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Rationale: Although patients with obstructive sleep apnea (OSA) have a higher risk for coronavirus disease (COVID-19) hospitalization, the causal relationship has remained unexplored. Objectives: To understand the causal relationship between OSA and COVID-19 by leveraging data from vaccination and electronic health records, genetic risk factors from genome-wide association studies, and Mendelian randomization. Methods: We elucidated genetic risk factors for OSA using FinnGen (total N = 377,277), performing genome-wide association. We used the associated variants as instruments for univariate and multivariate Mendelian randomization (MR) analyses and computed absolute risk reduction against COVID-19 hospitalization with or without vaccination. Results: We identified nine novel loci for OSA and replicated our findings in the Million Veteran Program. Furthermore, MR analysis showed that OSA was a causal risk factor for severe COVID-19 (P = 9.41 × 10−4). Probabilistic modeling showed that the strongest genetic risk factor for OSA at the FTO locus reflected a signal of higher body mass index (BMI), whereas BMI-independent association was seen with the earlier reported SLC9A4 locus and a MECOM locus, which is a transcriptional regulator with 210-fold enrichment in the Finnish population. Similarly, multivariate MR analysis showed that the causality for severe COVID-19 was driven by BMI (multivariate MR P = 5.97 × 10−6, β = 0.47). Finally, vaccination reduced the risk for COVID-19 hospitalization more in the patients with OSA than in the non-OSA controls, with respective absolute risk reductions of 13.3% versus 6.3%. Conclusions: Our analysis identified novel genetic risk factors for OSA and showed that OSA is a causal risk factor for severe COVID-19. The effect is predominantly explained by higher BMI and suggests BMI-dependent effects at the level of individual variants and at the level of comorbid causality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Obstructive sleep apnea is associated with increased blood pressure (BP). Obstructive sleep apnea treatment reduces BP with substantial variability, not explained by the apnea-hypopnea index, partly due to inadequate characterization of obstructive sleep apnea's physiological consequences, such as oxygen desaturation, cardiac autonomic response, and suboptimal treatment efficacy. We sought to examine whether a high baseline heart rate response (ΔHR), a marker of high cardiovascular risk in obstructive sleep apnea, predicts a larger reduction in post-treatment systolic BP (SBP). Furthermore, we aimed to assess the extent to which a reduction in SBP is explained by a treatment-related reduction in hypoxic burden (HB). METHODS: ΔHR and HB were measured from pretreatment and posttreatment polygraphy, followed by a 24-hour BP assessment in 168 participants treated with continuous positive airway pressure or nocturnal supplemental oxygen from the HeartBEAT study (Heart Biomarker Evaluation in Apnea Treatment). Multiple linear regression models assessed whether high versus mid (reference) ΔHR predicted a larger reduction in SBP (primary outcome) and whether there was an association between treatment-related reductions in SBP and HB. RESULTS: A high versus mid ΔHR predicted improvement in SBP (adjusted estimate, 5.8 [95% CI, 1.0–10.5] mm Hg). Independently, a greater treatment-related reduction in HB was significantly associated with larger reductions in SBP (4.2 [95% CI, 0.9–7.5] mm Hg per 2 SD treatment-related reduction in HB). Participants with substantial versus minimal treatment-related reductions in HB had a 6.5 (95% CI, 2.5–10.4) mm Hg drop in SBP. CONCLUSIONS: A high ΔHR predicted a more favorable BP response to therapy. Furthermore, the magnitude of the reduction in BP was partly explained by a greater reduction in HB. [ABSTRACT FROM AUTHOR]

Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain ("ventilatory instability"), which may thus herald cardiovascular treatment benefit. Objectives: To test the hypothesis that loop gain predicts changes in 24-hour mean blood pressure (MBP) in response to OSA therapy and compare its predictive value against that of other novel biomarkers. Methods: The HeartBEAT (Heart Biomarker Evaluation in Apnea Treatment) trial assessed the effect of 12weeks of continuous positive airway pressure (CPAP) versus oxygen versus control on 24-hour MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24-h MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arms, respectively. Overall, changes in 24-hour MBP were small, but interindividual variability was substantial (mean [standard deviation], 22 [8] and 1 [8] mmHg in the CPAP and oxygen arms, respectively). Higher loop gain was significantly associated with greater reductions in 24-hour MBP independent of covariates in the CPAP arm (21.5 to 21.9mmHg per 1-standard-deviation increase in loop gain; P<0.03) but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT 01086800). [ABSTRACT FROM AUTHOR]

