Obstructive Sleep Apnea Subjects Research Articles

Effect of Gender on Chronic Intermittent Hypoxic Fosb Expression in Cardiorespiratory-Related Brain Structures in Mice.

We aimed to delineate sex-based differences in neuroplasticity that may be associated with previously reported sex-based differences in physiological alterations caused by repetitive succession of hypoxemia-reoxygenation encountered during obstructive sleep apnea (OSA). We examined long-term changes in the activity of brainstem and diencephalic cardiorespiratory neuronal populations induced by chronic intermittent hypoxia (CIH) in male and female mice by analyzing Fosb expression. Whereas the overall baseline and CIH-induced Fosb expression in females was higher than in males, possibly reflecting different neuroplastic dynamics, in contrast, structures responded to CIH by Fosb upregulation in males only. There was a sex-based difference at the level of the rostral ventrolateral reticular nucleus of the medulla, with an increase in the number of FOSB/ΔFOSB-positive cells induced by CIH in males but not females. This structure contains neurons that generate the sympathetic tone and which are involved in CIH-induced sustained hypertension during waking hours. We suggest that the sex-based difference in neuroplasticity of this structure contributes to the reported sex-based difference in CIH-induced hypertension. Moreover, we highlighted a sex-based dimorphic phenomenon in serotoninergic systems induced by CIH, with increased serotoninergic immunoreactivity in the hypoglossal nucleus and a decreased number of serotoninergic cells in the dorsal raphe nucleus in male but not female mice. We suggest that this dimorphism in the neuroplasticity of serotoninergic systems predisposes males to a greater alteration of neuronal control of the upper respiratory tract associated with the greater collapsibility of upper airways described in male OSA subjects.

Regional brain tissue integrity in pediatric obstructive sleep apnea

Children with long-standing obstructive sleep apnea (OSA) show evidence of neural injury and functional deficits in behavioral and cognitive regulatory brain regions that are reflected in symptoms of altered cognitive performance and behaviors. While we earlier showed reduced gray matter volume and increased and reduced regional cortical thicknesses, such structural changes give little indication of the underlying pathology. Brain tissue integrity in pediatric OSA subjects can reflect the nature and extent of injury or structural adaptation, and can be assessed by entropy tissue texture, a measure of local changes in signal intensity patterns from high-resolution magnetic resonance images. We collected high-resolution T1-weighted magnetic resonance images from 10 pediatric OSA (age, 7.9 ± 1.1 years; apnea-hypopnea-index, 8.8 ± 3.0 events/hour; body-mass-index, 20 ± 6.7 kg/m2; 7 male) and 8 healthy controls (age, 8.8 ± 1.6 years; body-mass-index, 19.6 ± 5.9 kg/m2; 5 female). Images were bias-corrected and entropy maps calculated, individual maps were normalized to a common space, smoothed, and compared between groups (ANCOVA; covariates: age, gender; SPM12, uncorrected-threshold p < 0.005). No significant differences in age (p = .48), gender (p = .59), or body-mass-index (p = .63) emerged between groups. In OSA children, several brain sites including the pre-frontal cortex, middle and posterior corpus callosum, thalamus, hippocampus, and cerebellar areas showed reduced entropy values, indicating tissue changes suggestive of acute insults. No regions showed higher entropy values in OSA. Children suffering from OSA display predominantly acute tissue injury in neural regions principally localized within autonomic, respiratory, cognitive, and neuropsychologic control, functions that correspond to previously-reported comorbidities associated with OSA. A range of acute processes, including hypoxia/re-oxygenation, repeated arousals, and episodic hypercarbia, may have contributed to regional brain tissue integrity changes in pediatric OSA.

