• Agreement in the scoring of respiratory events and sleep among international sleep centers.

      Magalang, Ulysses J; Chen, Ning-Hung; Cistulli, Peter A; Fedson, Annette C; Gíslason, Thorarinn; Hillman, David; Penzel, Thomas; Tamisier, Renaud; Tufik, Sergio; Phillips, Gary; et al. (Associated Professional Sleep Societies, 2013-04)
      Abstract STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) guidelines for polysomnography (PSG) scoring are increasingly being adopted worldwide, but the agreement among international centers in scoring respiratory events and sleep stages using these guidelines is unknown. We sought to determine the interrater agreement of PSG scoring among international sleep centers. DESIGN: Prospective study of interrater agreement of PSG scoring. SETTING: Nine center-members of the Sleep Apnea Genetics International Consortium (SAGIC). MEASUREMENTS AND RESULTS: Fifteen previously recorded deidentified PSGs, in European Data Format, were scored by an experienced technologist at each site after they were imported into the locally used analysis software. Each 30-sec epoch was manually scored for sleep stage, arousals, apneas, and hypopneas using the AASM recommended criteria. The computer-derived oxygen desaturation index (ODI) was also recorded. The primary outcome for analysis was the intraclass correlation coefficient (ICC) of the apnea-hypopnea index (AHI). The ICCs of the respiratory variables were: AHI = 0.95 (95% confidence interval: 0.91-0.98), total apneas = 0.77 (0.56-0.87), total hypopneas = 0.80 (0.66-0.91), and ODI = 0.97 (0.93-0.99). The kappa statistics for sleep stages were: wake = 0.78 (0.77-0.79), nonrapid eye movement = 0.77 (0.76-0.78), N1 = 0.31 (0.30-0.32), N2 = 0.60 (0.59-0.61), N3 = 0.67 (0.65-0.69), and rapid eye movement = 0.78 (0.77-0.79). The ICC of the arousal index was 0.68 (0.50-0.85). CONCLUSION: There is strong agreement in the scoring of respiratory events among the SAGIC centers. There is also substantial epoch-by-epoch agreement in scoring sleep variables. Our results suggest that centralized scoring of PSGs may not be necessary in future research collaboration among international sites where experienced, well-trained scorers are involved.
    • Alzheimer's disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea.

      Owen, Jessica E; Benediktsdottir, Bryndis; Cook, Elizabeth; Olafsson, Isleifur; Gislason, Thorarinn; Robinson, Stephen R; 1School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Department of Sleep Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 4Department of Clinical Biochemistry, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 5Institute for Breathing and Sleep (IBAS), Austin Health, Heidelberg, Victoria, Australia. (Owen JE, Benediktsdottir B, Cook E, Olafsson I, Gislason T, Robinson SR. Alzheimer's disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea. Sleep. 2021 Mar 12;44(3):zsaa195. doi: 10.1093/sleep/zsaa195., 2021-03)
      Obstructive sleep apnea (OSA) involves intermittent cessations of breathing during sleep. People with OSA can experience memory deficits and have reduced hippocampal volume; these features are also characteristic of Alzheimer's disease (AD), where they are accompanied by neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques in the hippocampus and brainstem. We have recently shown reduced hippocampal volume to be related to OSA severity, and although OSA may be a risk factor for AD, the hippocampus and brainstems of clinically verified OSA cases have not yet been examined for NFTs and Aβ plaques. The present study used quantitative immunohistochemistry to investigate postmortem hippocampi of 34 people with OSA (18 females, 16 males; mean age 67 years) and brainstems of 24 people with OSA for the presence of NFTs and Aβ plaques. OSA severity was a significant predictor of Aβ plaque burden in the hippocampus after controlling for age, sex, body mass index (BMI), and continuous positive airway pressure (CPAP) use. OSA severity also predicted NFT burden in the hippocampus, but not after controlling for age. Although 71% of brainstems contained NFTs and 21% contained Aβ plaques, their burdens were not correlated with OSA severity. These results indicate that OSA accounts for some of the "cognitively normal" individuals who have been found to have substantial Aβ burdens, and are currently considered to be at a prodromal stage of AD. Keywords: Alzheimer’s disease; amyloid beta; continuous positive airway pressure; neurofibrillary tangles; tau.
    • Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation.

