Multi-ancestry genome-wide analysis identifies shared genetic effects and common genetic variants for self-reported sleep duration.

Both short (≤6 h per night) and long sleep duration (≥9 h per night) are associated with increased risk of chronic diseases. Despite evidence linking habitual sleep duration and risk of disease, the genetic determinants of sleep duration in the general population are poorly understood, especially outside of European (EUR) populations. Here, we report that a polygenic score of 78 European ancestry sleep duration single-nucleotide polymorphisms (SNPs) is associated with sleep duration in an African (n = 7288; P = 0.003), an East Asian (n = 13 618; P = 6 × 10-4) and a South Asian (n = 7485; P = 0.025) genetic ancestry cohort, but not in a Hispanic/Latino cohort (n = 8726; P = 0.71). Furthermore, in a pan-ancestry (N = 483 235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 73 loci are associated with genome-wide statistical significance. Follow-up of five loci (near HACD2, COG5, PRR12, SH3RF1 and KCNQ5) identified expression-quantitative trait loci for PRR12 and COG5 in brain tissues and pleiotropic associations with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.

Sleep duration and bone health measures in older men.

The associations between objective measures of sleep duration and bone outcomes in older men are unknown. No consistent, significant association was identified between sleep duration and bone mineral density (BMD) in the current analysis. However, future research should determine if vitamin D status modifies this relationship. INTRODUCTION: Prior studies, predominantly in women, reported that long and short self-reported sleep duration are associated with lower BMD. Associations between actigraphy-determined sleep duration and BMD or bone turnover markers (BTMs) in older men are unknown. METHODS: Men in The Osteoporotic Fractures in Men (MrOS) Study with wrist actigraphy and concurrent BMD assessment but without comorbidities affecting bone health were included. Sleep duration was considered as a continuous (N = 1926) and dichotomized variable where men were classified as getting the recommended (7-8 h/night; N = 478) or short (< 6 h/night; N = 577) sleep. The cross-sectional association between BMD, BTMs, and sleep duration was examined using a t test or linear regression, where appropriate, in unadjusted and adjusted models. RESULTS: There were no clinically or statistically significant differences in BMD at the L-spine, total hip, or femoral neck between men getting the recommended vs. short sleep duration, using actigraphy or self-reported sleep duration (all p ≥ 0.07). When sleep duration was considered as a continuous variable, femoral neck BMD was higher in men with longer self-reported sleep duration (ß = 0.006 ±0.003, p = 0.02), but this was not significant after further adjustment. In men with low 25OHD (< 20 ng/mL), longer actigraphy-determined sleep duration was associated with higher total hip BMD (ß = 0.016 ± 0.008; p = 0.04). Sleep duration and BTMs were not associated. CONCLUSION: Sleep duration was not associated with hip or L-spine BMD or BTMs in older men. Future research should determine if vitamin D status or other factors modify this relationship.

Mapping neurodevelopment with sleep macro- and micro-architecture across multiple pediatric populations.

Profiles of sleep duration and timing and corresponding electroencephalographic activity reflect brain changes that support cognitive and behavioral maturation and may provide practical markers for tracking typical and atypical neurodevelopment. To build and evaluate a sleep-based, quantitative metric of brain maturation, we used whole-night polysomnography data, initially from two large National Sleep Research Resource samples, spanning childhood and adolescence (total N = 4,013, aged 2.5 to 17.5 years): the Childhood Adenotonsillectomy Trial (CHAT), a research study of children with snoring without neurodevelopmental delay, and Nationwide Children's Hospital (NCH) Sleep Databank, a pediatric sleep clinic cohort. Among children without neurodevelopmental disorders (NDD), sleep metrics derived from the electroencephalogram (EEG) displayed robust age-related changes consistently across datasets. During non-rapid eye movement (NREM) sleep, spindles and slow oscillations further exhibited characteristic developmental patterns, with respect to their rate of occurrence, temporal coupling and morphology. Based on these metrics in NCH, we constructed a model to predict an individual's chronological age. The model performed with high accuracy (r = 0.93 in the held-out NCH sample and r = 0.85 in a second independent replication sample - the Pediatric Adenotonsillectomy Trial for Snoring (PATS)). EEG-based age predictions reflected clinically meaningful neurodevelopmental differences; for example, children with NDD showed greater variability in predicted age, and children with Down syndrome or intellectual disability had significantly younger brain age predictions (respectively, 2.1 and 0.8 years less than their chronological age) compared to age-matched non-NDD children. Overall, our results indicate that sleep architectureoffers a sensitive window for characterizing brain maturation, suggesting the potential for scalable, objective sleep-based biomarkers to measure neurodevelopment.

Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts.

CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown. OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables. METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets. RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative. CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.

Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.

AIMS/HYPOTHESIS: Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs. METHODS: We meta-analysed SNP associations with fasting glucose (FG) or insulin (FI) in AfAs from five cohorts in the Candidate Gene Association Resource. We: (1) calculated allele frequency differences, variations in linkage disequilibrium (LD), fixation indices (F(st)s) and integrated haplotype scores (iHSs); (2) tested EuA SNPs in AfAs; and (3) interrogated within ± 250 kb around each EuA SNP in AfAs. RESULTS: Allele frequency differences ranged from 0.6% to 54%. F(st) exceeded 0.15 at 6/16 loci, indicating modest population differentiation. All iHSs were <2, suggesting no recent positive selection. For 18 SNPs, all directions of effect were the same and 95% CIs of association overlapped when comparing EuA with AfA. For 17 of 18 loci, at least one SNP was nominally associated with FG in AfAs. Four loci were significantly associated with FG (GCK, p = 5.8 × 10(-8); MTNR1B, p = 8.5 × 10(-9); and FADS1, p = 2.2 × 10(-4)) or FI (GCKR, p = 5.9 × 10(-4)). At GCK and MTNR1B the EuA and AfA SNPs represented the same signal, while at FADS1, and GCKR, the EuA and best AfA SNPs were weakly correlated (r(2) <0.2), suggesting allelic heterogeneity for association with FG at these loci. CONCLUSIONS/INTERPRETATION: Few glycaemic SNPs showed strict evidence of transferability from EuA to AfAs. Four loci were significantly associated in both AfAs and those with EuA after accounting for varying LD across ancestral groups, with new signals emerging to aid fine-mapping.

Infant sugar sweetened beverage and 100% juice consumption: Racial/ethnic differences and links with fathers' consumption in a longitudinal cohort.

The consumption of sugar-sweetened beverages (SSB) and 100% juice before age 12 months is discouraged. We examine racial/ethnic differences in SSB and 100% juice consumption when infants were 6- and 12-months old and examine links between fathers' and infants' beverage consumption. Participants were from a longitudinal cohort of infants and their parents (recruited 2016-2018), followed from birth until the child was 24 months. In 2020, we analyzed data collected when infants were 6- (N = 352 infants and 168 fathers) and 12-months (N = 340 infants and 152 fathers) old. Based on maternal report, 13% of infants consumed 100% juice at 6 months and 31% at 12 months. Two percent of infants consumed SSB at 6 months and 7% at 12 months. In models adjusting for income and education, Black/African American (Black/AA) and Hispanic infants were 5-6 times as likely at 6 months and 3 times as likely at 12 months to consume 100% juice compared with non-Hispanic white and Asian infants. At 12 months, Black/AA and Hispanic infants were 6-7 times as likely to consume SSB than non-Hispanic white and Asian infants after adjusting for covariates. In unadjusted models, infants were more likely to consume 100% juice and SSB at 12 months when their fathers were high consumers (>12times/month) of the beverage; effects were no longer significant after adjusting for income, race/ethnicity, education and maternal beverage consumption. Results highlight the need to implement culturally responsive interventions promoting healthy beverage consumption in infants prior to birth and should concurrently target fathers, in addition to mothers.

