SLEEP Articles

Weight Loss and Obstructive Sleep Apnea: What Lies AHEAD?

Prefrontal Dysfunction in Obstructive Sleep Apnea: A Biomarker of Disease Severity?

Nonrestorative Sleep: A New Perspective

A New Pharmacological Treatment to Treat Obstructive Sleep Apnea?

The Brain in Obstructive Sleep Apnea: the Chickens Coming Home to Roost?

Long-Term Effect of Weight Loss on Obstructive Sleep Apnea Severity in Obese Patients with Type 2 Diabetes

Study Objectives:

To examine whether the initial benefit of weight loss on obstructive sleep apnea (OSA) severity at 1 year is maintained at 4 years.

Design:

Randomized controlled trial with follow-up at 1, 2, and 4 years.

Setting:

4 Look AHEAD clinical centers.

Participants:

Two hundred sixty-four obese adults with type 2 diabetes and OSA.

Interventions:

Intensive lifestyle intervention with a behavioral weight loss program or diabetes support and education.

Measurements:

Change in apnea-hypopnea index on polysomnogram.

Results:

The intensive lifestyle intervention group's mean weight loss was 10.7 ± 0.7 (standard error), 7.4 ± 0.7, and 5.2 ± 0.7 kg at 1, 2, and 4 years respectively, compared to a less than 1-kg weight loss for the control group at each time (P < 0.001). Apnea-hypopnea index difference between groups was 9.7 ± 2.0, 8.0 ± 2.0, and 7.7 ± 2.3 events/h at 1, 2 and 4 years respectively (P < 0.001). Change in apnea-hypopnea index over time was related to the amount of weight loss (P < 0.0001) and intervention, independent of weight loss (P = 0.001). Remission of OSA at 4 years was 5 times more common with intensive lifestyle intervention (20.7%) than diabetes support and education (3.6%).

Conclusions:

Among obese adults with type 2 diabetes and OSA, intensive lifestyle intervention produced greater reductions in weight and apnea-hypopnea index over a 4 year period than did diabetes support and education. Beneficial effects of intensive lifestyle intervention on apneahypopnea index at 1 year persisted at 4 years, despite an almost 50% weight regain. Effect of intensive lifestyle intervention on apnea-hypopnea index was largely, but not entirely, due to weight loss.

Citation:

Kuna ST; Reboussin DM; Borradaile KE; Sanders MH; Millman RP; Zammit G; Newman AB; Wadden TA; Jakicic JM; Wing RR; Pi-Sunyer FX; Foster GD; Sleep AHEAD Research Group. Long-term effect of weight loss on obstructive sleep apnea severity in obese patients with type 2 diabetes. SLEEP 2013;36(5):641-649.

Altered Resting-State Brain Activity in Obstructive Sleep Apnea

Study Objectives:

Structural and functional brain changes may contribute to neural dysfunction in patients with obstructive sleep apnea (OSA). However, the effect of OSA on resting-state brain activity has not been established. The objective of this study was to investigate alterations in resting-state functional connectivity (rsFC) of the common brain networks in patients with OSA and their relationships with changes in gray matter volume (GMV) in the corresponding brain regions.

Designs:

Resting-state functional and structural MRI data were acquired from patients with OSA and healthy controls. Seven brain networks were identified by independent component analysis. The rsFC in each network was compared between groups and the GMV of brain regions with significant differences in rsFC was also compared.

Setting:

University hospital.

Patients and Participants:

Twenty-four male patients with untreated OSA and 21 matched healthy controls.

Interventions:

N/A.

Measurements and Results:

OSA specifically affected the cognitive and sensorimotor-related brain networks but not the visual and auditory networks. The medial prefrontal cortex and left dorsolateral prefrontal cortex (DLPFC) showed decreased rsFC and GMV in patients with OSA, suggesting structural and functional deficits. The right DLPFC and left precentral gyrus showed decreased rsFC and unchanged GMV, suggesting a functional deficit. The right posterior cingulate cortex demonstrated increased rsFC and unchanged GMV, suggesting functional compensation. In patients with OSA, the rsFC of the right DLPFC was negatively correlated with the apnea-hypopnea index.

