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Study Objectives: To evaluate the impact of sleep disorders on non-motor symptoms in patients with Parkinson disease (PD). Design: This was a cross-sectional study. Patients with PD were evaluated for obstructive sleep apnea (OSA), restless legs syndrome (RLS), periodic limb movement syndrome (PLMS), and REM sleep behavior disorder (RBD). Cognition was assessed with the Montreal Cognitive Assessment and patients completed self-reported questionnaires assessing non-motor symptoms including depressive symptoms, fatigue, sleep complaints, daytime sleepiness, and quality of life. Setting: Sleep laboratory. Participants: 86 patients with PD (mean age = 67.4 ± 8.8 years; range: 47–89; 29 women). Interventions: N/A. Measurements and Results: Having sleep disorders was a predictor of overall non-motor symptoms in PD (R 2 = 0.33, p < 0.001) while controlling for age, PD severity, and dopaminergic therapy. These analyses revealed that RBD (p = 0.006) and RLS (p = 0.014) were significant predictors of increased non-motor symptoms, but OSA was not. More specifically, having a sleep disorder significantly predicted sleep complaints (ΔR 2 = 0.13, p = 0.006), depressive symptoms (ΔR 2 = 0.01, p = 0.03), fatigue (ΔR 2 = 0.12, p = 0.007), poor quality of life (ΔR 2 = 0.13, p = 0.002), and cognitive decline (ΔR 2 = 0.09, p = 0.036). Additionally, increasing number of sleep disorders (0, 1, or ≥ 2 sleep disorders) was a significant contributor to non-motor symptom impairment (R 2 = 0.28, p < 0.001). Conclusion: In this study of PD patients, presence of comorbid sleep disorders predicted more non-motor symptoms including increased sleep complaints, more depressive symptoms, lower quality of life, poorer cognition, and more fatigue. RBD and RLS were factors of overall increased non-motor symptoms, but OSA was not. Citation: Neikrug AB; Maglione JE; Liu L; Natarajan L; Avanzino JA; Corey-Bloom J; Palmer BW; Loredo JS; Ancoli-Israel S. Effects of sleep disorders on the non-motor symptoms of Parkinson disease. J Clin Sleep Med 2013;9(11):1119–1129.

When obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in the so-called \"overlap\" syndrome, a high risk for mortality and morbidity has been reported. There is controversy about the prevalence of OSA in people affected by COPD. The purpose of this study was to investigate objective meaures of sleep-disordered breathing in patients with moderate to severe COPD to test the hypothesis that COPD is associated with an increased prevalence of OSA. Fifty-four patients (54% men) with moderate to severe COPD were enrolled prospectively (mean ± SD, FEV1 = 42.8 ± 19.8% predicted, and FEV1/FVC = 42.3 ± 13.1). Twenty patients (37%) were on supplemental oxygen at baseline. Exercise tolerance; questionnaires related to symptoms, sleep, and quality of life; and home polysomnography were obtained. Forty-four patients had full polysomnography suitable for analysis. OSA (apnea-hypopnea index > 5/h) was present in 29 subjects (65.9%). Sleep efficiency was poor in 45% of subjects. OSA is highly prevalent in patients with moderate to severe COPD referred to pulmonary rehabilitation. Sleep quality is also poor among this selected group. These patients have greater-than-expected sleep-disordered breathing, which could be an important contributory factor to morbidity and mortality. Pulmonary rehabilitation programs should consider including a sleep assessment in patients with moderate to severe COPD and interventions when indicated to help reduce the impact of OSA in COPD.

Abstract Study Objectives: Recent studies implicate inadequate sleep duration and quality in metabolic disease. Fewer studies have examined the timing of sleep, which may be important because of its potential impact on circadian rhythms of metabolic function. We examined the association between sleep timing and metabolic risk among Hispanic/Latino adults. Methods: Cross-sectional data from community-based study of 13429 participants aged 18–74 years. People taking diabetic medications were excluded. Sleep timing was determined from self-reported bedtimes and wake times. Chronotype was defined as the midpoint of sleep on weekends adjusted for sleep duration on weekdays. Other measurements included body mass index (BMI), fasting glucose levels, estimated insulin resistance (HOMA-IR), glucose levels 2 hours post oral glucose ingestion, and hemoglobin A1c. Survey linear regression models tested associations between sleep timing and metabolic measures. Analyses were stratified by diabetes status and age-group when significant interactions were observed. Results: Among participants with diabetes, fasting glucose levels were positively associated with bedtime (approximately +3%/hour later, p < .01) and midpoint of sleep (approximately +2%/hour later, p < .05). In participants with and without diabetes combined, HOMA-IR was positively associated with midpoint of sleep (+1.5%/hr later, p < .05), and chronotype (+1.2%/hour later, p < .05). Associations differed by age-group. Among those < 36 years, later sleep timing was associated with lower BMI, lower fasting glucose, and lower HbA1c, but the opposite association was observed among older participants. Conclusions: Later sleep timing was associated with higher estimated insulin resistance across all groups. Some associations between sleep timing and metabolic measures may be age-dependent.

