The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*

Abstract

Objective: Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment in intensive care unit survivors. Relationships between 1) delirium duration and brain white matter integrity, and 2) white matter integrity and long-term cognitive impairment are poorly understood and could be explored using magnetic resonance imaging.

Design, setting, patients: A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors.

Measurements: Delirium was evaluated with the Confusion Assessment Method for the Intensive Care Unit and cognitive outcomes were tested at 3 and 12-month follow-up. Following the intensive care unit stay, fractional anisotropy, a measure of white matter integrity, was calculated quantitatively using diffusion tensor imaging with a 3-T magnetic resonance imaging scanner at hospital discharge and 3-month follow-up. We examined associations between 1) delirium duration and fractional anisotropy and 2) fractional anisotropy and cognitive outcomes using linear regression adjusted for age and sepsis.

Results: A total of 47 patients with a median age of 50 yrs completed the diffusion tensor imaging-magnetic resonance imaging protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower fractional anisotropy (i.e., reduced fractional anisotropy = white matter disruption) in the genu (-0.02; p = .04) and splenium (-0.01; p = .02) of the corpus callosum and anterior limb of the internal capsule (-0.02; p =.01) at hospital discharge. These associations persisted at 3 months for the genu (-0.02; p =.02) and splenium (-0.01; p = .004). Lower fractional anisotropy in the anterior limb of internal capsule at discharge and in genu of corpus callosum at three months was associated with worse cognitive scores at 3 and 12 months.

Conclusions: In this pilot investigation, delirium duration in the intensive care unit was associated with white matter disruption at both discharge and 3 months. Similarly, white matter disruption was associated with worse cognitive scores up to 12 months later. This hypothesis-generating investigation may help design future studies to explore these complex relationships in greater depth.

Conflict of interest statement

The authors have not disclosed any potential conflicts of interest.

Figures

Figure 1. Delirium Duration and Fractional Anisotropy in the Genu of the Corpus Callosum

The Figure1A shows a sagittal section of the average of all subjects’ FA images; white matter is therefore bright, while gray matter and CSF are dark. The genu of corpus callosum region of interest is overlaid in yellow. Increased duration of delirium was independently associated with reduced FA both at hospital discharge (Figure 1B) and at three-month follow-up (Figure 1C), after adjusting for age and presence of sepsis. FA 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. In Figure 1B and 1C, the circles show the point estimate of the association between FA and cognitive outcomes, and the dashed lines indicate the 95% confidence intervals.

Figure 2. Delirium Duration, and Fractional Anisotropy in the Anterior Limb of the Internal Capsule

The image in Figure 2A shows an axial section of the average of all subjects’ FA images; the anterior limb of the internal capsule region of interest is overlaid in red. Duration of delirium was independently associated with reduced FA in the anterior limb of the internal capsule (ALIC) at discharge (Figure 2B) and at three-month follow-up (Figure 2C), after adjusting for age and presence of sepsis. Brain FA values are shown on the y-axis. The x-axis is duration of delirium measured in days. In Figures 2B and 2C, the circles show the point estimate of the association between FA and cognitive outcomes, and the dashed lines indicate the 95% confidence intervals.

Figure 3. Fractional anisotropy (FA) and cognitive outcomes

Figure 3A) Lower FA in the anterior limb of the internal capsule (ALIC) (indicative of white matter disruption) at discharge was associated with worse attention scores at 3-month follow-up, after adjusting for age and presence of sepsis. Figure 3B) Lower FA (indicative of white matter disruption) in the genu of the corpus callosum (GCC) at 3-month was associated with better attention scores at 12-month follow-up, after adjusting for age and presence of sepsis. The solid black line shows the point estimate of the association between FA and cognitive outcomes, and the dash line indicates the 95% confidence interval.