      Arnardottir, Erna S; Nikonova, Elena V; Shockley, Keith R; Podtelezhnikov, Alexei A; Anafi, Ron C; Tanis, Keith Q; Maislin, Greg; Stone, David J; Renger, John J; Winrow, Christopher J; et al. (Amer Acad Sleep Medicine, 2014-10)
      To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation.
    • Carotid Artery Wall Thickness in Obese and Non-obese Adults with Obstructive Sleep Apnea Before and Following Positive Airway Pressure Treatment

      Kim, Jinyoung; Mohler, Emile R.; Keenan, Brendan T.; Maislin, David; Arnardottir, Erna Sif; Gislason, Thorarinn; Benediktsdottir, Bryndis; Gudmundsdottir, Sigrun; Sifferman, Andrea; Staley, Bethany; et al. (Oxford University Press, 2017-07-27)
      STUDY OBJECTIVES: Debate persists as to whether obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. The purpose of this study was to compare carotid intima-media thickness (IMT), an early sign of atherosclerosis, in obese and nonobese adults with OSA before and following positive airway pressure (PAP) treatment. METHODS: A total of 206 adults newly diagnosed with OSA with an apnea-hypopnea index (AHI) of 15-75 events/hour and 53 controls with AHI <10 were studied. Waist circumference was used to classify participants as obese and nonobese. Bilateral common carotid artery B-mode ultrasound was performed at baseline to assess IMT, arterial diameter, arterial-wall mass, and circumferential wall stress. Measurements were repeated in 118 participants with OSA who completed a 4-month PAP treatment and had an average daily use over that period of ≥4 hours/day. RESULTS: No significant differences in carotid IMT, diameter, or arterial-wall mass were present at baseline between participants with OSA and controls stratified by waist circumference, after adjusting for other cardiovascular risk factors. In participants with OSA, who had adequate PAP adherence over the 4-month treatment, carotid artery diameter significantly increased (mean change [95% confidence interval] = 0.13 [0.06, 0.20] mm; p = .0004), but no significant changes in carotid IMT, arterial-wall mass, and circumferential stress were observed in obese and nonobese participants. CONCLUSIONS: Regardless of obesity status, carotid IMT is not increased in adults with moderate to severe OSA versus controls and does not change following 4 months of PAP treatment.
    • Changing Faces of Obstructive Sleep Apnea: Treatment Effects by Cluster Designation in the Icelandic Sleep Apnea Cohort

