Brain dysfunction is prevalent in the critically ill elderly, presenting in the acute setting as delirium or coma or in the long-term as impairment in global cognition and executive functioning. This brain dysfunction results in increased hospital cost, length of stay, functional dependence, and mortality. The pathophysiology of this brain dysfunction remains unclear but likely involves endothelial dysfunction and injury to the blood brain barrier and neurons. With the increasing age of the population and continued high morbidity from critical illness states, the acute and long-term cognitive effects of critical illnes that are unique to the elderly must be studied, and the mechanistic roles of potential pathophysiological pathways such as endothelial dysfunction and neurologic injury in this brain dysfunction of the elderly must be elucidated. The overall objectives of this research project, therefore, focus on testing the global hypothesis that systemic endothelial dysfunction and neurologic injury lead to acute brain dysfunction during critical illness and long-term cognitive impairment after in survivors. This research will provide new insights into the pathophysiology of critical illness brain dysfunction, and this grant will allow the principal investigator to delve ito these pathophysiological mechanisms while gaining experience in the unique challenges of researching brain dysfunction in the elderly. The data obtained during this grant period will lead toward more detailed mechanistic studies by the principal investigator of brain dysfunction in the elderly. Importantly, the results of this line of research may lead to future therapeutic trials of endothelial or blood brain barrier modulation designed to improve the cognitive outcomes our elderly ICU patients.

Public Health Relevance

Brain dysfunction, commonly associated with critical illness in the elderly, has costly acute and long-term consequences but unclear pathophysiology. This research will provide new insights into the role of endothelial dysfunction and neurologic injury i this acute and long-term brain dysfunction from critical illness.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Research Grants (R03)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Wagster, Molly V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Schools of Medicine
United States
Zip Code
Vasilevskis, Eduard E; Chandrasekhar, Rameela; Holtze, Colin H et al. (2018) The Cost of ICU Delirium and Coma in the Intensive Care Unit Patient. Med Care 56:890-897
Boncyk, Christina; Nahrwold, Daniel A; Hughes, Christopher G (2018) Targeting light versus deep sedation for patients receiving mechanical ventilation. J Emerg Crit Care Med 2:
Han, Jin H; Hayhurst, Christina J; Chandrasekhar, Rameela et al. (2018) Delirium's Arousal Subtypes and Their Relationship with 6-Month Functional Status and Cognition. Psychosomatics :
Semler, Matthew W; Self, Wesley H; Wanderer, Jonathan P et al. (2018) Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med 378:829-839
Stollings, Joanna L; Thompson, Jennifer L; Ferrell, Benjamin A et al. (2018) Sedative Plasma Concentrations and Delirium Risk in Critical Illness. Ann Pharmacother 52:513-521
Hughes, Christopher G; Patel, Mayur B; Brummel, Nathan E et al. (2018) Relationships between markers of neurologic and endothelial injury during critical illness and long-term cognitive impairment and disability. Intensive Care Med 44:345-355
Hughes, Christopher G; Patel, Mayur B; Jackson, James C et al. (2017) Surgery and Anesthesia Exposure Is Not a Risk Factor for Cognitive Impairment After Major Noncardiac Surgery and Critical Illness. Ann Surg 265:1126-1133
Hayhurst, Christina J; Pandharipande, Pratik P; Hughes, Christopher G (2016) Intensive Care Unit Delirium: A Review of Diagnosis, Prevention, and Treatment. Anesthesiology 125:1229-1241
Orena, Eleonora F; King, Adam B; Hughes, Christopher G (2016) The role of anesthesia in the prevention of postoperative delirium: a systematic review. Minerva Anestesiol 82:669-83
Parker, Ryan O; King, Adam B; Hughes, Christopher G (2016) Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in non-intubated patients. J Thorac Dis 8:E596-8

Showing the most recent 10 out of 12 publications