Stephen P. Duntley

Prevalence of undiagnosed obstructive sleep apnea among adult surgical patients in an academic medical center.

BACKGROUND Obstructive sleep apnea (OSA) affects approximately 20% of US adults, of whom about 90% are undiagnosed. While OSA may increase risk of perioperative complications, its prevalence among surgical patients is unknown. We tested the feasibility of screening surgical patients for OSA and determined the prevalence of undiagnosed OSA. METHODS In a prospective, observational study adult surgical patients were screened for OSA in an academic hospital. Patients without an OSA diagnosis who screened high-risk were offered a home sleep study to determine if they had OSA. The results were compared with polysomnography (PSG) when available. Charts of high-risk patients were examined for postoperative complications. High-risk patients received targeted interventions as part of a hospital safety initiative. RESULTS There were 2877 patients screened; 661 (23.7%) screened high-risk for OSA, of whom 534 (81%) did not have diagnosed OSA. The portable sleep study detected OSA in 170/207 (82%) high-risk patients without diagnosed OSA. Twenty-six PSGs confirmed OSA in 19 of these patients. Postoperatively there were no respiratory arrests, two unanticipated ICU admissions, and five documented respiratory complications. CONCLUSION Undiagnosed OSA is prevalent in adult surgical patients. Implementing universal screening is feasible and can identify undiagnosed OSA in many surgical patients. Further investigation is needed into perioperative complications and their prevention for patients with undiagnosed OSA.

Sleep Quality and Preclinical Alzheimer Disease

IMPORTANCE Sleep and circadian problems are very common in Alzheimer disease (AD). Recent animal studies suggest a bidirectional relationship between sleep and β-amyloid (Aβ), a key molecule involved in AD pathogenesis. OBJECTIVE To test whether Aβ deposition in preclinical AD, prior to the appearance of cognitive impairment, is associated with changes in quality or quantity of sleep. DESIGN Cross-sectional study conducted from October 2010 to June 2012. SETTING General community volunteers at the Washington University Knight Alzheimers Disease Research Center. PARTICIPANTS Cognitively normal individuals (n = 145) 45 years and older were recruited from longitudinal studies of memory and aging at the Washington University Knight Alzheimers Disease Research Center. Valid actigraphy data were recorded in 142. The majority (124 of 142) were recruited from the Adult Children Study, in which all were aged 45 to 75 years at baseline and 50% have a parental history of late-onset AD. The rest were recruited from a community volunteer cohort in which all were older than 60 years and healthy at baseline. MAIN OUTCOME MEASURES Sleep was objectively measured using actigraphy for 2 weeks. Sleep efficiency, which is the percentage of time in bed spent asleep, was the primary measure of sleep quality. Total sleep time was the primary measure of sleep quantity. Cerebrospinal fluid Aβ42 levels were used to determine whether amyloid deposition was present or absent. Concurrent sleep diaries provided nap information. RESULTS Amyloid deposition, as assessed by Aβ42 levels, was present in 32 participants (22.5%). This group had worse sleep quality, as measured by sleep efficiency (80.4% vs 83.7%), compared with those without amyloid deposition, after correction for age, sex, and APOEε4 allele carrier status (P = .04). In contrast, quantity of sleep was not significantly different between groups, as measured by total sleep time. Frequent napping, 3 or more days per week, was associated with amyloid deposition (31.2% vs 14.7%; P = .03). CONCLUSIONS AND RELEVANCE Amyloid deposition in the preclinical stage of AD appears to be associated with worse sleep quality but not with changes in sleep quantity.

Effects of Age and Amyloid Deposition on Aβ Dynamics in the Human Central Nervous System

BACKGROUND The amyloid hypothesis predicts that increased production or decreased clearance of β-amyloid (Aβ) leads to amyloidosis, which ultimately culminates in Alzheimer disease (AD). OBJECTIVE To investigate whether dynamic changes in Aβ levels in the human central nervous system may be altered by aging or by the pathology of AD and thus contribute to the risk of AD. DESIGN Repeated-measures case-control study. SETTING Washington University School of Medicine in St Louis, Missouri. PARTICIPANTS Participants with amyloid deposition, participants without amyloid deposition, and younger normal control participants. MAIN OUTCOME MEASURES In this study, hourly cerebrospinal fluid (CSF) Aβ concentrations were compared with age, status of amyloid deposition, electroencephalography, and video recording data. RESULTS Linear increases were observed over time in the Aβ levels in CSF samples obtained from the younger normal control participants and the older participants without amyloid deposition, but not from the older participants with amyloid deposition. Significant circadian patterns were observed in the Aβ levels in CSF samples obtained from the younger control participants; however, circadian amplitudes decreased in both older participants without amyloid deposition and older participants with amyloid deposition. Aβ diurnal concentrations were correlated with the amount of sleep but not with the various activities that the participants participated in while awake. CONCLUSIONS A reduction in the linear increase in the Aβ levels in CSF samples that is associated with amyloid deposition and a decreased CSF Aβ diurnal pattern associated with increasing age disrupt the normal physiology of Aβ dynamics and may contribute to AD.

