Postoperative delirium — a sudden change in mental state marked by confusion, inattention, and altered thinking that can develop after surgery — is the most common postoperative complication in older adults. The phenomenon is associated with poor outcomes such as long-term cognitive decline and incident dementia. It can lead to a cascade of rehospitalizations, including stays in the intensive care (ICU) unit, post-acute care unit, or both.
But because delirium tends to occur more often in sicker patients, it has been unclear to what extent its link with cognitive decline is attributable to preexisting illness or frailty versus enduring effects of the delirium event itself.
A new study aimed to test that idea by following older adults after surgery and asking whether rehospitalizations, as a marker of illness and frailty, could explain the association between postoperative delirium and long-term cognitive decline.
The team — led by researchers at Harvard Medical School and the Warren Alpert Medical School of Brown University — found that postoperative delirium is a stronger predictor of long-term cognitive decline in older adults than rehospitalizations. While rehospitalizations and intensive care or post-acute rehabilitation stays were associated with long-term cognitive decline, those factors did not explain the impact of delirium on long-term brain health.
Results were published June 8 in JAMA Internal Medicine.
“We had anticipated that at least part of the effect of delirium on long-term cognition would be due to rehospitalizations which reflected serious medical conditions,” said senior author Sharon Inouye, HMS professor of medicine at Hebrew SeniorLife and director of the Aging Brain Center at the Hinda and Arthur Marcus Institute for Aging Research. “We were surprised to learn that rehospitalizations did not explain any of the effect of delirium on cognitive decline.”
This reinforces delirium’s inclusion in the list of modifiable factors that raise the risk of future cognitive decline and dementia, such as hypertension, high cholesterol, smoking, hearing loss, and depression.
Although the study can’t demonstrate causation, the findings challenge a widely held notion that delirium is simply a marker of a sicker patient and strengthen an argument that delirium itself could shape long-term brain health. This underscores the importance of delirium prevention and management in older adults undergoing surgery, the authors said, especially since strategies already exist to effectively reduce delirium rates — many of them developed by Inouye and colleagues.
Monitoring brain health after surgery
The researchers looked at data from the Successful Aging After Elective Surgery (SAGES) cohort, a long-term observational study funded by the National Institute on Aging at the National Institutes of Health that followed 560 adults aged 70 and older, measuring their cognition every six months for three years, then annually afterwards for up to six years.
Using a detailed cognitive testing battery comprised of 11 different tests, Inouye and colleagues found that cognitive changes after surgery are complex and that delirium can influence cognition for up to five years after it occurs.
As they expected, the researchers found that patients who experienced postoperative delirium were rehospitalized more often, and each rehospitalization was linked with a drop in cognitive performance over time.
The researchers also used statistical methods to ask whether the number and type of rehospitalizations — such as ICU or post-acute care stays — could change or explain the strength of the link between delirium and long-term cognitive decline. Contrary to their initial expectations, adjusting for those rehospitalizations did not significantly change the impact of delirium on long-term cognitive decline.
“We saw that delirium was associated with cognitive decline at a rate faster than what we would normally see with mild cognitive impairment, and the effect was not mediated by rehospitalization,” said Tammy Hshieh, HMS assistant professor of medicine at Brigham and Women’s Hospital and co-first author of the study.
The work “reinforces the crucial need to better understand and prevent delirium in older adults,” said co-first author Zachary Kunicki, assistant professor at Warren Alpert Medical School.
The authors note that future work will be needed to understand the biological mechanisms through which delirium may lead to cognitive decline.
Inouye and colleagues are also exploring how this connection works in the other direction: understanding why dementia is a risk factor for experiencing delirium, and how neurodegeneration, inflammation, and frailty may reduce the aging brain’s resilience to stresses like surgery and hospitalization.
Adapted from Hebrew SeniorLife and Mass General Brigham news releases.
In this audio interview from 2019, Inouye talks about her mission to prevent delirium in hospitalized patients. Discussion of the connection between delirium and dementia begins at 35:00.
Authorship, funding, disclosures
Additional authors include Tamara Fong, Edward R. Marcantonio, Eva Schmitt, Guoquan Xu, and Richard N. Jones. Additional collaborating institutions included Beth Israel Deaconess Medical Center.
The study was supported by the National Institutes of Health (grants R03AG075434, P01AG031720, and R33AG071744).
Inouye is editor-in-chief of JAMA Internal Medicine but did not participate in the journal review or decision-making about publication of this manuscript.