      Pien, Grace W; Ye, Lichuan; Keenan, Brendan T; Maislin, Greg; Björnsdóttir, Erla; Arnardottir, Erna Sif; Benediktsdottir, Bryndis; Gislason, Thorarinn; Pack, Allan I; 1 ] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA Show more [ 2 ] Northeastern Univ, Sch Nursing, Bouve Coll Hlth Sci, Boston, MA 02115 USA Show more [ 3 ] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA [ 4 ] Landspitali, Dept Sleep, Reykjavik, Iceland Show more [ 5 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland Show more [ 6 ] Univ Penn, Dept Med, Div Sleep Med, Perelman Sch Med, Philadelphia, PA 19104 USA (Oxford University Press, 2018-01-02)
      STUDY OBJECTIVES: Distinct clinical phenotypes of obstructive sleep apnea (OSA) have been identified: Disturbed Sleep, Minimally Symptomatic, and Sleepy. Determining whether these phenotypes respond differently to standard treatment helps us to create a foundation for personalized therapies. We compared responses to positive airway pressure (PAP) therapy in these clinical OSA phenotypes. METHODS: The study sample included 706 patients from the Icelandic Sleep Apnea Cohort with moderate-to-severe OSA who were prescribed PAP. Linear and logistic mixed models were used to compare 2-year changes in demographics, comorbid diseases, and sleep-related health issues within and across OSA clinical phenotypes. Relationships between changes in symptoms and PAP adherence were also examined. RESULTS: Overall, effect sizes were moderate to large when comparing sleepiness, insomnia-related, and apneic symptom changes in the Sleepy group with changes in other two groups, especially those in the Minimally Symptomatic group. Within the Disturbed Sleep group, PAP users and nonusers demonstrated similar changes in insomnia-related symptoms. The Minimally Symptomatic group remained relatively asymptomatic, but reported significant decreases in daytime sleepiness and physical fatigue; PAP users generally had larger improvements. The Sleepy group had reductions in nearly all measured symptoms, including large reductions in drowsy driving; almost all of these improvements were greater among PAP users than nonusers. CONCLUSIONS: OSA treatment response patterns differed by initial clinical phenotype and PAP adherence. Individuals with insomnia-related symptoms may require additional targeted therapy for these complaints. These findings underscore the need for a personalized approach to management that recognizes patients with a range of OSA presentations.
    • Differences in three-dimensional upper airway anatomy between Asian and European patients with obstructive sleep apnea.

      Xu, Liyue; Keenan, Brendan T; Wiemken, Andrew S; Chi, Luqi; Staley, Bethany; Wang, Zhifang; Wang, Jianjun; Benedikstdottir, Bryndis; Juliusson, Sigurdur; Pack, Allan I; et al. (Oxford University Press, 2020-05)
      Study objectives: This study evaluated differences in upper airway, soft tissues and craniofacial structures between Asians from China and Europeans from Iceland with OSA using three-dimensional magnetic resonance imaging (MRI). Methods: Airway sizes, soft tissue volumes, and craniofacial dimensions were compared between Icelandic (N = 108) and Chinese (N = 57) patients with oxygen desaturation index (ODI) ≥ 10 events/h matched for age, gender, and ODI. Mixed effects models adjusting for height or BMI and residual differences in age and ODI were utilized. Results: In our matched sample, compared to Icelandic OSA patients, Chinese patients had smaller BMI (p < 0.0001) and neck circumference (p = 0.011). In covariate adjusted analyses, Chinese showed smaller retropalatal airway size (p ≤ 0.002), and smaller combined soft tissues, tongue, fat pads, and pterygoid (all p ≤ 0.0001), but male Chinese demonstrated a larger soft palate volume (p ≤ 0.001). For craniofacial dimensions, Chinese demonstrated bigger ANB angle (p ≤ 0.0196), differently shaped mandibles, including shorter corpus length (p < 0.0001) but longer ramus length (p < 0.0001), and a wider (p < 0.0001) and shallower (p ≤ 0.0001) maxilla. Conclusions: Compared to Icelandic patients of similar age, gender and ODI, Chinese patients had smaller retropalatal airway and combined soft tissue, but bigger soft palate volume (in males), and differently shaped mandible and maxilla with more bony restrictions. Results support an ethnic difference in upper airway anatomy related to OSA, which may inform targeted therapies. Keywords: ethnicity; obstructive sleep apnea; three-dimensional magnetic resonance imaging; upper airway structure.
    • Effects and side-effects of surgery for snoring and obstructive sleep apnea--a systematic review

