Natural History of Cognitive Impairment in Critical Illness Survivors. A Systematic Review

Abstract

Long-term cognitive impairment is common among ICU survivors, but its natural history remains unclear. In this systematic review, we report the frequency of cognitive impairment in ICU survivors across various time points after ICU discharge that were extracted from 46 of the 3,350 screened records. Prior studies used a range of cognitive instruments, including subjective assessments (10 studies), single or screening cognitive test such as Mini-Mental State Examination or Trail Making Tests A and B (23 studies), and comprehensive cognitive batteries (26 studies). The mean prevalence of cognitive impairment was higher with objective rather than subjective assessments (54% [95% confidence interval (CI), 51-57%] vs. 35% [95% CI, 29-41%] at 3 months after ICU discharge) and when comprehensive cognitive batteries rather than Mini-Mental State Examination were used (ICU discharge: 61% [95% CI, 38-100%] vs. 36% [95% CI, 15-63%]; 12 months after ICU discharge: 43% [95% CI, 10-78%] vs. 18% [95% CI, 10-20%]). Patients with acute respiratory distress syndrome had higher prevalence of cognitive impairment than mixed ICU patients at ICU discharge (82% [95% CI, 78-86%] vs. 48% [95% CI, 44-52%]). Although some studies repeated tests at more than one time point, the time intervals between tests were arbitrary and dictated by operational limitations of individual studies or chosen cognitive instruments. In summary, the prevalence and temporal trajectory of ICU-related cognitive impairment varies depending on the type of cognitive instrument used and the etiology of critical illness. Future studies should use modern comprehensive batteries to better delineate the natural history of cognitive recovery across ICU patient subgroups and determine which acute illness and treatment factors are associated with better recovery trajectories.

Keywords: cognition disorders; cognitive dysfunction; critical care outcomes; critical illness; survivors.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. MMSE = Mini-Mental State Examination.

Figure 2.

Frequency of subjective cognitive impairment based on patient or relative reports. Open circles represent frequency reported by individual studies. Solid circles represent the aggregate frequency calculated based on all studies for that time point. Bars represent 95% confidence interval.

Figure 3.

Frequency of cognitive impairment based on Mini-Mental State Examination (MMSE) only versus other measures. Open symbols represent frequency reported by individual studies. Solid symbols represent the aggregate frequency calculated based on all studies for that time point. Bars represent 95% confidence interval (CI).

Figure 4.

Aggregate raw scores on the Mini-Mental State Examination (MMSE) over time. Open circles represent mean or median MMSE scores as reported by individual studies. Solid squares represent the weighted average (accounting for sample size) calculated based on all studies for that time point. Line represents trend over time based on the weighted average. Bars represent 95% confidence interval.

Figure 5.

Frequency of cognitive impairment in acute respiratory distress syndrome (ARDS) versus mixed population of ICU survivors. Open symbols represent frequency reported by individual studies. Solid symbols represent the aggregate frequency calculated based on all studies for that time point. Bars represent 95% confidence interval.

Figure 6.

Aggregate time to test completion for (A) Trail Making Test A and (B) Trail Making Test B. Solid circles represent the weighted average (accounting for sample size) calculated based on all studies for that time point. Line represents trend over time based on the weighted average. Bars represent 95% confidence interval. Note that across multiple time points from ICU discharge, both tests failed to detect cognitive impairment in their respective domains (cognitive processing speed for Test A and executive function for Test B). Open symbols represent frequency reported by individual studies.