Faculty Bibliography

Introduction: White Matter Hyperintensities (WMHs) have been associated with depressive symptoms, reduced cognitive function, and the development of stroke in late-life. Sleep Disordered Breathing (S

Introduction: The ApoE4 allele is a major risk factor for development of Alzheimer Disease (AD). Symptoms of AD include early deficits in spatial orientation and alterations in sleep. The effects of ApoE4 on sleep architecture and sleep-dependent memory consolidation are less known, particularly at earlier time points before clinical manifestations are apparent. We investigated the effects of ApoE4 allele on sleep architecture and overnight spatial navigational memory consolidation in cognitively normal elderly individuals. Methods: We recruited 29 cognitively normal elderly subjects (age = 67 +/- 9 years) who underwent one night of standard polysomnography. Subjects performed training and 3 timed trials before and after sleep on the same computer-generated 3D spatial maze. Improvement in average completion time after sleep was calculated. A 20-minute psychomotor vigilance test (PVT) was performed in the morning prior to the maze trials. ApoE genotype was determined from serum. Individuals with at least 1 ApoE4 were considered at risk carriers. Results: Of 29 subjects, 17 were control and 12 had at least one ApoE4 allele. Both groups were similar in age, total sleep time, sleep efficiency, sleep architecture, severity of sleep disordered breathing, PVT performance, and pre-sleep baseline maze performance. The control group had significant improvements in maze performance after sleep (390 + 135 sec vs 302 + 121 sec, p < 0.002) while ApoE4 carriers had no significant change in performance (349 + 159 sec vs 358 + 178 sec, p = 0.82). We observed a trend toward a difference in the median of individual changes in overnight performance between groups (28.8% vs-11.8% respectively, p = 0.066). Conclusion: Cognitively normal subjects with at least one ApoE4 allele showed a decreased ability to consolidate spatial navigational memory during sleep. Sleep-dependent spatial memory deficits observed may represent an endophenotype of ApoE4 genotype or may help establish risk for development of subsequent AD

Introduction: OSA is highly prevalent among WTC first-responders, but adherence to CPAP is often poor. In an ongoing study of nasal pathology and OSA and the effect of Cflex on adherence, we looked for correlations between prior physiological (AHI4%/RDI, gender, age, and treatment pressure) and psychological (subjective daytime sleepiness, insomnia, and depressed mood) factors and adherence to CPAP at one month. Methods: Subjects with OSA (AHI4% > 5/hr or AHIall > 15/hr) were recruited from the WTC Health Clinic. CPAP therapy was initiated at home with 3 or more days of autotitration, followed by fixed CPAP, randomly with/without Cflex. To date, 219 subjects (age 34-75, 27 female, AHI4% = 16.5 +/- 14.7, RDI = 32.3 +/- 16.4, ESS = 8.7 +/- 5) have completed a one-month treatment period. Mood and insomnia were assessed by questionnaire and subjective daytime sleepiness by Epworth Sleepiness Scale (ESS). CPAP adherence was assessed by %days > four hrs used in the last 2 weeks of treatment, and average hours used on all days or averaged on days CPAP was used. Independent sample t-tests were used to compare groups. Results: Subjects used CPAP for > 4hrs on 23.1 +/- 30.7% (mean +/- SD) of days used; average use-hours on all days were 1.8 +/- 2.3 hrs; and average use-hours on days CPAP was used were 2.6 +/- 2.3 hrs. Prior to CPAP, 35% of participants had significant sleep onset and/or maintenance insomnia. 31% had significant depressed mood scores. CPAP adherence did not differ between groups based on gender, severity of OSA, CPAP pressure > 10, ESS, or insomnia complaints. As in other studies, older age correlated weakly with CPAP adherence (r = 0.21, p < 0.01). Lower CPAP adherence may be associated with prior depressed mood (2.3 +/- 2.3hrs vs 2.7 +/- 2.3 hrs) but this did not reach significance (p = .24). Conclusion: CPAP adherence in these predominantly mild OSA subjects from a non-sleep-clinic population was poor and was not predicted by available physiological or psychological variables

