General anesthesia and surgery in some cases may hasten cognitive decline—or even the onset of Alzheimer’s disease. These findings from a study in 11 patients were presented at the 2011 annual meeting of the International Anesthesia Research Society (abstract S-242), and showed that levels of key molecular markers of neuronal injury increased in the days after patients underwent endoscopic procedures.


“We don’t know if this change has clinical relevance or not,” said study co-author Roderic Eckenhoff, MD, professor of anesthesia at the University of Pennsylvania, in Philadelphia. “But, at this point it’s an intriguing finding.”


Doctors have long known that a significant number of older adults experience cognitive changes in the weeks and months after undergoing general anesthesia and surgery. Immediately after procedures, up to 20% of people aged 65 years and older experience cognitive changes that last weeks, months or even longer, according to Dr. Eckenhoff. “This is a very, very common complaint from patients,” he said. “We don’t know what causes it. We know it happens.”


It also is not clear whether patients ever fully recover from that decline. Dr. Eckenhoff said the possibility that something about the surgical experience decreases cognition transiently, but also interacts with other brain pathways to cause problems that only emerge later. Results of in vitro and animal studies suggest that the combination of anesthesia and surgery can adversely affect the pathologic pathways underlying Alzheimer’s and other similar disease processes. Dr. Eckenhoff said that patients already vulnerable to neurodegeneration might be most at risk.


To better understand what happens in the human brain after general anesthesia and surgery, the investigators collected samples of cerebrospinal fluid (CSF) from eight women and three men (aged 53±6 years) undergoing surgery to correct idiopathic CSF leaks, for which lumbar catheters were placed. CSF samples were obtained before and immediately after surgery, and at six, 24 and 48 hours or until the catheter was removed. Approximately half of the patients received total IV anesthesia (TIVA); the remainder received inhaled anesthetics.


The investigators noted a significant increase in S100b and total tau—both markers of neuronal injury—after six hours. By 24 hours, tau had increased more than 200%. The proinflammatory biomarker interleukin-6 appeared to increase more in the inhalation group than in the TIVA group. “That would suggest that elements of our management—how we do general anesthesia—could in fact affect the progression of inflammatory cascades in the brain,” Dr. Eckenhoff told Anesthesiology News.


He cautioned that none of the data generated so far call for a change in practice. But there is enough evidence pointing to a problem to warrant more investigation. “The way I characterize it, there’s a smoking gun but no victim yet,” he said.


Dr. Eckenhoff said that although the data are compelling enough that he administers more regional anesthesia in his older patients whenever possible, he would “hesitate to tell other practitioners to change their practice. The data are still pretty weak at this point.” In the meantime, his group is investigating ways in which anesthesia does not cause cognitive decline.


The cognitive impact of anesthesia is a controversial research topic that has generated varied findings, according to Zhongcong Xie, MD, PhD, associate professor of anesthesia at Harvard Medical School and attending anesthesiologist at Massachusetts General Hospital, in Boston. “For a long time, people were thinking anesthesia is pretty safe,” he told Anesthesiology News. A patient who emerged from surgery with fully functioning heart and lungs would be assessed by many doctors as having no problems. But, he said, more and more doctors are beginning to accept that “maybe this is something we should be looking at—the brain.”


Dr. Xie, who was not involved with the current study, described it as a “good start.” What researchers really need, he said, are more human studies that measure the clinical impact of anesthetics. “If you want to have a final answer you should do a functional study, follow patients for 10 or more years and see if they develop Alzheimer’s disease. But, adequately powered prospective human studies would take many years to conduct and analyze.”


Looking at biomarkers is a good first step, Dr. Xie said. These biomarkers are present in high concentrations in CSF, but in order to sample a large, diverse group of patients, researchers have to find ways to measure their blood levels. Relevant animal studies also must be conducted that will complement human studies by establishing a mechanistic hypothesis and help formulate a strategy of prevention and treatment, he said.


Researchers should continue to investigate these patterns, including whether particular drugs or patient characteristics pose more of a risk, Dr. Xie said. “There are many patients with early stages of Alzheimer’s having surgery every year; we need to study if these drugs promote their disease.”


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Why would my surgeon and everybody else involved in my care prefer to give me brain damage over doing my surgery with ONLY regional anesthesia and a pain killer? Especially in light of the fact that I refused any sedation or general anesthetic? Here's an excellent statement; “For a long time, people were thinking anesthesia is pretty safe,” he told Anesthesiology News. A patient who emerged from surgery with fully functioning heart and lungs would be assessed by many doctors as having no problems. But, he said, more and more doctors are beginning to accept that “maybe this is something we should be looking at—the brain.”