Faculty Bibliography

OBJECTIVE: To examine whether the presence of sleep-disordered breathing (SDB) is associated with an earlier age at mild cognitive impairment (MCI) or Alzheimer disease (AD)-dementia onset in participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We also examined whether continuous positive airway pressure (CPAP) use is associated with delayed onset of cognitive decline. METHODS: From the ADNI cohort, 3 subsets with progressively stringent criteria were created in a step-wise manner. Age at MCI or AD-dementia onset was the main outcome variable. Analyses were performed separately for each subset in untreated SDB+ vs SDB- and untreated SDB+ vs CPAP+ groups. Chi-square and t tests were performed to examine between-group differences. Survival analyses were performed using the Kaplan-Meier method, compared by the log-rank test, and assessed by multivariate Cox regression adjusting for potential confounders. RESULTS: SDB+ patients had a younger age at MCI onset in all subsets (MC1: 72.63 vs 83.67; MC2: 72.15 vs 83.45; MC3: 77.40 vs 89.89; p < 0.01). SDB+ patients had a younger age at AD-dementia onset only in our most conservative subset (AC3: 83.46 vs 88.13; p < 0.05). In a combined outcome analysis, SDB+ patients had a younger age at onset to MCI or AD-dementia in all subsets. In subsets 1 and 2, CPAP use delayed the age at MCI onset (CMC1: 72.63 vs 82.10; CMC2: 72.11 vs 82.10; p < 0.01). CONCLUSIONS: Consistent with our hypothesis, the presence of SDB was associated with an earlier age at cognitive decline. Our findings in CPAP+ participants suggest that CPAP treatment of SDB may delay progression of cognitive impairment.

Introduction: Inspiratory flow limitation (IFL) is defined as a "flattened shape" of the inspiratory airflow contour detected by nasal cannula pressure during sleep and can indicate increased upper airway resistance especially in mild Sleep Related Breathing Disorders (SRBD). The objective of this study was to investigate the association between upper airway abnormalities and IFL in patients with mild SRBD. Methods: This study was derived from a general population study of 1,042 individuals. Were selected individuals without symptoms (with no significant pulmonary disease and no smoking) and with apnea-hypopnea index (AHI) below 5 events/hour of sleep, considered a "normal" group and individuals with symptoms and AHI between 5 and 15 events/hour considered as having mild Obstructive Sleep Apnea Syndrome (OSAS). 754 individuals were divided into 4 groups: group 1: AHI < 5/hour and < 30% of total sleep time (TST) with IFL (515 individuals), group 2: AHI < 5/hour and > 30% of TST with IFL (46 individuals), group 3: AHI: 5-15/hour and < 30% of TST with IFL (168 individuals) and group 4: AHI: 5-15/hour and > 30% of TST with IFL (25 individuals). Results: Individuals with complains of oral breathing demonstrated chance 2.7 folds larger of having mild OSAS with > 30% TST with IFL compared to mild OSAS with < 30%) of TST with IFL. Abnormal nasal structure increased chances of having mild OSAS with IFL > 30% 3.2 folds in comparison to normal with < 30% of TST with IFL. Those ones that had voluminous lateral wall demonstrated chance 4.2 folds larger of having mild OSAS with > 30% of TST with IFL compared to mild OSAS with < 30% of TST with IFL. Conclusion: More than 30% of TST with IFL detected in polysomnography was associated with nasal and palatal anatomical abnormalities in mild SRBD patients. IFL may be an additional parameter for evaluating upper airway obstruction in mild OSAS patients

Introduction: In cognitively normal elderly, short sleep duration is associated with deficits in cognitive performance while physical activity has shown to be protective and improve cognitive function. Actigraph monitoring systems are used to objectively assess sleep but also capture measures of physical activity during the daytime. The purpose of this study is to determine whether daytime activity and sleep duration have independent effects on cognition in normal elderly. Methods: 44 community dwelling cognitively normal (Clinical Dementia Rating = 0) elderly (Age 66.2 +/- 7.3, Gender (36.4%Male, 63.6% Female), non-depressed (Geriatric Depression Scale < 7) participants wore an actigraph (Octagonal Basic Motionlogger, Ambulatory Monitoring Inc, NY) for 7 consecutive days. Data were analyzed in the zero crossing mode for total sleep duration (TST), and mean daytime activity using the provided automated algorithm. All subjects underwent a standard neuropsychological test battery with subscales assessing immediate and delayed recall of orally presented paragraphs and verbal paired associates, digit span (backward and forward), and executive function (trail making test B [TMTB]). Results: Daytime Activity and TST were not correlated with each other. Short sleep duration was associated with longer completion times in the TMTB (r = -0.3, p < 0.05) while Daytime Activity was associated with better performance in verbal paired associates (r = 0.4, p < 0.01) and digit span backward (r = 0.4, p < 0.01). Daytime Activity and TST showed additive effects on verbal paired associates (Daytime Activity F change = 5.95, p < 0.05 and TST F change = 3.18, p < 0.1). Conclusion: Daytime Activity had a significant effect on cognition independent of sleep duration. While these preliminary findings should be interpreted with caution due to small sample size, our data suggest that in studies examining cognition in elderly subjects, actigraphic data should be analyzed for daytime activity in addition to sleep duration

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