Introduction: In an ongoing trial of initiating CPAP in World Trade Center Responders with OSA, we used AutoPAP followed by fixed CPAP with/without CPAPFlex. We report on compliance in the first 45 subjects whose average use of AutoPAP on nights used was > 2 hrs, and compare this to their early and late compliance on fixed pressure (FP). The data were not unblinded to CPAPFlex use. Methods: Compliance was measured as mean duration of use on nights used (hours +/- SEM) during 4 days of AutoPAP, during the 4 first days on fixed CPAP and 4 days at the end of 4 weeks of fixed CPAP. Subjects were grouped by OSA severity: mild(AHI4 greater than 30), moderate(AHI4: 15-30) and severe OSA(AHI4 greater than 30). Positional OSA(POSA) was defined as non-supine AHI < 5/hr. FP was determined by the 90th percentile pressure on AutoPAP. Results: 42 men and 3 women have been studied (ages 35-67); BMI 31.9 (range 23.2-52.8). 53% had mild, 27% moderate and 20% severe OSA. 49% had POSA (6/22 with moderate/severe OSA). In moderate and severe OSA there was no decrease in compliance from the initial AutoPAP period to FP (5.08 +/- 0.49 to 5.19 +/- 0.47hrs for moderate and 5.14 +/- 0.54 to 5.07 +/- 0.52hrs for severe). In contrast, for mild OSA compliance dropped from 5.57 +/- 0.32 to 4.61 +/- 0.31hrs; p < 0.005. Compliance after 4 weeks of FP did not drop further. In POSA, compliance also decreased significantly from AutoPAP to FP early (5.49 +/- 0.34 to 4.76 +/- 0.34 hours; p < 0.05), but 15/22 had mild OSA. FP late showed no further drop over the 4 weeks (4.76 +/- 0.34 vs versus 4.23 +/- 0.41). For those without POSA (6/23 with mild OSA) compliance did not change between AutoPAP and FP. Conclusion: Compliance in patients with mild and positional OSA drops off soon after initiation of PAP therapy. One explanation may be that they prefer AutoPAP to fixed CPAP pressures

Introduction: Health intervention is successful when messages are culturally and linguistically tailored to a specific population. The current study utilized a comprehensive approach involving multiple stakeholders to develop tailored health messages to promote awareness of sleep apnea among Blacks. Methods: We engaged several stakeholders (community-based organizations, patients, and healthcare providers) to develop and implementan online sleep educational inter vention. First round of focus groups were conducted with patients (N = 35; 71% Female, 100% Black, average age 45.2 years). Next, community leaders from churches, barbershops, and other organizations (N = 8, 75% Female, 87% Black, average age 48.1 years). Finally, interviews were conducted with healthcare providers (N = 6, 16% Female, 83% White, average age 51.2 years). All data collection was focused on barriers to awareness, diagnosis and treatment of sleep apnea. This paper presents results of the qualitative analysis conducted to inform the design of this community-engaged, linguistically and culturally tailored online sleep education program. Results: Analysis illuminated key barriers preventing sleep apnea awareness, including 1) low knowledge about the connection between daytime somnolence and associated sleep difficulties, 2) embarrassment about snoring and sleep apnea, and 3) inadequate healthcare access for effective treatments. The educational tool was designed using evidence-based approaches to diagnosis and treatment of sleep apnea, while acknowledging the primary themes identified in the focus groups. The tool was then refined with feedback from stakeholders (community members, sleep medicine doctors, and health communication experts. The TASHE resource included four key components, 1) tailored, population-appropriate reading level, 2) evidence-based tips and suggestions for sleep health and sleep apnea, 3) partnership with community-based organizations, and 4) cultural context. Conclusion: A conceptual model for tailored interventions in sleep medicine has been developed and implemented based on the principles of community-engaged research to ensure acceptability of tailored health messages and sustainability of the online sleep apnea educational program. The model developed can be used to structure the design and implementation of community-based, tailored sleep education programs that aim to promote sleep health at the population level