      Franklin, Karl A; Anttila, Heidi; Axelsson, Susanna; Gislason, Thorarinn; Maasilta, Paula; Myhre, Kurt I; Rehnqvist, Nina; Swedish Council on Technology Assessment in Health Care, Stockholm, Sweden. Karl.Franklin@lung.umu.se (Asoociated Professional Sleep Societies, 2009-01-01)
      STUDY OBJECTIVES: Many patients undergo surgery for snoring and sleep apnea, although the efficacy and safety of such procedures have not been clearly established. Our aim was systematically to review studies of the efficacy and adverse effects of surgery for snoring and obstructive sleep apnea. DESIGN: Systematic review. MEASUREMENTS: PubMed and Cochrane databases were searched in September 2007. Randomized controlled trials of surgery vs. sham surgery or conservative treatment in adults, with daytime sleepiness, quality of life, apnea-hypopnea index, and snoring as outcomes were included. Observational studies were also reviewed to assess adverse effects. Evidence of effect required at least two studies of medium and high quality reporting the same result. RESULTS: Four studies of benefits and 45 studies of adverse effects were included. There was no significant effect on daytime sleepiness and quality of life after laser-assisted uvulopalatoplasty and radiofrequency ablation. The apnea-hypopnea index and snoring was reduced in one trial after laser-assisted uvulopalatoplasty but not in another trial. Subjective snoring was reduced in one trial after radiofrequency ablation. No trial investigating the effect of any other surgical modality met the inclusion criteria. Persistent side-effects occurred after uvulopalatopharyngoplasty and uvulopalatoplasty in about half the patients and difficulty in swallowing, globus sensation and voice changes were especially common. CONCLUSIONS: Only a small number of randomized controlled trials with a limited number of patients assessing some surgical modalities for snoring or sleep apnea are available. These studies do not provide any evidence of effect from laser-assisted uvulopalatoplasty or radiofrequency ablation on daytime sleepiness, apnea reduction, quality of life or snoring. We call for research of randomized, controlled trials of surgery other than uvulopalatopharyngoplasty and uvulopalatoplasty, as they are related to a high risk of long-term side-effects, especially difficulty swallowing.
    • Facial phenotyping by quantitative photography reflects craniofacial morphology measured on magnetic resonance imaging in Icelandic sleep apnea patients.

      Sutherland, Kate; Schwab, Richard J; Maislin, Greg; Lee, Richard W W; Benedikstdsottir, Bryndis; Pack, Allan I; Gislason, Thorarinn; Juliusson, Sigurdur; Cistulli, Peter A; Royal N Shore Hosp, Dept Resp Med, Ctr Sleep Hlth & Res, St Leonards, NSW 2065, Australia, Univ Sydney, NHMRC Ctr Integrated Res & Understanding Sleep CI, Sydney, NSW 2006, Australia, Univ Penn, Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA, Univ Penn, Dept Med, Div Sleep Med, Philadelphia, PA 19104 USA, Gosford Hosp, Dept Resp Med, Gosford, Australia, Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia, Univ Iceland, Fac Med, Reykjavik, Iceland, Landspitali Univ Hosp Fossvogi, Dept Resp Med & Sleep, Reykjavik, Iceland, Natl Univ Hosp Iceland, Dept Otolaryngol, Reykjavik, Iceland (Amer Acad Sleep Medicine, 2014-05)
      (1) To determine whether facial phenotype, measured by quantitative photography, relates to underlying craniofacial obstructive sleep apnea (OSA) risk factors, measured with magnetic resonance imaging (MRI); (2) To assess whether these associations are independent of body size and obesity.
    • Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity.

      Qin, Hua; Keenan, Brendan T; Mazzotti, Diego R; Vaquerizo-Villar, Fernando; Kraemer, Jan F; Wessel, Niels; Tufik, Sergio; Bittencourt, Lia; Cistulli, Peter A; de Chazal, Philip; et al. (Oxford University Press, 2021-05)
      Study objectives: Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample. Methods: 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates. Results: Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009). Conclusions: Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients. Clinical trial information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966. Keywords: autonomic nervous activity; frequency domain analysis; heart rate variability; nonlinear dynamic analysis; obstructive sleep apnea; time domain analysis; wakefulness.
    • The interaction of obstructive sleep apnea and obesity on the inflammatory markers C-reactive protein and interleukin-6: the Icelandic Sleep Apnea Cohort.

