UTHealth Houston researchers have been awarded $2.8 million by the National Institute on Aging Alzheimer's Disease Initiative fund to identify possible biomarkers and mechanisms underlying perioperative neurocognitive disorder in older adults.
“For many years, physicians have observed that older patients may develop memory impairments and confusion following anesthesia and surgery. These conditions are collectively known as perioperative neurocognitive disorder, which includes postoperative delirium, delayed neurocognitive recovery, and postoperative neurocognitive disorder, but the reason of perioperative neurocognitive disorder remains poorly understood,” said Zhongcong Xie, MD, PhD, professor and vice president for translational perioperative research and innovation in the Department of Anesthesia, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston.
Perioperative neurocognitive disorder has been associated with increased morbidity and mortality, higher cost of care, and a greater risk of developing Alzheimer's disease and related dementias, according to Xie. Determining the specific biomarkers associated with these symptoms could help physicians and researchers identify ways to predict and prevent high-risk patients from developing these cognitive disorders in the future.
Throughout his career, Xie has mainly studied how anesthesia and surgery can affect the brain and cellular function and how those changes lead to perioperative neurocognitive disorder in animal models. Now, Xie and his team at UTHealth Houston will use this grant to recruit 400 patients for clinical study.
Researchers will collect blood samples and rectal swabs from patients before and after anesthesia and surgery. The samples will be transported to Xie’s laboratory, where researchers will characterize the gut microbiota and measure blood levels of tau, phosphorylated tau, and metabolites derived from gut microbiota. The accumulation of abnormal tau species and alterations in the gut microbiota may contribute to the development of neurological disorders, including dementia.
Previous research has revealed consistent phenotypes in certain patients with perioperative neurocognitive disorders. Researchers will assess cognitive function and delirium before anesthesia and surgery, immediately after anesthesia and surgery, 21 days after, and again at six months.
Physicians will use the findings of this study to identify patients at high risk of developing postoperative neurocognitive disorders before anesthesia and surgery and target interventions to prevent those disorders.
“The results of our proposed studies could challenge existing practices, guide strategies to prevent and treat perioperative neurocognitive disorder, and ultimately improve anesthesia and surgical care for older patients, particularly those at increased risk of developing Alzheimer’s disease and Alzheimer’s disease-related dementias,” Xie said.
The grant will span five years.
“This success showcases how collaborative research can lead to transformative research findings and innovative patient therapies,” said Holger Eltzschig, MD, PhD, the John P. and Kathrine G. McGovern Distinguished University Chair in the Department of Anesthesia, Critical Care and Pain Medicine at McGovern Medical School.
This grant marks the first NIH award presented to Xie since he joined UTHealth Houston in May 2025. With this award, he is now a lead investigator on five R01 grants.
“Dr. Xie is an international leader in the field, and we are fortunate to have recruited him. His latest major NIH grant will investigate innovative potential mechanisms underlying cognitive impairment and help shape the future of surgery,” said Dan Sessler, MD, professor and vice president for clinical and outcomes research in the Department of Anesthesia, Critical Care and Pain Medicine at McGovern Medical School.
Xie is grateful to the Center for Outcomes Research at the UTHealth Houston Institute of Perioperative Medicine for its warm welcome and for fostering opportunities to collaborate and advance clinical innovation for the future.
“Xie is an exceptional leader, innovator, and researcher who brings fresh ideas and energy to every endeavor. What makes him especially valuable to our research community is not only the quality and creativity of his science, but also his collaborative, approachable nature. He is a dedicated mentor who is deeply committed to supporting junior investigators and helping them develop their ideas and careers. This NIH award is well-deserved recognition of his innovative work and the important questions he is addressing in perioperative brain health,” said Alparslan Turan, MD, professor, assistant vice president for translational outcomes research, and vice chair for outcomes research at McGovern Medical School, as well as director of the Center for Outcomes Research.
Eltzschig, Sessler, and Turan were also key investigators on the study