Bidirectional Association Between Multimorbidity and Frailty and the Role of Depression in Older Europeans

Background: Although previous studies have reported an association between multimorbidity and frailty, its direction and mechanism remain unclear. This study aimed to investigate the direction of this association, as well as the role of depression among older Europeans. Methods: We used a cross-lagged panel design to evaluate the temporal relationship between multimorbidity and frailty and the role of depression. Multimorbidity status was assessed by the self-reporting of 14 chronic diseases. Frailty was assessed based on the frailty phenotype. The European-Depression Scale (EURO-D) was used to assess depression. Results: There was a bidirectional relationship between frailty and multimorbidity. More severe multimorbidity predicted greater frailty (beta = 0.159; p <.001) and vice versa (beta = 0.107; p <.001). All paths from multimorbidity to frailty were stronger than the paths from frailty to multimorbidity (b1-a1: beta = 0.051; p <.001). Likewise, early multimorbidity change was a significant predictive factor for late frailty change (beta = 0.064; p <.001) and vice versa (beta = 0.048; p <.001). Depression in Wave 5 (T5) mediated the association between frailty in Wave 4 (T4) and multimorbidity in Wave 6 (T6; indirect effect: beta = 0.004; bootstrap 95% confidence interval: 0.003, 0.006). Conclusions: A positive, bidirectional association was observed between multimorbidity and frailty. Depression may be a potential cause of an increased risk of multimorbidity later in life in frail older adults. Early monitoring of frailty and depression may slow the progression of multimorbidity, thereby interrupting the vicious cycle.