      Arnardottir, Erna S; Maislin, Greg; Schwab, Richard J; Staley, Bethany; Benediktsdottir, Bryndis; Olafsson, Isleifur; Juliusson, Sigurdur; Romer, Micah; Gislason, Thorarinn; Pack, Allan I; et al. (2012-07-01)
      STUDY OBJECTIVES: To assess the relative roles and interaction of obstructive sleep apnea (OSA) severity and obesity on interleukin-6 (IL-6) and C-reactive protein (CRP) levels. DESIGN: Cross-sectional cohort. SETTING: The Icelandic Sleep Apnea Cohort. PARTICIPANTS: 454 untreated OSA patients (380 males and 74 females), mean ± standard deviation age 54.4 ± 10.6 yr. MEASUREMENTS AND RESULTS: Participants underwent a sleep study, abdominal magnetic resonance imaging to measure total abdominal and visceral fat volume, and had fasting morning IL-6 and CRP levels measured in serum. A significantly higher correlation was found for BMI than visceral fat volume with CRP and IL-6 levels. Oxygen desaturation index, hypoxia time, and minimum oxygen saturation (SaO₂) significantly correlated with IL-6 and CRP levels, but apnea-hypopnea index did not. When stratified by body mass index (BMI) category, OSA severity was associated with IL-6 levels in obese participants only (BMI > 30 kg/m²). A multiple linear regression model with interaction terms showed an independent association of OSA severity with IL-6 levels and an interaction between OSA severity and BMI, i.e., degree of obesity altered the relationship between OSA and IL-6 levels. An independent association of OSA severity with CRP levels was found for minimum SaO₂ only. A similar interaction of OSA severity and BMI on CRP levels was found for males and postmenopausal women. CONCLUSIONS: OSA severity is an independent predictor of levels of IL-6 and CRP but interacts with obesity such that this association is found only in obese patients.
    • The Manifestations of Sleep Disturbances 16 Years Post-Trauma.

      Thordardottir, Edda Bjork; Hansdottir, Ingunn; Valdimarsdottir, Unnur Anna; Shipherd, Jillian C; Resnick, Heidi; Gudmundsdottir, Berglind; [ 1 ] Univ Iceland, Sch Hlth Sci, Fac Med, Ctr Publ Hlth Sci, Reykjavik, Iceland [ 2 ] Univ Iceland, Sch Hlth Sci, Fac Psychol, Reykjavik, Iceland [ 3 ] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA [ 4 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden [ 5 ] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA [ 6 ] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA [ 7 ] Med Univ South Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA [ 8 ] Natl Univ Hosp Iceland, Mental Hlth Serv, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 9 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland (Oxford Univ Press, 2016)
      Limited data exist on the association between trauma and sleep across developmental stages, particularly trauma experienced in childhood and sleep in adulthood. We assessed sleep quality across the developmental spectrum among avalanche survivors 16 years after exposure as compared to a matched comparison cohort.
    • Molecular signatures of obstructive sleep apnea in adults: a review and perspective

      Arnardottir, Erna S; Mackiewicz, Miroslaw; Gislason, Thorarinn; Teff, Karen L; Pack, Allan I; Center for Sleep and Respiratory Neurobiology, Division of Sleep Medicine/Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. ernasif@landspitali.is (2009-04-01)
      The consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep.
    • Neuropathological investigation of cell layer thickness and myelination in the hippocampus of people with obstructive sleep apnea.