ASSOCIATION OF TASK-3 GENETIC POLYMORPHISMS WITH OBSTRUCTIVE SLEEP APNOEA

Objective: Objectives: To evaluate the relationship between human TASK-3 gene polymorphisms and obstructive sleep apnea (OSA), and to explore the genetic mechanism of OSA Design and method: Methods: 176 subjects with non-OSA and 169 subjects with severe OSA by full night polysomnography were selected. We chose three represent single nucleotide polymorphisms (SNPs) such as rs2615374, rs3808403 and rs888345, according to principle of linkage disequilibrium (r2 > 0.8) and minimum allele frequency (MAF) > 5%. Blood samples were collected from all subjects and genotyping was performed on DNA extracted from blood cells by Kompetitive Allele Specifc PCR. Results: The significant differences in additive model (GG 39.2% vs 52.1%, AG 47.5% vs 39.9%,AA 13.3% vs 8.0%, P = 0.047), alleles (A 37% vs 27.9%,G 63% vs 72.1%, P = 0.014) and dominant model (GG 39.2% vs 52.1%,GA+AA 60.8% vs 47.9%, P = 0.02) of rs2615374 were observed between severe and non OSA subjects. The distributions of additive (CC 23.3% vs 35.9%,CT 61.6% vs 43.1%,TT 15.1% vs 21.0%, P = 0.005) and dominant model (CC 23.3% vs 35.9%,CT+TT 76.7% vs 64.1%, P = 0.015) of rs3808403 were also significantly different between two groups. CT+TT genotype of rs3808403 was considered as risk factors for Severe OSA (CT+TT: [OR] = 2.09, 95%CI: 1.16–3.78, P = 0.014). In addition, Mutant group of rs2615374 and rs3808403 showed significantly higher triglyceride levels than wild group. Conclusions: Conclusions: The polymorphisms of rs2615374 and rs3808403 in the TASK-3 gene were associated with incidence of OSA, and CT+TT genotype of rs3808403 locus was a risk factor for severe OSA among the Chinese people. However, further studies should be conducted to confirm this association.

Correlations between Waist and Neck Circumferences and Obstructive Sleep Apnea Characteristics.

The body mass index (BMI), an estimate of body fat, provides a rather imprecise indication of risk for obstructive sleep apnea (OSA). We examined whether other measures, including waist and neck circumference, provide improved indicators of risk in treatment-naïve OSA subjects. We studied 59 OSA subjects [age, 48.8±10.0 years; BMI, 31.9±6.6 kg/m2; apnea-hypopnea-index (AHI), 38.5±23.0 events/hour; sleep efficiency index (SEI, n=52), 78.6±14.4%; lowest oxygen saturation (SaO2 nadir), 79.5±8.0%; systolic blood pressure (BP), 127.4±15.7 mmHg; diastolic BP, 80.1±9.1 mmHg; 43 male), and determined waist and neck circumferences (waist, 107.4±15.3 cm; neck, 41.8±4.7 cm), daytime sleepiness [Epworth sleepiness scale (ESS), 8.7±4.6], sleep quality [Pittsburgh sleep quality index (PSQI), 8.5±4.1], depression levels [Beck depression inventory II (BDI-II), 6.6±5.7), and anxiety levels [Beck anxiety inventory (BAI), 6.2±7.2]. We used partial correlation procedures (covariates, age and gender) to examine associations between BMI, waist, and neck circumferences vs. AHI, sleep, and neuropsychological variables. BMI, waist, and neck circumferences were significantly correlated with SaO2 nadir (BMI; r=-0.423, p=0.001; waist; r=-0.457, p<0.001; neck; r=-0.263, p=0.048), AHI (BMI; r=0.349, p=0.008; waist; r=0.459, p<0.001; neck; r=0.276, p=0.038), and systolic BP (BMI; r=0.354, p=0.007; waist; r=0.321, p=0.015; neck; r=0.388, p=0.003). SEI was significantly correlated with waist circumference (r=0.28, p=0.049), but higher with BMI (r=0.291, p=0.04). No other significant waist or neck correlations emerged. This study suggests that waist and neck measures correlate better than BMI with select disease severity (SaO2 nadir and AHI) in OSA subjects. The findings offer an easily-measured, ancillary means to assess OSA risk.

Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.

IntroductionBrain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting‐state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting‐state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores.MethodsWe acquired resting‐state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0‐Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender).ResultsObstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para‐hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic‐striatal‐cortical FC in OSA showed relationships with behavioral and neuropsychological variables.ConclusionsThe compromised hippocampal‐cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate‐cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA.

Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) affects 2-5% of all children and is associated with cognitive and behavioral deficits, resulting in poor school performance. These psychological deficits may arise from brain injury, as seen in preliminary findings of lower gray matter volume among pediatric OSA patients. However, the psychological deficits in OSA are closely related to functions in the cortex, and such brain areas have not been specifically assessed. The objective was to determine whether cortical thickness, a marker of possible brain injury, is altered in children with OSA. We examined regional brain cortical thicknesses using high-resolution T1-weighted magnetic resonance images in 16 pediatric OSA patients (8 males; mean age ± SD = 8.4 ± 1.2 years; mean apnea/hypopnea index ± SD = 11 ± 6 events/h) and 138 controls (8.3 ± 1.1 years; 62 male; 138 subjects from the NIH Pediatric MRI database) to identify cortical thickness differences in pediatric OSA subjects. Cortical thinning occurred in multiple regions including the superior frontal, ventral medial prefrontal, and superior parietal cortices. The left side showed greater thinning in the superior frontal cortex. Cortical thickening was observed in bilateral precentral gyrus, mid-to-posterior insular cortices, and left central gyrus, as well as right anterior insula cortex. Changes in cortical thickness are present in children with OSA and likely indicate disruption to neural developmental processes, including maturational patterns of cortical volume increases and synaptic pruning. Regions with thicker cortices may reflect inflammation or astrocyte activation. Both the thinning and thickening associated with OSA in children may contribute to the cognitive and behavioral dysfunction frequently found in the condition.

Serum ferritin and obstructive sleep apnea-epidemiological study.

Ferritin is an intracellular iron storage protein and a marker of inflammation. Studies have shown that subjects with obstructive sleep apnea (OSA) have higher levels of circulating pro-inflammatory cytokines, but little is known about the association between ferritin and OSA. The aims of the study were to evaluate serum ferritin (S-Ferritin) levels in OSA patients compared to levels in the general population and also examine the effect of obesity level and treatment with positive airway pressure (PAP) on S-Ferritin levels. The OSA subjects (n = 796) were part of the Icelandic Sleep Apnea Cohort. The control subjects (n = 637) were randomly chosen Icelanders who participated in an epidemiological study. Propensity score (PS) methodologies were employed to minimize selection bias and strengthen causal inferences when comparing non-randomized groups. S-Ferritin levels were measured and all participants answered the same detailed questionnaire about sleep and health. Only OSA patients underwent a sleep study and were re-invited for a 2-year follow-up. S-Ferritin levels were significantly higher in OSA males than controls (213.3 vs. 197.3μg/L, p = 0.007). However, after adjusting for confounders and using our PS methodology, no significant difference was found. S-Ferritin levels were not correlated with severity of OSA, obesity level, or clinical symptoms. Also, no significant change in S-Ferritin levels was found with 2years of PAP treatment. S-Ferritin levels are comparable in OSA patients and controls and do not change consistently with obesity level or PAP treatment in our sample.

Influencing factors on CPAP adherence and anatomic characteristics of upper airway in OSA subjects.

