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. 2025 Oct:76:605-613.
doi: 10.1016/j.jare.2024.12.021. Epub 2024 Dec 17.

Exploring the mediating roles of depression and cognitive function in the association between sarcopenia and frailty: A Cox survival analysis approach

Yan Zhu  1 , Haojie Yin  2 , Xianli Zhong  1 , Qin Zhang  3 , Li Wang  4 , Rong Lu  5 , Ping Jia  6
Affiliations

Exploring the mediating roles of depression and cognitive function in the association between sarcopenia and frailty: A Cox survival analysis approach

Yan Zhu et al. J Adv Res. 2025 Oct.

Abstract

Background: Despite earlier research indicating a potential link between the development of sarcopenia and an elevated risk of frailty, the lack of comprehensive prospective data on the correlation between sarcopenia and frailty incidence leaves open the question of whether depression and cognitive function mediate this association.

Objective: The principal aim of the current investigation was to evaluate the intricate interplay among sarcopenia, depression, and cognitive function collectively influence the risk of developing frailty.

Methods: The participants included in this study were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS), which collectively encompassed a total of 3,108 participants. To examine the interrelationships among sarcopenia, depression, cognitive function, and the incidence of frailty, we employed Cox regression models along with structural equation modelling, while making necessary adjustments for baseline demographic characteristics and various lifestyle factors.

Results: During a 4-year follow-up, we documented 753 frailty events. Compared to those with nonsarcopenia, those with possible sarcopenia and sarcopenia presented risk ratios for frailty events of 1.354 (95 % CI: 1.156, 1.586) and 1.514 (95 % CI: 1.203, 1.907), respectively. Stratified analyses by different statuses of sarcopenia further revealed that the significant effect of depression on frailty was present across all groups (nonsarcopenia, possible sarcopenia and sarcopenia), whereas the effect of cognitive function on frailty was limited to the non-sarcopenia and possible sarcopenia groups. Mediation analysis showed that sarcopenia was correlated not only with frailty through depression and cognitive function separately but also through a chain-mediated effect of depression and cognitive function together.

Conclusions: Sarcopenia is associated with frailty, depression and cognitive function playing partial, mediating roles. Frailty's susceptibility to depression and cognitive function differs based on sarcopenia status. Therefore, comprehensive interventions that include sarcopenia screening, interventions, improvements in depression, the promotion of mental health, and delays in cognitive decline will be more effective in preventing and delaying frailty. This effectiveness is particularly relevant for middle-aged and older adults who reside in China.

Keywords: Cognitive function; Depression; Frailty; Sarcopenia.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

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Graphical abstract
Fig. 1
Fig. 1
Flow diagram for participants included in the study.
Fig. 2
Fig. 2
The path coefficient (β) from dummy variables, depression and cognitive function to frailty status.
See this image and copyright information in PMC

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