In-hospital Delirium Linked to Long-term Cognitive Decline

Erik Greb

July 20, 2020

Delirium that occurs during hospitalization is associated with long-term cognitive decline, new research suggests.

Results of a systematic review and meta-analysis of 24 studies show that both surgical and nonsurgical patients who experienced delirium had worse neurocognitive outcomes 3 months later in comparison with their counterparts who did not have delirium.

Despite "significant heterogeneity" among the studies, the results are consistent with the hypothesis that delirium is not an epiphenomenon but is a cause of cognitive decline, researchers note.

Dr Terry Goldberg

"Delirium may have long-term, not just near-term, effects on cognition," lead author Terry E. Goldberg, PhD, professor of medical psychology at Columbia University Irving Medical Center, New York City, told Medscape Medical News.

"Delirium might be driving this decline," and the potential mechanism for the association is neuroinflammation, Goldberg added.

The findings were published online July 13 in JAMA Neurology.

Postsurgical Delirium Common

The rate of delirium among patients who have undergone surgery ranges from 11% to 51%. Among those in intensive care units (ICUs), the rate of delirium may be as high as 82%.

Delirium is associated with increased morbidity. A recent meta-analysis showed that it was also linked to a nearly twofold increase in mortality risk.

However, previous studies of the relationship between delirium and cognition have used divergent populations and outcomes, the investigators note.

To clarify this relationship, the investigators conducted a systematic review and meta-analysis. They searched for observational studies that measured cognition using objective tests at least 3 months after an episode of delirium.

Delirium was diagnosed according to validated scales, such as the Confusion Assessment Method (CAM), The Diagnostic and Statistical Manual of Mental Disorders, and The International Classification of Diseases. Each eligible study included patients with and patients without delirium. The investigators excluded studies that used only self-report or informant-report outcomes.

To measure effect size, the researchers calculated Hedges g. They gauged study heterogeneity using I 2.

The researchers included 24 studies, encompassing a total of 3562 patients with delirium and 6987 patients without delirium. The mean number of participants per study was 441.7. Participants' mean age at baseline was 75.4 years, and the mean percentage of men was 46.9%.

The mean proportion of participants with delirium was 37.2%, and the mean duration of follow-up was 2.4 years. CAM was the most frequently used instrument to assess delirium. The Mini–Mental State Examination was the most frequently used instrument to evaluate cognition.

Consistent Results

In every study, the group with delirium had worse neurocognitive outcomes at 3 or more months than the group without delirium.

The summary g of the meta-analysis was 0.47, indicating a medium effect size and a highly statistically significant result. The g equated to an odds ratio of cognitive decline of 2.30 among patients with delirium.

Two studies were judged to be of low quality, but they did not significantly influence g.

When studies that used discrete cognitive outcomes, such as dementia or the absence of dementia, were compared with those that used continuous cognitive measures, the difference between groups of studies was not significant. However, the g in both types of study was highly significant.

The percentage of nonsurgical patients at baseline in a study did not significantly influence its outcome. This result suggests that the relationship between delirium and cognitive decline is similar between surgical and nonsurgical patients, the investigators note.

To determine whether delirium is an epiphenomenon that accompanies cognitive decline, the researchers also examined studies that included only individuals who were without cognitive impairment, studies with high proportions of participants who had cognitive impairment, and studies that performed baseline cognitive matching.

Results of these analyses support the idea that delirium is a cause of cognitive decline. However, the studies' observational design makes confirming causality difficult.

Still, the findings could prompt neurologists to screen patients to identify those at increased risk for cognitive decline, the researchers note.

"If a patient has a surgery or is admitted to the ICU, ask about delirium," said Goldberg. "If it was present, monitor the patient for long-term cognitive decline," such as over a 2-year period, he added.

A Major Health Concern

Commenting on the findings for Medscape Medical News, Ronald C. Petersen, MD, PhD, director of the Mayo Clinic Alzheimer's Disease Research Center, Rochester, Minnesota, noted that delirium is a major health concern that suggests the possibility of future cognitive problems. It can also increase morbidity during a hospitalization and can prolong length of a hospital stay.

A limitation of the current meta-analysis was the heterogeneity of the studies it included, said Petersen, who was not involved with the research.

"Meta-analyses are powerful, but underlying study variability can compromise the conclusions," he said.

In addition, the precise causative relationship between delirium and long-term cognitive decline requires explanation, he added.

"This study showed strong associations but not a mechanistic explanation. Nevertheless, early recognition of delirium can improve outcomes," Petersen said.

The study was funded by the Departments of Anesthesiology and Biostatistics at Columbia University Irving Medical Center. Goldberg and Petersen have reported no relevant financial relationships.

JAMA Neurol. Published online July 13, 2020. Abstract

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