Although continuous positive airway pressure (CPAP) is the most effective treatment modality, poor adherence still remains a problem for obstructive sleep apnea (OSA) treatment and there is little evidence regarding how this might be improved. This study aims to analyze the anatomic and clinical factors of OSA subjects who failed to comply with CPAP therapy.The medical records of 47 OSA subjects who received CPAP therapy as a first-line treatment modality were retrospectively reviewed. The medical records were reviewed for demographic and polysomnographic data and anatomic findings of the nasal cavity and oropharynx.24 patients who adhered to CPAP therapy and 23 patients who were nonadherent were enrolled in the study. There were no statistically significant differences in sleep parameters between CPAP-adherent patients and CPAP nonadherent subjects. Mean body mass index of CPAP nonadherent group was significantly higher than CPAP adherent group. Higher grades of septal deviation and hypertrophic change of the inferior turbinate were observed more in the CPAP nonadherent group. In addition, CPAP nonadherent subjects showed considerably bigger tonsils and higher grade palatal position comparing with the CPAP adherent subjects. Subjective discomfort including inconvenience, mouth dryness, and chest discomfort were the main problems for OSA subjects who did not comply with CPAP therapy.Excessive upper airway blockage in the nasal cavity and oropharynx was predominant in CPAP nonadherent subjects, which might cause the reported subjective discomfort that reduces CPAP compliance. Therefore, resolution of these issues is needed to enhance CPAP compliance for control of OSA.

Alteration in upper airway dilator muscle coactivation during sleep: comparison of patients with obstructive sleep apnea and healthy subjects.

In patients with obstructive sleep apnea (OSA), substantial increases in genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal airflow. We have previously suggested that sleep-induced alteration in tongue muscle coordination may explain this finding, as retractor muscle coactivation was reduced during sleep compared with wakefulness. The present study was undertaken to evaluate whether these alterations in dilator muscle activation during sleep play a role in the pathogenesis of OSA and whether coactivation of additional peripharyngeal muscles (non-GG muscles: styloglossus, geniohyoid, sternohyoid, and sternocleidomastoid) is also impaired during sleep. We compared GG and non-GG muscle electromyographic (EMG) activity in 8 patients with OSA and 12 healthy subjects during wakefulness while breathing through inspiratory resistors with the activity observed during sleep toward the end of flow limitation, before arousal, at equivalent esophageal pressures. During wakefulness, resistive breathing triggered increases in both GG and non-GG muscle activity. During sleep, flow limitation was associated with increases in GG-EMG that reached, on average, >2-fold the level observed while awake. In contrast, EMGs of the non-GG muscles, recorded simultaneously, reached, on average, only ~2/3 the wakefulness level. We conclude that during sleep GG activity may increase to levels that substantially exceed those sufficient to prevent pharyngeal collapse during wakefulness, whereas other peripharyngeal muscles do not coactivate during sleep in both patients with OSA and healthy subjects. We speculate that upper airway muscle dyssynchrony during sleep may explain why GG-EMG activation fails to alleviate flow limitation and stabilize airway patency during sleep. NEW & NOTEWORTHY Pharyngeal obstruction during sleep may trigger genioglossus activity to levels substantially exceeding those observed during wakefulness, without ameliorating flow limitation. In contrast, other peripharyngeal muscles exhibit a much lower activity during sleep in both patients with obstructive sleep apnea and healthy subjects. Coordinated muscular synergy stabilizes the pharynx despite relatively low activity while awake, yet even higher genioglossal activity allows the pharynx to obstruct when simultaneous activity of other dilator muscles is inadequate during sleep.

Impact of obstructive sleep apnea on blood pressure and cardiovascular risk factors in Japanese men: A cross-sectional study in work-site group

