% had >2 comorbid conditions. Relative to matched non-insomnia controls, beneficiaries with insomnia demonstrated greater 12-month HCRU at every point of service (all p values< 0.001). The incident rate ratio for non-insomnia inpatient visits was RR (95% CI) = 1.96 (1.85,2.08); for non-insomnia outpatient visits was 2.24 (2.23,2.24); and for non-insomnia related ED visits was 1.60 (1.57,1.63). Insomnia is associated with substantially increased healthcare resource utilization in the US military health system. Future research should seek to advance personalized medicine approaches to improve outcomes of evidence-based insomnia care. U.S. Department of Defense HT94022210006.

BACKGROUND:Obstructive sleep apnea (OSA) is common and costly in the U.S. military health system (MHS). OSA is associated with poor health outcomes as well as increased economic burden borne by the Defense Health Agency. The MHS lacks the capacity to meet the available demand for sleep specialty care. Thus, most military OSA care is provided by private sector TRICARE-contracted civilian providers. Given the burden of OSA and limited access to OSA care, optimizing OSA care within the MHS is vital. TELE-SLEEP OSA is a randomized, parallel group, single blind, controlled clinical trial comparing OSA telehealth care to standard private sector TRICARE. METHODS:Participants will include 160 active-duty family members and Defense Enrollment Eligibility Reporting System beneficiaries who are referred for OSA consultation. Following informed consent, participants will complete baseline assessments prior to randomization. Participants randomized to private sector TRICARE will receive treatment as usual, including positive airway pressure (PAP) therapy. Participants randomized to OSA telehealth care will undergo telehealth consultation with a board-certified sleep medicine specialist, undergo home sleep apnea testing, receive auto-titrating PAP therapy, and receive ongoing support from educator-level sleep navigators throughout the study. Quantitative follow-up assessments will be completed at 30 and 90 days after treatment initiation. Qualitative focus groups to assess participant satisfaction and other implementation outcomes will be conducted with participants from both treatment groups. Outcomes include PAP adherence (primary outcome), OSA symptoms, implementation, and cost-effectiveness. CONCLUSION:Our telemedicine approach to OSA treatment aims to reduce costs and improve health outcomes within the MHS. CLINICAL TRIAL REGISTRATION:NCT07121452.

Falls are the primary cause of mild traumatic brain injury (mTBI) among older adults, yet limited research has examined patterns of clinical care, mobility, and subsequent fall risk in this population. The objective of this study was to evaluate outpatient physical or occupational therapy (PT/OT) referral patterns and assess physical function and fall risk status of older adults with mTBI. We analyzed acute care and 2-week post-mTBI assessment data from a prospective cohort study of adults aged 65 and older with mTBI treated at a level 1 trauma center and six affiliated hospitals 2023-2025 and meeting eligibility criteria. Of 625 that were confirmed eligible, 155 consented to participate in the study. Of these, five were missing the 2-week assessment and nine were missing PT/OT referral information, leaving 141 in the current study. The exposure of interest was referral to PT/OT at discharge, obtained from medical records. Two-week post-mTBI assessments included the Short Physical Performance Battery (SPPB) and the Four-Square Step Test (FSST). Statistical comparisons between exposure groups were made using Fisher's exact test, Student's t-test or the Wilcoxon rank-sum test. Participants (n = 141) were on average 76.1 (standard deviation 7.3) years old and 56.0% female. Falls were the primary cause of mTBI (89%). At the 2-week assessment, participants demonstrated poor physical performance: 53% had impaired SPPB (<10), 62% had impaired FSST (>15 sec), and 65% had slow gait speeds (<0.80 m/s), all indicative of elevated fall risk. Only 34 (24%) were referred to PT/OT at discharge. Those referred were more likely to have received an inpatient PT/OT consultation (97% vs. 22%, p < 0.001). Among participants not referred to PT/OT, 46% had impaired SPPB, 58% had impaired FSST, and 60% had slow gait speed, indicating high fall risk. Less than a quarter of older adults with primarily fall-related mTBI received any discharge PT/OT referral despite clear mobility and balance deficits. This critical gap in post-discharge rehabilitation underscores a disconnect between fall-prevention guidelines and clinical practice, leaving many older adults at high risk of recurrent falls and injuries.