Conclusions:

OSA specifically affects resting-state functional connectivity in cognitive and sensorimotor-related brain networks, which may be related to the impaired cognitive and motor functions in these patients.

Citation:

Zhang Q; Wang D; Qin W; Li Q; Chen B; Zhang Y; Yu C. Altered resting-state brain activity in obstructive sleep apnea. SLEEP 2013;36(5):651-659.

Mirtazapine Provokes Periodic Leg Movements during Sleep in Young Healthy Men

Study Objectives:

Recent evidence suggests that certain antidepressants are associated with an increase of periodic leg movements (PLMS) that may disturb sleep. So far, this has been shown in patients clinically treated for depression and in cross-sectional studies for various substances, but not mirtazapine. It is unclear whether antidepressants induce the new onset of PLMS or only increase preexisting PLMS, and whether this is a general property of the antidepressant or only seen in depressed patients. We report here the effect of mirtazapine on PLMS in young healthy men.

Design:

Open-labeled clinical trial (NCT00878540) including a 3-week preparatory phase with standardized food, physical activity, and sleep-wake behavior, and a 10-day experimental inpatient phase with an adaptation day, 2 baseline days, and 7 days with mirtazapine.

Setting:

Research institute.

Participants:

Twelve healthy young (20-25 years) men.

Interventions:

Seven days of nightly intake (22:00) of 30 mg mirtazapine.

Measurements and results:

Sleep was recorded on 2 drug-free baseline nights, the first 2 drug nights, and the last 2 drug nights. Eight of the 12 subjects showed increased PLMS after the first dose of mirtazapine. Frequency of PLMS was highest on the first drug night and attenuated over the course of the next 6 days. Three subjects reported transient restless legs symptoms.

Conclusions:

Mirtazapine provoked PLMS in 67% of young healthy males. The effect was most pronounced in the first days. The possible role of serotonergic, noradrenergic and histaminergic mechanisms in mirtazapine-induced PLMS is discussed.

Citation:

Fulda S; Kloiber S; Dose T; Lucae S. Mirtazapine provokes periodic leg movements during sleep in young healthy men. SLEEP 2013;36(5):661-669.

Differentiating Nonrestorative Sleep from Nocturnal Insomnia Symptoms: Demographic, Clinical, Inflammatory, and Functional Correlates

Study Objectives:

Recent studies have suggested that nonrestorative sleep (NRS) symptoms may be distinct from nocturnal insomnia symptoms (NIS). However, there is limited information on the demographic, medical, and biologic correlates of NRS independent from NIS in the general population. This report presents the sociodemographic correlates, patterns of comorbidity with other sleep and physical disorders, C-reactive protein (CRP) levels, and general productivity associated with NIS and NRS in a nationally representative sample of US adults.

Design:

National Health and Nutrition Examination Survey (NHANES).

Setting:

The 2005-2008 surveys of the general population in the United States.

Participants:

There were 10,908 individuals (20 years or older)

Interventions:

N/A.

Measurements and Results:

Respondents were classified by the presence or absence of NIS and NRS. Compared with those without insomnia symptoms, respondents with NIS were older and had lower family income and educational levels than those with NRS. In addition, there was a significant association between NIS and cardiovascular disease, whereas NRS was associated with other primary sleep disorders (including habitual snoring, sleep apnea, and restless legs syndrome), respiratory diseases (emphysema and chronic bronchitis), thyroid disease, and cancer as well as increased CRP levels. In addition, the study participants with NRS only reported poorer scores on the Functional Outcomes of Sleep Questionnaire (FOSQ) than those without insomnia symptoms or those with NIS only.

Conclusions:

These findings suggest that there are substantial differences between NIS and NRS in terms of sociodemographic factors, comorbidity with other sleep and physical disorders, increased CRP level, and functional impairment. An inflammatory response might play a unique role in the pathogenesis of NRS.

Citation:

Zhang J; Lamers F; Hickie IB; He JP; Feig E; Merikangas KR. Differentiating nonrestorative sleep from nocturnal insomnia symptoms: demographic, clinical, inflammatory, and functional correlates. SLEEP 2013;36(5):671-679.

