Faculty Bibliography

BACKGROUND: Obstructive sleep apnea (OSA) is a sleep disorder that disproportionately affects African Americans (hereafter referred to as blacks). Moreover, blacks may underutilize sleep services including overnight polysomnography. Thus, OSA among blacks may go undiagnosed and untreated, which has significant health consequences, including hypertension, diabetes, cognitive impairment, and daytime sleepiness. DESIGN AND METHODS: This two-arm randomized controlled trial will assign 200 participants to a culturally and linguistically tailored web-based sleep educational platform. The website will be developed to ensure that the content is user friendly and that it is readable and acceptable by the target community. Participants will receive login information to a password-protected website and will have access to the website for 2 months. Study assessments will be collected at baseline, 2 months (post-enrollment) and at 6 months (follow-up). We will use qualitative and quantitative methods to develop tailored materials and to ascertain whether tailored materials will increase OSA knowledge and OSA health literacy by comparing blacks exposed to tailored materials versus those exposed to standard sleep health literature. We hypothesize that exposure to tailored OSA information will improve OSA health literacy. DISCUSSION: Few studies have investigated the racial/ethnic disparities in relation to OSA screening and treatment comparing blacks and whites. Moreover, we know of no interventions designed to increase OSA knowledge and health literacy among blacks. Use of the Internet to disseminate health information is growing in this population. Thus, the Internet may be an effective means to increase OSA health literacy, thereby potentially increasing utilization of sleep-related services in this population. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov, reference number NCT02507089 . Registered on 21 July 2015.

STUDY OBJECTIVES: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Abeta). We thus aimed to examine relationships between concentrations of Abeta42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. METHODS: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Abeta42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Abeta42 groups to compare SWS bout length using survival analyses. RESULTS: A significant inverse correlation was found between CSF Abeta42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Abeta42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Abeta42. CONCLUSIONS: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Abeta42, suggesting that disturbed sleep might drive an increase in soluble brain Abeta levels prior to amyloid deposition.

The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2-4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults.

STUDY OBJECTIVES: To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. METHODS: Subjects were recruited from multiple community sources for National Institutes of Health supported studies or normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders. RESULTS: Levels of orexin-A, amyloid beta 42 (Abeta42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 +/- 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Abeta42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available. CONCLUSIONS: Orexin-A is associated with increased P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT01962779.

The consolidation of spatial navigational memory during sleep is supported by electrophysiological and behavioral evidence. The features of sleep that mediate this ability may change with aging, as percentage of slow-wave sleep is canonically thought to decrease with age, and slow waves are thought to help orchestrate hippocampal-neocortical dialog that supports systems level consolidation. In this study, groups of younger and older subjects performed timed trials before and after polysomnographically recorded sleep on a 3D spatial maze navigational task. Although younger subjects performed better than older subjects at baseline, both groups showed similar improvement across presleep trials. However, younger subjects experienced significant improvement in maze performance during sleep that was not observed in older subjects, without differences in morning psychomotor vigilance between groups. Older subjects had sleep quality marked by decreased amount of slow-wave sleep and increased fragmentation of slow-wave sleep, resulting in decreased slow-wave activity. Across all subjects, frontal slow-wave activity was positively correlated with both overnight change in maze performance and medial prefrontal cortical volume, illuminating a potential neuroanatomical substrate for slow-wave activity changes with aging and underscoring the importance of slow-wave activity in sleep-dependent spatial navigational memory consolidation.

AIM: The aim of this study was to evaluate the National Institute of Health (NIH)-funded PRIDE Institute in Behavioral Medicine and Sleep Disorders Research at New York University (NYU) Langone Medical Center. The NYU PRIDE Institute provides intensive didactic and mentored research training to junior underrepresented minority (URM) faculty. METHOD: The Kirkpatrick model, a mixed-methods program evaluation tool, was used to gather data on participant's satisfaction and program outcomes. Quantitative evaluation data were obtained from all 29 mentees using the PRIDE REDcap-based evaluation tool. In addition, in-depth interviews and focus groups were conducted with 17 mentees to learn about their experiences at the institute and their professional development activities. Quantitative data were examined, and emerging themes from in-depth interviews and focus groups were studied for patterns of connection and grouped into broader categories based on grounded theory. RESULTS: Overall, mentees rated all programmatic and mentoring aspects of the NYU PRIDE Institute very highly (80-100%). They identified the following areas as critical to their development: research and professional skills, mentorship, structured support and accountability, peer support, and continuous career development beyond the summer institute. Indicators of academic self-efficacy showed substantial improvement over time. Areas for improvement included tailoring programmatic activities to individual needs, greater assistance with publications, and identifying local mentors when K awards are sought. CONCLUSIONS: In order to promote career development, numerous factors that uniquely influence URM investigators' ability to succeed should be addressed. The NYU PRIDE Institute, which provides exposure to a well-resourced academic environment, leadership, didactic skills building, and intensive individualized mentorship proved successful in enabling URM mentees to excel in the academic environment. Overall, the institute accomplished its goals: to build an infrastructure enabling junior URM faculty to network with one another as well as with senior investigators, serving as a role model, in a supportive academic environment.

Achondroplasia is the most common inherited disorder of bone growth (skeletal dysplasia). Despite this fact, consistent and evidence-based management approaches to recognized, life-threatening complications, such as foramen magnum stenosis, are lacking. This study aims to outline best practice, based on evidence and expert consensus, regarding the diagnosis, assessment, and management of foramen magnum stenosis in achondroplasia during infancy. A panel of 11 multidisciplinary international experts on skeletal dysplasia was invited to participate in a Delphi process. They were: 1) presented with a list of 26 indications and a thorough literature review, 2) given the opportunity to anonymously rate the indications and discuss in face to face discussion; 3) edit the list and rate it in a second round. Those indications with more than 80% agreement were considered as consensual. After two rounds of rating and a face-to-face meeting, consensus was reached to support 22 recommendations for the evaluation and treatment of foramen magnum stenosis in infants with achondroplasia. These recommendations include indications for surgical decompression, ventriculomegaly, and hydrocephalus, sleep-disordered breathing, physical exams and the use of polysomnography and imaging in this condition. We present a consensus-based best practice guidelines consisting of 22 recommendations. It is hoped that these guidelines will lead to more uniform and structured evaluation, standardizing care pathways, and improving mortality and morbidity outcomes for this cohort. (c) 2015 Wiley Periodicals, Inc.