Faculty Bibliography

Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA.

Alveolar hypoventilation defined by an increase in PaCO2 occurs due to either reduced minute ventilation and/or increased dead space. Mild alveolar hypoventilation may be observed in healthy subjects during sleep. Sleep hypoventilation is accentuated in disease states with potential carryover to the daytime, producing chronic hypercapnia during wakefulness due to failure of compensation during sleep and/or during wakefulness. Elevation of blood bicarbonate concentration, although appropriate to defend blood pH, provides a mechanism for perpetuation of a chronic hypercapnic state due to blunting of respiratory drive. 2014 Elsevier Inc. All rights reserved

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: 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!