Developing postoperative delirium remains the strongest predictor of long-term cognitive decline in older adults, according to a study published in JAMA Internal Medicine.

Researchers followed older surgical patients to determine whether post-op setbacks, such as rehospitalizations or intensive care stays, explained delirium’s lasting damage to brain health.

While rehospitalizations and post-acute rehabilitation stays were associated with accelerated cognitive decline, the study found they did not account for the long-term impact of delirium.

“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,” says first author Zachary J. Kunicki, PhD, an assistant professor of psychiatry and human behavior.

Delirium is the most common post-op complication in older adults, often triggering a cascade of secondary medical care. However, the study revealed that delirium independently drives cognitive deterioration—at a pace faster than typical mild cognitive impairment—for up to five years after surgery.

“We had anticipated that at least part of the effect of delirium on long-term cognition would be due to rehospitalizations,” says senior author Sharon K. Inouye, MD, professor of medicine at Harvard. “We were surprised to learn that rehospitalizations did not explain the effects.”

The team analyzed data from a study of 560 adults aged 70 and older, which evaluated participants using 11 detailed cognitive tests for up to six years. Although hospital readmissions were more frequent among patients who experienced delirium, the trajectory of their cognitive decline remained distinctly accelerated regardless of subsequent medical events.

Because secondary health crises fail to explain why delirium damages long-term cognition, researchers emphasize the urgent need to uncover the underlying biological mechanisms and prioritize clinical prevention.