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

Identification of factors that increase the hazard of dementia is critical for early intervention and management. Cholecystectomy, which affects the metabolism and storage of bile acid, is a potential risk factor for dementia. We aimed to determine whether cholecystectomy increases the hazard of dementia onset in older adults, regardless of subtype.

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 aged 60 years 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 10^th 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.

A total of 227,987 individuals (mean age 70.36 years; 51.1% male) were included in the cholecystectomy group, and 110,998 individuals (mean age 69.31 years, 45.8% male) were included in the control group. In an unadjusted Cox proportional hazards model, the hazard ratio for dementia in the cholecystectomy group was 1.148 (95% confidence interval [CI], 1.123-1.172; P < 0.001). This modest but statistically significant increase in the hazard of dementia in the cholecystectomy group remained consistent after model adjustment (1.071; 95% CI, 1.048-1.095; P < 0.001), propensity score matching (1.086; 95% CI, 1.060-1.114; P < 0.001), and inverse probability of treatment weighting (1.081; 95% CI, 1.066-1.096; P < 0.001).

Our findings indicate that cholecystectomy is associated with a modestly increased hazard of dementia after adjustment for relevant covariates. This association should be interpreted as a population-level signal rather than a clinically actionable risk factor, and may inform future research on links between cognitive decline and biliary function.