Grip strength in the association between frailty and new-onset depression in older adults: a multinational longitudinal study.

<h4>Background</h4>Frailty is a multidimensional geriatric syndrome characterized by cumulative physiological decline. While associated with various adverse outcomes, the longitudinal relationship between frailty and new-onset depression across diverse national populations remains insufficiently explored. This study investigated the association between the Frailty Index (FI) and new-onset depression in three large aging cohorts.<h4>Methods</h4>This multinational longitudinal cohort study included community-dwelling adults aged ≥50 years from three nationally representative aging cohorts: the Health and Retirement Study (HRS), the English Longitudinal Study of Aging (ELSA), and the Survey of Health, Aging and Retirement in Europe (SHARE). Frailty was assessed using a deficit accumulation-based frailty index (FI). New-onset depression was defined by validated CES-D 8 or EURO-D scores among participants free of depression at baseline. Associations were estimated using Cox proportional hazards, Fine-Gray competing risk, and discrete-time logistic regression models. Dose-response patterns were examined using restricted cubic splines, and mediation analysis evaluated the role of grip strength.<h4>Results</h4>Over median follow-ups of 8 (HRS), 2 (ELSA), and 4 (SHARE) years, 749, 973, and 7,821 participants developed new-onset depression, respectively. Cohort-specific incidence rates were 34.5% in HRS (749/2, 171), 18.6% in ELSA (973/5, 223), and 30.4% in SHARE (7, 821/25, 721). Adjusted analyses showed the FI was consistently associated with depression risk across all cohorts. Each one-unit FI increase was associated with an approximately 4% higher risk (HR = 1.04, <i>p</i> < 0.001 for all cohorts). Participants in the highest FI quartile had significantly elevated risk compared to the lowest. Results were robust across all statistical models. Restricted cubic splines indicated a nonlinear association, which was partially mediated by grip strength.<h4>Conclusion</h4>Frailty is an independent predictor of new-onset depression in older adults across diverse international populations. Early frailty identification and targeted multidimensional interventions-including grip strength enhancement, structured physical activity, nutritional optimization, and psychosocial support-may help reduce depression incidence and promote healthy aging.