Sex-specific brain injury and symptoms in sleep apnea

项目摘要 阻塞性睡眠呼吸暂停（OSA）发生在成年人群中20%的男性和10%的女性中，并且是一种严重的睡眠呼吸暂停。 心血管疾病和死亡的独立危险因素。尽管女性的患病率较低， 阻塞性睡眠呼吸暂停综合征患者比男性患者表现出更严重的神经心理学后果。的原因 与OSA相关的健康问题尚不清楚，治疗这种疾病的唯一临床指南是 持续气道正压通气（CPAP）;该治疗有助于通气，但不能解决心理问题 合并症会导致严重的抑郁症状由于这些合并症是由大脑调节的， 其机制是由于OSA中间歇性缺氧造成的神经调节受损。我们发现人们 阻塞性睡眠呼吸暂停综合征显示大脑中调节认知和情绪的区域受到了损伤，包括海马体。我们 早期的研究表明，女性阻塞性睡眠呼吸暂停综合征患者的损伤程度更大，症状更严重 男性OSA患者。此外，虽然我们发现未经治疗的OSA患者的认知能力较低， 我们的试验数据显示CPAP解决了这些缺陷;这种认知的改善伴随着一种 解决海马认知亚区（CA 1）的海马损伤。然而，CPAP没有 改善抑郁症状或抑郁相关亚区（后海马）海马损伤 CA 2/3，尾部）。因此，我们假设在OSA中，1）大脑结构和心理之间存在联系 CPAP对认知功能和结构有积极影响，但对抑郁症状无影响 或抑郁症相关的结构。我们将在60名新诊断的OSA女性和男性中测试这些假设 与疾病严重程度相匹配。我们将评估六个月的CPAP对症状和脑损伤的影响 在OSA患者中。我们将评估海马损伤的基础上精确的区域体积测量从高- 分辨率MRI扫描。认知能力将通过蒙特利尔认知评估（莫卡）进行测量 工具，和抑郁症状与九项患者健康问卷（PHQ-9）。我们将评估 分别在女性和男性中：1）CPAP可逆转哪些海马变化，2）莫卡和 PHQ-9评分与CA 1和海马后部区域的损伤相关，以及3）是否改变 症状的变化与损伤的变化有关。研究结果将提供证据， OSA的情绪症状与海马体的脑损伤有关，无论治疗是解决大脑还是 心理缺陷，以及这种缺陷是否在患有这种疾病的女性中更严重。我们会控制年龄- 相关变化和6-12个月CPAP效果。这些发现将有助于 解释阻塞性睡眠呼吸暂停的性别特异性损伤，并建议对症状进行干预。这些发现可能指向CPAP 对于可逆损伤（例如，炎症），将“重新训练”脑回路的治疗，或神经保护 防止进一步损伤的方法（例如，增强脑血流量，呼吸练习）。

PROJECT SUMMARY Obstructive sleep apnea (OSA) occurs in 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 neuropsychological consequences than men with the disorder. The causes of the health problems associated with OSA are unclear, and the only clinical guideline for treating the disorder is continuous positive airway pressure (CPAP); that treatment helps ventilation, but does not resolve psychological comorbidities such high depressive symptoms. Since these comorbidities are regulated by the brain, a possible mechanism is impaired neural regulation due to injury from intermittent hypoxia in OSA. We found that people with OSA show brain injury brain in regions that regulate cognition and mood, including the hippocampus. Our earlier study showed female OSA patients have an even greater extent of injury and higher levels of symptoms than male OSA patients. Furthermore, while we found lower cognitive performance in untreated OSA patients, our pilot data showed CPAP resolving these deficits; this improvement in cognition was accompanied by a resolution of the hippocampal injury in a cognitive subregion of the hippocampus (CA1). However, CPAP did not improve depressive symptoms or hippocampal injury in depression-related subregions (posterior hippocampus CA2/3, tail). We therefore hypothesize that in OSA there is 1) a link between brain structure and psychological function, and 2) a positive impact of CPAP on cognitive function and structure, but not on depressive symptoms or depression-related structure. We will test these hypotheses in 60 newly-diagnosed OSA females and males matched for disease severity. We will assess the influence of six months of CPAP on symptoms and brain injury in the OSA patients. We will assess hippocampal injury based on precise regional volume measures from high- resolution MRI scans. Cognitive performance will be measured with the Montreal Cognitive Assessment (MoCA) tool, and depressive symptoms with the nine-item Patient Health Questionnaire (PHQ-9). We will assess separately in females and males 1) what hippocampal changes are reversible with CPAP, 2) whether MoCA and PHQ-9 scores are associated with injury in the CA1 and posterior hippocampus regions, and 3) whether changes in symptoms are associated with changes in injury. The findings will provide evidence whether cognitive and mood symptoms in OSA relate to brain injury in the hippocampus, and whether treatment resolves the brain or psychological deficits, and whether such deficits are worse in women with the disorder. We will control for age- related changes and 6-12 month CPAP effects in subsets of 30 control and OSA subjects. The findings will help explain sex-specific injury in OSA, and suggest interventions for symptoms. These findings may point to CPAP for reversible injury (e.g., inflammation), to therapies that will “retrain” brain circuitry, or to neuroprotection approaches to prevent further injury (e.g., enhance cerebral blood flow, breathing exercises).