Association of delirium with long-term cognitive decline

1. Delirium was significantly associated with long-term cognitive decline.

2. Across all studies, delirium groups demonstrated worse cognitive outcomes than control groups.

Evidence Rating Level: 2 (Good)

Study Rundown: Delirium is viewed as an acute onset, potentially fluctuating state of disorganized thought or altered levels of consciousness. Postoperative recovery can often include delirium, which is also common among patients with cardiogenic shock, sepsis, respiratory failure, or other critical illnesses. Delirium is associated with increased mortality and may also be associated with neurodegenerative processes. However, long-term cognitive outcomes among patients experiencing delirium have not been comprehensively investigated via meta-analysis in both surgical and nonsurgical settings.

This meta-analysis of 23 studies sought to determine whether or not delirium was independently associated with cognitive decline. Further, and if it does serve as a risk factor, authors aimed to determine whether delirium could be causative or an epiphenomenon among the population itself. Results suggested that delirium was significantly associated with long-term cognitive decline. Among all studies, delirium patients demonstrated worse cognition at the final time point compared to the control groups. The most significant sources of variance were number of covariates controlled, baseline cognitive matching, and duration of follow-up. Causality is difficult to determine within observational studies. Thus, further research is necessary to manipulate delirium and track prospective cognitive outcomes.

Click to read the study in JAMA Neurology

Relevant Reading: Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial

In-Depth [meta-analysis]:

This meta-analysis included 1,583 articles published between January 1, 1965 and December 31, 2018, which were comprised of 24 studies (n delirium = 3,562; controls = 6,987). One of these studies was excluded from quantitative analyses due to being deemed an outlier. All included articles consisted of comparisons between delirium and no delirium among either surgical or nonsurgical populations, objective measures of cognitive outcomes, and a final point of ≥3 months after episode of delirium.

A significant association was discovered between long-term cognitive decline and delirium (Hedges g = 0.45, 95% CI 0.34 to 0.57, p < 0.001). Across all 23 included studies, those experiencing delirium demonstrated worsened cognition at the final point of study. Between-study variability in g was also determined to be high (I² = 0.81). Significant sources of variance included duration of follow-up (p < 0.001), baseline cognitive matching (p = 0.003), and number of covariates controlled (p < 0.001). Age was not a significant source of variance between studies. Following multivariable meta-regression with four variables (age, duration, covariate count, baseline matching/adjustment), the total R² was 0.86 (p < 0.001) thus accounting for 70% of I² heterogeneity.

Establishing causality in observational studies is rendered complicated. This meta-analysis investigated groups that characterize cognitive impairment, such as Alzheimer’s disease. With the hypothesis that delirium results in cognitive decline, comparisons of these groups, ceteris paribus, were thought to be non-significant. However, the mean g of these studies were reported as 0.44 and consistent with expectations given the authors’ hypothesis.

Image: PD

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