This proposal for a K24 renewal will continue to : (1) provide protected time and support to Dr. Ayappa while she mentors graduate students, post-doctoral fellows and junior faculty pursuing careers in patient-oriented research of sleep disorders; (2) conduct clinical research in patients with sleep disordered breathing (SDB) including obstructive sleep apnea (OSA) and (3) augment her capabilities to conduct patient-oriented research and mentoring. Dr Ayappa is actively involved in research in pathophysiology, diagnosis, treatment and outcomes of SDB that provides research opportunities for mentoring. Obstructive sleep apnea (OSA) is a highly prevalent disorder affecting 15-50% of the US population. Untreated OSA has significant morbidity and mortality including cardiovascular and neurocognitive impairment. Multiple ongoing projects will provide mentoring and patient oriented research opportunities for Dr. Ayappa's mentees. The first project will examine the mechanistic pathways involved in the high prevalence of OSA in World Trade Center (WTC) dust exposed subjects. We recently identified chronic rhinosinistis (CRS) as an independent risk factor for OSA in this population that was associated with inflammation, but was not due to increased nasal resistance. We will (i) test if damage to the upper airway sensory apparatus contributes to OSA in WTC responders with CRS and (ii) identify predominant OSA phenotypic traits in WTC responders and compare them to OSA patients from a sleep clinic. (U01OH011481) The second project (funded by Fisher & Paykel Healthcare) involves development and testing of novel algorithms for non-invasive ventilation in patients with obesity hypoventilation syndrome. These include application of pressures exclusively during sleep (for comfort) and automatic titration of pressures to ensure efficacy. The third area of research in collaboration with Ricardo Osorio, MD examines the relationship between sleep and Alzheimer's Disease (AD). We will extend our prior work in our well characterized longitudinal cohort of cognitively normal older adults in whom we recently demonstrated that OSAwas associated with markers of increased amyloid burden over a 2 year follow-up (1R01HL118624, R01AG056031). We will follow these subjects for an additional 4 years to test the longitudinal effects of slow wave sleep and OSA severity on amyloid deposition. We will also examine (R01AG056531) whether sleep disturbances, which are more common among African-Americans when compared to whites, are one of the factors that explain increases in amyloid burden. The activities outlined in the proposal are directed toward Dr Ayappa's career development. The mentoring work will address the need for new researchers in sleep medicine. The experimental work provides learning opportunities for mentees and is relevant for understanding the physiology of OSA and its outcomes, its diagnosis and treatment with potential for improving health and quality of life in millions of patients who suffer from sleep apnea.

Public Health Relevance

Obstructive sleep apnea (OSA) affects 15-50% of the adult U.S. population. The present study contributes towards knowledge related to diagnosis, treatment and outcomes of sleep and sleep disordered breathing including evaluation of (i) pathophysiology and treatment of OSA seen in WTC responders (ii) the relationship between sleep, memory and Alzheimer's Disease and (iii) new modes of ventilation in obesity hypoventilation patients. The mentoring work will address the need for researchers in sleep disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL109156-07
Application #
9938661
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Brown, Marishka
Project Start
2013-08-01
Project End
2024-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Gumb, Tyler; Twumasi, Akosua; Alimokhtari, Shahnaz et al. (2018) Comparison of two home sleep testing devices with different strategies for diagnosis of OSA. Sleep Breath 22:139-147
Varga, Andrew W; Ducca, Emma L; Kishi, Akifumi et al. (2016) Effects of aging on slow-wave sleep dynamics and human spatial navigational memory consolidation. Neurobiol Aging 42:142-149
Osorio, Ricardo S; Ducca, Emma L; Wohlleber, Margaret E et al. (2016) Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects. Sleep 39:1253-60
Jean-Louis, Girardin; Ayappa, Indu; Rapoport, David et al. (2016) Mentoring junior URM scientists to engage in sleep health disparities research: experience of the NYU PRIDE Institute. Sleep Med 18:108-17
Varga, Andrew W; Wohlleber, Margaret E; Giménez, Sandra et al. (2016) Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid A?42 Levels in Cognitively Normal Elderly. Sleep 39:2041-2048
Ayappa, Indu; Sunderram, Jag; Black, Kathleen et al. (2015) A comparison of CPAP and CPAPFLEX in the treatment of obstructive sleep apnea in World Trade Center responders: study protocol for a randomized controlled trial. Trials 16:403
Osorio, R S; Pirraglia, E; Gumb, T et al. (2014) Imaging and cerebrospinal fluid biomarkers in the search for Alzheimer's disease mechanisms. Neurodegener Dis 13:163-5
Osorio, Ricardo S; Ayappa, Indu; Mantua, Janna et al. (2014) Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals. Neurobiol Aging 35:1318-24
Varga, Andrew W; Kishi, Akifumi; Mantua, Janna et al. (2014) Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory. J Neurosci 34:14571-7