Associations of Self-Reported Sleep Duration and Snoring with Colorectal Cancer Risk in Men and Women

Study Objectives:

We assessed the relationship between sleep duration, snoring and colorectal cancer risk.

Design:

Prospective cohort studies.

Setting:

United States.

Participants:

A total of 30,121 men aged 41 to 79 years in the Health Professionals Follow-up Study and 76,368 women aged 40 to 73 years in the Nurses' Health Study.

Interventions:

None.

Measurements and Results:

We queried information on sleep duration and snoring in 1986/87. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs, 95% CIs). We documented 1,973 incident colorectal cancer cases (709 men and 1,264 women) over a 22-year follow-up period. Compared to sleep an average 7 h, ≥ 9 h of sleep was significantly associated with a higher risk of colorectal cancer among men (HR = 1.35, 95% CI: 1.00, 1.82), and to a lesser degree, among women (HR = 1.11, 95% CI: 0.85, 1.44). The risk associated with longer sleep was restricted to individuals who regularly snored (men: HR = 1.80, 95% CI: 1.14, 2.84; women: HR = 2.32, 95% CI: 1.24, 4.36) and to overweight individuals (i.e., BMI ≥ 25 kg/m²) (men: HR = 1.52, 95% CI: 1.04, 2.21; women: HR = 1.37, 95% CI: 0.97, 1.94). Short sleep duration (≤ 5 h) was not associated with an increased risk of colorectal cancer in the entire sample or in subgroups stratified by snoring or BMI.

Conclusions:

Longer sleep duration was associated with an increased risk of developing colorectal cancer among individuals who were overweight or snored regularly. This observation raises the possibility that sleep apnea and its attendant intermittent hypoxemia may contribute to cancer risk.

Citation:

Zhang X; Giovannucci EL; Wu K; Gao X; Hu F; Ogino S; Schernhammer ES; Fuchs CS; Redline S; Willett WC; Ma J. Associations of self-reported sleep duration and snoring with colorectal cancer risk in men and women. SLEEP 2013;36(5):681-688.

Caenorhabditis-in-Drop Array for Monitoring C. elegans Quiescent Behavior

Study Objectives:

To develop a method, called Caenorhabditis-in-Drop (CiD), encapsulating single worms in aqueous drops, for parallel analysis of behavioral quiescence in C. elegans nematodes.

Design:

We designed, constructed, and tested a device that houses an array of aqueous droplets laden with individual worms. The droplets are separated and covered by immiscible, biocompatible oil. We modeled gas exchange across the aqueous/oil interface and tested the viability of the encapsulated animals. We studied the behavior of wild-type animals; of animals with a loss of function mutation in the cGMP-dependent protein kinase gene egl-4; of animals with a loss of function mutation in the gene kin-2, which encodes a cAMP-dependent protein kinase A regulatory subunit; of animals with a gain-of-function mutation in the gene acy-1, which encodes an adenylate cyclase; and of animals that express high levels of the EGF protein encoded by lin-3.

Measurements and Results:

We used CiD to simultaneously monitor the behavior of 24 worms, a nearly 5-fold improvement over the prior best methodology. In support of our gas exchange models, we found that worms remain viable on the chip for 4 days, past the 12-h period needed for observation, but show reduced longevity to that measured on an agar surface. Measurements of duration of lethargus quiescence and total leth-argus quiescence showed reduced amounts as well as reduced variability relative to prior methods. There was reduced lethargus quiescence in animals that were mutant for kin-2 and for acy-1, supporting a wake-promoting effect of PKA in C. elegans, but no change in lethargus quiescence in egl-4 mutants. There was increased quiescence in animals that expressed kin-2 in the nervous system or over-expressed EGF.

