Anesthesia, Surgery May Double Dementia Risk

Megan Brooks

March 11, 2014

Anesthesia and surgery significantly increase the risk for dementia, new research suggests.

A large population-based study conducted by investigators at the Neurological Institute in Taipei Veterans General Hospital, in Taipei City, Republic of China, showed that the risk of developing dementia nearly doubled within 3 to 7 years of anesthesia and surgery. In addition, the average time to dementia diagnosis was shorter in patients who had anesthesia and surgery compared with their counterparts who did not undergo these procedures.

The study adds to "growing concerns that anesthetic agents may have neurodegenerative complications," study investigator Jong-Ling Fuh, MD, of the Neurological Institute, told Medscape Medical News.

"In vitro and animal studies showed that inhaled anesthetic drugs can promote amyloid beta oligomerization and impair memory. However, it remains controversial whether anesthesia and surgery contribute to the development of dementia in human studies," she said.

"This population-based study provides statistically sound evidence for the association of dementia with anesthesia and surgery. Our findings support the view that patients who undergo anesthesia and surgery may be at increased risk of dementia."

"Although we do not know how to mitigate the risk of dementia after anesthesia and surgery at this point, physicians and surgeons should be more vigilant about the possible development of long-term cognitive decline postoperatively in patients who have undergone anesthesia and surgery," Dr. Fuh added.

The study was published in the March issue of the British Journal of Psychiatry.

Need for More Research

Using the Taiwan National Health Insurance Research Database, Dr. Fuh and colleagues extracted the records of 24,901 patients aged 50 years and older who underwent anesthesia for surgery between 2004 and 2007, and a control group of 110,972 randomly selected individuals matched for age and sex. They excluded anyone with a history of cancer, dementia, Parkinsonism, stroke, or brain operations.

During 3 to 7 years of follow-up, 661 patients in the anesthesia group (2.65%) and 1539 in the control group (1.39%) were diagnosed with dementia. Alzheimer's disease accounted for the majority of these cases.

Dementia occurred sooner in the anesthesia group (mean 907 days) than in the control group (mean, 1104 days; P < .0001).

After adjusting for hypertension, hyperlipidemia, depression, and Charlson index, patients who underwent anesthesia and surgery had an estimated 1.99-fold increased risk of developing dementia (95% confidence interval [CI], 1.81 - 2.17; P < .001). The risk for dementia after anesthesia was increased similarly in men and women.

The risk was greatest with regional anesthesia (adjusted hazard ratio [HR], 1.80; 95% CI, 1.57 - 2.07), followed by intravenous/intramuscular anesthesia (HR, 1.60; 95% CI, 1.11 - 2.30) and general anesthesia (HR, 1.46; 95% CI, 1.28 - 1.68).

Of the 8 types of surgery, 5 were associated with an increased risk for dementia (dermatologic, musculoskeletal, genitourinary, digestive, and eye surgery). Ear, nose, and throat (ENT), respiratory, and cardiovascular surgery was not associated with increased dementia risk.

Dr. Fuh said "caution must be exercised in asserting causality between development of dementia and anesthesia-associated neurotoxicity. More clinical studies are needed to investigate the association and causality between anesthesia with surgery and subsequent dementia."

Red Flags and Caveats

Commenting on the findings for Medscape Medical News, Roderic G. Eckenhoff, MD, professor and vice-chair of research, Department of Anesthesia and Critical Care, University of Pennsylvania in Philadelphia, who was not involved in the study, said that sometimes surgery is necessary, but in cases of elective surgery, patients may want to think twice.

However, he cautioned that the study has some "big red flags" and said this "is an area in need of further clarification."

"If it's surgery, is it the actual surgery, or the anesthesia, or is it the stress of being in the hospital? It's probably all those things combined, but it's probably the surgical procedure itself that causes the largest risk, at least that's what we believe," Dr. Eckenhoff said.

"This is a good additional study, and its real strength is its size," Dr. Eckenhoff said.

"Even when corrected for comorbidity, they found a significant effect of having had surgery in the past and risk for dementia. The level of risk is about consistent with some of the other studies performed," he noted.

What's "very concerning," he said, is that the demographics and comorbidity are "significantly different" in the surgery group and the control group, "although they did try to correct for that."

Still, "a big red flag and qualifier with this study is that the patients needing surgery are in fact different than the patients who don't need surgery. It may be those differences and not the fact that they had surgery itself that account for the difference in propensity for getting dementia," Dr. Eckenhoff said.

"I think in the end we are going to find that there are small populations of people that are more vulnerable to another insult like surgery and who go downhill more quickly afterwards. The challenge is to figure out who those people are, and that's going to require really good biomarkers," said Dr. Eckenhoff.

The study was supported by Taipei Veterans General Hospital and other noncommercial entities. The authors have disclosed no relevant financial relationships.

Br J Psychiatry. 2014;204:188-193. Abstract

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