Suboptimal sleep and incident cardiovascular disease among African Americans in the Jackson Heart Study (JHS).

BACKGROUND: Suboptimal sleep, including insufficient/long sleep duration and poor sleep quality, is a risk factor for cardiovascular disease (CVD) common but there is little information among African Americans, a group with a disproportionate CVD burden. The current study examined the association between suboptimal sleep and incident CVD among African Americans. METHODS: This study included 4,522 African Americans without CVD at baseline (2000-2004) of the Jackson Heart Study (JHS). Self-reported sleep duration was defined as very short (<6 h/night), short (6 h/night), recommended (7-8 h/night), and long (≥9 h/night). Participants' self-reported sleep quality was defined as "high" and "low" quality. Suboptimal sleep was defined by low quality sleep and/or insufficient/long sleep duration. Incident CVD was a composite of incident coronary heart disease and stroke. Associations between suboptimal sleep and incident CVD were examined using Cox proportional hazards models over 15 follow-up years with adjustment for predictors of CVD risk and obstructive sleep apnea. RESULTS: Sample mean age was 54 years (SD = 13), 64% female and 66% reported suboptimal sleep. Suboptimal sleep was not associated with incident CVD after covariate adjustment [HR(95% CI) = 1.18(0.97-1.46)]. Long [HR(95%CI) = 1.32(1.02-1.70)] and very short [HR(95% CI) = 1.56(1.06-2.30)] sleep duration were associated with incident CVD relative to recommended sleep duration. Low quality sleep was not associated with incident CVD (p = 0.413). CONCLUSIONS: Long and very short self-reported sleep duration but not self-reported sleep quality were associated with increased hazard of incident CVD.

Heightened sleep propensity: a novel and high-risk sleep health phenotype in older adults.

OBJECTIVES: To reveal sleep health phenotypes in older adults and examine their associations with time to 5-year all-cause and cardiovascular mortality. DESIGN: Prospective longitudinal cohorts. SETTING: The Study of Osteoporotic Fractures and Outcomes of Sleep Disorders in Older Men Study. PARTICIPANTS: N = 1722 men and women aged ≥65 years matched 1:1 on sociodemographic and clinical measures. MEASUREMENTS: Self-reported habitual sleep health characteristics (satisfaction, daytime sleepiness, timing, efficiency, and duration) measured at an initial visit and longitudinal follow-up for mortality. RESULTS: Latent class analysis revealed 3 sleep health phenotypes: (1) heightened sleep propensity (HSP; medium to long duration, high sleepiness, high efficiency/satisfaction; n = 322), (2) average sleep (AS; medium duration, average efficiency, high satisfaction, low sleepiness; n = 1,109), and (3) insomnia with short sleep (ISS; short to medium duration, low efficiency/satisfaction, moderate sleepiness; n = 291). Phenotype predicted time to all-cause mortality (χ2 = 9.4, P = .01), with HSP conferring greater risk than AS (hazard ratio [95% confidence interval] = 1.48 [1.15-1.92]) or ISS (1.52 [1.07-2.17]), despite ISS reporting the poorest mental and physical health. Although sex did not formally moderate the relationship between phenotype and mortality, subgroup analyses indicated that these findings were driven primarily by women. Phenotype did not predict cardiovascular mortality. CONCLUSIONS: These analyses support the utility of examining multidimensional sleep health profiles by suggesting that the combination of long sleep, high efficiency/satisfaction, and daytime sleepiness-previously identified as independent risk factors-may be components of a single high-risk sleep phenotype, HSP. Further investigation of sex differences and the mechanisms underlying mortality risk associated with HSP is warranted.

Using linkage analysis to identify quantitative trait loci for sleep apnea in relationship to body mass index.