Conclusions:

CiD is useful for the analysis of behavioral quiescence during lethargus as well as during the adult stage C. elegans. The method is expandable to parallel simultaneous monitoring of hundreds of animals and for other studies of long-term behavior. Using this method, we were successful in measuring, for the first time, quiescence in kin-2(ce179) and in acy-2(ce2) mutants, which are hyperactive. Our observations also highlight the impact of environmental conditions on quiescent behavior and show that longevity is reduced in CiD in comparison to agar surfaces.

Citation:

Belfer SJ; Chuang HS; Freedman BL; Yuan J; Norton M; Bau HH; Raizen DM. Caenorhabditis-in-drop array for monitoring C. elegans quiescent behavior. SLEEP 2013;36(5):689-698.

Sensitization of Upper Airway Mechanoreceptors as a New Pharmacologic Principle to Treat Obstructive Sleep Apnea: Investigations with AVE0118 in Anesthetized Pigs

Study Objectives:

Drug treatment for obstructive sleep apnea (OSA) is desirable because at least 30% of patients do not tolerate continuous positive airway pressure (CPAP) treatment. The negative pressure reflex (NPR) involving superficially located mechanoreceptors in the upper airway (UA) is an important mechanism for UA patency inhibitable by topical UA anesthesia (lidocaine). The NPR may serve as a target for pharmacological intervention for a topical treatment of OSA. The objective was to determine the effect of pharmacological augmentation of the NPR on UA collapsibility.

Design:

We developed a model of UA collapsibility in which application of negative pressures caused UA collapses in spontaneously breathing α-chloralose-urethane anesthetized pigs as indicated by characteristic tracheal pressure and air flow changes.

Setting:

N/A.

Patients or Participants:

N/A.

Interventions:

N/A.

Measurements and Results:

The potassium channel blocker AVE0118 administered topically to the UA in doses of 1, 3, and 10 mg per nostril sensitized the NPR, shifting the mechanoreceptor response threshold for the genioglossus muscle to more positive pressures (P < 0.001; n = 6 per group) and dose-dependently inhibited UA collapsibility. Ten mg of AVE0118 prevented UA collapses against negative pressures of -150 mbar (P < 0.01) for > 4 h in all pigs, while in control pigs the UA collapsed at -50 mbar or less negative pressures. The effect of AVE0118 was abolished by UA lidocaine anesthesia. Acute intravenous administration of naloxone or acetazolamide was ineffective; paroxetine and mirtazepine were weakly effective and fluoxetine was moderately effective in line with reported clinical efficacy.

Conclusion:

Topical administration of AVE0118 to the UA is a promising pharmacologic approach for the treatment of OSA.

Citation:

Wirth KJ; Steinmeyer K; Ruetten H. Sensitization of upper airway mechanoreceptors as a new pharmacologic principle to treat obstructive sleep apnea: investigations with AVE0118 in anesthetized pigs. SLEEP 2013;36(5):699-708.

Obstructive Sleep Apnea as a Risk Factor for Cerebral White Matter Change in a Middle-Aged and Older General Population

Study Objective:

Obstructive sleep apnea (OSA) contributes to the development of systemic hypertension, and hypertension strongly predicts the development of white matter change (WMC). Thus, it is plausible that OSA mediates WMC. The goal of the current study is to determine whether a contextual relationship exists between OSA and cerebral WMC.

Design:

Cross-sectional analyses conducted in a population-based study.

Setting:

Korean community-based sample from the Korean Genome and Epidemiology Study (KoGES) who attended examinations in 2011 at a medical center.

Participants:

There were 503 individuals (mean ± SD, age 59.63 ± 7.48 y) who were free of previously diagnosed cardiovascular and neurologic diseases.

Measurements and Results:

Participants underwent 1-night polysomnography and were classified as no OSA (obstructive apnea-hypopnea index [AHI] < 5, n = 289), mild OSA (AHI 5-15, n = 161), and moderate to severe OSA (AHI ≥ 15, n = 53). WMC was identified with brain magnetic resonance imaging (MRI) and was found in 199 individuals (39.56%). Multivariate logistic regression analyses adjusted for covariates revealed that moderate to severe OSA was significantly associated with the presence of WMC (odds ratio [OR] 2.08, 95%, confidence interval [CI] 1.05-4.13) compared with no OSA. Additional adjustment of hypertension to the model did not alter the significance of the association (OR 2.03, 95% CI 1.02-4.05).

