This Paul B. Beeson Career Development Award in Aging will provide an opportunity for Dr. Ehlenbach to become an independent physician-scientist focused on measuring and improving long-term outcomes after critical illness among older adults, with particular expertise in cognitive outcomes. Individuals 65 years old and older disproportionately bear the burden of critical illness in the United States. Numerous studies have demonstrated that cognitive impairment following critical illness is common and often permanent. Since age is the strongest risk factor for dementia in general, older individuals may be at increased risk for significant cognitive impairment after critical illness. In this application Dr. Ehlenbach proposes a research plan to further characterize associations between critical illness and cognitive outcomes in individuals 65 years old and older. The first two aims take advantage of his ongoing collaboration with the Group Health Research Institute and its ongoing population based prospective cohort study of aging and dementia, the Adult Changes in Thought (ACT) study. For the third aim of this study he plans to identify a new cohort of survivors of critical illness from Harborview Medical Center who are 65 years old and older. Specifically, Dr. Ehlenbach plans to 1) obtain clinical data from hospitalizations experienced by ACT study participants to evaluate associations between specific critical illness syndromes and cognitive outcomes;2) investigate associations between critical illness and neuropathological outcomes;and 3) test hypotheses regarding the association between specific physiologic derangements or critical care therapies and cognitive outcomes. Dr. Ehlenbach proposes a career development plan that utilizes formal coursework, focused mentoring from his advisory committee, and the development and application of new skills in the design, implementation, and analysis of clinical research. The rich academic environment at the University of Washington is ideal for Dr. Ehlenbach's training and has allowed him to assemble an advisory committee whose members possess expertise in geriatrics and aging research, the evaluation of cognitive function including advanced psychometrics, the pathological mechanisms of age related neurodegeneration, and research in the intensive care unit setting with a focus on long term outcomes after critical illness. Dr. Larson, the primary mentor, is a successful investigator and recognized expert in aging research and is the Principal Investigator on the Adult Changes in Thought study. Dr. J. Randall Curtis, the co-mentor, is an internationally recognized expert on critical care research with a specific focus on long-term outcomes and end-of-life care. PUBLIC HEALTH RELEVANCE: Critical illnesses that require treatment in an intensive care unit such as respiratory failure and life-threatening infections are very common in the United States, and those 65 years of age and older are at the highest risk of suffering such illnesses. More and more people are surviving because treatments for critical illness have improved in recent decades, but we are learning that many people suffer significant health problems that arise from these illnesses. This project has the goal of improving our understanding of the ways that critical illness can affect brain function in older individuals, and will help direct future studies to minimize the risk of this problem.