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

Abstract

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 cm(3) [-3.89, -0.32]; p = .03) and hippocampal volumes at discharge (-0.58 cm(3) [-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.

Conflict of interest statement

The authors have not disclosed any potential conflicts of interest

Figures

Figure 1. Delirium Duration and Ventricle-to-Brain Ratio in ICU Patients

Increased duration of delirium was independently associated with smaller overall brain volumes (defined by ventricle-to-brain ratio [VBR]) both at hospital discharge and at three-month follow-up, after adjusting for age, highest SOFA score in the ICU, and presence of sepsis. Increased VBR indicates increase in cerebral spinal fluid due to loss of brain volume. VBR is shown on the y-axis of figures 1a and 1b. The x-axis for all figures represents the duration of delirium measured in days. The solid black line indicates adjusted brain volume for a given value of delirium duration, adjusted for confounders; the 'ribbon' indicates the 95% confidence bounds.

Figure 2. Delirium Duration, Hippocampal and Superior Frontal Lobe Volumes

Longer duration of delirium was independently associated with smaller volumes in the hippocampus at discharge (2A at discharge and 2B at three-month follow-up) and the superior portion of the frontal lobe at both scans (2C at discharge and 2D at three-month follow-up). Brain volumes are shown in cm3 on the y-axis. The x-axis is duration of delirium measured in days. The solid black line indicates adjusted brain volume for a given value of delirium duration, adjusted for confounders; the 'ribbon' indicates the 95% confidence bounds.

Figure 3. Representative example of lateral ventricle size in 46-year-old female and 42-year-old female ICU survivors with no preexisting cognitive impairment

Axial T1-weighted brain images in 2 ICU survivors. Figure 3a depicts relatively normal ventricular volume (see arrow) in a 46-year-old female who did not experience delirium in the ICU. Patient had a history of respiratory and heart failure. She was admitted to a medical ICU due to acute respiratory distress syndrome (ARDS) and was subsequently intubated and managed through the ICU without ever developing delirium. Figure 3b depicts enlarged ventricles (see arrow) in a 42-year-old female who did develop delirium in the ICU. Patient was admitted to the hospital after reporting fever and dyspnea with a chest X-ray and other laboratory data confirming community acquired pneumonia and ARDS. The patient was admitted to the ICU and mechanically ventilated, experiencing 12 days of delirium and then resolution. There was no preexisting history of neurological impairment, and surrogate questioning for preexisting cognitive impairment was also negative