We studied the effect of continuous positive airway pressure (CPAP) treatment on sympathetic nervous activity in 38 patients with obstructive sleep apnea. Randomized, placebo-controlled trial. Patients underwent polysomnography on three occasions in a clinical research center, and had BP monitored over 24 h at home. All of the patients had sleep apnea with a respiratory disturbance index (RDI) > 15. The patients were randomized blindly to CPAP or placebo (CPAP at ineffective pressure) treatment. Prior to therapy, the number of apneas and the severity of nocturnal hypoxia correlated significantly with daytime urinary norepinephrine (NE) levels, but not nighttime urinary NE levels. CPAP treatment lowered daytime BP from 99 ± 2 mm Hg to 95 ± 3 mm Hg (mean ± SEM) and nighttime BP from 93 ± 3 mm Hg to 88 ± 3 mm Hg. Placebo CPAP treatment decreased both day and night mean BP only 2 mm Hg. CPAP, but not placebo, treatment lowered daytime plasma NE levels by 23%, daytime urine NE levels by 36%, daytime heart rate by 2.6 beats/min, and increased lymphocyteβ 2-adrenergic receptor sensitivity (all p < 0.05). The effect of CPAP treatment on nighttime urine NE levels and heart rate did not differ from placebo treatment. There was a suggestion of an effect of placebo CPAP treatment on nighttime measures, but not on daytime measures. We conclude that daytime sympathetic nervous activation is greater with more severe sleep apnea. CPAP treatment diminished the daytime sympathetic activation; the potential nighttime effect of CPAP treatment was obscured by a small placebo effect.

Objective: Patients with obstructive sleep apnea (OSA) commonly have cognitive complaints, particularly in attention, and report decreased quality of life. We examined how vigilance and sustained attention, as assessed by the Psychomotor Vigilance Task (PVT), were related to quality of life after controlling for apnea severity and depression in subjects with OSA. Subjects and Methods: Fifty-seven patients with newly diagnosed and untreated OSA had their sleep monitored with polysomnography. Quality of life was assessed by the Short Form-36 health survey questionnaire (SF-36). Mood was assessed by the Center for Epidemiologic Studies-Depression (CES-D) Scale. After sleep monitoring and psychological assessments were performed, the 10-minute PVT was administered. The main outcome variables were PVT lapse count and average response time (RT). Simple correlations and multiple linear regression were used to examine the association between PVT performance and age, body mass index, sleep variables, apnea hypopnea index, oxygen desaturation index, and CES-D. Results and Conclusion: Both the PVT lapse count and RT were significantly associated with the SF-36 physical component summary score (PCS). In multiple linear regression, PVT RT was an independent predictor of the SF-36 PCS (full model R 2 = 0.331, p = 0.003). PVT lapse was also an independent predictor of the SF-36 PCS (full model R 2 = 0.320, p = 0.004). However, neither PVT RT nor lapse was a significant independent predictor of the SF-36 mental component summary score (MCS). Only CES-D was an individual predictor of the SF-36 MCS (β = −0.676, p < 0.001). Impairments in sustained attention and vigilance may underlie the limitations in physical health-related quality of life reported by people with OSA, even after controlling for demographic variables, apnea severity, and depression. Citation: Lee IS; Bardwell W; Ancoli-Israel S; Natarajan L; Loredo JS; Dimsdale JE. The relationship between psychomotor vigilance performance and quality of life in obstructive sleep apnea. J Clin Sleep Med 2011;7(3):254–260.

Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability. To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts. Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration. Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10 for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10 ). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility. These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.