Sleep deprivation during pregnancy and maternal and fetal outcomes: Is there a relationship?

Sleep duration in the population has been declining. Women occupy an increasingly prominent place in the work force without reducing most of their responsibilities at home. Consequently, sleep needs are often pushed to the bottom of womens daily priority list. Prior research has indicated that sleep deprivation is associated with higher levels of pro-inflammatory serum cytokines. This is important because higher plasma concentrations of pro-inflammatory serum cytokine levels are associated with postpartum depression and adverse birth outcomes such as preterm delivery. However, little research has directly examined how sleep deprivation may affect maternal and fetal outcomes. This review summarizes the existing data on the effect of sleep deprivation during pregnancy on maternal and fetal outcomes. We review supporting evidence for the hypotheses that sleep deprivation during pregnancy increases the risk of preterm delivery and postpartum depression, and that systemic inflammation is the causal mechanism in the association. Prior research on sleep in pregnancy has been limited by varying data collection methods, subjective self-reported sleep measures, small and non-representative samples, cross-sectional designs; descriptive or non-hypothesis driven studies. Future research with longitudinal study designs is needed to allow examination of the effect of sleep deprivation on adverse maternal and fetal outcomes.

Learning, Memory, and Executive Control in Individuals With Obstructive Sleep Apnea Syndrome

A range of neuropsychological deficits have been identified in individuals with obstructive sleep apnea syndrome (OSAS) and have been related to disruptions in function of the frontal cortex of the brain. We hypothesized that impairments in the use of strategic, frontally-mediated processes that facilitate learning and memory would be associated with deficits in the long-term episodic memory of verbal material (i.e., word lists). We evaluated 28 adults with OSAS and 24 controls (ranging from 28 to 60 years of age) using the California Verbal Learning Test. General executive abilities were assessed using the Wisconsin Card Sorting Test, Letter fluency, and Category fluency. Individuals with OSAS exhibited poorer recall across learning trials, less efficient use of semantic clustering, and poorer use of semantic cues. Retention of previously encoded information and recognition, however, were intact. With the exception of letter fluency, deficits were not observed in general executive control. Results are discussed within the context of disruptions in the interactions between long-term memory and executive abilities that are subserved by frontal and distal brain regions.

The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome

OBJECTIVES To determine the prevalence of obstructive sleep apnea syndrome (OSAS) in a population of premenopausal women with polycystic ovarian syndrome (PCOS) and to study the impact of obesity on the increased prevalence of OSAS in this population. METHODS Twenty-three premenopausal women with definite PCOS, and no prior diagnosis of a sleep disorder, were recruited from gynecology clinics. An investigator interviewed them, for symptoms of excessive sleepiness, their body mass index (BMI) was calculated, and they underwent overnight polysomnography. RESULTS Sixteen of 23 (69.6%) met criteria for OSAS. Five were treated with continuous positive airway pressure. Confidence interval was 47.7-84.5%. An increased respiratory disturbance index (RDI) did not correlate with higher BMI. CONCLUSIONS OSAS is significantly more prevalent in this population than in a population of obese women. There was no correlation between obesity and severity of the OSAS. Obesity is not the cause of this increased prevalence of OSAS in a population of women with PCOS.

Identification of a biomarker for sleep drive in flies and humans

It is a common experience to sacrifice sleep to meet the demands of our 24-h society. Current estimates reveal that as a society, we sleep on average 2 h less than we did 40 years ago. This level of sleep restriction results in negative health outcomes and is sufficient to produce cognitive deficits and reduced attention and is associated with increased risk for traffic and occupational accidents. Unfortunately, there is no simple quantifiable marker that can detect an individual who is excessively sleepy before adverse outcomes become evident. To address this issue, we have developed a simple and effective strategy for identifying biomarkers of sleepiness by using genetic and pharmacological tools that dissociate sleep drive from wake time in the model organism Drosophila melanogaster. These studies have identified a biomarker, Amylase, that is highly correlated with sleep drive. More importantly, both salivary Amylase activity and mRNA levels are also responsive to extended waking in humans. These data indicate that the fly is relevant for human sleep research and represents a first step in developing an effective method for detecting sleepiness in vulnerable populations.

Adherence, reports of benefits, and depression among patients treated with continuous positive airway pressure.