Introduction Veteran populations are frequently diagnosed with mental health conditions such as substance use disorder and PTSD. These conditions are associated with adverse outcomes including a higher risk of suicide. The Veterans Health Administration (VHA) has designed a robust mental health system to address these concerns. Veterans can access mental health treatment in acute inpatient, residential, and outpatient settings. Residential programs play an important role in meeting the needs of veterans who need more structure and support. Residential specialty types in the VHA include general mental health, substance use disorder, PTSD, and homeless/work programs. These programs are affiliated with a DVA facility (i.e. medical center). Although residential care can improve outcomes, there is evidence that some patients are discharged from these settings before achieving the program endpoint. These unplanned discharges are referred to using language such as against medical advice, self-discharge, or irregular discharge. Concerningly, unplanned discharges are associated with patient harm including death by suicide. Although there is some initial evidence to locate factors that predict irregular discharge in VHA residential programs, no work has been done to examine features associated with irregular discharge in each residential specialty. Methods We conducted a retrospective cohort study of patients who were discharged from VHA residential treatment programs between January 2018 and September 2022. We included the following covariates: Principal diagnosis, gender, age, race/ethnicity, number of physical health conditions, number of mental health diagnostic categories, marital status, risk of homelessness, urbanicity, and service connection. We considered two discharge types: Regular and irregular. We used logistic regression to determine the odds of irregular discharge using models stratified by bed specialty as well as combined odds ratios and 95% CIs across program specialties. The primary purposes are to identify factors that predict irregular discharge and to determine if the factors are consistent across bed specialties. In a secondary analysis, we calculated facility-level adjusted rates of irregular discharge, limiting to facilities with at least 50 discharges. We identified the amount of residual variation that exists between facilities after adjusting for patient factors. Results A total of 279 residential programs (78,588 patients representing 124,632 discharges) were included in the analysis. Substance use disorder and homeless/work programs were the most common specialty types. Both in the overall and stratified analyses, the number of mental health diagnostic categories and younger age were predictors of irregular discharge. In the facility analysis, there was substantial variation in irregular discharge rates across residential specialties even after adjusting for all patient factors. For example, PTSD programs had a mean adjusted irregular discharge rate of 15.3% (SD: 7.4; range: 2.1–31.2; coefficient of variation: 48.4%). Conclusions Irregular discharge is a key concern in VHA residential care. Patient characteristics do not account for all of the observed variation in rates across residential specialty types. There is a need to develop specialty-specific measures of irregular discharge to learn about system-level factors that contribute to irregular discharge. These data can inform strategies to avoid harms associated with irregular discharge. [ABSTRACT FROM AUTHOR]

Rationale: Obstructive sleep apnea (OSA) has been hypothesized to be a risk factor in interstitial lung disease (ILD) and is associated with radiological markers that may represent the earlier stages of ILD. Prior studies have been limited by their cross-sectional design and potential confounding by body habitus. Objectives: To test the hypothesis that OSA severity is associated with more high-attenuation areas (HAAs) on computed tomography and worse lung function over time among older community-dwelling adults. Methods: We used data from participants in the MESA (Multi-Ethnic Study of Atherosclerosis) who had apnea-hypopnea index (AHI) measured from polysomnography (2010-2013), high attenuation areas (HAAs, 2600 to 2250 Hounsfield units, n = 784), assessments from exams 5 (2010-2012) and 6 (2016-2018) full-lung computed tomography scans, and spirometry assessments (n = 677). Linear mixed-effects models with random intercept were used to examine associations of OSA severity (i.e., AHI and hypoxic burden) with changes in HAAs, total lung volumes, and forced vital capacity (FVC) between exams 5 and 6. Potential confounders were adjusted for in the model, including age, sex, smoking history, height, and weight. Results: Among those with a higher AHI there were more men and a higher body mass index. Participants with AHI>15 events/h and in the highest hypoxic burden quartile each had increases in HAAs of 11.30% (95% confidence interval [CI], 3.74-19.35%) and 9.85% (95% CI, 1.40-19.01%) per 10 years, respectively. There was a more rapid decline in total lung volumes imaged and FVC among those with AHI>15 events/h of 220.2 ml (95% CI, 47.8-392.5 ml) and 3.63% (95% CI, 0.43-6.83%) per 10 years, respectively. Conclusions: A greater burden of hypoxia related to obstructive events during sleep was associated with increased lung densities over time and a more rapid decline in lung volumes regardless of body habitus. Our findings suggest OSA may be a contributing factor in the early stages of ILD. [ABSTRACT FROM AUTHOR]

