ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
This article is part of the Research TopicBridging Sarcopenia and Cognitive Decline: Mechanistic Insights and Therapeutic StrategiesView all articles
Sarcopenia and cognitive impairment: a multidimensional study of clinical associations, shared genetics, and causal links
Provisionally accepted
- Huazhong University of Science and Technology, Wuhan, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective To comprehensively investigate the relationship between sarcopenia and cognitive impairment by examining their clinical associations, shared genetic architecture, and potential causal links, using a multidimensional approach. Methods To assess the sarcopenia and cognitive impairment risk, multivariable-adjusted logistic regression was conducted on Wuhan Junshan Community data. Utilizing large-scale GWAS summary statistics, we identified potential genetic overlaps between sarcopenia and cognitive impairment. Cross-trait pleiotropic analyses were conducted to uncover shared genetic loci and pleiotropic genes between these conditions. Comprehensive functional annotation and tissue-specific expression analyses were then performed to characterize the biological roles of these shared genetic factors. Finally, we employed Mendelian randomization (MR) approaches to examine potential causal relationships between sarcopenia and cognitive impairment. Results In this study, we recruited 575 participants for this observational study. Multivariable-adjusted logistic regression revealed a significant positive association between sarcopenia and cognitive impairment risk (OR = 2.89, 95% CI: 1.61-5.20). Genomic analysis revealed that there was a significant genetic correlation between sarcopenia and cognitive impairment, and 19 pairs of significantly correlated trait combinations were identified. Pleiotropic analysis revealed 79 risk loci and 428 pleiotropic genes such as FoxO3 and SLC39A8, which were enriched in neurodegenerative pathway and FoxO signaling pathway. MR analysis showed that appendicular lean mass and usual walking pace had potential causal protective effects on cognitive function, while low hand grip strength had the opposite effect. Conclusion This study provides evidence for both clinical and genetic links between sarcopenia and cognitive impairment, uncovering their potential biological mechanisms.
Keywords: Sarcopenia, cognitive impairment, genetic correlation, pleiotropic analysis, Mendelian randomization
Received: 18 Sep 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Kemeng, Huang, Mc, Zhang, Li, Luo and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ping He, pinghe@hust.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.