Risk of Dementia After Cholecystectomy in Older Adults: A Nationwide Retrospective Study (Preprint)

BACKGROUND Identification of factors that increase the hazard of dementia, such as cholecystectomy, is critical for early intervention and management. Cholecystectomy, which affects the metabolism and storage of bile acid, is a potential risk factor for dementia. OBJECTIVE We aimed to determine whether cholecystectomy increases the hazard of dementia onset in older adults, regardless of subtype. METHODS This retrospective observational study used data from the Korean Health Insurance Review and Assessment Service database for patients who underwent cholecystectomy or appendectomy from 2013 to 2022. Patients 60 years of age or older who had a cholecystectomy (Q7380) were included in the study group (294,008 eligible participants; 66,021 excluded), and those who had an appendectomy (Q2861, Q2862, Q2863) were included in the control group (125,961 eligible participants; 14,963 excluded). Incidence of dementia, regardless of subtype, was defined using International Classification of Diseases 10th Revision Codes (F00, F01, F02, F03, G23.1, G30, G31.0, G31.1, G31.8). Propensity score matching and inverse probability of treatment weighting were performed for all independent variables (age, sex, hypertension, diabetes, dyslipidemia, depressive disorder, Charlson Comorbidity Index). Cox proportional hazard regression analyses were performed to assess the hazard ratio of dementia. RESULTS A total of 227,987 individuals (mean age 70.36 years; 51.12% male) were included in the cholecystectomy group, and 110,998 individuals (mean age 69.31 years, 45.81% male) were included in the control group. In an unadjusted Cox proportional hazard model, the hazard ratio for dementia in the cholecystectomy group was 1.148 (95% confidence interval 1.123 to 1.172; P <.0001). The significantly elevated hazard for dementia in the cholecystectomy group was maintained after model adjustment (1.071, 95% confidence interval 1.048 to 1.095; P <.0001), propensity score matching (1.086, 95% confidence interval 1.060 to 1.114; P <.0001), and inverse probability of treatment weighting (1.081, 95% confidence interval 1.066 to 1.096; P <.0001). CONCLUSIONS Our findings suggest that cholecystectomy is associated with an increased hazard of any dementia, even after controlling for other medical history and the effect of surgery. These findings underscore the need to monitor for cognitive decline in cholecystectomy patients and to further explore the relationship between cognitive decline and biliary function.