ABSTRACTIt has been shown that obstructive sleep apnea (OSA) is related to hypertension and cardiovascular disease; however, the prevalence of OSA in general population and the impact of it on blood pressure especially in Japan has not been well determined. We have conducted a screening test for OSA from 2003 to 2011. In addition, a cross-sectional analysis was performed in 2012 to determine the association of OSA and cardiovascular risk factors in Japanese men (18–69 years of age; mean age, 44.4 ± 0.2). The study group consisted of 2208 male employees, and OSA was evaluated by using the 4% oxygen desaturation index and apnea-hypopnea index (AHI). The prevalence of mild-to-moderate (5≤AHI<30) and severe (AHI≥30) OSA in the studied subjects were 7.1%, and 6.1%, respectively. Among the 135 severe OSA subjects, 105 (77.8%) had been treated with continuous positive airway pressure. Both systolic and diastolic blood pressures (DBP) were significantly increased in the subjects with severe OSA compared with those without OSA. These associations in DBP remained observed after adjustment for age, body mass index (BMI), estimated glomerular filtration rate, HbA1c, current alcohol intake, current smoking habits, and OSA treatment. DBP in severe OSA subjects were significantly increased in 1807 subjects who were not treated for hypertension or OSA. However, the levels of blood pressures were not decreased by OSA treatment. These results suggest that the prevalence of OSA is relatively high in middle-aged Japanese men and that blood pressures were elevated in the subjects with severe OSA.

Use of Mutual Information and Transfer Entropy to Assess Interaction between Parasympathetic and Sympathetic Activities of Nervous System from HRV

Obstructive sleep apnea (OSA) is a common sleep disorder that often associates with reduced heart rate variability (HRV) indicating autonomic dysfunction. HRV is mainly composed of high frequency components attributed to parasympathetic activity and low frequency components attributed to sympathetic activity. Although, time domain and frequency domain features of HRV have been used to sleep studies, the complex interaction between nonlinear independent frequency components with OSA is less known. This study included 30 electrocardiogram recordings (20 OSA patient recording and 10 healthy subjects) with apnea or normal label in 1-min segment. All segments were divided into three groups: N-N group (normal segments of normal subjects), P-N group (normal segments of OSA subjects) and P-OSA group (apnea segments of OSA subjects). Frequency domain indices and interaction indices were extracted from segmented RR intervals. Frequency domain indices included nuLF, nuHF, and LF/HF ratio; interaction indices included mutual information (MI) and transfer entropy (TE (H→L) and TE (L→H)). Our results demonstrated that LF/HF ratio was significant higher in P-OSA group than N-N group and P-N group. MI was significantly larger in P-OSA group than P-N group. TE (H→L) and TE (L→H) showed a significant decrease in P-OSA group, compared to P-N group and N-N group. TE (H→L) were significantly negative correlation with LF/HF ratio in P-N group (r = −0.789, p = 0.000) and P-OSA group (r = −0.661, p = 0.002). Our results indicated that MI and TE is powerful tools to evaluate sympathovagal modulation in OSA. Moreover, sympathovagal modulation is more imbalance in OSA patients while suffering from apnea event compared to free event.

Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea.

In obese subjects with obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) may be linked to systemic and adipose tissue inflammation. We obtained abdominal subcutaneous adipose tissue biopsies from OSA and non-OSA obese (BMI > 35) subjects at baseline and after 24 weeks (T1) of weight-loss intervention plus continuous positive airway pressure (c-PAP) or weight-loss intervention alone, respectively. OSA subjects were grouped according to good (therapeutic) or poor (subtherapeutic) adherence to c-PAP. At baseline, anthropometric and metabolic parameters, serum cytokines, and adipose tissue mRNA levels of obesity-associated chemokines and inflammatory markers were not different in OSA and non-OSA subjects. At T1, body weight was significantly reduced in all groups. Serum concentrations of IL-2, IL-4, IL-6, MCP-1, PDGFβ, and VEGFα were reduced by therapeutic c-PAP in OSA subjects and remained unaltered in non-OSA and subtherapeutic c-PAP groups. Similarly, adipose tissue mRNA levels of macrophage-specific (CD68, CD36) and ER stress (ATF4, CHOP, ERO-1) gene markers, as well as of IL-6, PDGFβ, and VEGFα, were decreased only in the therapeutic c-PAP group. CIH does not represent an additional factor increasing systemic and adipose tissue inflammation in morbid obesity. However, in subjects with OSA, an effective c-PAP therapy improves systemic and obesity-associated inflammatory markers. Ministero dell'Università e della Ricerca and Progetti di Rilevante Interesse Nazionale.