To understand the genetics of sleep apnea, we evaluated the relationship between the apnea hypopnea index (AHI) and body mass index (BMI) through linkage analysis to identify genetic loci that may influence AHI and BMI jointly and AHI independent of BMI. Haseman-Elston sibling regression was conducted on AHI, AHI adjusted for BMI and BMI in African-American and European-American pedigrees. A comparison of the magnitude of linkage peaks was used to assess the relationship between AHI and BMI. In EAs, the strongest evidence for linkage to AHI was on 6q23-25 and 10q24-q25, both decreasing after BMI adjustment, suggesting loci with pleiotropic effects. Also, a promising area of linkage to AHI but not BMI was observed on 6p11-q11 near the orexin-2 receptor, suggesting BMI independent pathways. In AAs the strongest evidence of linkage for AHI after adjusting for BMI was on chromosome 8p21.3 with linkage increasing after BMI adjustment and on 8q24.1 with linkage decreasing after BMI adjustment. Novel linkage peaks were also observed in AAs to both BMI and AHI on chromosome 13 near the serotonin-2a receptor. These analyses suggest genetic loci for sleep apnea that operate both independently of BMI and through BMI-related pathways.

Heritability of upper airway dimensions derived using acoustic pharyngometry.

Acoustic pharyngometry represents a simple, quick noninvasive method of measuring upper airway dimensions, which are predictive of sleep apnoea risk. The aim of the present study was to assess the genetic basis of upper airway size as determined using pharyngometry. Participants in the Cleveland Family Study aged >14 yrs underwent three acoustic pharyngometric measurements. Variance component models adjusted for age and sex were used to estimate the heritability of pharyngometry-derived airway measures. A total of 568 out of 655 (87%) subjects provided pharyngometric curves of sufficient quality. Although African-Americans tended to show narrower airways compared with white subjects, heritability patterns were similar in these two groups. The minimum cross-sectional area exhibited a heritability of 0.34 in white subjects and 0.39 in African-Americans, suggesting that 30-40% of the total variance in this measure is explained by shared familial factors. Estimates were unchanged after adjustment for body mass index or neck circumference. In contrast, oropharyngeal length did not show significant heritability in either ethnic group. The minimum cross-sectional area of the oropharynx is a highly heritable trait, suggesting the presence of an underlying genetic basis. These findings demonstrate the potential utility of acoustic pharyngometry in dissecting the genetic basis of sleep apnoea.

Shared genetic basis for obstructive sleep apnea and adiposity measures.

INTRODUCTION: Obesity and obstructive sleep apnea each have a substantial genetic basis and commonly coexist in individuals. The degree to which the genetic underpinnings for these disorders overlap has not been previously quantified. METHODS: A total of 1802 individuals from 310 families in the Cleveland Family Study underwent home sleep studies as well as standardized assessment of body mass index (BMI) and circumferences at the waist, hip and neck. In 713 participants with laboratory sleep studies, fasting blood samples were assayed for leptin, adiponectin and resistin. Variance component models were used to estimate heritability and genetic correlations. RESULTS: The heritability of the apnea hypopnea index (AHI) was 0.37+/-0.04 and 0.33+/-0.07 for home and laboratory sleep studies, respectively. The genetic correlations between AHI and anthropomorphic adiposity measures ranged from 0.57 to 0.61, suggesting that obesity can explain nearly 40% of the genetic variance in sleep apnea. The magnitude of the genetic correlations between apnea severity and adipokine levels was substantially less than those with anthropomorphic measures, ranging from 0.11 to 0.46. After adjusting for BMI, no significant genetic correlation with apnea severity was observed for any of the other adiposity measures. CONCLUSIONS: Substantial but not complete overlap in genetic bases exists between sleep apnea and anthropomorphic indices of adiposity, and this overlap accounts for more than one-third of the genetic variance in apnea severity. These findings suggest that genetic polymorphisms exist that importantly influence sleep apnea susceptibility through both obesity-dependent and -independent pathways.

The association between sleep duration and obesity in older adults.

