Association of the red blood cell distribution width-to-albumin ratio with incident depression and depressive symptom trajectories in older adults

The ratio of red blood cell distribution width to albumin (RAR) is a systemic blood-based marker associated with adverse health outcomes. Although cross-sectional studies have suggested a link between RAR and depression, its longitudinal association with the incidence and long-term course of late-life depression has not yet been established. We aimed to address this knowledge gap using data from a large cohort of older adults. This longitudinal cohort study used data from the Health and Retirement Study (2016–2022). The analysis of incident depression included 6,151 U.S. adults aged ≥ 60 years who were free of depression at baseline. Multivariable Cox regression was used to assess the association, and restricted cubic splines were applied to examine the dose-response relationship. In a subcohort of 5,588 participants, group-based trajectory modeling was used to identify depressive symptom trajectories, and their association with baseline RAR was examined using multinomial logistic regression. During a median follow-up of 6 years, 1,287 participants developed incident depression. In the fully adjusted model, each 1-unit increase in baseline RAR was associated with a 19% higher risk of incident depression (HR = 1.19; 95% CI: 1.06–1.33). Compared with the lowest quartile, the highest RAR quartile was associated with a higher risk of incident depression (HR = 1.20; 95% CI: 1.01–1.42). The dose-response analysis indicated a linear relationship (P for non-linearity = 0.961). Four distinct symptom trajectories were identified: “Non-depressed” (28.11%), “Low-stable” (40.89%), “Moderate-progressive” (25.42%), and “High-progressive” (5.58%). Compared with the “Non-depressed” group, higher baseline RAR was associated with greater odds of membership in the “High-progressive” (OR = 1.31; 95% CI: 1.11–1.55) and “Moderate-progressive” (OR = 1.36; 95% CI: 1.07–1.73) groups. In this large, nationally representative cohort of older adults, higher baseline RAR was longitudinally associated with an increased risk of incident depression and a subsequent long-term trajectory of worsening depressive symptoms.