Constructing a patient-specific computer model of the upper airway in sleep apnea patients.

The use of computer simulation to develop a high-fidelity model has been proposed as a novel and cost-effective alternative to help guide therapeutic intervention in sleep apnea surgery. We describe a computer model based on patient-specific anatomy of obstructive sleep apnea (OSA) subjects wherein the percentage and sites of upper airway collapse are compared to findings on drug-induced sleep endoscopy (DISE). Basic science computer model generation. Three-dimensional finite element techniques were undertaken for model development in a pilot study of four OSA patients. Magnetic resonance imaging was used to capture patient anatomy and software employed to outline critical anatomical structures. A finite-element mesh was applied to the volume enclosed by each structure. Linear and hyperelastic soft-tissue properties for various subsites (tonsils, uvula, soft palate, and tongue base) were derived using an inverse finite-element technique from surgical specimens. Each model underwent computer simulation to determine the degree of displacement on various structures within the upper airway, and these findings were compared to DISE exams performed on the four study patients. Computer simulation predictions for percentage of airway collapse and site of maximal collapse show agreement with observed results seen on endoscopic visualization. Modeling the upper airway in OSA patients is feasible and holds promise in aiding patient-specific surgical treatment. NA. Laryngoscope, 128:277-282, 2018.

O163 Autonomic nervous system dysfunction in patients with high obstructive sleep apnea risk

Objectives The aim of this study was to compare autonomic nervous system (ANS) function in subjects with high OSA (obstructive sleep apnea) risk versus subjects with low OSA risk. Methods Out of 47 consecutive subjects enrolled (22 females, mean age 48.23 ± 16.09 years), 27 had high OSA risk and 20 had low OSA risk according to the Berlin Questionnaire (BQ). They all underwent standardized battery of ANS testing, including blood pressure and heart rate response to Valsalva maneuver, deep breathing test and head up tilt table test. Respiratory sinus arrhythmia (RSA), Valsalva ratio (VR) were determined and cardiovagal score of the Composite Autonomic Scoring Scale (CASS) was determined. Adrenergic score was calculated from the blood pressure response during Valslava maneuver and tilt table test. Finally heart rate variability (HRV) was determined in supine and standing positions. Results High OSA risk subjects had lower RSA compared to low OSA risk subjects (9.96 ± 5.45 vs. 15.17 ± 8.94, p = 0.022). Also VR was lower in subject with high OSA risk versus low OSA risk subjects (1.55 ± 0.34 vs. 1.83 ± 0.41, p = 0.024). There where no significant differences in CASS adrenergic score and HRV between groups. Discussion Pathogenesis of ANS dysfunction in OSA is not elucidated. Sympathetic hyperactivity leads to hypertension but can hardly explain higher cardiac morbidity and mortality. Further research is warranted to investigate the role of vagal down regulation in OSA pathogenesis. Conclusion High OSA risk is associated with vagal down regulation. Significance These findings confirms presence of vagal down regulation which might reflect central nervous system damage in OSA and also might contribute to cardiac morbidity and mortality.

Restoration of Sleep Architecture after Maxillomandibular Advancement: Success Beyond the Apnea–Hypopnea Index

While effects of maxillomandibular advancement (MMA) on respiratory parameters for patients with obstructive sleep apnea (OSA) are well described, effects on sleep architecture before and after MMA are not. A retrospective cohort analysis on sleep architecture was examined in 10 OSA patients who underwent MMA surgery between July 2013 and November 2014, and had prespecified complete polysomnography (PSG) datasets. Sleep stages were examined relative to a Western European population-based control group. All of the respiratory parameters improved significantly post MMA. Rapid eye movement (REM) latency decreased from 178.0±142.8 to 96.6±64.5min (P=0.035). %NREM (non-rapid eye movement)1 (P=0.045) and %WASO (wakefulness after sleep onset) (P=0.006) decreased, while %REM increased (P=0.002) after MMA. WASO decreased from 64.2±57min to 22.4±15.4min (P=0.017). Preoperatively, OSA subjects showed significantly lower sleep efficiency (P=0.016), sleep onset latency (P=0.015), and % REM (P<0.001) than the normative population dataset, while post MMA there was a significant decrease in %NREM1 sleep (P<0.001) and in %WASO (P<0.001). MMA results in a marked decrease in WASO and increase in REM, and to a lesser extent NREM sleep. Patients after MMA show values similar to population controls except for a lower WASO.