BACKGROUND: Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults. METHODS: Wrist actigraphy was performed for a mean (s.d.) of 5.2 (0.9) nights in 3055 men (age: 67-96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70-99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity. RESULTS: Compared to those sleeping an average of 7-8 h per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 h was associated with a body mass index (BMI) that was on average 2.5 kg/m(2) (95% confidence interval (CI): 2.0-2.9) greater in men and 1.8 kg/m(2) (95% CI: 1.1-2.4) greater in women. The odds of obesity (BMI >or= 30 kg/m(2)) was 3.7-fold greater (95% CI: 2.7-5.0) in men and 2.3-fold greater in women (95% CI: 1.6-3.1) who slept less than 5 h. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia and daytime sleepiness. CONCLUSIONS: In older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.

Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource.

Sleep spindles are characteristic electroencephalogram (EEG) signatures of stage 2 non-rapid eye movement sleep. Implicated in sleep regulation and cognitive functioning, spindles may represent heritable biomarkers of neuropsychiatric disease. Here we characterize spindles in 11,630 individuals aged 4 to 97 years, as a prelude to future genetic studies. Spindle properties are highly reliable but exhibit distinct developmental trajectories. Across the night, we observe complex patterns of age- and frequency-dependent dynamics, including signatures of circadian modulation. We identify previously unappreciated correlates of spindle activity, including confounding by body mass index mediated by cardiac interference in the EEG. After taking account of these confounds, genetic factors significantly contribute to spindle and spectral sleep traits. Finally, we consider topographical differences and critical measurement issues. Taken together, our findings will lead to an increased understanding of the genetic architecture of sleep spindles and their relation to behavioural and health outcomes, including neuropsychiatric disorders.

Childhood obesity patterns and relation to middle-age sleep apnoea risk: the Bogalusa Heart Study.

BACKGROUND: Obese adults have a higher risk of obstructive sleep apnoea (OSA); however, the relationship between childhood obesity and adult OSA risk is unclear. Objectives This study aimed to examine overweight/obesity (OW) in childhood and risk of OSA in middle age. METHODS: Childhood OW status was classified as never OW, weight cycling, persistent OW and incident OW. After 35 years of follow-up, high risk for OSA was determined by a positive score in ≥2 domains on the Berlin Questionnaire with obesity removed from scoring. RESULTS: At initial assessment, mean (SD) age was 9.9 (2.9) years, and 23.9% were OW. Overall, 25.7% had scores indicating a high risk for OSA. Compared with participants who were never OW, those with persistent OW and incident OW were 1.36 (95%CI: 1.04-1.77) and 1.47 (1.11-1.96) times more likely to be high risk for OSA, after adjustment for multiple risk factors and adult OW status. Participants with an OW duration of 1-4 years, 5-8 years, and 8+ years were 0.96 (0.44-2.09), 1.20 (0.70-2.04) and 1.52 (1.22-1.90) times more likely to be high risk for OSA compared with those who were never OW (P for trend: 0.0002). CONCLUSIONS: These results suggest that childhood OW is associated with a high risk of OSA in middle age.

Race differences in the association between multivitamin exposure and wheezing in preterm infants.

OBJECTIVE: We aimed to determine whether vitamin D exposure, as estimated by use of multivitamins, is positively or negatively associated with recurrent wheezing in infants born preterm. STUDY DESIGN: This prospective cohort study enrolled 300 infants, born at 28(0/7) to 34(6/7) weeks gestational age, and conducted follow-up at 3-, 6-, 9- and 12-month adjusted age. RESULT: Black (55.9%) and non-black (36.6%) infants experienced recurrent wheezing. Adjusted odds ratios (ORs) for the association between multivitamin exposure at 3 months and recurrent wheezing were 2.15 (95% confidence interval (CI): 0.97, 4.75) for black and 0.43 (95% CI: 0.19, 0.96) for non-black infants with an interaction by race (P=0.003). In lag-effect models, ORs were 2.69 (95% CI: 1.41, 5.14) for black and 0.50 (95% CI: 0.27, 0.92) for non-black infants. CONCLUSION: Differences by race were seen in association between multivitamins and wheezing; population heterogeneity should be considered when evaluating vitamin supplementation.