      Owen, Jessica E; BenediktsdÓttir, Bryndis; Gislason, Thorarinn; Robinson, Stephen R; 1 School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia. 2 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3 Department of Sleep Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. (Oxford University Press, 2019-01-01)
      Obstructive sleep apnea (OSA) is commonly associated with memory impairments. Although MRI studies have found volumetric differences in the hippocampus of people with OSA compared with controls, MRI lacks the spatial resolution to detect changes in the specific regions of the hippocampus that process different types of memory. The present study performed histopathological investigations on autopsy brain tissue from 32 people with OSA (17 females and 15 males) to examine whether the thickness and myelination of the hippocampus and entorhinal cortex (EC) vary as a function of OSA severity. Increasing OSA severity was found to be related to cortical thinning in the molecular layer of the dentate gyrus (r2 = 0.136, p = 0.038), the CA1 (overall, r2 = 0.135, p = 0.039; layer 1, r2 = 0.157, p = 0.025; layer 2, r2 = 0.255, p = 0.003; and layer 3, r2 = 0.185, p = 0.014) and in some layers of the EC (layer 1, r2 = 0.186, p = 0.028; trend in layer 3, r2 = 0.124, p = 0.078). OSA severity was also related to decreased myelin in the deep layers but not the superficial layers of the EC (layer 6, r2 = 0.282, p = 0.006; deep white matter, r2 = 0.390, p = 0.001). Patients known to have used continuous positive airway pressure (CPAP) treatment showed no significant reductions in cortical thickness when compared with controls, suggesting that CPAP had a protective effect. However, CPAP did not protect against myelin loss. The regions of decreased cortical thickness and demyelination are locations of synaptic connections in both the polysynaptic (episodic and spatial) and direct (semantic) memory pathways and may underpin the impairments observed in episodic, semantic, and spatial memory in people with OSA.
    • Recognizable clinical subtypes of obstructive sleep apnea across international sleep centers: a cluster analysis

      Keenan, Brendan T; Kim, Jinyoung; Singh, Bhajan; Bittencourt, Lia; Chen, Ning-Hung; Cistulli, Peter A; Magalang, Ulysses J; McArdle, Nigel; Mindel, Jesse W; Benediktsdottir, Bryndis; et al. (Oxford University Press, 2018-03)
      STUDY OBJECTIVES: A recent study of patients with moderate-severe obstructive sleep apnea (OSA) in Iceland identified three clinical clusters based on symptoms and comorbidities. We sought to verify this finding in a new cohort in Iceland and examine the generalizability of OSA clusters in an international ethnically diverse cohort. METHODS: Using data on 972 patients with moderate-severe OSA (apnea-hypopnea index [AHI] ≥ 15 events per hour) recruited from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC), we performed a latent class analysis of 18 self-reported symptom variables, hypertension, cardiovascular disease, and diabetes. RESULTS: The original OSA clusters of disturbed sleep, minimally symptomatic, and excessively sleepy replicated among 215 SAGIC patients from Iceland. These clusters also generalized to 757 patients from five other countries. The three clusters had similar average AHI values in both Iceland and the international samples, suggesting clusters are not driven by OSA severity; differences in age, gender, and body mass index were also generally small. Within the international sample, the three original clusters were expanded to five optimal clusters: three were similar to those in Iceland (labeled disturbed sleep, minimal symptoms, and upper airway symptoms with sleepiness) and two were new, less symptomatic clusters (labeled upper airway symptoms dominant and sleepiness dominant). The five clusters showed differences in demographics and AHI, although all were middle-aged (44.6-54.5 years), obese (30.6-35.9 kg/m2), and had severe OSA (42.0-51.4 events per hour) on average. CONCLUSIONS: Results confirm and extend previously identified clinical clusters in OSA. These clusters provide an opportunity for a more personalized approach to the management of OSA.
    • Symptoms of insomnia among patients with obstructive sleep apnea before and after two years of positive airway pressure treatment.

      Björnsdóttir, Erla; Janson, Christer; Sigurdsson, Jón F; Gehrman, Philip; Perlis, Michael; Juliusson, Sigurdur; Arnardottir, Erna S; Kuna, Samuel T; Pack, Allan I; Gislason, Thorarinn; et al. (Amer Acad Sleep Medicine, 2013-12)
      To assess the changes of insomnia symptoms among patients with obstructive sleep apnea (OSA) from starting treatment with positive airway pressure (PAP) to a 2-y follow-up.