Conclusions:

Moderate to severe OSA is an independent risk factor for WMC in middle-aged and older individuals. Thus, early recognition and treatment of OSA could reduce the risk of stroke and vascular dementia.

Citation:

Kim H; Yun CH; Thomas RJ; Lee SH; Seo HS; Cho ER; Lee SK; Yoon DW; Suh S; Shin C. Obstructive sleep apnea as a risk factor for cerebral white matter change in a middle-aged and older general population. SLEEP 2013;36(5):709-715.

Sleep Disordered Breathing and Gestational Hypertension: Postpartum Follow-up Study

Background:

Gestational hypertension (GH) is a newly recognized risk factor for adverse cardiovascular events later in life. Sleep disordered breathing (SDB) is an established risk factor for adverse cardiovascular events. Recent research has suggested that women with GH may have an increased rate of SDB during pregnancy, but it is not known if this higher rate of SDB persists into the postpartum state.

Objective:

To assess whether women with GH continue to have an increased rate of SDB compared to healthy pregnant women, after the physiologic changes of pregnancy resolve.

Methods:

We previously studied women with GH and uncomplicated pregnancies with sleep questionnaires and level 1 polysomnography. Participants were invited to participate in repeat testing 1-2 years postpartum. Respiratory disturbance index (RDI) differences were assessed.

Results:

Eighteen subjects (11 GH and 7 healthy) had complete follow-up data available for comparison with antepartum data. This group was representative of the initial antepartum cohort. Women with GH experienced a decrease in mean RDI from antepartum to postpartum (12.0 ± 12.3 vs 2.9 ± 2.9; P = 0.02). Healthy women did not experience the same change (2.8 ± 5.3 vs 2.1 ± 3.2; P = 0.81). Postpartum comparisons showed the mean RDI of women with GH had decreased to be similar to that of healthy women (P = 0.75).

Conclusions:

SDB in women with gestational hypertension improved in the postpartum state to levels indistinguishable from our healthy subjects. This suggests that the physiologic effects of pregnancy may have had a pathologic role in the development of antepartum SDB in women with GH.

Citation:

Reid J; Glew RA; Skomro R; Fenton M; Cotton D; Olatunbosun F; Gjevre J; Guilleminault C. Sleep disordered breathing and gestational hypertension: postpartum follow-up study. SLEEP 2013;36(5):717-721.

Short Sleep Duration Combined with Obstructive Sleep Apnea is Associated with Visceral Obesity in Korean Adults

Study Objectives:

To determine whether short sleep duration alone or combined with obstructive sleep apnea (OSA) is associated with regional body fat including abdominal visceral fat area (VFA) among Korean adults.

Design:

Cross-sectional study.

Setting:

Ansan, South Korea.

Participants:

There were 838 community participants age 40-69 y from the Korean Genome and Epidemiology Study.

Measurements and Results:

Subjective habitual sleep duration and OSA were defined based on a structured sleep questionnaire and a home portable sleep study, respectively. Abdominal VFA and hepatic fat components were assessed by computed tomography. Adjusted mean VFA and hepatic fat were highest in the shortest sleep duration group (< 5 h) and decreased linearly with increasing sleep duration. Individuals with OSA (apnea-hypopnea index ≥ 5) had a higher body mass index, waist circumference, percent body fat, VFA, and hepatic fat than those without OSA after adjusting for age and sex. The adjusted odds ratio (OR) for visceral obesity (VFA ≥ 100 cm²) was 2.05 (95% confidence interval [CI], 1.09-3.86) in individuals sleeping less than 5 h compared with those sleeping longer than 7 h, and 1.57 (95% CI, 1.08-2.26) in individuals with OSA compared with those without OSA, after adjusting for all confounding factors including body mass index. A combination of short sleep duration (< 5 h) and OSA substantially increased the OR for visceral obesity (OR, 4.40, 95% CI, 1.80-10.77) compared with those who slept longer (≥ 7 h) without OSA.