Hypopnea, a floating metric: implications for prevalence, morbidity estimates, and case finding.

The respiratory disturbance index (RDI) is the most frequently used metric to characterize sleep-disordered breathing. Clinically, the RDI is used to classify disease status and guide treatment decisions. For research purposes, the RDI is used to describe population distributions of sleep-disordered breathing. Its popularity as a cardinal disease-defining measure, however, may not be justified given that standardized criteria do not exist for defining hypopnea, a key component of the RDI. This paper reviews sources of variability in identifying hypopneas, including: the magnitude of changes in breathing amplitude necessary to describe breathing as "reduced" (from "discernible" to >50%), variations in the utilization of sensors with different sensitivities to detect airflow/ventilation (i.e. thermocouples, thermistors, and pressure transducers), and differential use of data on oxygen saturation and arousals to discriminate normal breathing from hypopneas. The extent to which disparate approaches influence the overall RDI and population estimates of disease also is discussed.

Predictors of sleep-disordered breathing in children with a history of tonsillectomy and/or adenoidectomy.

STUDY OBJECTIVES: To identify predictors of sleep-disordered breathing (SDB) in children who have undergone self-reported tonsillectomy and/or adenoidectomy (TA). DESIGN: Observational study of pediatric participants in a longitudinal genetic-epidemiological cohort study of SDB. SETTING: Community-based; studies conducted at participants' homes PARTICIPANTS: 577 children age <18 (10.8+/-4.2 SD) years; 53% female; 48% Black; 76% with a family member identified with SDB. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Medical history assessed by questionnaire. Physical measures made directly. SDB was assessed with overnight inhome cardio-respiratory monitoring. 10% of children (n=60) had had aTA 5.5+/-4.6 yrs previously. An Apnea-Hypopnea Index (AHI, events/hr) > or =5 was found in a higher proportion of children with a reported TA than in children with no history of out surgery (35% vs. 13.7%, p<.001). A TA was reported more frequently for non-Blacks than for Blacks (13.6% non-Blacks, 6.9% Blacks, p=.02). Among children who had a TA, significant predictors of SDB (AHI> or =5) were: Black ethnicity (SDB in 57% vs. 24% of Blacks vs. non-Blacks; adjusted odds ratio (OR): 3.85; 95% CI: 1.11, 13.33) and obesity (OR 3.98; 95% Cl: 1.05, 15.08). SDB also tended to be greater in children with a family member with SDB (OR 2.87; 95% CI: 0.65, 12.07). CONCLUSIONS: Black children were less likely to have undergone TA but more likely to have SDB after TA surgery. These findings underscore the need to follow children post-TA and for evidence-based studies that define the role of TA in the management of pediatric adenotonsillar disease.

Neuropsychological function in mild sleep-disordered breathing.

Although a broad range of neuropsychological deficits has been reported in patients with severe sleep disordered breathing (SDB), little is known about the impact of mild SDB on neuropsychological performance. In this study, we compared neuropsychological test performance in two groups of carefully screened volunteers who differed clearly according to the respiratory disturbance index (RDI). Controls (n = 20) were identified on the basis of an RDI < 5; cases (n = 32) had an RDI in the range of 10-30. Cases and controls were well matched with regard to IQ, age, and sex. Cases had significantly more self-reported snorting and apneas and a higher body mass index than controls but did not differ according to sleepiness as measured by either the multiple sleep latency test or the Epworth sleepiness scale. An extensive battery of neuropsychological and performance tests was administered after an overnight sleep study. Cases performed significantly more poorly on a visual vigilance task (perceptual sensitivity, d': 2.24 +/- 0.64 vs. 2.70 +/- 0.53, p = 0.01, for cases and controls, respectively) and a test of working memory, the Wechsler adult intelligence scale-revised digits backwards test (6.12 +/- 2.20 vs. 7.55 +/- 2.22, p = 0.02), than controls. The groups did not differ in their performance on other tests of memory, information processing, and executive functioning. In summary, subjects with mild SDB may manifest a vigilance deficit in the absence of substantial sleepiness. Subjects with a mildly elevated RDI (10-30) without sleepiness do not appear to suffer appreciable deficits in more complex neuropsychological processes (e.g. executive functions).

