Cognitive skills are the crucial abilities required to manage money, maintain employment, and live independently. Long-term cognitive impairment (LTCI) is a disabling loss of these skills that can persist for months to years. LTCI frequently occurs after primary brain injury (e.g., traumatic brain injury, hypoxia), but older LTCI research has not characterized primary brain injury using NIH Common Data Elements in Imaging, the contributions of polytrauma, and the time-course of the critical illness, including secondary brain injury (i.e., delirium). In our recent large study of ICU patients without primary brain injury, over 50% of patients had LTCI and nearly 50% were newly unemployed at one-year post-discharge. In-hospital delirium was the major independent risk factor for LTCI. Surprisingly, this delirium-related LTCI was similar to the LTCI seen in past studies after moderate traumatic brain injury. Thus, both primary and secondary brain injury are associated with LTCI, yet they have not been studied together. There is an unmet need to define the independent risks of primary brain injury and delirium in LTCI. The trauma ICU patient is at combined risk for primary brain and/or multisystem injuries, secondary brain injury, and critical illness; these critically injured patients are the unique population to address this knowledge gap. Therefore, our FIRST HYPOTHESIS is that delirium duration is an independent risk for the severity of LTCI, controlling for confounders of co-morbidities, socioeconomic status, pre-injury employment, primary brain injury, polytrauma, and critical illness.
AIM 1 will address this hypothesis by defining the independent risks of primary and secondary brain injury on the severity of LTCI among 900 trauma ICU subjects. But, LTCI's real-world impact on employment has not been explained or adjusted for the above confounders and social factors. Accordingly, our SECOND HYPOTHESIS is that LTCI severity is an independent risk for lower level of employment, adjusting for similar confounders.
AIM 2 will delineate the independent risk of LTCI severity on employment among trauma ICU survivors. Lastly, LTCI pathogenesis may be related to persistent inflammation. So, our THIRD HYPOTHESIS is that hospital discharge biomarkers of persistent inflammation will be independent risks for LTCI severity, adjusting for similar confounders.
AIM 3 will explore the mechanistic role of plasma inflammatory biomarkers on LTCI severity among trauma ICU survivors.

Public Health Relevance

PUBLIC HEALTH RELEVANCE: Cognitive skills are essential to live independently, manage finances, maintain employment, and function in society. Loss of these cognitive skills puts a tremendous burden on society as seen with dementias, Alzheimer's disease, and traumatic brain injury. The INSIGHT-ICU Study (Illuminating Neuropsychological dysfunction and Systemic Inflammatory mechanisms Gleaned after Hospitalization in Trauma-ICU Study) is the first comprehensive and longitudinal long-term cognitive impairment study after traumatic injury. The societal impact of long-term cognitive impairment after trauma is immense given that these patients are young and constitute a large proportion of employable adults.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Somers, Scott D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
United States
Zip Code
Humble, Stephen S; Wilson, Laura D; Wang, Li et al. (2018) Prognosis of diffuse axonal injury with traumatic brain injury. J Trauma Acute Care Surg 85:155-159
Mirhoseini, Mina F; Hamblin, Susan E; Moore, W Paul et al. (2018) Antioxidant supplementation and atrial arrhythmias in critically ill trauma patients. J Surg Res 222:10-16
Chen, You; Patel, Mayur B; McNaughton, Candace D et al. (2018) Interaction patterns of trauma providers are associated with length of stay. J Am Med Inform Assoc 25:790-799
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
Patel, Mayur B; Bednarik, Josef; Lee, Patricia et al. (2018) Delirium Monitoring in Neurocritically Ill Patients: A Systematic Review. Crit Care Med 46:1832-1841
Marra, Annachiara; Pandharipande, Pratik P; Girard, Timothy D et al. (2018) Co-Occurrence of Post-Intensive Care Syndrome Problems Among 406 Survivors of Critical Illness. Crit Care Med 46:1393-1401
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 :
Kim, Dae Hyun; Mahesri, Mufaddal; Bateman, Brian T et al. (2018) Longitudinal Trends and Variation in Antipsychotic Use in Older Adults After Cardiac Surgery. J Am Geriatr Soc 66:1491-1498
Hsu, Cindy H; Haac, Bryce E; Drake, Mack et al. (2018) EAST Multicenter Trial on targeted temperature management for hanging-induced cardiac arrest. J Trauma Acute Care Surg 85:37-47
Holzmacher, Jeremy L; Reynolds, Cassandra; Patel, Mayur et al. (2018) Platelet transfusion does not improve outcomes in patients with brain injury on antiplatelet therapy. Brain Inj 32:325-330

Showing the most recent 10 out of 20 publications