Amyloid Burden in Obstructive SleepApnea.

To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2±5.1/h; age 58.5±4.1 years; 9 male) and 19 controls (AHI 1.8±1.3/h; age 58.5±4.2 years; 9 male) underwent 60-min dynamic 11C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease.

0142 DECREASED REGIONAL HOMOGENEITY IN THE DEFAULT MODE NETWORK IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Obstructive sleep apnea (OSA) subjects show structural brain injury in a set of interacting cortical sites, the ventral medial prefrontal (vMPF), inferior parietal lobule (IPL), and posterior cingulate cortices (PCC). These areas constitute a unique resting-state circuit dubbed the “default mode network” (DMN), involved in thoughtless behavior, self-referential processing, sleep, and mood regulation. However, the relationship between OSA severity and the DMN integrity remains unclear, a concern, since mood disorders are common in OSA. Our aim was to examine DMN and the relationships with apnea-hypopnea index (AHI) using regional homogeneity (ReHo) procedures in OSA. We acquired resting-state functional MRI scans from 67 newly-diagnosed, treatment-naïve OSA (age 48.0 ± 9.2years; AHI, 35.6 ± 23.5 events/hour; 51 male) and 73 healthy controls (age 47.1 ± 9.3years; 56 male) using a 3.0-Tesla scanner, and assessed mood (Beck Depression Inventory II, BDI-II; Beck Anxiety Inventory, BAI) as well as sleep variables (Epworth Sleepiness Scale, ESS; Pittsburgh Sleep Quality Index, PSQI). After standard pre-processing steps, we calculated whole-brain ReHo maps of each subject by evaluating homogeneity similarity between each voxel and nearest neighbours, normalized to a common space. The ReHo maps were compared between groups using ANCOVA, and correlated with AHI using partial correlation procedures within OSA subjects (FDR corrected p<0.05; covariates: age and gender). No significant differences in age or gender appeared between groups. Both sleep (ESS, 9.8 ± 4.9 vs 5.1 ± 3.5; PSQI, 8.8 ± 4.1 vs 3.6 ± 2.4) and mood scores (BDI-II, 8.4 ± 8.1 vs 3.7 ± 4.9; BAI, 9.4 ± 11.0 vs 3.4 ± 4.5) were significantly higher in OSA over control subjects (p<0.01). Significantly reduced ReHo appeared in multiple sites of the DMN, including the vMPF, IPL, and PCC in OSA compared to controls. Lower ReHo in the PCC was associated with higher AHI within OSA subjects (r=-0.526, p<0.001). DMN is compromised in OSA, indicating that this resting-state network may mediate affected mood and sleep issues. The finding of a negative relationship between AHI and regional synchrony of neural activities in the DMN indicates that disease severity can contribute significantly to DMN integrity, and consequently, mood behaviors mediated by that circuitry. This research was funded by the NIH R01 HL113251 and R01NR015038.