This guideline establishes clinical practice recommendations for combination treatment of chronic insomnia disorder in adults, defined here as treatment with cognitive-behavioral therapy for insomnia (CBT-I) started concurrently with pharmacotherapy. The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to those recommendations based on a systematic review of the literature and an assessment of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process. The task force provided a summary of the relevant literature, the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. The following recommendations are intended as a guide for clinicians on the use of combination treatment for chronic insomnia disorder in adults. Each recommendation statement is assigned a strength (“Strong” or “Conditional”). A “Strong” recommendation (i.e., “We recommend…”) is one that clinicians should follow under most circumstances. A “Conditional” recommendation (i.e., “We suggest…”) is one that requires that the clinician use clinical knowledge and experience and strongly consider the patient’s values and preferences to determine the best course of action. One recommendation includes a remark that provides additional context to guide clinicians with implementation of this recommendation. Conditional recommendation for: 1. In adults with chronic insomnia disorder, the AASM suggests the use of combination treatment with CBT-I plus insomnia medication over insomnia medication alone. (Conditional recommendation, low certainty of evidence). Conditional recommendation against: 2. In adults with chronic insomnia disorder, the AASM suggests against the use of combination treatment of CBT-I plus insomnia medication over CBT-I alone. (Conditional recommendation, low certainty of evidence). Remark: Patients who place higher value on increasing total sleep time early in the course of treatment, and/or who place lower value on reducing daytime symptoms with treatment, may reasonably select combination treatment versus CBT-I alone.

This systematic review provides supporting evidence for the accompanying clinical practice guideline on combination treatment for chronic insomnia disorder in adults. The American Academy of Sleep Medicine (AASM) commissioned a task force (TF) of sleep medicine experts. A systematic review was conducted to identify studies that compared the use of combination treatment (behavioral-psychological treatment used concurrently with pharmacological treatment) to therapy with behavioral-psychological or pharmacological treatments. Statistical analyses were performed to determine the clinical meaningfulness of using various interventions to treat chronic insomnia in adults. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search resulted in 1,179 articles, out of which 15 articles provided data suitable for meta-analyses. The TF provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.

To compare the differences in the risk of cardiovascular disease (CVD) events between narcolepsy type 1 (NT1) and type 2 (NT2) among patients with narcolepsy, while accounting for real-world use of stimulants. Using the 2005–2023 MarketScan Commercial and Medicare Supplemental databases, we identified patients newly diagnosed with narcolepsy, either NT1 or NT2, using International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification diagnosis codes. Stabilized inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the NT1 and NT2 groups. Primary outcomes included time to first (1) composite CVD event and (2) major adverse cardiovascular event (MACE). We used multivariable Cox proportional hazards regression models following IPTW to estimate adjusted hazard ratios (AHRs), accounting for time-fixed and time-varying covariates, including stimulant use. Individual cardiovascular outcomes were assessed separately, and analyses were stratified by age and sex. After IPTW, the overall effective sample size was 30,154 patients (NT1 = 3,068, NT2 = 27,086; mean [SD] age, 39.8 [16.5] years; 61.8

Study objectives To determine the association between adherence to positive airway pressure and healthcare costs among a national sample of older adults with comorbid obstructive sleep apnea (OSA) and common chronic conditions.Methods Our data source was a random sample of Medicare administrative claims for years 2016-2019. Inclusion criteria included age >= 65 years and new diagnosis of OSA. Exclusion criteria included evidence of prior OSA treatment during the 12 months prior to the index date, active cancer, or end-stage renal disease. OSA was defined using physician-assigned diagnostic codes. Common chronic conditions included chronic obstructive pulmonary disease, congestive heart failure, depression, hypertension, type 2 diabetes mellitus, obesity, and stroke. Based on Medicare policy, individuals were classified as adherers, nonadherers, or noninitiators. Risk adjustment was based on the Centers for Medicare and Medicaid Hierarchical Condition Categories approach developed by the Centers for Medicaid and Medicare Service specifically to estimate anticipated costs. To examine the impact of PAP adherence on costs, we employed a weighted DID regression framework to account for baseline variations in health status and other confounding factors.Results Participants included 28 220 Medicare beneficiaries with comorbid OSA. Of these, 45% were adherent to PAP, 10% were nonadherent, and 44% did not initiate PAP. Relative to noninitiators, beneficiaries who initiated PAP displayed $195 reduced per-member per-month costs over 24 months. This finding remained consistent across all seven medical and psychiatric subgroups, as well as among individuals with multimorbidity.Conclusions In this national analysis of Medicare beneficiaries with common chronic conditions, PAP adherence was associated with reduced costs over 24 months.

