Posttraumatic Stress Disorder and Cognitive Decline in Women

描述（由申请人提供）：创伤后应激障碍（PTSD）是美国人群中普遍存在的一种使人衰弱的精神障碍，在女性中尤为常见：每9名女性中就有1名在其一生中符合诊断标准。PTSD是前哨应激相关精神障碍，以下丘脑-垂体-肾上腺轴和神经内分泌失调为特征；动物模型和人类相关研究已经将HPA轴和神经内分泌功能的失调与多种认知过程、大脑结构和功能的改变联系起来。然而，关于创伤后应激障碍及其相关的失调应激反应是否会导致认知能力下降的问题仍然存在，因为现有的研究报告的结果相互矛盾。了解创伤后应激障碍与认知健康的关系——包括影响关联的因素，如症状的持续时间和强度，以及关联的潜在机制，如睡眠质量、健康状况、心血管疾病——可以为旨在减轻创伤后应激障碍可能对认知健康构成的任何风险的干预措施提供信息。我们建议对来自护士健康研究II的54282名年龄在48-65岁之间的女性进行PTSD和随后的认知功能检查，这些女性是1989年以来追踪的PTSD详细数据的亚队列的一部分。女性目前的年龄在48-65岁之间。我们的主要目的是评估创伤后应激障碍（独立于抑郁症）是否与中年妇女认知能力下降有关，并收集有关认知变化的初步数据。为了实现这一目标，我们将利用一个简短的、经过验证的、计算机化的认知电池（CogState），使这些精通计算机的护士能够高效地收集数据。作为第二个目标，我们将评估创伤后应激障碍与认知的任何关系的具体因素，包括作为中介和效果调节剂的因素，这些因素可以作为干预的目标。先前关于创伤后应激障碍和认知的研究主要集中在特定人群的小样本上，比如大屠杀幸存者，或者主要是男性军人或退伍军人的大样本。这一应用代表了一个独特的机会，可以开始利用大量现有的女性群体，以非常低的成本了解创伤后应激障碍在更广泛人群中的更大范围的影响。女性患创伤后应激障碍的风险是男性的两倍，因此，了解创伤后应激障碍对女性认知的影响具有重大的公共卫生意义。最后，除了直接解决我们的目标，我们将产生重要的数据，规划未来的研究PTSD，以及其他感兴趣的领域；例如，这个年龄组的认知变化率的初步数据将使我们能够适当地设计推动PTSD与认知之间关系的机制的前瞻性研究，包括其他健康、心理健康和生活方式变量。

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) is a pervasive and debilitating mental disorder in the U.S. population and particularly common among women: 1 in 9 women will meet criteria for the diagnosis during their lives. PTSD is the sentinel stress-related mental disorder and is characterized by hypothalamic-pituitary-adrenal axis and neuroendocrine dysregulation; animal models and human correlational studies have linked such dysregulation in the HPA axis and neuroendocrine function to alterations in multiple cognitive processes, brain structure, and function. However, questions remain as to whether PTSD and its associated dysregulated stress response produce cognitive decrements as extant studies report conflicting results. Understanding the relation of PTSD and cognitive health -- including elements influencing an association, such as duration and intensity of symptoms and mechanisms underlying an association, such as sleep quality, health status, cardiovascular disease -- could inform interventions aimed at mitigating any risks PTSD may pose for cognitive health. We propose to examine PTSD and subsequent cognitive function within 54,282 women age 48-65 years from the Nurses' Health Study II, who are part of a sub-cohort followed since 1989 with detailed data on PTSD. Women are currently age 48-65 years. Our primary aim is to evaluate if PTSD, independent of depression, is associated with worse cognition in middle-aged women and to collect preliminary data on cognitive change. In accomplishing this aim, we will utilize a brief, validated, computerized cognitive battery (CogState), allowing highly efficient daa collection in these computer-savvy nurses. As a secondary aim we will evaluate specific elements of any relation of PTSD to cognition, including factors acting as mediators and effect modifiers, which could be targeted for interventions. Prior work on PTSD and cognition has focused on small samples from specific populations, such as Holocaust survivors or larger samples of primarily male military personnel or veterans. This application represents a unique opportunity to begin to leverage a large, existing cohort of women to understand the larger scope of effects of PTSD in the broader-based population - at very modest cost. Women's risk of PTSD is twice that of men' risk and, therefore, understanding the impact of PTSD on cognition in women of great public health importance. Finally, in addition to directly addressing our Aims, we will generate important data for planning future research on PTSD, and other areas of interest as well; for example, preliminary data on rates of cognitive change in this age group will allow us to appropriately design prospective studies of the mechanisms driving the relation between PTSD and cognition, including other health, mental health and lifestyle variables.