Faculty Bibliography

Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Abeta-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Abeta-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Abeta-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Abeta-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.

Introduction: Evaluating the dynamics of sleep stage transitions may yield new insights into underlying mechanisms of human sleep physiology. Most PSG-assessed sleep variables are substantially trait-like, with large differences between subjects, but whether interindividual differences in sleep stage transitions are also trait-like has not been studied. Here we report on stable and robust interindividual differences in sleep stage transitions in healthy young adults. Methods: N = 25 subjects (29 + 6 years, 14 females) underwent two successive baseline PSGs followed by a recovery PSG after 36 h total sleep deprivation in a strictly controlled laboratory environment (all TIB 22:00-10:00). PSG records were scored visually according to the criteria of Rechtschaffen and Kales; stages S3 and S4 were combined into slow wave sleep (SWS). Trait-like interindividual differences were assessed by calculating intraclass correlation coeficients (ICCs) across the baseline and recovery nights for the frequencies of the transitions between stages wake (W), REM, S1, S2 and SWS. Results: The most common transitions were W-to-S1 (average frequency: 20.8), S1-to-S2 (20.8), S2-to-SWS (20.7), SWS-to-S2 (18.2), S2-to-W (14.9), REM-to-W (9.2), S2-to-REM (7.6), W-to-S2 (6.8), S2-to-S1 (6.0), S1-to-W (5.9), W-to-REM (4.2), REM-to-S2 (3.4) and S1-to-REM (3.1). ICCs for these transitions were all statistically signiicant (P < 0.05). ICCs were substantial (> 0.6) for transitions S1-to- S2 and W-to-S2; moderate (0.4-0.6) for W-to-S1, S2-to-W, REM-to-W, S2-to-REM, S1-to-W, W-to-REM, REM-to-S2 and S1-to-REM; and fair (0.2-0.4) for S2-to-SWS, SWS-to-S2 and S2-to-S1. In the recovery night after 36 h sleep deprivation, as compared to the baseline nights, the frequencies of transitions W-to-S1, S1-to-S2 and S2-to-W were signiicantly decreased and transitions S2-to-REM and REM-to-S2 were signiicantly increased (P < 0.05). Nonetheless, the magnitude of the trait-like interindividual differences consistently exceeded the magnitude of!

Introduction: Reliable assessment of inspiratory low limitation (IFL), characterized by lattening on a nasal pressure transducer tracing and likely relecting increased upper airway resistance, could enhance evaluation of sleep-disordered breathing, particularly among symptomatic patients with a low apnea-hypopnea index (AHI). However, the assessment of IFL is not standardized and despite the variety of manual and automated methods reported, few have been rigorously validated. We report here on the current agreement seen across multi-center manual scoring, with the long-term goal of developing a standardized, consensus-based approach for visual scoring of IFL in sleep studies. Methods: Consensus scoring rules for IFL were developed at each of 4 laboratories (McGill, Harvard, NYU, Instituto Do Sono). A total of 1000 epochs, sampled from 5 sleep studies on pregnant women with low AHI and varying degrees of IFL, were independently evaluated. Using software to tag each breath manually, 8 scorers rated IFL as follows: normal (N), intermediate (I) and deinitely low limited (FL). Breath-by-breath agreement was tabulated. Results: Of 5283 scored breaths, 1139 (21.6%) had > 80% agreement and were comprised of 52% FL-breaths, 16% I-breaths and 32% Nbreaths. The overall agreement across all breaths revealed an intra-class correlation coeficient of 0.46 (95% CI 0.41, 0.51). The agreement across breath categories was fair for FL-breaths (kappa = 0.36), poor for I-breaths (kappa = 0.12) and fair for N-breaths (kappa = 0.37). Conclusion: In this initial assessment, trained scorers from different sleep centers working with local deinitions of IFL varied substantially in their scoring, indicating that IFL is likely inconsistently identiied in clinical and research settings. Further work is required to establish a standardized, consensus-based approach that can then be applied to validate automated algorithms and evaluate relationships between IFL and clinical outcomes where AHI is low, such as in pregnancy and p!