Reliability of scoring respiratory disturbance indices and sleep staging.

STUDY OBJECTIVES: Unattended, home-based polysomnography (PSG) is increasingly used in both research and clinical settings as an alternative to traditional laboratory-based studies, although the reliability of the scoring of these studies has not been described. The purpose of this study is to describe the reliability of the PSG scoring in the Sleep Heart Health Study (SHHS), a multicenter study of the relation between sleep-disordered breathing measured by unattended, in-home PSG using a portable sleep monitor, and cardiovascular outcomes. DESIGN: The reliability of SHHS scorers was evaluated based on 20 randomly selected studies per scorer, assessing both interscorer and intrascorer reliability. RESULTS: Both inter- and intrascorer comparisons on epoch-by-epoch sleep staging showed excellent reliability (kappa statistics >0.80), with stage 1 having the greatest discrepancies in scoring and stage 3/4 being the most reliably discriminated. The arousal index (number of arousals per hour of sleep) was moderately reliable, with an intraclass correlation (ICC) of 0.54. The scorers were highly reliable on various respiratory disturbance indices (RDIs), which incorporate an associated oxygen desaturation in the definition of respiratory events (2% to 5%) with or without the additional use of associated EEG arousal in the definition of respiratory events (ICC>0.90). When RDI was defined without considering oxygen desaturation or arousals to define respiratory events, the RDI was moderately reliable (ICC=0.74). The additional use of associated EEG arousals, but not oxygen desaturation, in defining respiratory events did little to increase the reliability of the RDI measure (ICC=0.77). CONCLUSIONS: The SHHS achieved a high degree of intrascorer and interscorer reliability for the scoring of sleep stage and RDI in unattended in-home PSG studies.

Relationship between sleepiness and general health status.

One commonly used instrument for evaluating general health and functional status is the medical outcomes survey short form 36 (MOS). Scores obtained from this instrument are known to vary with chronic diseases and depression. However, the degree to which these health dimensions may be influenced by sleep quality or sleepiness is not well understood. A cross-sectional study was performed on the association between general health status, as determined by the MOS, with sleepiness, assessed using a standardized questionnaire [the Epworth sleepiness scale (ESS)] and the multiple sleep latency test (MSLT). One hundred twenty-nine subjects (68 women), aged 25-65 years, without severe chronic medical or psychiatric illnesses, underwent an overnight sleep study, followed by an MSLT (consisting of a series of four attempts at napping at 2-hour intervals), and completed the MOS and the ESS. The mean MSLT score was 11 +/- 2 minutes, (range 2-20) and the mean ESS score was 10 +/- 5 (range 0-24). Scores for the MOS dimensions "general health perceptions", "energy/fatigue", and "role limitations due to emotional problems" were correlated significantly with ESS scores (r = -0.30, -0.41, and -0.30, respectively; p values were all < 0.001). The MSLT was also significantly correlated with "energy/fatigue" (r = -0.19; p < 0.05). After considering the effects of chronic illness and/or body mass index in a multiple hierarchical regression analysis, sleepiness, as assessed by the ESS score, explained 8% of the variance in general health perceptions, 17% of the variance in energy/fatigue, 6% of the variance in the summary measure of well-being, and 3% of the variance in the summary measure of functional status. The variation of MOS scores with sleepiness, unrelated to age or chronic disease, suggests that measures of general health status may be broadly influenced by sleepiness and sleep quality. These data suggest that 1) sleepiness has an important impact on general health and functional status, specifically influencing self-perceptions regarding energy/fatigue; 2) a more specific assessment of sleepiness in general health evaluations may help explain some of the observed variability in these measures across subjects; and 3) general health measures may be useful in the evaluations of patients with sleep disorders.