Conclusion:

Short sleep duration and OSA are independently associated with visceral obesity in adults. The association is particularly strong in short sleepers with OSA.

Citation:

Kim NH; Lee SK; Eun CR; Seo JA; Kim SG; Choi KM; Baik SH; Choi DS; Yun CH; Kim NH; Shin C. Short sleep duration combined with obstructive sleep apnea is associated with visceral obesity in Korean adults. SLEEP 2013;36(5):723-729.

Insomnia Does Not Appear to be Associated With Substantial Structural Brain Changes

Study Objectives:

Sleep has been demonstrated to significantly modulate brain plasticity and the manifestation of mental disorders. However, previous studies on the effect of disrupted sleep on brain structure have reported inconsistent results. The goal of the current study was to investigate brain morphometry in a well-characterized large sample of patients with primary insomnia (PI) in comparison with good sleeper controls.

Design:

Automated parcellation and pattern recognition approaches were supplemented by voxelwise analyses of gray and white matter volumes to analyze magnetic resonance images. All analyses included age, sex, and total intracranial volume as covariates.

Setting:

Department of Psychiatry and Psychotherapy of the University of Freiburg Medical Center.

Participants:

There were 28 patients with PI (10 males; 18 females; age 43.7 ± 14.2 y) and 38 healthy, good sleepers (17 males; 21 females; age 39.6 ± 8.9 y).

Interventions:

N/A.

Results:

No significant between-group differences were observed in any of the investigated brain morphometry variables.

Conclusions:

Altered brain function in insomnia does not appear to have a substantial effect on brain morphometry on a macroscopic level.

Citation:

Spiegelhalder K; Regen W; Baglioni C; Klöppel S; Abdulkadir A; Hennig J; Nissen C; Riemann D; Feige B. Insomnia does not appear to be associated with substantial structural brain changes. SLEEP 2013;36(5):731-737.

A Randomized Controlled Trial of Problem-Solving Therapy Compared to Cognitive Therapy for the Treatment of Insomnia in Adults

Study Objectives:

To compare the efficacy of problem-solving therapy (PST) combined with behavioral sleep strategies to standard cognitive therapy (CT) combined with behavioral sleep strategies in the treatment of insomnia.

Design:

A six-week randomized controlled trial with one month follow-up.

Setting:

The Australian National University Psychology Clinic, Canberra, Australia.

Participants:

Forty-seven adults aged 18-60 years recruited from the community meeting the Research Diagnostic Criteria for insomnia.

Interventions:

Participants received 6 weeks of treatment including one group session (sleep education and hygiene, stimulus control instructions and progressive muscle relaxation) followed by 5 weeks of individual treatment of PST or CT.

Measurements and Results:

Primary outcomes included sleep efficiency (SE) from sleep diaries, the Insomnia Severity Index (ISI), and the Pittsburgh Sleep Quality Index (PSQI). Secondary measures assessed dysfunctional sleep beliefs, problem-solving skills and orientations, and worry. Both treatments produced significant post therapy improvements in sleep which were maintained at 1 month follow-up (on SE Cohen d = 1.42, 95% CI 1.02-1.87 for PST; d = 1.26, 95% CI 0.81-1.65 for CT; on ISI d = 1.46, 95% CI 1.03-1.88 for PST; d = 1.95, 95% CI 0.52-2.38 for CT; for PSQI d = 0.97, 95% CI 0.55-1.40 for PST and d = 1.34, 95% CI 0.90-1.79 for the CT). There were no differences in PST and CT in the size or rate of improvement in sleep although CT produced a significant faster rate of decline in negative beliefs about sleep than PST and there was a trend (P = 0.08) for PST to produce a faster rate of improvement in negative problem orientation than CT.

Conclusions:

The results provide preliminary support for problem solving treatment as an equally efficacious alternative component to cognitive therapy in psychological interventions for insomnia.

Citation:

Pech M; O'Kearney R. A randomized controlled trial of problem-solving therapy compared to cognitive therapy for the treatment of insomnia in adults. SLEEP 2013;36(5):739-749.