Rationale: Central sleep apnea (CSA) is associated with high mortality. Current knowledge stems from studies with limited sample size (<100 subjects) and in homogeneous populations such as heart failure (HF).Objectives: To address this knowledge gap, we compared the mortality pattern and time to death between the CSA and obstructive sleep apnea (OSA) patients in the large Veterans Health Administration patient population, utilizing the big data analytic approach.Methods: This is a retrospective study using national Veterans Health Administration electronic medical records from October 1, 1999, through September 30, 2020. We grouped the patients with underlying sleep disorders into CSA and OSA, using ICD9 and ICD10 codes. We applied Cox regression analysis to compare the mortality rate and hazard ratio (HR) among the two groups and adjusted (aHR) by gender, race, body mass index (BMI), age, and Charlson comorbidity index. In CSA groups, a machine-learning algorithm was used to determine the most important predictor of time to death. Further subgroup analysis was also performed in patients that had comorbid heart failure.Results: Evaluation of patients resulted in 2961 grouped as CSA and 1,487,353 grouped as OSA. Patients with CSA were older (61.8±15.6 years) than those with OSA (56.7±13.9 years). A higher proportion of CSA (25.1%) patients died during the study period when compared to the OSA cohort (14.9%). The aHR was 1.53 (95 % CI 1.43, 4.65). Presence of HF history of cerebrovascular disease, hemiplegia, and having BMI <18.5 were among the highest predictors of mortality in CSA. The subgroup analysis revealed that the presence of HF was associated with increased mortality both in CSA (HR 7.4; 95% CI 6.67,8.21) and OSA (HR 4.3; 95% CI 4.26,4.34) groups.Conclusions: Clinically diagnosed CSA was associated with a shorter time to death from the index diagnostic date. Almost one fifth of CSA patients died within five years of diagnosis. The presence of HF, history of cerebrovascular disease and hemiplegia, male sex, and being underweight were among the highest predictors of mortality in CSA. CSA was associated with higher mortality than OSA, independent of associated comorbidity. [ABSTRACT FROM AUTHOR]

Objective: Mortality from opioid use disorder (OUD) can be reduced for patients who receive opioid agonist treatment (OAT). In the United States (US), OATs have different requirements including nearly daily visits to a dispensing facility for methadone but weekly to monthly prescriptions for buprenorphine. Our objective was to compare mortality rates for buprenorphine and methadone treatments among a large sample of US patients with OUD. Methods: We measured all‐cause mortality, overdose mortality, and suicide mortality among US Department of Veterans Affairs patients with a diagnosis of OUD who received OAT from 2010 through 2019. We leveraged substantial and sustained regional variation in prescribing buprenorphine versus methadone as an instrumental variable (IV) and used inverse propensity of treatment weighting to balance relevant covariates across treatment groups. We compared mortality with true two‐stage IV using both probit and linear probability models, as well as a reduced form IV model, adjusting for demographics and health status. Results: Our cohort consisted of 61,997 patients with OUD who received OAT, of whom 92.7% were male with a mean age of 47.9 (SD = 14.1) years. Patients were followed for a median of 2 (IQR = 1,4) calendar years. Across regional terciles, mean methadone prescribing was 4.8%, 19.5%, and 75.1% of OAT patients. All models identified significant reductions in all‐cause and suicide mortality for buprenorphine relative to methadone. For example, predicted all‐cause mortality from the probit model was 169.7 per 10,000 person years (95% CI, 157.8, 179.6) in the lowest tercile of methadone prescribing compared with 206.1 (95% CI, 196.0, 216.3) in the highest tercile. No difference was identified for overdose mortality. Conclusion: We found significantly lower all‐cause mortality and suicide mortality rates for buprenorphine compared with methadone. Our results support the less restrictive prescribing practices for buprenorphine as OAT in the US. [ABSTRACT FROM AUTHOR]

Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes. Objectives: To search for rare variants contributing to OSA severity. Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry. Measurements and Main Results: Linkage analysis in the CFS identified a suggestive linkage peak on chromosome 7q31 (LOD = 2.31). Gene-based analysis identified 21 noncoding rare variants in CAV1 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons (P = 7.4 × 10-8). These noncoding variants together significantly contributed to the linkage evidence (P < 10-3). Follow-up analysis revealed significant associations between these variants and increased CAV1 expression, and increased CAV1 expression in peripheral monocytes was associated with lower AHI (P = 0.024) and higher minimum overnight oxygen saturation (P = 0.007). Conclusions: Rare variants in CAV1, a membrane-scaffolding protein essential in multiple cellular and metabolic functions, are associated with higher CAV1 gene expression and lower OSA severity, suggesting a novel target for modulating OSA severity. [ABSTRACT FROM AUTHOR]

