Association Between the Combined Effects and Joint Trajectories of Depression and Frailty and the Risk of Digestive Diseases: A Longitudinal Study

Background and Aims Digestive diseases, including gastrointestinal and liver disorders, are prevalent and contribute significantly to morbidity, healthcare costs, and reduced quality of life, particularly among middle‐aged adults. Frailty, characterized by reduced physiological reserve, and depression, a common psychological disorder, have both been linked to an increased risk of these conditions. However, the combined impact of frailty and depression on digestive diseases remains poorly understood. This study aimed to examine the combined effects and joint trajectories of frailty and depression on the risk of digestive diseases in middle‐aged adults and explore potential mechanisms of their interaction. Methods We conducted a prospective cohort study using data from the China Health and Retirement Longitudinal Study, involving 7876 participants aged 45 and above. Participants were classified into three frailty categories (robust, pre‐frail, frail) and assessed for depression. The incidence of digestive, gastrointestinal, and liver diseases was monitored over a median follow‐up of 9 years. We utilized Cox regression models to evaluate the individual and joint effects of frailty and depression on disease risk. Results During follow‐up, 2076 participants developed new digestive system diseases (26.36% incidence). Frailty and depression were independently associated with increased risks of digestive (hazard ratio [HR] for frail = 2.00, HR for depression = 1.61), gastrointestinal (HR for frail = 2.08, HR for depression = 1.67), and liver diseases (HR for frail = 2.14, HR for depression = 1.31). No significant multiplicative or additive interactions between the two were observed. Mediation analysis indicated that depression mediated 17.4% of the relationship between frailty and digestive diseases, whereas frailty mediated 18.8% of the relationship between depression and digestive diseases. The combined frailty and depression index improved predictive accuracy for all disease outcomes. In the joint trajectory analysis, the group with consistently higher depression scores and faster increases in the frailty index had the highest risk for all diseases. Conclusions Integrated assessment of frailty and depression should be prioritized in residual risk stratification and primary prevention strategies for digestive diseases.