The September issue of the journal Anesthesiology features a study linking the apolipoprotein E (APOE) e4 gene variant to the risk of postoperative delirium, a common postoperative complication in elderly patients.
"Our study showed that APOE e4 carrier status was associated with an increased risk for early postoperative delirium, after controlling for known demographic and clinical risk factors," says Dr. Jacqueline M. Leung of University of California, San Francisco.
The study included 190 elderly patients, average age 72.5 years, undergoing major surgery (other than heart surgery). A standard assessment was used to test for confusion and other symptoms of delirium. In addition, DNA samples were obtained to determine whether patients were carriers of the APOE e4 gene, which has been linked to an increased risk of late-onset Alzheimer's disease.
About 15 percent of patients had symptoms of postoperative delirium on the first and second days after surgery. On DNA analysis, 24 percent of patients were APOE e4 gene carriers.
Patients with APOE e4 had a higher rate of postoperative delirium: about 28 percent, compared to 11 percent of those who did not carry the APOE e4 gene. After adjustment for other risk factors—including older age, change in postoperative pain levels, and previous central nervous system disorders—patients who had at least one copy of the APOE e4 variant gene were nearly four times more likely to develop postoperative delirium.
Postoperative delirium is a relatively common side effect in elderly patients undergoing major surgery. A potentially prolonged and disabling problem, postoperative delirium has been linked to increased rates of nursing home placement and in-hospital death.
"Despite this prevalence and clinical importance, no specific causative factor has been identified," according to Dr. Leung.
Previous population studies have suggested that the APOE e4 gene variant is associated with increased rates of dementia, including the late-onset form of Alzheimer's disease (developing after age 65), and cognitive decline. (Other genes, but not APOE e4, have been linked to an increased risk of early-onset Alzheimer's disease.)
The new study suggests that APOE e4 may be a genetic risk factor for postoperative delirium. "This research is important in that it is one of the first studies in a large group of patients to investigate if there is a genetic predisposition to postoperative delirium," says Dr. Leung.
"Our results suggest that genetic predisposition plays a role, and may interact with anesthetic/surgical factors contributing to the development of early postoperative delirium," Dr. Leung adds. Further studies will be needed to determine how APOE e4 leads to an increased risk of postoperative delirium, including possible interactions with other risk factors. Another key question will be whether APOE e4 carriers who develop postoperative delirium are at increased risk for later cognitive impairment.