Accountable care organization (ACO) legislation was designed to improve patient outcomes by inducing greater coordination of care and adoption of best practices. Therefore, it is of interest to assess whether greater uniformity occurs among practices comprising an ACO post ACO formation. We develop a mixed‐effect model with a difference‐in‐difference design to evaluate the effect of a patient receiving care from an ACO on patient outcomes and adapt this model to examine whether an ACO is associated with increased uniformity across its constituent practices. The task is complicated by the organizations within an ACO forming an additional layer in the multilevel model, due to medical practices and hospitals that form an ACOs being nested within the ACO, making the number of levels of the model variable and the dimension of the parameter space time‐varying. We develop the model and a procedure for testing the hypothesis that ACO formation was associated with increased uniformity among its constituent practices. We apply our procedure to a cohort of medicare beneficiaries followed over 2009‐2014. Although there is extensive heterogeneity of becoming an ACOs across practices, we find that the formation of an ACO appears to be associated with greater uniformity of patient outcomes among its constituent practices. [ABSTRACT FROM AUTHOR]

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Objectives: Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. Methods: ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; nCPAP:ncontrol = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). Measurements and Main Results: The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; P < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) (P < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; P = 0.6). Conclusions: The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy. [ABSTRACT FROM AUTHOR]

The study aims to investigate whether primary care physicians manage to see a sufficient number of Medicare patients each year in order to be able to detect differences between practices in quality and cost performances. The results indicate that there are very few physicians that are able to measure such differences.

Background Patient safety-based interventions aimed at lethal means restriction are effective at reducing death by suicide in inpatient mental health settings but are more challenging in the outpatient arena. As an alternative approach, we examined the association between quality of mental healthcare and suicide in a national healthcare system. Methods We calculated regional suicide rates for Department of Veterans Affairs (VA) Healthcare users from 2013 to 2017. To control for underlying variation in suicide risk in each of our 115 mental health referral regions (MHRRs), we calculated standardised rate ratios (SRRs) for VA users compared with the general population. We calculated quality metrics for outpatient mental healthcare in each MHRR using individual metrics as well as an Overall Quality Index. We assessed the correlation between quality metrics and suicide rates. Results Among the 115 VA MHRRs, the age-adjusted, sex-adjusted and race-adjusted annual suicide rates varied from 6.8 to 92.9 per 100 000 VA users, and the SRRs varied between 0.7 and 5.7. Mean regional-level adherence to each of our quality metrics ranged from a low of 7.7% for subspecialty care access to a high of 58.9% for care transitions. While there was substantial regional variation in quality, there was no correlation between an overall index of mental healthcare quality and SRR. Conclusion There was no correlation between overall quality of outpatient mental healthcare and rates of suicide in a national healthcare system. Although it is possible that quality was not high enough anywhere to prevent suicide at the population level or that we were unable to adequately measure quality, this examination of core mental health services in a well-resourced system raises doubts that a quality-based approach alone can lower population-level suicide rates. [ABSTRACT FROM AUTHOR]

Objective. Sleep-disordered breathing (SDB) in children is reportedly associated with problem behaviors suggestive of attention-deficit/hyperactivity disorder; however, there are few data on the relation of SDB to problem behaviors in the general pediatric population. The goal of this study was to assess the prevalence of SDB symptoms in 5-year-old children and their relation to sleepiness and problem behaviors. Methods. A population-based, cross-sectional survey was conducted of a birth cohort of children who were born in eastern Massachusetts. Subjects were 3019 5-year-old children (1551 boys, 1468 girls) who were enrolled in the Infant Care Practices Study and whose mothers were contacted within 3 months of their child&apos;s fifth birthday. A parent-completed questionnaire was used to ascertain the presence and intensity of snoring and other SDB symptoms and the presence of daytime sleepiness and problem behaviors. Parent-reported hyperactivity, inattention, and aggressiveness were each assessed by a single question that was validated against the Conners&apos; Parent Rating Scale. SDB was defined as frequent or loud snoring; trouble breathing or loud, noisy breathing during sleep; or witnessed sleep apnea. Results. Parent-reported hyperactivity (19%) and inattention (18%) were common, with aggressiveness (12%) and daytime sleepiness (10%) reported somewhat less often. SDB symptoms were present in 744 (25%) children. Compared with children without snoring or other symptoms of SDB, children with SDB symptoms were significantly more likely to have parent-reported daytime sleepiness (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.7-2.8) and problem behaviors, including hyperactivity (OR: 2.5; CI: 2.0-3.0), inattention (OR: 2.1; 95% CI: 1.7-2.6), and aggressiveness (OR: 2.1; 95% CI: 1.6-2.6). These associations remained significant after adjustment for sex, race/ethnicity, maternal education level, maternal marital status, household income, and respiratory health history. Conclusions. SDB symptoms are common in 5-year-old children and are associated with an increased risk of daytime sleepiness and with problem behaviors suggestive of attention-deficit/hyperactivity disorder. Pediatrics 2003;112:870-877; snoring, sleep-disordered breathing, sleep apnea, behavior, hyperactivity., ABBREVIATIONS. SDB, sleep-disordered breathing; OSA, obstructive sleep apnea; ICPS, Infant Care Practices Study; FYFQ, Five-Year Follow-up Questionnaire; CPRS, Conners' Parent Rating Scale; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, [...]

