Abstract
BACKGROUND: Depression and sedentary behavior are prevalent among older adults, including cancer survivors, and are independently associated with increased mortality risk. However, their combined impact on mortality, potential nonlinear relationships remain understudied. This study investigates the independent and combined effects of depression and sedentary behavior on mortality and examines any nonlinear thresholds among both cancer survivors and non-cancer older adults. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we analyzed a sample of 1,430 cancer survivors and 4,393 non-cancer older adults (aged 65 years or older). Depression severity was measured using the Patient Health Questionnaire-9 (PHQ-9), and sedentary behavior was quantified by self-reported daily sitting time. Cox proportional hazards models with interaction terms and restricted cubic splines (RCS) were employed to evaluate associations and nonlinear relationships. RESULTS: Depression was independently associated with increased mortality risk (HR: 1.26, 95% CI: 1.08–1.47), particularly among males (HR: 1.87). Prolonged sedentary behavior (≥ 6 h/day) was also independently associated with higher mortality (HR: 1.45, 95% CI: 1.24–1.69). The combined presence of depression and prolonged sedentary behavior (≥ 6 h/day) was associated with the highest mortality risk (HR: 1.81, 95% CI: 1.05–3.14). Although the formal interaction term was not statistically significant (p = 0.529), the combined effect exceeded either factor alone, suggesting potential additive risk. However, the wide confidence interval indicates considerable uncertainty. RCS analysis identified a threshold effect for sedentary behavior: mortality risk increased sharply beyond 4 h/day of sitting. CONCLUSION: Depression and sedentary behavior appear to have an additive impact on mortality risk in older adults, with their combined presence associated with elevated risk. While the formal interaction was not statistically significant, the clinical pattern suggests that addressing both factors concurrently may be important for improving survival outcomes in aging populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-025-06766-z.