Objectives: To examine if reported obstructive sleep apnea (OSA) symptom improvement, baseline depressive symptoms, or polysomnographically measured sleep parameters are associated with adherence to continuous positive airway pressure (CPAP). CPAP is a highly effective treatment for OSA. Low adherence to CPAP therapy is common and poorly understood. Depression and lack of perceived benefits from CPAP are possible reasons for low adherence. Methods: Seventy-eight patients evaluated for OSA at a sleep medicine center agreed to participate in the study; 54 patients completed all study assessments. The Beck Depression Inventory (BDI) and the functional outcomes of sleep questionnaire (FOSQ) were administered before polysomnographic evaluation. A card embedded in the CPAP device electronically recorded adherence. The BDI and FOSQ were administered 1 to 2 months after the baseline measurements were obtained. Results: Baseline depressive symptoms were not correlated with mean duration of CPAP use per night. Reported improvements in OSA symptoms were correlated positively with CPAP adherence. There were significant positive correlations between improvement in depressive symptoms and OSA symptoms after initiation of CPAP therapy. The polysomnographic variables measured did not predict improvement in daytime OSA symptoms or CPAP adherence. Post hoc analyses suggested that those individuals with baseline Apnea Hypopnea Index (AHI) between 40 and 80 experienced more symptom improvement than those with AHI <40 or >80. Conclusions: Patients with the greatest level of CPAP adherence also reported the greatest improvement in OSA symptoms. Patients who continued to experience OSA symptoms after CPAP treatment also tended to have more depressive symptoms after CPAP treatment. AHI = Apnea Hypopnea Index; BDI = Beck Depression Inventory; CPAP = continuous positive airway pressure; FOSQ = functional outcomes of sleep questionnaire; OSA = obstructive sleep apnea.

Notch Signaling Modulates Sleep Homeostasis and Learning after Sleep Deprivation in Drosophila

The role of the transmembrane receptor Notch in the adult brain is poorly understood. Here, we provide evidence that bunched, a negative regulator of Notch, is involved in sleep homeostasis. Genetic evidence indicates that interfering with bunched activity in the mushroom bodies (MBs) abolishes sleep homeostasis. Combining bunched and Delta loss-of-function mutations rescues normal homeostasis, suggesting that Notch signaling may be involved in regulating sensitivity to sleep loss. Preventing the downregulation of Delta by overexpressing a wild-type transgene in MBs reduces sleep homeostasis and, importantly, prevents learning impairments induced by sleep deprivation. Similar resistance to sleep loss is observed with Notch(spl-1) gain-of-function mutants. Immunohistochemistry reveals that the Notch receptor is expressed in glia, whereas Delta is localized in neurons. Importantly, the expression in glia of the intracellular domain of Notch, a dominant activated form of the receptor, is sufficient to prevent learning deficits after sleep deprivation. Together, these results identify a novel neuron-glia signaling pathway dependent on Notch and regulated by bunched. These data highlight the emerging role of neuron-glia interactions in regulating both sleep and learning impairments associated with sleep loss.

Depression predicts self-reported sleep quality in patients with obstructive sleep apnea.

Objective: Depression is a common problem in patients with obstructive sleep apnea. The objective of this study was to examine whether depression is independently associated with lower self-reported sleep quality in patients with obstructive sleep apnea (OSA), after controlling for polysomnographic measures of sleep. Methods: The sample comprised 135 patients who had been referred to a university teaching hospital’s multidisciplinary sleep medicine center for polysomnographic evaluation of OSA. The median age of the subjects was 45 (mean age, 46 years) 55% were female, 69% were white, 31% were black, and their mean body mass index was 37.9 ± 11.2 kg/m2. Self-reported sleep quality during the past 2 weeks was assessed by the insomnia severity index. Polygraphic measures of sleep quality included the respiratory disturbance index, sleep onset latency, arousals for no apparent reason, sleep efficiency, and periodic leg movements associated with arousal. Depressive symptoms were assessed by the Beck Depression Inventory. Results: None of the polygraphic measures of sleep quality was related to self-reported sleep quality or depression. Oxygen desaturation was correlated with self-reported sleep quality (r = 0.21, p = .02). Depression correlated with self-reported sleep quality (r = 0.55, p < .0001). In a multiple regression analysis, depression remained a significant predictor of self-reported sleep quality after controlling for all of the polysomnographic measures of sleep quality (F = 9.65, partial r2 = 0.28 p = .0001). Conclusion: Depression is a better predictor of self-reported sleep quality than are polysomnographic measures of sleep in patients with OSA. AFNAR = arousals for no apparent reason; BDI = Beck Depression Inventory; BMI = body mass index; CPAP = continuous positive air pressure; HSC = Human Studies Committee; ISI = Insomnia Severity Index; OSA = obstructive sleep apnea; PLMA = periodic limb movements associated with arousal; PSG = polysomnography; RDI = Respiratory Disturbance Index; REM = rapid eye movement; SOL = sleep onset latency.