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.

PUBLIC HEALTH RELEVANCE: 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. The overall goal of this proposal s to examine whether PTSD is associated with decrements is cognitive function in middle-aged women and to identify modifiable mechanisms underlying the association. The results of this study will inform research, policy and practice by identifying malleable and robust risk factors fo PTSD-related cognitive decrements and will inform interventions aimed halting cognitive decline in women with PTSD.