Regular Exercise Prevents Sleep Deprivation Associated Impairment of Long-Term Memory and Synaptic Plasticity in The CA1 Area of the Hippocampus

Study Objectives:

The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area.

Experimental Design:

Animals were conditioned to run on treadmills for 4 weeks then deprived of sleep for 24 h using the columns-in-water method. We tested the effect of exercise and/or S-D on behavioral performance using a post-learning paradigm in the radial arm water maze (RAWM) and in vivo extracellular recording in the CA1 area. The levels of L-LTP-related molecules in the CA1 area were then assessed both before and after L-LTP induction.

Measurements and Results:

After 24 h of S-D, spatial long-term memory impairment in the RAWM and L-LTP suppression was prevented by 4 weeks of regular exercise. Regular exercise also restored the S-D-associated decreases in the basal levels of key signaling molecules such as: calcium/calmodulin kinase IV (CaMKIV), mitogen-activated protein kinase (MAPK/ERK), phosphorylated cAMP response element-binding protein (P-CREB) and brain derived neurotrophic factor (BDNF), in the CA1 area. After L-LTP induction, regular exercise also prevented the S-D-induced down regulation of BDNF and P-CREB protein levels.

Conclusions:

The results suggest that our exercise protocol may prevent 24-h S-D-induced impairments in long-term memory and LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CREB and BDNF associated with S-D.

Citation:

Zagaar M; Dao A; Levine A; Alhaider I; Alkadhi K. Regular exercise prevents sleep deprivation associated impairment of long-term memory and synaptic plasticity in the CA1 area of the hippocampus. SLEEP 2013;36(5):751-761.

Vascular Inflammation and Sleep Disordered Breathing in a Community-Based Cohort

Study Objectives:

Sleep disordered breathing is associated with cardiovascular disease. The pathophysiologic mechanisms remain unclear, but enhanced vascular inflammation is implicated. We sought to evaluate the association of sleep disordered breathing with biomarkers of inflammation.

Design:

Cross-sectional, observational.

Setting:

Community-based.

Participants:

There were 900 participants from the Framingham Heart Study site of the Sleep Heart Health Study (52% females, mean age 60 y, 23% ethnic minorities).

Interventions:

None.

Measurements:

We assessed circulating levels of nine inflammatory biomarkers in relation to polysomnographically-derived apnea-hypopnea index and hypoxemia index (% sleep time with oxyhemoglobin saturation < 90%). Multivariable models were adjusted for demographics, smoking, cardiovascular diseases, diabetes, and other potential confounders, without and with adjustment for body mass index.

Results:

With multivariable adjustment not including body mass index, the apnea-hypopnea index was associated with C-reactive protein, inter-leukin-6, fibrinogen, intercellular adhesion molecule-1, and P-selectin levels and hypoxemia index was associated with C-reactive protein, interleukin-6, and fibrinogen levels. After adjustment for body mass index, only the association of interleukin-6 with sleep disordered breathing remained significant: the adjusted mean serum interleukin-6 level was 2.93, 3.14, 3.34, and 4.62 pg/mL, respectively, in participants with apnea-hypopnea index < 5, 5-14.9, 15-29.9, and ≥ 30 events/h (P = 0.01 for trend) and 2.97, 3.01, 3.35, and 4.85 pg/mL, respectively, in participants with hypoxemia index < 0.5, 0.5-4.9, 5-9.9, and ≥ 10% of sleep time (P = 0.02 for trend).

Conclusions:

In a community-based sample, sleep disordered breathing is associated with higher levels of interleukin-6, a marker of myocardial infarction risk and mortality. Adiposity may mediate the increased levels of C-reactive protein, fibrinogen, intercellular adhesion molecule-1, and P-selectin observed in sleep disordered breathing.

Citation:

Chami HA; Fontes JD; Vasan RS; Keaney JF; O'Connor GT; Larson MG; Benjamin EJ; Gottlieb DJ. Vascular Inflammation and sleep disordered breathing in a community-based cohort. SLEEP 2013;36(5):763-768.

