Long-term cognitive impairment after critical illness

Abstract

Background: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized.

Methods: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders.

Results: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months.

Conclusions: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Figure 1. Global Cognition Scores in Survivors of Critical Illness

The box-and-whisker plots show the age-adjusted global cognition scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; with a population age-adjusted mean [±SD] of 100±15, and lower scores indicating worse global cognition) at 3 months (light-gray boxes) and 12 months (dark-gray boxes), according to age. For each box-and-whisker plot, the horizontal bar indicates the median, the upper and lower limits of the boxes the interquartile range, and the ends of the whiskers 1.5 times the interquartile range. Outliers are shown as black dots. The green dashed line indicates the age-adjusted population mean (100) for healthy adults, and the green band indicates the standard deviation (15). Also shown are the expected population means for mild cognitive impairment (MCI), moderate traumatic brain injury (TBI), and mild Alzheimer's disease on the basis of other cohort studies. Expected population means for MCI and Alzheimer's disease are shown only for patients 65 years of age or older, since RBANS population norms for these disorders have been generated only in that age group.

Figure 2. Duration of Delirium and Global Cognition Score at 12 Months

Longer durations of delirium were independently associated with worse RBANS global cognition scores at 12 months. Point estimates and the 95% confidence interval for these relationships are shown by the blue line and the gray band, respectively. RBANS global cognition scores have age-adjusted population norms, with a mean (±SD) score of 100±15. Rug plots show the distribution of the durations of delirium. Although delirium could be assessed for up to 30 days in the study, the x axis is truncated at 10 days because 90% of the patients had delirium for 10 days or less; all available data were used in the multivariable modeling. As one example, in a comparison of patients with no delirium and those with 5 days of delirium (the 25th and 75th percentile values of delirium duration in our cohort), with all other covariates held constant (at the median or mode of the covariate), patients with 5 days of delirium had RBANS global cognition scores at 12 months that were an average of 5.6 points lower than the scores for patients with no delirium.