Anesthesia Exposure and Risk of Dementia and Alzheimer's Disease: A Prospective Study

Abstract

Objectives: To evaluate the associations between anesthesia and dementia or Alzheimer's disease (AD) risk using prospectively collected data.

Design: Cohort study.

Participants: Community-dwelling members of the Adult Changes in Thought cohort aged 65 and older and free of dementia at baseline (N = 3,988).

Measurements: Participants self-reported all prior surgical procedures with general or neuraxial (spinal or epidural) anesthesia at baseline and reported new procedures every 2 years. People undergoing high-risk surgery with general anesthesia, other surgery with general anesthesia, and other surgery with neuraxial anesthesia exposures were compared with those with no surgery and no anesthesia. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia and AD associated with time-varying lifetime and recent (past 5 years) anesthesia exposures.

Results: At baseline, 254 (6%) people reported never having anesthesia; 248 (6%) had had one or more high-risk surgeries with general anesthesia, 3,363 (84%) had had one or more other surgeries with general anesthesia, and 123 (3%) had had one or more surgeries with neuraxial anesthesia. High-risk surgery with general anesthesia was not associated with greater risk of dementia (HR = 0.86, 95% CI = 0.58-1.28) or AD (HR = 0.95, 95% CI = 0.61-1.49) than no history of anesthesia. People with any history of other surgery with general anesthesia had a lower risk of dementia (HR = 0.63, 95% CI = 0.46-0.85) and AD (HR = 0.65, 95% CI = 0.46-0.93) than people with no history of anesthesia. There was no association between recent anesthesia exposure and dementia or AD.

Conclusion: Anesthesia exposure was not associated with of dementia or AD in older adults.

Keywords: Alzheimer's disease; anesthesia; dementia; older adults; surgery.

Figure 1. Hierarchical classification methods for lifetime and recent anesthesia exposures

Each of the 3 examples below illustrates the hierarchy we used to classify participants’ lifetime and recent exposures to anesthesia as time-varying exposures. Figure 1 provides examples of how we classified lifetime and recent anesthesia exposure. Each line represents the time from baseline to end of follow-up. For example, the first bar shows a person who reported no anesthesia exposure before baseline. In year 3, he reported a general anesthesia procedure and had his exposure classified as such. In year 7, he reported a high-risk surgery and had his exposure classified as such. His exposure remained “high-risk surgery” until the end of follow-up, even though he reported a general anesthesia procedure in year 9, because high-risk surgery trumped general surgery in our exposure hierarchy. Similarly, in example 2, the general anesthesia procedure reported before baseline trumped the neuraxial anesthesia procedure reported in year 3; and the general anesthesia procedure was trumped by the high-risk procedure in year 7. In the third example looking at recent anesthesia exposure, exposures only last for 5 years unless they are trumped by another procedure in the hierarchy. So the first general anesthesia procedure exposure defined exposure status for 4 years until it was trumped by a high-risk surgery procedure. The high-risk procedure defined exposure status for 5 years even though another general anesthesia procedure occurred in year 9. Once 5 years had elapsed after the high-risk exposure, the person would be classified as exposed to the prior general anesthesia procedure for 2 more years or until the end of follow-up, whichever came first.