Objective: Understanding the effectiveness of medication treatment for opioid use disorder to decrease the risk of suicide mortality may inform clinical and policy decisions. The authors sought to describe the effect of medications for opioid use disorder (MOUD) on risk of suicide mortality.Methods: This was a retrospective cohort study in Department of Veterans Affairs (VA) patients from 2003 to 2017. The authors linked three data sources: the VA Corporate Data Warehouse, Centers for Medicare and Medicaid Services Claims Data, and the VA-Department of Defense Mortality Data Repository. The exposure of interest was MOUD, including starting periods (first 14 days on treatment), stopping periods (first 14 days off treatment), stable time on treatment, and stable time off treatment (reference category). The main outcome measures included suicide mortality, external-cause mortality, and all-cause mortality in the 5 years following initiation of MOUD.Results: Over 60,000 VA patients received MOUD. Patients were typically male (92.8%) and their mean age was 46.5 years (SD=13.1). After adjusting for demographic characteristics, mental health and physical health conditions, and health care utilization, the adjusted hazard ratio during stable MOUD was 0.45 (95% CI=0.32, 0.63) for suicide mortality, 0.35 (95% CI=0.31, 0.40) for external-cause mortality, and 0.34 (95% CI=0.31, 0.37) for all-cause mortality. MOUD starting periods were associated with an adjusted hazard ratio for suicide mortality of 0.55 (95% CI=0.25, 1.21), and MOUD stopping periods were associated with an adjusted hazard ratio for suicide mortality of 1.38 (95% CI=0.82, 2.34).Conclusions: Treatment with MOUD was associated with a substantial reduction in suicide mortality as well external causes of mortality and all-cause mortality. [ABSTRACT FROM AUTHOR]

Abstract: Mental health lacks robust measures to assess patient safety. Unplanned discharge is common in mental health populations and associated with poor outcomes. Clarifying whether unplanned discharge varies across settings may highlight the need to develop measures to reduce harms associated with this event. Unplanned discharge rates were compared across the Department of Veterans Affairs' acute inpatient and residential mental health treatment settings from 2009 to 2019. Logistic regression was used to create facility-level, adjusted unplanned discharge rates stratified by setting. Results were described using central tendency. Among 847,661 acute inpatient discharges, the mean unplanned discharge rate was 3.3% (range, 0%-18%). Among 358,117 residential discharges, the mean unplanned discharge rate was 17.9% (range, 1%-48.3%). Unplanned discharge is a marked problem in mental health, with large variation across treatment settings. Unplanned discharge should be measured as part of patient safety efforts. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer's disease risk. Methods: We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia‐free Framingham Heart Study participants (62.65 ± 8.7 years, 50.9% male). Additionally, we explored insomnia symptoms combined with self‐reported short habitual sleep duration and effect modification by apolipoprotein E (APOE) ε4 allele status. Results: More severe insomnia symptoms were associated with lower performance on global cognition, and immediate and delayed Logical Memory recall, especially when insomnia symptoms were combined with short sleep duration. The association between insomnia symptoms and poorer memory recall was more pronounced in APOE ε4 allele carriers. Discussion: Insomnia symptom severity was associated with worse subsequent global cognitive and memory performance, which was especially apparent in APOE ε4 allele carriers, suggesting that poor sleep might be particularly detrimental when the brain is already vulnerable to neurodegeneration. [ABSTRACT FROM AUTHOR]