- Email: [email protected]
Morbid obesity and women age are related to the obstructive sleep apnea syndrome
Abstracts / Sleep Medicine 14S (2013) e93–e164
Pilot quantitative analyses of rem sleep without atonia in children and adolescents with rem sleep behavior disorder K. Hancock 1, S. Mccarter 2, E. St. Louis 3, S. Kotagal 4, R. Lloyd 5, B. Boeve 3 1 Mayo Medical School, United States 2 Mayo Clinic College of Medicine, United States 3 Mayo Center for Sleep Medicine, Departments of Medicine and Neurology, United States 4 Mayo Center for Sleep Medicine, Departments of Pediatrics and Neurology, United States 5 Mayo Center for Sleep Medicine, Department of Pediatrics, United States
Introduction: Growing evidence suggests that idiopathic REM sleep behavior disorder (RBD) may be a forme fruste of synucleinopathy neurodegeneration in older adults. The clinical significance of REM sleep without atonia (RSWA) and overt RBD in children and adolescents remains unclear. Furthermore, the lower age bound for occurrence of RSWA, the neurophysiologic substrate for RBD, is not well established. This pilot quantitative analysis of RSWA in pediatric patients with clinical RBD or RSWA – to our knowledge the first such data available in children – aims to determine the relationship between age, RBD symptoms, and RSWA. Materials and methods: We analyzed phasic and tonic RSWA according to established methods in 12 RBD/RSWA patients and 12 age-gender matched controls with primary snoring who underwent polysomnography (PSG) at Mayo Clinic between 2008 and 2013, and reviewed medical records to determine RSWA or RBD diagnosis. We then measured phasic muscle activity durations and made group comparisons of phasic, tonic, and ‘‘any’’ muscle activity percentage densities as well as phasic muscle activity burst durations with non-parametric statistical tests. Multiple regression models were fit to explore potential associations between clinical and muscle activity dependent variables. Results: Among the 12 RSWA/RBD cases, 7 were male, with a mean (range) age of 8.6 (1–17) years when PSG was performed. One RBD patient received clomipramine; no others were on medications associated with RSWA. Phasic and tonic densities were no different between cases and controls, although there appeared to be a subgroup of RSWA/RBD cases with higher phasic densities. Univariate regression analyses demonstrated that higher phasic density was associated with increasing age (p = 0.009 for chin and p = .004 for ‘‘any’’ muscle activity). Anterior tibialis phasic burst duration was significantly longer in the RSWA/RBD group compared to controls (p = 0.02), prolonged to a degree similar to that of adult RBD subjects. Multivariate regression demonstrated an independent association of anterior tibialis phasic burst duration with RBD/RSWA diagnosis, controlling for age. Conclusion: In our pilot study, the earliest detectable manifestation of RSWA appears to be increased phasic burst duration in anterior tibialis. We also found that phasic muscle activity density increases with age in pediatric patients. We plan continued analysis in an expanded group of pediatric subjects to better elucidate the influences of age and RBD symptoms on quantitative RSWA metrics. Acknowledgements: The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. 1 UL1 RR024150-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. http://dx.doi.org/10.1016/j.sleep.2013.11.339
e149
Self- and parent reported sleep problems in children and youths with epilepsy. Preliminary findings from a study in a tertiary epilepsy center B. Hansen 1, K. Alfstad 2, B. Van Roy 1, M. Lossius 2 1 Division of Mental Health, Akershus University Hospital, Norway 2 National Centre for Epilepsy, Department of Children and Youth, Division for Surgery and Clinical Ne, Norway