Introduction: Sleep apnea severity, characterized by an increasing Apnea-Hypopnea-Index (AHI), correlates with increased incidence of cardiovascular morbidity. A subgroup of patients with obstructive sleep apnea (OSA) has respiratory events predominantly during REM sleep. Given the relatively low proportion of REM sleep to total sleep time, these patients often have low overall AHIs. It remains unclear whether exclusively REM-related OSA is associated with increased incidence of cardiovascular complications despite a low overall AHI. This study assesses the cardiovascular risk in patients with exclusively REM-related OSA. Methods: Data was obtained on 4455 adults enrolled in the Sleep Heart Health Study who had previously undergone polysomnography and been prospectively followed for cardiovascular complications such as coronary artery disease, myocardial infarction, or stroke up to ten years after the initial sleep study. OSA was defined by AHI4% overall and in REM and NREM sleep periods. The participants were classified into 4 groups based on the presence or absence of sleepdisordered breathing during REM versus NREM sleep as follows: 1. REM-related OSA (AHI4%-REM > 5/h and AHI4%-NREM 5/h and AHI4%-NREM > 5/h, n = 1326), and 4. no OSA (AHI4%-REM < 5/h and AHI4%-NREM < 5/h, n = 1614). Results: The mean AHI4% was 1.1/h in participants without OSA, 4.8/h in participants with REM-related OSA, 9.5/h in participants with NREM-related OSA, and 20.6/h in participants with overall OSA (p < 0.001). Of the participants without OSA, 16.7% had at least one new cardiovascular event, compared to 22.7% of participants with REM-related OSA, 28.5% of participants with NREM-related OSA, and 28.8% of participants with overall OSA (p < 0.001). Conclusion: REM-related sleep apnea is associated with an increased risk of cardiovascular complications despite an overall low AHI that might not prompt treatment consideration

Introduction: Both hippocampal electrophysiology and behavioral performance evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. While rodent models suggest REM sleep's importance in spatial navigational memory, a similar role for REM sleep has never been examined in humans. Materials and methods: Given the increased severity of obstructive sleep apnea (OSA) in REM associated with REM skeletal muscle atonia, we hypothesized disrupting human REM sleep via sleepstage specific OSA would impair proper consolidation of spatial memories. We recruited subjects with severe OSA who are well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-timemonitoring of the polysomnogram (PSG) provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individual subjects spent two different nights in the lab, during which subjects performed timed trials before and after sleep on one of two unique but equally difficult computer-generated 3D spatial mazes. One night's sleepwas normally consolidated with use of therapeutic CPAP throughout, while on the other night, CPAP was reduced only in REM sleep allowing REM OSA to recur. Results: REM disruption via this method caused reduction of REM sleep and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow wave sleep. We observed improvements in maze completion time, distance traveled, and distance spent backtracking after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the degree of improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. Conclusion: In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA

Introduction: Familial dysautonomia (FD)-patients are at risk of sudden unexplained death, particularly during sleep. Respiratory abnormalities and reduced arousability might contribute to fatalities. Aim: To assess respiratory abnormalities and arousability in FD during sleep. Methods: 11 FD-patients (28 +/- 11 years) and 11 healthy persons (28 +/- 11 years) underwent polysomnographic recording during one night. We assessed sleep stages, apneas (>90% air flow reduction) and hypopneas (>30% decrease in airflow with >4% oxygen-desaturation). Arousals were defined as >3 sec abrupt shift in electroencephalographic frequencies to alpha- or theta-activity or frequencies >16Hz. We tested differences between FD-patients and controls by U-test or Fisher's exact test (significance: p < 0.05). Results: Percentage of sleep stages was similar in FD-patients and controls. 107 apneas occurred in 10 FD-patients. Apneas were followed by 74 oxygen-desaturations and 4 arousals. 9 Apneas were followed by desaturation and arousal. Only 5 apneas (p < 0.001) occurred in 2 controls (p > 0.05) and were followed by 2 oxygen desaturations (p=0.001) and 1 arousal (p > 0.05). No apneas were followed by desaturation and arousal. Hypopneas were the most frequent respiratory event and occurred primarily during sleep stage 1 and 2. In all FD-patients, we recorded 362 hypopneas with subsequent oxygen-desaturation that were followed by only 51 arousals. 12 hypopneas (p < 0.001) occurred in 3 controls (p=0.085) and were followed by 3 arousals (p=0.002)