Delirium, or acute confusional state, is a common, costly, life-threatening, and potentially preventable problem for older persons. Despite its clinical and health policy implications, the epidemiology and long-term outcomes of delirium remain poorly understood. Delirium is conceptualized as acute brain failure, which like heart failure has multiple causes but independently leads to poor outcomes. This Program Project seeks to elucidate novel risk markers (including biomarkers, neuroimaging and reserve markers) and to examine the contribution of delirium to long-term cognitive and functional decline. Importantly, this Program Project will utilize innovative interdisciplinary approaches that will facilitate the translation of findings from the laboratory to the hospital bedside and the community. Four Projects are proposed addressing several interlocked hypotheses and cross-linking aims, and exploring: the long-term cognitive and functional outcomes of delirium (Project 1);plasma biomarkers for delirium and long-term decline (Project 2);neuroimaging markers for delirium and long-term decline (Project 3);and the role of cognitive and brain reserve in delirium and long-term decline (Project 4). All Projects involve a prospective cohort of 500 older patients scheduled for major surgery who are free of dementia, and who will be enrolled in the community prior to surgery and followed prospectively for 18-36 months from their initial hospitalization with serial evaluations for neuropsychological and functional outcomes. Thus, this work will be unique in characterizing the baseline status of patients prior to the index surgery and delirium onset. The work of the 4 Projects will be supported by 3 Cores: the Administrative Core (Core A), the Epidemiology Core (Core B), and the Data Management and Statistical Analysis Core (Core C). Core A will provide the leadership and organizational structure to ensure integration, efficiency, and productivity. Core B will assemble, maintain, and follow the prospective cohort for the Projects. Core C will provide data management and statistical analysis for all Projects and Cores. This Project brings together an extremely strong, committed, and experienced team of interdisciplinary investigators within a highly supportive research environment. Moreover, the Project holds substantial promise to elucidate the contribution of delirium to long-term cognitive and functional decline, to identify novel risk markers, and to provide an innovative conceptualization of delirium as a potentially reversible contributor to dementia, laying the groundwork for future intervention studies to address this important area.

Public Health Relevance

Delirium, a sudden severe confusion, frequently occurs in older persons following hospitalization or surgery and leads to poor recovery. The project will examine the causes and long-term effects of delirium, using state-of-the-art strategies such as biomarkers and brain imaging techniques. The findings will help us find new approaches to prevent delirium and its poor outcomes.

National Institute of Health (NIH)
Research Program Projects (P01)
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Study Section
Special Emphasis Panel (ZAG1)
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Wagster, Molly V
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Hebrew Rehabilitation Center for Aged
United States
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Saczynski, Jane S; Kosar, Cyrus M; Xu, Guoquan et al. (2014) A tale of two methods: chart and interview methods for identifying delirium. J Am Geriatr Soc 62:518-24
Inouye, Sharon K; Westendorp, Rudi G J; Saczynski, Jane S (2014) Delirium in elderly people. Lancet 383:911-22
Gross, Alden L; Jones, Richard N; Fong, Tamara G et al. (2014) Calibration and validation of an innovative approach for estimating general cognitive performance. Neuroepidemiology 42:144-53
Inouye, Sharon K; Marcantonio, Edward R; Metzger, Eran D (2014) Doing Damage in Delirium: The Hazards of Antipsychotic Treatment in Elderly Persons. Lancet Psychiatry 1:312-315
Neufeld, Karin J; Nelliot, Archana; Inouye, Sharon K et al. (2014) Delirium diagnosis methodology used in research: a survey-based study. Am J Geriatr Psychiatry 22:1513-21
Inouye, Sharon K; Kosar, Cyrus M; Tommet, Douglas et al. (2014) The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts. Ann Intern Med 160:526-33
Xie, Zhongcong; Swain, Celeste A; Ward, Sarah A P et al. (2014) Preoperative cerebrospinal fluid ?-Amyloid/Tau ratio and postoperative delirium. Ann Clin Transl Neurol 1:319-328
Herzig, Shoshana J; Rothberg, Michael B; Cheung, Michael et al. (2014) Opioid utilization and opioid-related adverse events in nonsurgical patients in US hospitals. J Hosp Med 9:73-81
Marcantonio, Edward R; Ngo, Long H; O'Connor, Margaret et al. (2014) 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med 161:554-61
Fick, Donna M; Steis, Melinda R; Waller, Jennifer L et al. (2013) Delirium superimposed on dementia is associated with prolonged length of stay and poor outcomes in hospitalized older adults. J Hosp Med 8:500-5

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