Introduction: Introduction Sleep problems are common in childhood epilepsy; however studies are mainly based on parental reports. How children and youths with epilepsy report their sleep, and how self- and parent reports correlate is largely unknown. Studies in typically developing children yield higher frequencies of sleep problems when children are used as informants, with low to moderate correlations between self- and parent reports. Sleep problems in children with epilepsy may exacerbate seizure frequency, impair cognitive and behavioral functioning, and reduce quality of life, thus reliable assessment of sleep is important in this population. Objectives To investigate the prevalence of sleep problems and the correlation between self- and parent reported sleep problems in children and youths with epilepsy. Materials and methods: We report preliminary findings from 53 children and youths aged 10–19 years with generalized or focal epilepsy, referred to a tertiary epilepsy treatment center in Norway. They are participants in a larger ongoing study on psychiatric symptoms and executive dysfunction in children and youths with epilepsy. Sleep problems were measured at time of inclusion by selfreport on the Sleep Self Report (SSR), and parent report on the Children’s Sleep Habit Questionnaire (CSHQ). Results: 40.5 % of children and youths reported to have ‘‘problems with sleep’’, while 58.3% of parents reported clinically significant sleep problems (total CSHQ score above 41) in their children. The correlations between corresponding items in the self-report (SSR) and the parent report (CSHQ) were all significant (p values between 0.03 and <0.001), with the exception of ‘‘sleeps too little’’ and ‘‘moves to someone else’s bed’’. Mean correlation coefficients (Spearman’s rho) for significant correlations were 0.55 (range 0.37–0.69). Conclusion: Sleep problems were commonly reported by both children and parents. There were significant correlations between selfand parent reports on the majority of sleep problems. Our findings suggest a stronger agreement between self-and parent reports in children and youths with epilepsy compared to typically developing children. Acknowledgements: The study was financed by Oslo University Hospitaland grants from the Norwegian branch of the International League Against Epilepsy (ILAE). http://dx.doi.org/10.1016/j.sleep.2013.11.340
Morbid obesity and women age are related to the obstructive sleep apnea syndrome J. Perez, F. Sánchez-Narváez, A. Labra, R. Haro Sleep disorders Clinic, UNAM, Mexico
Introduction: The obstructive sleep apnea syndrome (OSAS) is characterized by a history of snoring and upper airway recurrent obstruction, leading to sleep fragmentation and excessive day time somnolence. Its prevalence is higher in men (2:1), and it has been reported that older women have a higher risk for its appearance. The main objective our work was to relate BMI, age with OSAS in obese women.
e150
Abstracts / Sleep Medicine 14S (2013) e93–e164
Materials and methods: In this study, we included 39 women with morbid obesity, with a BMI higher tan 30. All of them underwent an overnight polysomnography. We performed lineal regression and correlation tests for the statistical analysis. Results: The mean age for these women was 40.6 + 1.77, the mean BMI 45.10 + 1.53 and the mean of AHI was 45.21 + 7.5. Pearson correlation IAH–BMI showed 0.727⁄, AHI-age 0.435⁄, BMI-age 0.17. IAHBMI R2 = 0.52⁄. Lineal regression AHI–BMI-age, R = 0.79⁄, R2 = 0.63⁄, (⁄P < 0.01). Risk factor for OSAS with BMI Odds ratio 3.3⁄, with a confidence interval CI (2.3–4.3), and age odds ratio 1.3⁄, CI (0.4–2.2) ⁄ P < 0.01. Conclusion: These data suggest a strong correlation between OSAS, BMI and age in women. There is a significant correlation between AHI and BMI. This relation increases when age is included. We did not find any relation between BMI and age. It is necessary to include more groups of women, with normal weight and overweight. http://dx.doi.org/10.1016/j.sleep.2013.11.341
Restoration of orexin signaling in the dorsal raphe and locus coeruleus differntially ameliorate symptoms of narcoleptic mice E. Hasegawa 1, M. Yanagisawa 2, B. Roth 3, T. Sakurai 1, M. Mieda 1 1 Kanazawa University, Fac. Med, Japan 2 UTSW, Japan 3 UNC, Japan
Introduction: Loss of orexin neurons is associated with narcolepsy in the human, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Mice lacking orexin peptides, as well as those lacking orexin receptors (OX1R / ; OX2R / mice), display a phenotype similar to narcolepsy, highlighting a critical role of orexin signaling in the maintenance of wakefulness. However, precise neural mechanisms downstream to orexin neurons have remained uncertain. Materials and methods: We generated recombinant adeno-associated viruses (AAV) to express either OX1R or OX2R fused to EGFP and stereotaxically microinjected into the of OX1R / ; OX2R / mice, then recorded EEG/EMG to score sleep/wakefulness states. The