Postoperative delirium serves as strongest predictor of cognitive decline

Researchers found postoperative delirium was strongly associated with long-term cognitive decline and the effect was not explained by rehospitalizations, highlighting the long-term impact of delirium on brain health.

Developing postoperative delirium remains the strongest predictor of long-term cognitive decline, a new study finds. Researchers from Mass General Brigham, Hebrew SeniorLife, and Brown University followed older adults after surgery to determine if illness and frailty, might explain part of the effect of delirium on cognitive decline. Researchers found that while rehospitalizations and intensive care or post-acute rehabilitation stays were associated with long-term cognitive decline, they did not help to explain the effect of delirium on long-term brain health. Results are published in JAMA Internal Medicine.

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. This was surprising because we thought rehospitalization would explain at least some of the effect of delirium on long-term cognitive decline. Future work needs to be done to better understand the important connections between delirium and long-term brain health."

Tammy T. Hshieh, MD MPH, first author, geriatrician, Division of Aging, Mass General Brigham's Department of Medicine

Delirium is the most common post-operative complication in older adults and is associated with poor outcomes, including functional decline, long-term cognitive decline and incident dementia. It can lead to a cascade of rehospitalizations, including potential stays in the Intensive Care Unit (ICU), post-acute care (PAC) unit, or both.

The current study looked at data from the SAGES cohort, which followed 560 adults, aged 70 years and older, measuring their cognition every six months for 36 months, then annually afterwards for up to six years. Using a detailed cognitive testing battery comprised of 11 different tests, investigators found that cognitive changes after surgery are complex and that delirium influences cognition up to five years after it occurs. Each rehospitalization was associated with cognitive decline on cognitive battery testing and delirium was associated with more marked cognitive decline per year. Rehospitalizations were more common among patients who developed delirium.

"Our findings build on the past work of the SAGES team," said co-first author Zachary J. Kunicki, PhD, MS, MPH, Assistant Professor at the Warren Alpert Medical School of Brown University, "Showing that people who develop postoperative delirium decline at a faster pace than those who do not, and this faster decline is not explainable by rehospitalizations during follow-up, reinforces the crucial need to better understand and prevent delirium in older adults."

Contrary to the researchers' expectations, rehospitalization did not significantly change the impact of delirium on long-term cognitive decline. The authors note that future work will be needed to understand the mechanisms that explain why delirium is associated with long-term cognitive decline.

"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 K. Inouye, MD, MPH, Harvard Professor and Director, Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research at Hebrew Senior Life. "However, we were surprised to learn that rehospitalizations did not explain the effects of delirium on subsequent cognitive decline."

Source:
Journal reference:

Hshieh, T., et al. (2026) Rehospitalization as a mediator of the association of post-operative delirium with cognitive decline in older adults. JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2026.1910. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2850105

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