REM sleep estimation based on autonomic dynamics using R–R intervals

Objective. We developed an automatic algorithm to determine rapid eye movement (REM) sleep on the basis of the autonomic activities reflected in heart rate variations. Approach. The heart rate variability (HRV) parameters were calculated using the R–R intervals from an electrocardiogram (ECG). A major autonomic variation associated with the sleep cycle was extracted from a combination of the obtained parameters. REM sleep was determined with an adaptive threshold applied to the acquired feature. The algorithm was optimized with the data from 26 healthy subjects and obstructive sleep apnea (OSA) patients and was validated with data from a separate group of 25 healthy and OSA subjects. Main results. According to an epoch-by-epoch (30 s) analysis, the average of Cohen’s kappa and the accuracy were respectively 0.63 and 87% for the training set and 0.61 and 87% for the validation set. In addition, the REM sleep-related information extracted from the results of the proposed method revealed a significant correlation with those from polysomnography (PSG). Significance. The current algorithm only using R–R intervals can be applied to mobile and wearable devices that acquire heart-rate-related signals; therefore, it is appropriate for sleep monitoring in the home and ambulatory environments. Further, long-term sleep monitoring could provide useful information to clinicians and patients for the diagnosis and treatments of sleep-related disorders and individual health care.

Real-time multislice MRI during continuous positive airway pressure reveals upper airway response to pressure change.

To determine if a real-time magnetic resonance imaging (RT-MRI) method during continuous positive airway pressure (CPAP) can be used to measure neuromuscular reflex and/or passive collapsibility of the upper airway in individual obstructive sleep apnea (OSA) subjects. We conducted experiments on four adolescents with OSA and three healthy controls, during natural sleep and during wakefulness. Data were acquired on a clinical 3T scanner using simultaneous multislice (SMS) RT-MRI during CPAP. CPAP pressure level was alternated between therapeutic and subtherapeutic levels. Segmented airway area changes in response to rapid CPAP pressure drop and restoration were used to estimate 1) upper airway loop gain (UALG), and 2) anatomical risk factors, including fluctuation of airway area (FAA). FAA significantly differed between OSA patients (2-4× larger) and healthy controls (Student's t-test, P < 0.05). UALG and FAA measurements indicate that neuromuscular reflex and passive collapsibility varied among the OSA patients, suggesting the presence of different OSA phenotypes. Measurements had high intrasubject reproducibility (intraclass correlation coefficient r > 0.7). SMS RT-MRI during CPAP can reproducibly identify physiological traits and anatomical risk factors that are valuable in the assessment of OSA. This technique can potentially locate the most collapsible airway sites. Both UALG and FAA possess large variation among OSA patients. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1400-1408.

The association of NOV/CCN3 with obstructive sleep apnea (OSA): preliminary evidence of a novel biomarker in OSA.

Obstructive sleep apnea (OSA) has a strong association with cardiovascular and metabolic abnormalities, although the mechanism driving this association is not well established. NOV/CCN3, a multifunctional extracellular matrix protein, may play a mechanistic and/or prognostic role in these associations. We hypothesized that patients with OSA, which primarily affects obese individuals, will have increased levels of NOV, and that NOV can serve as a biomarker in patients to predict OSA as well as metabolic and cardiac risk. Ten morbidly obese and 10 healthy lean subjects underwent overnight polysomnography (PSG) and clinical evaluation. Blood samples were analyzed for NOV levels, adiponectin and IL-6. OSA was found in nine obese subjects and three lean subjects. NOV levels were significantly higher in the OSA vs. no OSA group (2.1 ± 0.9 vs. 1.3 ± 0.8, p < 0.03). NOV levels were significantly higher in the obese vs. lean group (2.2 ± 0.3 vs. 1.4 ± 0.2-fold change, p < 0.03). Among lean subjects, NOV levels were significantly higher in the OSA vs. no OSA group (2.1 ± 0.9 vs. 1.0 ± 0.4, p < 0.05). NOV and AHI were positively correlated (ρ = 0.49, p = 0.033). IL-6 and adiponectin differences in obese vs. lean and OSA vs. no OSA were consistent with an inflammatory phenotype in obese subjects and OSA subjects. NOV is a novel biomarker of the presence and severity of OSA and a potential marker of future cardiovascular and metabolic disease in OSA patients.