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The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: The VISIONS cohort magnetic resonance imaging study*

Gunther, Max L. PhD; Morandi, Alessandro MD, MPH; Krauskopf, Erin BS; Pandharipande, Pratik MD, MSCI; Girard, Timothy D. MD, MSCI; Jackson, James C. PsyD; Thompson, Jennifer MPH; Shintani, Ayumi K. PhD; Geevarghese, Sunil MD, MSCI; Miller, Russell R. III MD, MPH; Canonico, Angelo MD; Merkle, Kristen BA; Cannistraci, Christopher J. MS; Rogers, Baxter P. PhD; Gatenby, J. Chris PhD; Heckers, Stephan MD, MSC; Gore, John C. PhD; Hopkins, Ramona O. PhD; Ely, E. Wesley MD, MPH

doi: 10.1097/CCM.0b013e318250acc0
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Objective: Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment.

Design, Setting, and Patients: A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock.

Measurements: Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes.

Results: A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months.

Conclusions: These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

From the Department of Psychiatry (MLG, JCJ, SH), Vanderbilt University Medical Center; Department of Radiological Sciences (MLG, BPR, JCG, SH, JoCG), Vanderbilt University Medical Center; Vanderbilt University Institute of Imaging Sciences (MLG, KM, CJC, BPR, JCG, JoCG); Center for Quality of Aging (MLG, AM, TDG, JCJ, EWE), Vanderbilt University Medical Center; Department of Medicine (MLG, AM, TDG, JCJ, EWE), Center for Health Services Research, Vanderbilt University School of Medicine; Department of Veterans Affairs Medical Center (MLG); Department of Psychology (MLG), Vanderbilt University, Nashville, TN; Department of Psychiatry (MLG), Southern Methodist University, Dallas, TX; Department of Medicine (AM, TDG, EWE), Division of Allergy, Pulmonary, Critical Care Medicine, Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN; Department of Psychology (EK, ROH), Brigham Young University, Provo, UT; Anesthesia Service (PP), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System; Department of Anesthesiology (PP), Division of Critical Care, Vanderbilt University School of Medicine; Geriatric Research, Education and Clinical Center Service (MLG, TDG, JCJ, EWE), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System; Department of Biostatistics (JT, AKS), Vanderbilt University School of Medicine; Division of Hepatobiliary Surgery & Liver Transplantation (SG), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine (RRM, ROH), Pulmonary and Critical Care Division, Intermountain Medical Center, Murray, UT; Department of Medicine (AC), Saint Thomas Hospital, Nashville, TN; Neuroscience Center (ROH), Brigham Young University, Provo, UT; and Department of Biomedical Engineering (BPR, JCG, JoCG), Vanderbilt University Medical Center, Nashville, TN.

*See also p. 2230.

Supported, in part, by the National Institutes of Health (AG027472, AG034257, RR024975, EB001628), Saint Thomas Foundation (Nashville, TN), and Veterans Affairs Tennessee Valley Geriatric Research, Education, and Clinical Center (GRECC).

Dr. Gunther is employed by Vanderbilt University. Dr. Pandharipande received honoraria from Hospira Inc, Orion Pharma, and GlaxoSmithKline. Dr. Girard received honoraria from Hospira Inc. Dr. Geevarghese has consulted for Baxter Healthcare, Onyx Pharma, and the Nexavar Advisory Board. The remaining authors have not disclosed any potential conflicts of interest.

Address reprint requests and correspondence to: E. Wesley Ely, MD, MPH, Professor of Medicine, 6109 Medical Center East, Vanderbilt University, Nashville, TN 37232-8300. E-mail:

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins