Trajectories of Frailty and Depression and Their Associations with the Risk of Gastrointestinal and Liver Disease: Findings from China Health and Retirement Longitudinal Study and Validation of Survey of Health, Aging and Retirement in Europe

Background: Evidence of the relationship between frailty and depression trajectories and digestive disease in real-world populations remains insufficient. Investigating the long-term dynamic effects of frailty and depression may provide valuable insights for clinical intervention and the precise classification of risk factors for gastrointestinal or liver disease. In the study, we aimed to elucidate the aforementioned association among two representative cohorts. Methods: The CHARLS dataset represents a cohort of 10,303 participants over 40 years of age in China, with a follow-up period from 2011 to 2018. First, a group-based trajectory modeling method was used to identify combined trajectories of frailty and depression over a 7-year follow-up period. Frailty was assessed using the frailty index, while depression was measured using CESD10 scores. Binary logistic models and discrete survival models were applied to explore the associations between combined frailty–depression trajectories and the outcomes of gastrointestinal or liver diseases. Second, after excluding participants with baseline gastrointestinal or liver diseases, a binary logistic regression model was used to analyze the association between baseline frailty and depression and disease outcomes, with the results presented as odds ratios (ORs) and 95% confidence intervals (CIs). Third, Cox proportional hazards models with restricted cubic splines were applied to estimate the association between the baseline frailty index or CESD 10 scores and disease risk, with the results expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Comprehensive sensitivity analyses and subgroup stratifications supported the findings. The SHARE dataset was used as validation to prove the reliability of the conclusions. The SHARE cohort comprises 5834 participants 40 years of age and older in Europe, with a follow-up period from 2011 to 2017, and uses the frailty index to assess frailty and the EURO-D scale to assess depression. A binary logistic regression model was used to analyze the association between the trajectory groups and disease outcomes after excluding participants with baseline gastrointestinal diseases, with the results presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Three distinct combined trajectories were identified in the CHARLS cohort: G1 (59.7%), stable and robust with no depression; G2 (31.5%), moderate persistent frailty and depression; and G3 (8.8%), escalating frailty and high depression. In the fully adjusted binary model, compared with G1, the risk of gastrointestinal disease was elevated in G2 (OR = 1.94, 95% CI: 1.67–2.24) and G3 (OR = 2.73, 95% CI: 2.12–3.53). Similarly, the risk of liver disease was evidently elevated in G2 (OR = 1.72, 95% CI: 1.38–2.13) and G3 (OR = 3.44, 95% CI: 2.50–4.75). The SHARE findings were consistent with those from CHARLS, with three similar trajectory groups identified in the SHARE cohort. Compared with G1, the risk of gastrointestinal disease was evidently elevated in G2 (OR = 2.035, 95% CI: 1.359, 3.048) and G3 (OR = 4.588, 95% CI: 2.561, 8.218) in the fully adjusted model. Conclusions: Trajectories of frailty and depression were significantly correlated with increased occurrence of gastrointestinal and liver disease, with the results remaining robust across various sensitivity analyses and external cohort validations. A limitation of this study is that the outcome measures are based on self-reported data, which may be subject to measurement bias. These findings highlight the importance of sustained integrated physical–mental approaches and precise psychological screening and classification for the prevention and treatment of gastrointestinal and liver disease.