Introduction: Sleep scoring performed using the 10-20 system is usually performed in the laboratory with a trained technician applying electrodes. Home monitoring of sleep is made easier by self-application of limited number of electrodes positioned only on the face. We evaluated moving the F4 lead to the forehead and scoring sleep using this and a bipolar chin EMG only. This study examines agreement for sleep scoring using full polysomnography compared to scoring using these modiied leads. Methods: 21 subjects (11M/10F) who were undergoing full in-laboratory polysomnography for evaluation of obstructive sleep apnea had one frontal lead moved to the forehead. Conventional sleep scoring from the unmodiied F4, C4, EOG and EMG was performed by an experienced sleep technologist using AASM rules. Limited monitoring (LM) sleep scoring was done independently by 2 scorers while viewing only the modiied F4 and chin EMG. For each study, epoch-by-epoch agreement was tabulated (i) between each scorer's LM scoring and full PSG AASM scoring and (ii) between scorers LM scoring. Results: 17,786 epochs were scored (669-990 epochs/subject). The mean agreement between LM and full PSG was 78% (range 59-88%/ subject) for scorer 1 and 80% (range 66-92%/subject) for scorer 2. For both scorers agreement between LM and full PSG for epochs scored as sleep or wake scoring only was 93% (range 75-98%) and for REM vs NREM was 93% (83-99%). For LM alone, inter-scorer agreement was 78% (range 63-88%), 91% for sleep-wake (range 76-97%) and 88% for REM vs NREM (range 78-90%). Conclusion: Repositioning of F4 EEG to the forehead and scoring from this and chin EMG resulted in excellent discrimination of sleep from wake and REM from NREM sleep. Inter-scorer LM epoch-by-epoch agreement across all stages is similar to that seen between scorers using full polysomnograpy and suggests its utility in the home

Introduction: In obstructive sleep apnea (OSA) treated with a mandibular advancement device Remmers et al recently showed that therapeutic outcome was predicted by a titration study in the laboratory using a remotely controlled mandibular positioner (RCMP, SomnoMed MATRxTM, Zephyr Sleep Technologies Inc., Canada). Furthermore this study showed that optimal titration could be established in a single night. We report on use of the RCMP in a clinical sleep practice. Methods: 30 patients (22M/8F, BMI 26 + 3 kg/m2) with pre-treatment AHI (AHIDx) < 30/hr (n = 18), or AHIDx > 30/hr who refused CPAP (n = 12) were studied with RCMP during a full night polysomnography (PSG). Baseline and maximum jaw advancement (ADVmax) was determined prior to study by a dentist. During PSG, RCMP was progressively advanced past baseline to ADVmax until all obstructive events were eliminated (ADVopt), or until the patient expressed discomfort. AHIRCMP was calculated as the sum of apneas and hypopneas (30% reduction in low with 3% O2 desaturation or arousal) divided by the sleep time limited to the section of the RCMP study with optimal/maximal advancement. Successful titration was deined as AHIRCMP < 15. If pre-treatment AHIDx was < 20, a 50% reduction was also required. Results: Titration was successful in 20 subjects. (AHIDx = 34 + 9/hr vs AHIRCMP = 9 + 7/hr). ADVopt was within 2 mm of ADVmax in 15/20 patients. In the remaining 5 patients the ADVopt was 2-5 mm lower than ADVmax. Titration resulted in no beneit in 10 subjects (AHIDx = 27 + 26/hr vs AHIRCMP = 24 + 11/hr). Conclusions: The RCMP system was used to advance the dental device over a range of jaw advancements and was tolerated by all subjects. In 20/30 subjects successful titration was obtained during the one night titration, with 25% of these subjects requiring less than maximal advancement. Lack of beneit was predicted in 10/30 subjects. The long-term utility of suboptimal advancement, prediction of futility and sustained eficacy need to be addressed separate!

Introduction: Obstructive sleep apnea (OSA) is generally deined as the conluence of sleep disordered breathing (S