Extreme Sleep Durations and Increased C-Reactive Protein: Effects of Sex and Ethnoracial Group

Study Objectives:

We hypothesize that extremes of sleep duration are associated with elevated C-reactive protein (CRP), a pro-inflammatory marker for cardiovascular disease risk.

Design:

Cross-sectional.

Setting:

Population-based research.

Participants:

Nationally representative sample of 2007-2008 National Health and Nutrition Examination Survey participants (n = 5,587 adults).

Interventions:

None.

Measurements and Results:

Associations between CRP and self-reported total sleep time (TST) were examined. Explanatory models considered contributions of sex, age, race/ethnicity, body mass index (BMI), and BMI squared (BMI²). Models also explored the role of insomnia symptoms, sleep apnea, active medical illness, and antidiabetic/antihypertensive treatment. Differential patterns among race/ethnicity groups were examined using interactions and stratified analyses. Nonlinear relationships between CRP and TST were assessed using polynomial and multinomial regression models (< 5, 5, 6, 7, 8, 9, and > 9 h). Linear and squared terms were significant in all models in the complete sample, with notable differences by sex and ethnoracial group. Overall, in models adjusted for sociodemographics and BMI, different patterns were observed for non-Hispanic white (elevated CRP for < 5 h and > 9 h), black/African-American (elevated CRP for < 5 h and 8 h), Hispanic/Latino (elevated CRP for > 9 h), and Asian/ Other (higher in 9 and > 9 h and lower in 5 h and 6 h) groups. Ethnoracial groups also demonstrated patterning by sex.

Conclusion:

In a representative sample of American adults, elevated CRP was associated with extreme sleep durations. Sex, race/ethnicity, sleep disorders, and medical comorbidity influenced these associations. Differences in CRP along these dimensions should be considered in future research on sleep related disparities influencing cardiometabolic disease risk.

Citation:

Grandner MA; Buxton OM; Jackson N; Sands M; Pandey A; Jean-Louis G. Extreme sleep durations and increased C-reactive protein: effects of sex and ethnoracial group. SLEEP 2013;36(5):769-779.

Sleep Estimates Using Microelectromechanical Systems (MEMS)

Study Objectives:

Although currently more affordable than polysomnography, actigraphic sleep estimates have disadvantages. Brand-specific differences in data reduction impede pooling of data in large-scale cohorts and may not fully exploit movement information. Sleep estimate reliability might improve by advanced analyses of three-axial, linear accelerometry data sampled at a high rate, which is now feasible using microelectromechanical systems (MEMS). However, it might take some time before these analyses become available. To provide ongoing studies with backward compatibility while already switching from actigraphy to MEMS accelerometry, we designed and validated a method to transform accelerometry data into the traditional actigraphic movement counts, thus allowing for the use of validated algorithms to estimate sleep parameters.

Design:

Simultaneous actigraphy and MEMS-accelerometry recording.

Setting:

Home, unrestrained.

Participants:

Fifteen healthy adults (23-36 y, 10 males, 5 females).

Interventions:

None.

Measurements:

Actigraphic movement counts/15-sec and 50-Hz digitized MEMS-accelerometry.

Analyses:

Passing-Bablok regression optimized transformation of MEMS-accelerometry signals to movement counts. Kappa statistics calculated agreement between individual epochs scored as wake or sleep. Bland-Altman plots evaluated reliability of common sleep variables both between and within actigraphs and MEMS-accelerometers.

Results:

Agreement between epochs was almost perfect at the low, medium, and high threshold (kappa = 0.87 ± 0.05, 0.85 ± 0.06, and 0.83 ± 0.07). Sleep parameter agreement was better between two MEMS-accelerometers or a MEMS-accelerometer and an actigraph than between two actigraphs.

Conclusions:

The algorithm allows for continuity of outcome parameters in ongoing actigraphy studies that consider switching to MEMS-accelerometers. Its implementation makes backward compatibility feasible, while collecting raw data that, in time, could provide better sleep estimates and promote cross-study data pooling.

Citation:

te Lindert BHW; Van Someren EJW. Sleep estimates using microelectromechanical systems (MEMS). SLEEP 2013;36(5):781-789.