subtype of orexin receptors expressed was determined according to expression of endogenous orexin receptors in wild-type mice. Results: We found that targeted restoration of orexin receptor expressions in noradrenergic neurons of the locus coeruleus and in serotonergic neurons of the dorsal raphe in OX1R / ; OX2R / mice differentially inhibited pathological fragmentation of wakefulness (i.e., sleepiness) and direct transitions from wakefulness to REM sleep (cataplexy-like episode), respectively. Furthermore, pharmacogenetic activation of these neurons using DREADD technology significantly ameliorated narcolepsy of mice lacking orexin neurons. Conclusion: These results suggest that orexin neurons consolidate wakefulness and suppress cataplexy by activating locus coeruleus noradrenergic and dorsal raphe serotonergic neurons, respectively. Our success in improving narcoleptic symptoms by DREADD may lead to a novel type of gene therapy. Acknowledgements: This study was supported in part by Grantsin-Aid for Scientific Research (B) and for Challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (M.M.), by the Mochida Memorial Foundation for Medical and Pharmaceutical Research (M.M.), and by the Cabinet Office, Government of Japan through its _gFunding Program for Next Generation World-Leading Researchers_h (T.S.). We thank Dr. Karl Deisseroth for pAAV-DIO-hChR2 (H134R)-EYFPWPRE-pA; Dr. Scott M. Sternson for pAAV-FLEX-rev- ChR2mCherry;
Dr. Kwang-Soo Kim for the PRSx8 promoter; Dr. Masahiko Watanabe for the anti-GFP antibody; and Dr. Arun Srivastava for pACG-2Y730F. http://dx.doi.org/10.1016/j.sleep.2013.11.342
Clinical correlates of periodic limb movements in sleep in parkinson’s disease in Egypt A. Mansour, T. Kamel, M. Yaser, T. Asaad, H. Aref, N. Salah Faculty of Medicine, Ain Shams University, Egypt
Introduction: Patients with Parkinson’s disease (PD) are prone to sleep disturbances and disorders, with a prevalence of 78–98% (Norlinah et al., 2009). One of the common sleep disturbances that might occur in PD is periodic limb movement disorder (PLMD) which have been found to be more common in PD than in controls (Freedom, 2007). Both RLS and PLM are sensitive to dopamine and dopamine agonists being drugs of choice for these disorders (Chaudhuri et al., 2006). Objective: The aim of the current study was to investigate the frequency of periodic limb movements in sleep (PLMS) in Parkinson’s disease (PD) and their impact on nocturnal sleep and correlation with severity of parkinsonian symptoms. Materials and methods: 36 Parkinson’s disease (PD) patients were enrolled from involuntary movement outpatient clinic in Ain Shams University hospital and submitted to clinical assessment by unified Parkinson disease scale (UPDRS) part III, Hamilton depression scale, structured sheet for sleep questionnaire, Pittsburg sleep scale, Epwarth sleepiness scale and polysomnography. Patients were divided into two groups based on their PLMS index (PLMSI): PLMSI >15(PLMS +ve) and PLMSI <15 (PLMS ve). Results: There were 8 (22.2%) PD patients in the PLMS +ve group and 28 (77.8%) patients in the PLMS ve group. Assessment by UPDRS (III) revealed an association between PLMS + status and greater PD motor symptoms severity, in addition to lower sleep quality reflected by higher scores of PITTSBURG scale in the PLMS +ve. No significant group differences were detected on PSG measures. Conclusion: We observed that PLMS occurred frequently in PD and increased with more severe PD. Although PLMS did not affect objective sleep, it was associated with increased sleep complaints and reduced sleep quality. Overall, our findings support the association between PLMS and PD as well as the clinical relevance of sleep disturbances in PD. http://dx.doi.org/10.1016/j.sleep.2013.11.343
Multi-scale entropy-based measures of electroencephalogram during sleep as quantitative criteria for chronic insomnia D. He 1, A. Gamaldo 2, M. Smith 3, R. Allen 4, C. Gamaldo 5, R. Salas 5 1 Johns Hopkins University, School of Medicine, Division of Health Sciences Informatics, United States 2 National Institute on Aging, Laboratory of Behavioral Neuroscience, United States 3 Johns Hopkins University, School of Medicine, Department of Psychiatry and Behavioral Medicine, United States 4 Johns Hopkins University, School of Medicine, Department of Neurology, United States 5 Johns Hopkins Univeristy, School of Medicine, Department of Neurology, Neuro-Sleep Division, United States
