Association of allostatic load with frailty trajectories and the mediating role of depressive symptoms

Background: Frailty is a dynamic, age-related condition marked by progressive loss of resilience. Its risk factors include socioeconomic status and physiological stress burden, such as allostatic load score (ALS), remain unclear. This study aims to examine the role of depression in the association between ALS and frailty trajectories. Methods: We analyzed data from 5885 LEAD cohort participants aged 25-82 years at baseline and from 3564 participants with follow-up data. Frailty status (robust, pre-frail, frail) was defined using the Fried phenotype, and transitions between visits were assessed. ALS was calculated from 14 parameters spanning cardiovascular, metabolic, and body composition measures. Associations of ALS with frailty status at baseline and with frailty transitions at follow-up were examined, and depressive symptoms were tested as a mediator. Results: At baseline, 62.3% of participants were robust, 36.2% pre-frail, and 1.5% frail. Between visits, 16.3% transitioned to a worse frailty stage, while 17.7% improved. Higher ALS was linked to increased odds of being pre-frail/frail at baseline (OR 1.11; 95% CI: 1.08-1.15), and to a higher risk of transitioning from robust to prefrail/frail (RRR 1.06; 95% CI: 1.02-1.09). Depressive symptoms mediated 35% (95% CI: 25-47%) of the crosssectional and 17% (95% CI: 6.6-43%) of the longitudinal association between ALS and frailty. Conclusions: Socioeconomic factors influenced frailty onset but not its progression, whereas depressive symptoms mediated approximately 17% of the effect of ALS on frailty development over time. These findings highlight the importance of exploring the effect of interventions for depression on frailty progression.