INTRODUCTION: Concerns about falling (CaF) are common in older adults and may act as a chronic stressor affecting physical activity, psychological well-being and physiological regulation. This study examined the impact of a 16-week multimodal exercise intervention on CaF, stress pathways, and peripheral inflammation in older adults. METHODS: In the randomized, controlled FEARFALL study, 160 community-dwelling older adults (aged >= 70 years) were assigned to either an intervention group (IG) or a sham control group (SCG). The IG received a multimodal exercise program, while the SCG engaged in low-intensity activities. Three psychological questionnaires were used to assess CaF: Falls Efficacy Scale-International (FES-I) (fear of falling); Falls Efficacy Scale-International Avoidance Behavior (FES-IAB) (avoidance behavior); Updated Perceived Control of Falling Scale (UP-CoF) (perceived control). Hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) activity was determined using saliva samples (cortisol, alpha-amylase), inflammatory markers using blood samples (C-reactive protein (CRP), Interleukin 6 (IL-6)). RESULTS: There were significant improvements in CaF over time and perceived control in both groups (FES-I: beta -6.645, 95% -CI -10.56 to -2.73, p = 0.001; UP-CoF: beta 3.911, 95% -CI 1.24 to 6.58, p = 0.004). Diurnal cortisol slope normalized after the intervention (beta -0.014, 95% -CI -0.03 to 0.00, p = 0.014), while other neuroendocrine and inflammatory markers remained unchanged. CONCLUSION: A multimodal short-term intervention reduced psychological aspects of CaF, while physiological stress and inflammatory parameters may require more intensive or longer-term interventions. Findings support CaF as a biopsychosocial stressor and highlight the efficacy of multimodal programs in enhancing coping in older adults.

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