Pilot quantitative analyses of rem sleep without atonia in children and adolescents with rem sleep behavior disorder K. Hancock 1, S. Mccarter 2, E. St. Louis 3, S. Kotagal 4, R. Lloyd 5, B. Boeve 3 1 Mayo Medical School, United States 2 Mayo Clinic College of Medicine, United States 3 Mayo Center for Sleep Medicine, Departments of Medicine and Neurology, United States 4 Mayo Center for Sleep Medicine, Departments of Pediatrics and Neurology, United States 5 Mayo Center for Sleep Medicine, Department of Pediatrics, United States
Introduction: Growing evidence suggests that idiopathic REM sleep behavior disorder (RBD) may be a forme fruste of synucleinopathy neurodegeneration in older adults. The clinical significance of REM sleep without atonia (RSWA) and overt RBD in children and adolescents remains unclear. Furthermore, the lower age bound for occurrence of RSWA, the neurophysiologic substrate for RBD, is not well established. This pilot quantitative analysis of RSWA in pediatric patients with clinical RBD or RSWA – to our knowledge the first such data available in children – aims to determine the relationship between age, RBD symptoms, and RSWA. Materials and methods: We analyzed phasic and tonic RSWA according to established methods in 12 RBD/RSWA patients and 12 age-gender matched controls with primary snoring who underwent polysomnography (PSG) at Mayo Clinic between 2008 and 2013, and reviewed medical records to determine RSWA or RBD diagnosis. We then measured phasic muscle activity durations and made group comparisons of phasic, tonic, and ‘‘any’’ muscle activity percentage densities as well as phasic muscle activity burst durations with non-parametric statistical tests. Multiple regression models were fit to explore potential associations between clinical and muscle activity dependent variables. Results: Among the 12 RSWA/RBD cases, 7 were male, with a mean (range) age of 8.6 (1–17) years when PSG was performed. One RBD patient received clomipramine; no others were on medications associated with RSWA. Phasic and tonic densities were no different between cases and controls, although there appeared to be a subgroup of RSWA/RBD cases with higher phasic densities. Univariate regression analyses demonstrated that higher phasic density was associated with increasing age (p = 0.009 for chin and p = .004 for ‘‘any’’ muscle activity). Anterior tibialis phasic burst duration was significantly longer in the RSWA/RBD group compared to controls (p = 0.02), prolonged to a degree similar to that of adult RBD subjects. Multivariate regression demonstrated an independent association of anterior tibialis phasic burst duration with RBD/RSWA diagnosis, controlling for age. Conclusion: In our pilot study, the earliest detectable manifestation of RSWA appears to be increased phasic burst duration in anterior tibialis. We also found that phasic muscle activity density increases with age in pediatric patients. We plan continued analysis in an expanded group of pediatric subjects to better elucidate the influences of age and RBD symptoms on quantitative RSWA metrics. Acknowledgements: The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. 1 UL1 RR024150-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. http://dx.doi.org/10.1016/j.sleep.2013.11.339
e149
Self- and parent reported sleep problems in children and youths with epilepsy. Preliminary findings from a study in a tertiary epilepsy center B. Hansen 1, K. Alfstad 2, B. Van Roy 1, M. Lossius 2 1 Division of Mental Health, Akershus University Hospital, Norway 2 National Centre for Epilepsy, Department of Children and Youth, Division for Surgery and Clinical Ne, Norway
