Postoperative Delirium Is Strongly Associated with Long-Term Cognitive Decline

Research published today in JAMA Internal Medicine finds that developing postoperative delirium remains the strongest predictor of long-term cognitive decline. While rehospitalizations, intensive care, and post-acute rehabilitation stays are associated with long-term cognitive decline, they are still not as impactful on brain health as delirium itself. 

The study, “Rehospitalization as a mediator of the association of post-operative delirium with cognitive decline in older adults,” was based on data from a long-term observational study funded by NIH Grant No. P01AG031720 to Sharon K. Inouye, MD, MPH, director of Aging Brain Center at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research and professor at Harvard Medical School.

“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 first author Tammy T. Hshieh, MD, MPH, assistant scientist at the Marcus Institute and geriatrician in the Division of Aging in Mass General Brigham’s Department of Medicine. “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.” 

“Our exciting findings in this manuscript build on the past work of the SAGES team,” said Zachary J. Kunicki, PhD, MS, MPH, first study co-author and 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.”

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. “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 Dr. Inouye, the senior author on the study. “However, we were surprised to learn that the effects of delirium were not explained by the number of types of rehospitalizations.” 

The SAGES cohort has followed 560 older adults (age 70 and older), measuring their cognition every 6 months for 36 months, then annually afterward for up to 6 years. Using a detailed cognitive testing battery, comprised of 11 different tests, researchers found that cognitive changes after surgery are complex and that delirium influences cognition up to 5 years after it occurs. Each rehospitalization was associated with cognitive decline on cognitive battery testing. Delirium was associated with more marked cognitive decline per year. Rehospitalizations were more common among patients who developed delirium (adjusted incidence rate ratio 1.42). 

“We found that after adjustment for combined rehospitalizations and for each type of rehospitalization, there was only a minimal, non-significant percent change (-6% to -9%) in the effect of delirium on cognitive decline,” said co-senior author Richard N. Jones, ScD, professor at the Warren Alpert Medical School of Brown University. “Contrary to our expectations, rehospitalizations did not significantly change the impact of delirium on long-term cognitive decline.” 

Authors: Tammy T. Hshieh, MD, MPH; Zachary J. Kunicki, PhD, MS, MPH; Tamara G. Fong, MD, PhD; Edward R. Marcantonio, MD, SM; Eva Schmitt, PhD; Guoquan Xu, MD, PhD; Richard N. Jones, ScD; and Sharon K. Inouye, MD, MPH.

Collaborating institutions include the Warren Alpert Medical School of Brown University, Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Harvard Medical School, and Hebrew SeniorLife.

The study was supported by Grants No. R03AG075434 (T.T.H.), P01AG031720 (S.K.I.), R33AG071744 (S.K.I./R.N.J.) from the National Institute on Aging. 

About Hebrew SeniorLife
Hebrew SeniorLife is a national leader working to create a world where aging is defined by possibility, not limitation. We care for more than 4,500 older adults each day across seven campuses throughout Greater Boston, and offer support for families in the aging journey. Our services include in-home care, outpatient therapies, an outpatient memory clinic, short- and long-term inpatient care, hospice, independent and assisted living, and affordable housing with services. We conduct influential research on aging at our Hinda and Arthur Marcus Institute for Aging Research, which has a grant portfolio of $87 million, and train future health care workers at the Lunder CareForce Institute. Hebrew SeniorLife is a Harvard Medical School affiliate. Follow us on our blog, Facebook, Instagram, and LinkedIn.  

About the Hinda and Arthur Marcus Institute for Aging Research
Scientists at the Marcus Institute seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity, and productivity into advanced age. The Marcus Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment, and cure of disease; advance the standard of care for older people; and inform public decision-making.

About Brigham and Women’s Hospital 
Brigham and Women’s Hospital (BWH), a founding member of Mass General Brigham and a principal teaching affiliate of Harvard Medical School, has been a leader in patient care, medical research, and education since its founding in 1832. Today, BWH is an internationally recognized 793-bed academic medical center that cares for patients from across New England and around the world. The hospital is home to more than 4,000 physicians and scientists and over 1,200 medical residents and fellows training across virtually every medical and surgical specialty. BWH consistently ranks among the top hospitals in the nation by U.S. News World Report and is a leader in biomedical research, with one of the largest hospital-based research programs in the United States, receiving over $700 million annually in research funding. Brigham and Women’s Hospital is committed to advancing health equity, pioneering innovative treatments, and training the next generation of health care leaders. For more information about Brigham and Women’s Hospital, visit brighamandwomens.org or follow us on Facebook, X (Twitter), Instagram, and LinkedIn.

About the Warren Alpert Medical School 
The Warren Alpert Medical School is the medical school of Brown University, located in Providence, Rhode Island, United States. Established in 1811, the school was among the first in the nation to offer academic medical education. Today, Alpert Medical School is a component of Brown’s Division of Biology and Medicine, which also includes the Program in Biology. (A third component of the Division, the Program in Public Health, became the Brown University School of Public Health on July 1, 2013.) Together with the Medical School’s seven affiliated teaching hospitals, the Division attracts over $240 million in external research funding per year. The fourth most selective medical school in the United States, Alpert Medical School earned rankings of twenty-fourth for primary care education and thirty-first for research in the 2014 U.S. News & World Report rankings. Graduates of Alpert Medical School are accepted into competitive residency programs and leading medical centers.