Abstract Rationale Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. Objectives To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. Methods The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18–74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. Measurements and Main Results The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6–39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3–4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. Conclusions Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

Introduction: Obstructive sleep apnea (OSA) is common among patients with Alzheimer’s disease (AD). Untreated OSA exacerbates the cognitive and functional deficits. Continuous positive airway pressure (CPAP) has recently been shown to have beneficial effects on cognition in AD. Little attention has focused on the long-term benefits of CPAP in these patients. Methods: This was an exploratory study of sustained CPAP use (mean use = 13.3 months, SD = 5.2) among a subset of participants from an initial 6-week randomized clinical trial (RCT) of CPAP in patients with mild to moderate AD. Follow-up included 5 patients who continued CPAP (CPAP+) after completion of the RCT and 5 patients who discontinued CPAP (CPAP−), matched by time of completion of the initial study. A neuropsychological test battery and sleep/mood questionnaires were administered and effect sizes were calculated. Results: Even with a small sample size, sustained CPAP use resulted in moderate-to-large effect sizes. Compared to the CPAP− group, the CPAP+ group showed less cognitive decline with sustained CPAP use, stabilization of depressive symptoms and daytime somnolence, and significant improvement in subjective sleep quality. Caregivers of the CPAP+ group also reported that their own sleep was better when compared to the final RCT visit and that their patients psychopathological behavior was improved. Conclusion: The results of this preliminary study raise the possibility that sustained, long-term CPAP treatment for patients with AD and OSA may result in lasting improvements in sleep and mood as well as a slowing of cognitive deterioration. Prospective randomized controlled research trials evaluating these hypotheses are needed. Citation: Cooke JR; Ayalon L; Palmer BW; Loredo JS; Corey-Bloom J; Natarajan L; Liu L; Ancoli-Israel S. Sustained use of CPAP slows deterioration of cognition, sleep, and mood in patients with Alzheimer’s disease and obstructive sleep apnea: a preliminary study. J Clin Sleep Med 2009 ;5(4):305–309.

Abstract Study objective: To assess the extent to which objective sleep patterns vary among U.S. Hispanics/Latinos. Methods: We assessed objective sleep patterns in 2087 participants of the Hispanic Community Health Study/Study of Latinos from 6 Hispanic/Latino subgroups aged 18–64 years who underwent 7 days of wrist actigraphy. Results: The age- and sex-standardized mean (SE) sleep duration was 6.82 (0.05), 6.72 (0.07), 6.61 (0.07), 6.59 (0.06), 6.57 (0.10), and 6.44 (0.09) hr among individuals of Mexican, Cuban, Dominican, Central American, Puerto Rican, and South American heritage, respectively. Sleep maintenance efficiency ranged from 89.2 (0.2)% in Mexicans to 86.5 (0.4)% in Puerto Ricans, while the sleep fragmentation index ranged from 19.7 (0.3)% in Mexicans to 24.2 (0.7)% in Puerto Ricans. In multivariable models adjusted for age, sex, season, socioeconomic status, lifestyle habits, and comorbidities, these differences persisted. Conclusions: There are important differences in actigraphically measured sleep across U.S. Hispanic/Latino heritages. Individuals of Mexican heritage have longer and more consolidated sleep, while those of Puerto Rican heritage have shorter and more fragmented sleep. These differences may have clinically important effects on health outcomes.

Continuous positive airway pressure (CPAP) prediction formulas can potentially simplify the treatment of obstructive sleep apnea (OSA). However, they can be difficult to derive and validate. We tested a statistical method to derive and validate a CPAP prediction formula using the same sample population. Seventy-six OSA patients underwent polysomnography and CPAP titration. Anthropometric measures, sleep parameters, and the Epworth sleepiness scale (ESS) were evaluated as predictors. All subsets regression was used to determine the optimum number of variables in the model. The Bayes information criterion was used to find the best-fit model. The model was then evaluated by a tenfold cross-validation procedure. Subjects were obese (BMI 31.3 +/- 5.4) and had significant daytime somnolence (ESS 11.9 +/- 5). Mean respiratory disturbance index (RDI) was 53.5 +/- 31.3. The ESS was not predictive of titrated CPAP. The best-fit model included three variables (CPAP(pred) = 30.8 + RDI x 0.03 - nadir saturation x 0.05 - mean saturation x 0.2). This model explained 67% of the variance. Our data and the literature suggest that a combination of two to three factors is predictive of titrated CPAP: RDI, oxyhemoglobin saturation, and obesity. Except for RDI, the specific factors vary in each population. A CPAP prediction formula that explains a high proportion of the titrated CPAP variance can be easily derived from parameters measured during the diagnostic work-up of OSA patients using a unique statistical model that allows derivation and validation of the formula in the same test population.