Alzheimer's Dementia After Exposure to Anesthesia and Surgery in the Elderly: A Matched Natural Experiment Using Appendicitis

Abstract

Objective: The aim of this study was to determine whether surgery and anesthesia in the elderly may promote Alzheimer disease and related dementias (ADRD).

Background: There is a substantial conflicting literature concerning the hypothesis that surgery and anesthesia promotes ADRD. Much of the literature is confounded by indications for surgery or has small sample size. This study examines elderly patients with appendicitis, a common condition that strikes mostly at random after controlling for some known associations.

Methods: A matched natural experiment of patients undergoing appendectomy for appendicitis versus control patients without appendicitis using Medicare data from 2002 to 2017, examining 54,996 patients without previous diagnoses of ADRD, cognitive impairment, or neurological degeneration, who developed appendicitis between ages 68 through 77 years and underwent an appendectomy (the ''Appendectomy'' treated group), matching them 5:1 to 274,980 controls, examining the subsequent hazard for developing ADRD.

Results: The hazard ratio (HR) for developing ADRD or death was lower in the Appendectomy group than controls: HR = 0.96 [95% confidence interval (CI) 0.94-0.98], P < 0.0001, (28.2% in Appendectomy vs 29.1% in controls, at 7.5 years). The HR for death was 0.97 (95% CI 0.95-0.99), P = 0.002, (22.7% vs 23.1% at 7.5 years). The HR for developing ADRD alone was 0.89 (95% CI 0.86-0.92), P < 0.0001, (7.6% in Appendectomy vs 8.6% in controls, at 7.5 years). No subgroup analyses found significantly elevated rates of ADRD in the Appendectomy group.

Conclusion: In this natural experiment involving 329,976 elderly patients, exposure to appendectomy surgery and anesthesia did not increase the subsequent rate of ADRD.

Figure 1:

Kaplan-Meier plots of survival without ADRD post appendectomy event.

Figure 2:. Cumulative Hazard Plots:

(i) the cumulative hazard of dying or developing ADRD for both the treated and control groups; (ii) the cumulative hazard of dying without developing ADRD and (iii) the cumulative hazard of developing ADRD in those who did not die. All plots also censor on loss to end of study or managed care (which do not report claims used for the ADRD definition).