Genomes and Genes
Obstructive Sleep Apnea, Gender Biology, and Autonomic Regulation
Principal Investigator: PAUL MICHAEL MACEY
Abstract: DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) occurs in close to 20% of men and 10% of women in the adult population, and is an independent risk factor for cardiovascular disease and death. Despite the lower prevalence in women, female OSA patients show more severe cardiovascular and neuropsychological consequences than men with the disorder. The causes of the health problems associated with OSA are unclear, and there are few clinical guidelines for treating symptoms other breathing support with positive airway pressure (PAP);that support assists ventilation, but does little to restore sympathetic dysfunction, one factor that likely contributes to hypertension and other cardiovascular sequelae in the syndrome. Since sympathetic outflow is regulated by the brain, a possible contribution to the cardiovascular sequelae is impaired regulation due to neural injury from the intermittent hypoxia and other characteristics of OSA. We showed such injury in OSA together with deficient cardiovascular control in many brain regions, including the insular cortex, an area that integrates higher brain processing and sensory input to modulate brainstem and hypothalamic autonomic outflow. Our R21 data show that female OSA patients have an even greater extent of insular cortex injury and dysfunction than male OSA patients. We therefore hypothesize that in OSA patients, the insular cortex has impaired function due to injury, resulting in less effective cardiovascular regulation, and these effects are especially severe in female OSA patients. We will evaluate brain structure with diffusion tensor imaging, brain function with functional magneti resonance imaging (fMRI), and cardiovascular function with heart rate measurements during three autonomic challenges, an inspiratory apnea, Valsalva maneuver, and static hand grip. We will localize the insular cortex subdivisions involved in sympathetic modulation from high-resolution MRI scans. We will study 144 people across four age-matched groups: newly-diagnosed OSA females and males matched for disease severity, and healthy control females and males. Females will be assessed for menopausal and hormonal status, with the aim of balancing the numbers of pre- and post-menopausal women, and including hormonal factors in statistical models. In males and females, the findings will show whether disrupted neural regulation of sympathetic activity occurs in OSA, whether that dysfunction is paralleled by brain injury, and whether cardiovascular responsiveness is also impaired. We will also perform an exploratory assessment of the effects of 3 months of PAP treatment on autonomic function in 15 male and 15 female patients, and gather evidence as to whether autonomic central function can recover, at least in the short term. A lack of recovery would suggest additional treatments to PAP should be investigated. Findings of worse effects of OSA in women would highlight the need to broaden OSA treatment, which currently solely focuses on resolving breathing disruptions for moderate and severe OSA, and is typically ignored in mild OSA in women, despite evidence that mild OSA in females is accompanied by severe cardiovascular characteristics.
Funding Period: 2013-06-01 - 2018-03-31
more information: NIH RePORT
- Sleep-disordered breathing: effects on brain structure and functionRonald M Harper
Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA 90095, USA Brain Research Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA Electronic address
Respir Physiol Neurobiol 188:383-91. 2013..Sleep-disordered breathing should be viewed as a condition that includes central nervous system injury and impaired function; the processes underlying injury remain unclear. ..
- Regional cerebral blood flow alterations in obstructive sleep apneaSantosh K Yadav
Department of Neurobiology, University of California at Los Angeles, Los Angeles, CA 90095, USA
Neurosci Lett 555:159-64. 2013..The asymmetric CBF declines in motor regulatory areas may contribute to loss of coordination between upper airway and diaphragmatic musculature, and lead to further damage in the syndrome. ..
- Heart rate responses to autonomic challenges in obstructive sleep apneaPaul M Macey
University of California at Los Angeles School of Nursing, University of California Los Angeles, Los Angeles, California, United States of America Brain Research Institute, David Geffen School of Medicine at University of California Los Angeles, University of California Los Angeles, Los Angeles, California, United States of America
PLoS ONE 8:e76631. 2013..The dysfunctions may reflect central injury in the syndrome, and suggest autonomic deficiencies that may contribute to further tissue and functional pathologies...
- Accelerated echo-planar J-resolved spectroscopic imaging in the human brain using compressed sensing: a pilot validation in obstructive sleep apneaM K Sarma
From the Departments of Radiological Sciences M K S, R N, R K, J P V, J F, M A T
AJNR Am J Neuroradiol 35:S81-9. 2014....
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