The objective is to determine whether the white matter injury in obstructive sleep apnea (OSA) results from myelin or axonal damage, and whether those changes are in acute or chronic stages. OSA is a common and progressive syndrome accompanied by severe cardiovascular, metabolic, memory, emotional, and cognitive deficits, presumably stemming from compromised neural processes induced by intermittent hypoxia and perfusion changes accompanying the condition. The need to determine myelin vs axonal injury rests with interventions for neuroprotection to prevent further injury;specific treatment protocols exist for myelin vs axonal protection. We also need to know whether these fiber changes are recent, or have been in place for long periods, an insight necessary for potential recovery by ventilatory-only support procedures, rather than neural protection intervention. Both gray and white matter tissues are affected in OSA;however, the nature of the white matter changes which interconnect gray matter structures is unknown. We will assess whether the changes in white matter over the entire brain are in acute or chronic stages, and whether regional fibers are showing changes in myelin or axons. We will also assess fiber characteristics of selected fiber bundles which, from evidence of others, are known to contribute to cardiovascular, memory and affect deficits prominent in OSA. Studies will use recently-diagnosed, treatment naive, moderate-to-severe OSA subjects and age- and gender-matched control subjects. The pathological stage of white matter injury will be examined by diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI)-based mean diffusivity and mean kurtosis indices. Myelin vs axonal changes will be assessed by DTI and DKI-based axial diffusivity and axial kurtosis, and radial diffusivity and radial kurtosis measures, which show axonal and myelin changes, respectively. We will use both DTI and DKI techniques, since each procedure offers unique advantages. More detailed myelin evaluation will be performed by magnetization transfer imaging (MTI) procedures. Finally the number of fibers, mean length, and other fiber characteristics will be evaluated by fiber tractography. Our preliminary data suggest that the white matter injury in OSA principally is in an early stage, and largely arise from changes in myelin, although axonal changes also appeared in particular sites in newly-diagnosed patients. The cardiovascular and neuropsychological sequelae of OSA are severe, and are prominent in targets for the condition, obese, older males and post-menopausal women. Protection against the neural changes underlying the pathologies would significantly contribute to national health care. These studies have the potential to determine white matter pathological changes in OSA, and thus point to interventions most appropriate for neural protection and recovery in the syndrome.]

Public Health Relevance

Obstructive sleep apnea (OSA) occurs in at least 10% of adult Americans, and is accompanied by gray matter loss and white matter changes in brain sites that regulate a range of autonomic, neuropsychologic, and physiologic functions affected in the syndrome. We will use common and specialized [magnetic resonance imaging] procedures to determine the nature of axonal pathology (axonal injury or myelin damage) and stage of pathological development (acute vs chronic) in recently-diagnosed, treatment-naive OSA subjects. Understanding the pathological stage and the nature of the white matter changes is essential to unveil the mechanisms involved in the functional sequelae of OSA, and to determine appropriate intervention strategies for neuroprotection and rehabilitation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Laposky, Aaron D
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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