Gender Differences in Neural Deficits Associated with Obstructive Sleep Apnea

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）在美国折磨着2000万成年人，并且与发病率和死亡率增加有关。该疾病的发病率和合并症的主要男女差异尚不清楚。然而，在初步研究中，我们发现与OSA相关的神经损伤的位置和范围存在性别差异。由于阻塞性睡眠呼吸暂停患者的脑部变化可能与生理和神经心理特征有关，因此男女差异可以解释该疾病的一些性别差异。在试图将神经变化与健康状况的综合指标联系起来之前，我们的目的是验证OSA相关神经损伤的性别差异。我们将评估64名有或无OSA的受试者，男女平均分配；所有的阻塞性睡眠呼吸暂停研究对象都将在最近被诊断出患有睡眠障碍并接受治疗。我们将通过扩散张量成像指数（分数各向异性和平均扩散率）、T2弛豫时间和区域灰质体积测量来评估全脑结构，并根据性别和OSA状态、其他潜在的显著影响（性别、年龄、体重指数）和双向相互作用建模。此外，我们将通过贝克抑郁量表- ii和OSA严重程度（呼吸暂停低通气指数）来评估抑郁症状的神经影响。研究结果将确定哪些大脑区域在与阻塞性睡眠呼吸暂停相关的神经损伤方面表现出较大的男性和女性差异；受影响的特定结构的功能作用将在未来的研究中用于选择相关的健康状况测量。例如，如果与抑郁相关的区域受到影响，后续研究将包括对心理健康状况的全面评估。了解性别在阻塞性睡眠呼吸暂停脑损伤中的作用，对于了解综合征的进展和合并症的发展，以及考虑对男性和女性患者采取不同的治疗策略具有重要意义。公共卫生相关性：这项研究将比较患有阻塞性睡眠呼吸暂停（OSA）的男性和女性的脑损伤，OSA是一种导致健康状况不佳和过早死亡的睡眠疾病。我们将使用核磁共振成像来观察男性的脑损伤是否比女性多或少。我们将研究与女性而非男性阻塞性睡眠呼吸暂停综合症相关的特定大脑区域，比如抑郁症。如果两性之间在损伤程度和大脑受影响的部位上存在重要差异，我们未来的研究将着眼于这些大脑变化是否能解释我们在OSA中看到的男女健康差异。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) afflicts 20 million adults in the United States, and is associated with increased morbidity and mortality. Major male-female differences in the incidence and co-morbidities of the disorder are poorly understood. However, in preliminary studies, we found gender differences in the location and extend of neural injury associated with OSA. Since brain changes occurring with OSA may contribute to physiologic and neuropsychological characteristics, male-female differences could explain some of the gender differences in the disorder. Before attempting to related neural changes to comprehensive measures of health status, we aim to verify the gender differences in neural injury associated with OSA. We will assess 64 subjects with and without OSA, split evenly between males and females; all OSA subjects will be recently diagnosed and untreated for the sleep disorder. We will assess whole-brain structure with diffusion tensor imaging indices (fractional anisotropy and mean diffusivity), T2 relaxation time, and regional gray matter volume measures, modeled by gender and OSA status, and other potentially significant effects (sex, age, body mass index) and two-way interactions. We will additionally assess neural influences of depressive symptoms as measure by the Beck Depression Inventory-II, and OSA severity (apnea-hypopnea index). The findings will establish which brain areas show large male-female differences in neural injury associated with OSA; the functional roles of the particular structures affected will be used in future studies to select relevant health status measurements. For example, if depression-related regions are affected, follow-on studies will include comprehensive assessment of mental health status. Understanding the role of gender in brain injury occurring with OSA is important for understanding syndrome progression and development of co-morbidities, and for considering different treatment strategies for male and female patients. PUBLIC HEALTH RELEVANCE: This study will compare the brain damage between men and women with Obstructive Sleep Apnea (OSA), a sleep illness that leads to poor health and early death. We will use magnetic resonance imaging to see whether there is more or less brain injury in males than females. We will look at specific brain regions that are related to the problems that women but not men with OSA have, such as depression. If there are important differences between the sexes in the amount of damage, and places in the brain that are affected, our future studies will look to see if those brain changes explain the male-female health differences we see in OSA.