Introduction: Introduction Sleep problems are common in childhood epilepsy; however studies are mainly based on parental reports. How children and youths with epilepsy report their sleep, and how self- and parent reports correlate is largely unknown. Studies in typically developing children yield higher frequencies of sleep problems when children are used as informants, with low to moderate correlations between self- and parent reports. Sleep problems in children with epilepsy may exacerbate seizure frequency, impair cognitive and behavioral functioning, and reduce quality of life, thus reliable assessment of sleep is important in this population. Objectives To investigate the prevalence of sleep problems and the correlation between self- and parent reported sleep problems in children and youths with epilepsy. Materials and methods: We report preliminary findings from 53 children and youths aged 10–19 years with generalized or focal epilepsy, referred to a tertiary epilepsy treatment center in Norway. They are participants in a larger ongoing study on psychiatric symptoms and executive dysfunction in children and youths with epilepsy. Sleep problems were measured at time of inclusion by selfreport on the Sleep Self Report (SSR), and parent report on the Children’s Sleep Habit Questionnaire (CSHQ). Results: 40.5 % of children and youths reported to have ‘‘problems with sleep’’, while 58.3% of parents reported clinically significant sleep problems (total CSHQ score above 41) in their children. The correlations between corresponding items in the self-report (SSR) and the parent report (CSHQ) were all significant (p values between 0.03 and <0.001), with the exception of ‘‘sleeps too little’’ and ‘‘moves to someone else’s bed’’. Mean correlation coefficients (Spearman’s rho) for significant correlations were 0.55 (range 0.37–0.69). Conclusion: Sleep problems were commonly reported by both children and parents. There were significant correlations between selfand parent reports on the majority of sleep problems. Our findings suggest a stronger agreement between self-and parent reports in children and youths with epilepsy compared to typically developing children. Acknowledgements: The study was financed by Oslo University Hospitaland grants from the Norwegian branch of the International League Against Epilepsy (ILAE). http://dx.doi.org/10.1016/j.sleep.2013.11.340
Morbid obesity and women age are related to the obstructive sleep apnea syndrome J. Perez, F. Sánchez-Narváez, A. Labra, R. Haro Sleep disorders Clinic, UNAM, Mexico
Introduction: The obstructive sleep apnea syndrome (OSAS) is characterized by a history of snoring and upper airway recurrent obstruction, leading to sleep fragmentation and excessive day time somnolence. Its prevalence is higher in men (2:1), and it has been reported that older women have a higher risk for its appearance. The main objective our work was to relate BMI, age with OSAS in obese women.
e150
Abstracts / Sleep Medicine 14S (2013) e93–e164
Materials and methods: In this study, we included 39 women with morbid obesity, with a BMI higher tan 30. All of them underwent an overnight polysomnography. We performed lineal regression and correlation tests for the statistical analysis. Results: The mean age for these women was 40.6 + 1.77, the mean BMI 45.10 + 1.53 and the mean of AHI was 45.21 + 7.5. Pearson correlation IAH–BMI showed 0.727⁄, AHI-age 0.435⁄, BMI-age 0.17. IAHBMI R2 = 0.52⁄. Lineal regression AHI–BMI-age, R = 0.79⁄, R2 = 0.63⁄, (⁄P < 0.01). Risk factor for OSAS with BMI Odds ratio 3.3⁄, with a confidence interval CI (2.3–4.3), and age odds ratio 1.3⁄, CI (0.4–2.2) ⁄ P < 0.01. Conclusion: These data suggest a strong correlation between OSAS, BMI and age in women. There is a significant correlation between AHI and BMI. This relation increases when age is included. We did not find any relation between BMI and age. It is necessary to include more groups of women, with normal weight and overweight. http://dx.doi.org/10.1016/j.sleep.2013.11.341
Restoration of orexin signaling in the dorsal raphe and locus coeruleus differntially ameliorate symptoms of narcoleptic mice E. Hasegawa 1, M. Yanagisawa 2, B. Roth 3, T. Sakurai 1, M. Mieda 1 1 Kanazawa University, Fac. Med, Japan 2 UTSW, Japan 3 UNC, Japan
Introduction: Loss of orexin neurons is associated with narcolepsy in the human, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Mice lacking orexin peptides, as well as those lacking orexin receptors (OX1R / ; OX2R / mice), display a phenotype similar to narcolepsy, highlighting a critical role of orexin signaling in the maintenance of wakefulness. However, precise neural mechanisms downstream to orexin neurons have remained uncertain. Materials and methods: We generated recombinant adeno-associated viruses (AAV) to express either OX1R or OX2R fused to EGFP and stereotaxically microinjected into the of OX1R / ; OX2R / mice, then recorded EEG/EMG to score sleep/wakefulness states. The subtype of orexin receptors expressed was determined according to expression