With the growing prevalence of Alzheimer’s disease (AD) and AD-related dementias (ADRD), investigators have sought to identify modifiable risk factors that if addressed, can slow cognitive decline and delay AD/ADRD. Obstructive sleep apnea (OSA) affects a billion people worldwide and is linked to serious health consequences, including AD/ADRD. Treatments for OSA (e.g., continuous positive airway pressure [CPAP]), are available and highly effective when used as prescribed. Even so, there is ongoing debate about how these therapies influence cognitive outcomes, largely stemming from the limited number of studies with sufficient follow-up time to account for the extended preclinical phase during which OSA affects patients’ AD/ADRD pathology. In 2022, our team was awarded an R01 from the NIA to investigate the relationship between OSA and cognitive decline and AD/ADRD onset, and whether CPAP can reduce the risk of these negative cognitive outcomes. We are using data from two NIA-funded cohort studies, the Health and Retirement Study (HRS) and the National Health and Aging Trends Study (NHATS), with linked Medicare claims accessed via the newly established NIA LINKAGE Enclave to address these questions. Ultimately, our study leverages nationally representative cohort studies of older adults linked to real-world data to generate insights for dementia prevention. In this presentation, we will a) provide an overview of OSA and its link to cognitive outcomes, b) outline our study’s aims, c) describe our use of HRS and NHATS data linked with Medicare claims, and d) discuss the importance of the NIA LINKAGE Enclave in effectuating our vision.

Emerging evidence links narcolepsy to major adverse cardiovascular events (MACE). While narcolepsy typically manifests early in life, it remains unclear whether cardiovascular disease (CVD) also develops early. We hypothesized that narcolepsy elevates the risk of cardiometabolic conditions from childhood into later life, potentially explaining the heightened MACE risk in persons with narcolepsy (PWN). We conducted a retrospective cohort study using MarketScan® Commercial and Medicare Supplemental databases (2005-2021). PWN were identified by ≥2 outpatient claims for narcolepsy using International Classification of Diseases–Clinical Modification diagnosis codes. A control group of persons without narcolepsy/hypersomnolence was created using propensity score matching (1:3 ratio). Index date was the first narcolepsy diagnosis for PWN and corresponding encounter date for matched controls. Individuals with pre-existing CVD, MACE, hypertension, hyperlipidemia, diabetes, or metabolic fatty liver disease during the year prior to the index date (baseline period), to ensure balanced demographics, comorbidities, and baseline medication use between with and without narcolepsy groups. Cox regression models assessed the association between narcolepsy and time to incident hypertension, hyperlipidemia, and diabetes, adjusting for baseline and time-varying narcolepsy medication (i.e., wake-promoting agents, stimulants, and oxybate) use. Analyses were stratified by age groups (≤25[pediatric], 26–44[adults], 45–65[middle-aged], and >65yrs[older adults]). The cohort included 22,293 PWN and 63,709 without narcolepsy/hypersomnolence. Mean±SD age was 35.5±14.0 years (63.7% female). PWN had a significantly higher risk of hypertension (adjusted hazard ratio[aHR]:1.44, 95% Confidence Interval[CI]:1.34–1.54), hyperlipidemia (aHR:1.48, 95% CI:1.39–1.57), and diabetes (aHR:1.61, 95% CI:1.40–1.83) compared to those without narcolepsy. These outcomes were elevated across all age groups except older adults (>65yrs). Notably, in the pediatric cohort(< 25yrs), PWN showed nearly double the risk of hypertension (aHR:2.01, 95% CI:1.60–2.53), hyperlipidemia (aHR:1.84, 95% CI:1.53–2.23), and diabetes (aHR:2.37, 95% CI:1.66–3.37) compared to those without narcolepsy/hypersomnolence. Using a large U.S. claims database, narcolepsy was associated with a significantly increased risk of hypertension, hyperlipidemia, and diabetes across all age groups, with strongest associations observed in younger individuals. Early onset of cardiometabolic risk factors indicate prolonged exposure, potentially increasing the likelihood of MACE later in life and possibly shifting their onset to earlier ages. Funding: Sleep Research Society Foundation (23-FRA-001)