Does General Anesthesia Pose an Alzheimer’s Risk?

Authors: Michael Vlessides

Anesthesiology News

Research has found a potential relationship between general anesthesia and Alzheimer’s disease, based on a systematic review and meta-analysis by Korean investigators. The authors were quick to add that the findings should be interpreted with caution, given the heterogeneity and bias in the analysis.

Alzheimer’s disease has grown to become a significant concern for patients undergoing surgery and anesthesia, according to Hyun Kang, MD, PhD, MPH, a professor of anesthesiology and pain medicine at Chung-Ang University Hospital, in Seoul, South Korea.

“However, studies investigating the relationship between general anesthesia and Alzheimer’s disease have yielded inconsistent results,” Dr. Kang said. “Therefore, the objectives of this systematic review and meta-analysis were to determine the association between administration of general anesthesia and Alzheimer’s disease, and to verify whether anesthesia is an independent risk factor for dementia.”

The studies included in the analysis were assessed for quality using the Newcastle-Ottawa Scale. The researchers also assessed the heterogeneity of estimates across all included studies, as well as publication bias. The list of studies for the final analysis (Table) included 255,618 patients.

Quantifying the Risk

Presenting the study at the 2018 annual meeting of the American Society of Anesthesiologists (abstract A1185), Dr. Kang reported that the risk for Alzheimer’s disease was significantly increased with previous exposure to general anesthesia (pooled effect size, 1.15; 95% CI, 1.10-1.20; P<0.001).

The investigators also conducted various subgroup analyses. These analyses showed that general anesthesia exposure was associated with a significantly increased pooled effect size for Alzheimer’s disease in case-control studies (1.15; 95% CI, 1.07-1.22; P<0.001), cohort studies (1.15; 95% CI, 1.09-1.22; P<0.001), case ascertainment with clinical diagnosis (1.23; 95% CI, 1.18-1.29; P<0.001), and exposure assessment with medical records (1.21; 95% CI, 1.16-1.26; P<0.001). After adjustment for suspected publication bias, the findings became statistically nonsignificant.

“In conclusion, we observed a significant association between general anesthesia and Alzheimer’s disease,” Dr. Kang said. “However, considering the heterogeneity and publication bias that we observed, we urge caution when interpreting this analysis. Furthermore, it may be impossible to discriminate between the influence of surgery and anesthesia. Therefore, further large-scale studies are needed to reduce the risk of bias.”

Separating the relative effects of surgery and anesthesia is challenging, as Dr. Kang’s audience reminded him. “I think this issue of discriminating general anesthesia and surgery—and even the conditions that lead people to surgery—from other factors i s one of the difficulties in these types of studies,” commented Marcos F. Vidal Melo, MD, PhD, the director of translational and clinical research at Massachusetts General Hospital, in Boston.

“We cannot discriminate between the surgery itself and the general anesthesia in terms of its influence on Alzheimer’s disease,” Dr. Kang replied. “For example, cardiac surgery is known to increase the risk of postoperative cognitive dysfunction. So, we should do more studies that control for the risk of surgery.”