of endogenous orexin receptors in wild-type mice. Results: We found that targeted restoration of orexin receptor expressions in noradrenergic neurons of the locus coeruleus and in serotonergic neurons of the dorsal raphe in OX1R / ; OX2R / mice differentially inhibited pathological fragmentation of wakefulness (i.e., sleepiness) and direct transitions from wakefulness to REM sleep (cataplexy-like episode), respectively. Furthermore, pharmacogenetic activation of these neurons using DREADD technology significantly ameliorated narcolepsy of mice lacking orexin neurons. Conclusion: These results suggest that orexin neurons consolidate wakefulness and suppress cataplexy by activating locus coeruleus noradrenergic and dorsal raphe serotonergic neurons, respectively. Our success in improving narcoleptic symptoms by DREADD may lead to a novel type of gene therapy. Acknowledgements: This study was supported in part by Grantsin-Aid for Scientific Research (B) and for Challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (M.M.), by the Mochida Memorial Foundation for Medical and Pharmaceutical Research (M.M.), and by the Cabinet Office, Government of Japan through its _gFunding Program for Next Generation World-Leading Researchers_h (T.S.). We thank Dr. Karl Deisseroth for pAAV-DIO-hChR2 (H134R)-EYFPWPRE-pA; Dr. Scott M. Sternson for pAAV-FLEX-rev- ChR2mCherry;
Dr. Kwang-Soo Kim for the PRSx8 promoter; Dr. Masahiko Watanabe for the anti-GFP antibody; and Dr. Arun Srivastava for pACG-2Y730F. http://dx.doi.org/10.1016/j.sleep.2013.11.342
Clinical correlates of periodic limb movements in sleep in parkinson’s disease in Egypt A. Mansour, T. Kamel, M. Yaser, T. Asaad, H. Aref, N. Salah Faculty of Medicine, Ain Shams University, Egypt
Introduction: Patients with Parkinson’s disease (PD) are prone to sleep disturbances and disorders, with a prevalence of 78–98% (Norlinah et al., 2009). One of the common sleep disturbances that might occur in PD is periodic limb movement disorder (PLMD) which have been found to be more common in PD than in controls (Freedom, 2007). Both RLS and PLM are sensitive to dopamine and dopamine agonists being drugs of choice for these disorders (Chaudhuri et al., 2006). Objective: The aim of the current study was to investigate the frequency of periodic limb movements in sleep (PLMS) in Parkinson’s disease (PD) and their impact on nocturnal sleep and correlation with severity of parkinsonian symptoms. Materials and methods: 36 Parkinson’s disease (PD) patients were enrolled from involuntary movement outpatient clinic in Ain Shams University hospital and submitted to clinical assessment by unified Parkinson disease scale (UPDRS) part III, Hamilton depression scale, structured sheet for sleep questionnaire, Pittsburg sleep scale, Epwarth sleepiness scale and polysomnography. Patients were divided into two groups based on their PLMS index (PLMSI): PLMSI >15(PLMS +ve) and PLMSI <15 (PLMS ve). Results: There were 8 (22.2%) PD patients in the PLMS +ve group and 28 (77.8%) patients in the PLMS ve group. Assessment by UPDRS (III) revealed an association between PLMS + status and greater PD motor symptoms severity, in addition to lower sleep quality reflected by higher scores of PITTSBURG scale in the PLMS +ve. No significant group differences were detected on PSG measures. Conclusion: We observed that PLMS occurred frequently in PD and increased with more severe PD. Although PLMS did not affect objective sleep, it was associated with increased sleep complaints and reduced sleep quality. Overall, our findings support the association between PLMS and PD as well as the clinical relevance of sleep disturbances in PD. http://dx.doi.org/10.1016/j.sleep.2013.11.343
Multi-scale entropy-based measures of electroencephalogram during sleep as quantitative criteria for chronic insomnia D. He 1, A. Gamaldo 2, M. Smith 3, R. Allen 4, C. Gamaldo 5, R. Salas 5 1 Johns Hopkins University, School of Medicine, Division of Health Sciences Informatics, United States 2 National Institute on Aging, Laboratory of Behavioral Neuroscience, United States 3 Johns Hopkins University, School of Medicine, Department of Psychiatry and Behavioral Medicine, United States 4 Johns Hopkins University, School of Medicine, Department of Neurology, United States 5 Johns Hopkins Univeristy, School of Medicine, Department of Neurology, Neuro-Sleep Division, United States