ObjectiveTo examine associations between gastrointestinal and hepatic diseases (GIHD) and long-term depressive symptom trajectories in older adults across diverse cultural and healthcare settings.MethodsLongitudinal data from four aging cohorts were harmonized: CHARLS (China), SHARE (Europe), HRS (United States), and KLOSA (South Korea), comprising 40,161 adults aged ≥60 years with 4-6 follow-up waves. Group-based trajectory modeling (GBTM) identified distinct depressive symptom trajectories. Multinomial logistic regression, adjusted for baseline depressive symptoms and covariates, estimated odds of trajectory membership. Random-effects meta-analysis with Hartung-Knapp correction pooled cohort-specific estimates. Inverse probability weighting (IPW) and E-values assessed robustness to confounding.ResultsThree trajectories were identified in all cohorts: Stable Low, Increasing Mild, and Stable High. After adjustment for baseline depressive symptoms, GIHD independently predicted Stable High trajectory membership (pooled OR = 1.73, 95% CI: 1.31-2.28; I2 = 21.2%). Upper gastrointestinal disorders showed exceptional cross-cultural consistency (pooled OR = 1.80, 95% CI: 1.69-1.92; I2 = 0%). Liver disease was significantly associated in CHARLS (OR = 2.64, 95% CI: 1.15-6.07) but not in KLOSA. Associations were consistent across sexes (P for interaction = 0.417). IPW confirmed robustness (CHARLS OR = 1.40; SHARE OR = 1.11), and E-values indicated resistance to unmeasured confounding (E-value = 1.97).ConclusionsChronic gastrointestinal conditions independently predict persistent severe depressive trajectories in older adults across four countries. The zero heterogeneity for upper gastrointestinal disorders suggests a gut-brain axis mechanism, supporting systematic depression screening in geriatric gastroenterology practice.
Gut-Brain Axis