Dr. Ina Djonlagic is a board-certified neurologist and sleep specialist. She is an associate physician at Brigham and Women's Hospital and an Instructor in Medicine at Harvard Medical School. Her long-term goal is to develop a productive academic career as an independent investigator conducting research in the field of sleep- dependent plasticity in patient populations. This proposal describes a 5-year career development award to foster Dr. Djonlagic's scientific development including knowledge and skills in clinical research methodologies, pulmonary physiology, quantitative EEG analysis and genetics so that the award will ultimately lead to a successful RO1 preparation. The proposed career development plan incorporates the collaboration with the mentors and a network of experienced scientific and clinical researchers designed to provide an intense, closely mentored, patient-oriented research experience in association with a comprehensively structured didactic curriculum to enhance her knowledge in the area of biostatistics and research methods. Dr. Djonlagic's mentors for the award are Dr. Atul Malhotra, Associate Professor of Medicine at Harvard Medical School and Medical Director of the Sleep Disorders Research Program at Brigham and Women's Hospital as well as Dr. Robert Stickgold, an Associate Professor of Psychiatry at Harvard Medical School and Director of the Center for Sleep and Cognition at Beth Israel Deaconess Medical Center. Dr. Malhotra is trained in pulmonary, critical care, and sleep medicine, and is internationally known for his research in sleep- related respiratory physiology. He has considerable support from the National Heart, Lung, and Blood Institute, and an Established Investigator Award from the American Heart Association. He recently received a K24 mentoring award from the NIH to help protect his time solely for the purpose of developing young trainees. He is a mentor on the T32 training grant of the Sleep Division at HMS, and has published over 90 original articles related to sleep apnea. Dr. Stickgold is a leading researcher in the field of sleep, learning and memory. He is also a is a mentor on the T32 training grant of the Sleep Division at HMS and has published numerous articles in preeminent journals such as Science, Nature and Nature Neuroscience on these topics. Both have a well- established record of successfully mentoring and training post-doctoral fellows (M.D.s and Ph.D.s), clinical research fellows, postdoctoral fellows, graduate students and undergraduate students for careers in clinical research. Both laboratories are part of a rich network of dynamic research scientists and are under the umbrella of the Division of Sleep Medicine at Harvard Medical School, which with its affiliated institutions currently has over 70 faculty members and promotes outstanding opportunities for training and personal development. This research proposal builds on previous work and preliminary data Dr. Djonlagic has compiled while working with Drs. Stickgold and Malhotra. Dr. Malhotra and Dr. Stickgold are close colleagues as over 5 years. Their offices are within 30 feet of one another, which enables them to interact regularly to discuss research projects and science. The goal of the proposed research is to test the hypothesis that the pathophysiological mechanisms of OSA (as determined by changes in sleep parameters, number of arousals, measures of hypoxemia, assessment of EEG power spectrum), lead to deterioration in sleep-dependent memory consolidation across memory systems, with the genetic marker APO54 as a modulator. In addition the effects of CPAP in reversing some or all of the measured cognitive deficits will be assessed. Daytime effects of OSA on cognition have often been attributed to other factors such as personality, psychiatric disorders, and general learning disability or in elderly populations to the effects of aging given the overlap in cognitive impairment related to OSA with common neurocognitive disorders. This diagnostic uncertainty can lead to a delay in disease recognition and treatment. Having a better understanding of the impact of OSA on cognitive function is therefore important for healthcare providers in order to improve diagnostic sensitivity and specificity, and to provide appropriate and timely treatment. Ultimately, this research has the opportunity to provide critical information that may in due course alter how sleep apnea is defined and thus provide a major impact on the care of sleep apnea patients. PUBLIC HEALTH RELEVANCE: Project Narrative Daytime effects of OSA on cognition have often been attributed to other factors such as personality, psychiatric disorders, and general learning disability or in elderly populations to the effects of aging given the overlap in cognitive impairment related to OSA with common neurocognitive disorders. This diagnostic uncertainty can lead to a delay in disease recognition and treatment. Having a better understanding of the impact of OSA on cognitive function is therefore important for healthcare providers in order to improve diagnostic sensitivity and specificity, and to provide appropriate and timely treatment. Ultimately, this research has the opportunity to provide critical information that may in due course alter how sleep apnea is defined and thus provide a major impact on the care of sleep apnea patients.