Key Takeaways & Executive Findings
- •• Sarcopenia-related traits (fat-free mass, grip strength, walking speed) are positively causally associated with cognitive function in European populations. • Walking speed shows the strongest positive causal effect on cognitive function (OR=3.069), suggesting it may be a key indicator. • Reverse analysis indicates cognitive function only causally affects walking speed, not muscle mass or grip strength. • The study supports the 'muscle-brain axis' hypothesis and suggests sarcopenia could be a predictor for cognitive impairment.
Abstract
BACKGROUND: In recent years, multiple epidemiological studies have suggested a potential pathological link between sarcopenia and cognitive impairment. However, due to methodological limitations in traditional observational studies and difficulties in controlling confounding factors, their genetic-level causal relationship has not yet been fully elucidated. OBJECTIVE: To systematically analyze the causal relationship and underlying pathogenesis between sarcopenia and cognitive impairment in European populations using Mendelian randomization methods. METHODS: This study utilized genome-wide association study (GWAS) summary data for sarcopenia-related phenotypes (whole-body fat-free mass, hand grip strength, and walking speed) from the UK Biobank, and cognitive function GWAS summary data from the IEU database. After rigorous threshold filtering and linkage disequilibrium clumping, bidirectional Mendelian randomization analyses were performed. Forward analysis used sarcopenia-related traits as exposures and cognitive function as the outcome; reverse analysis swapped the direction. Inverse variance weighting was the primary analysis method, supplemented by weighted median, MR-Egger regression, and robust adjusted profile scoring. Heterogeneity and sensitivity analyses were conducted to ensure robustness. RESULTS AND CONCLUSION: Forward MR-IVW analysis showed that whole-body fat-free mass (OR=1.091, 95%CI: 1.001-1.188, P=0.045), left hand grip strength (OR=1.283, 95%CI: 1.077-1.527, P=0.005), right hand grip strength (OR=1.220, 95%CI: 1.022-1.456, P=0.027), and walking speed (OR=3.069, 95%CI: 1.997-4.717, P<0.001) were significantly positively associated with cognitive function. Reverse analysis showed that cognitive function had a significant positive causal effect only on walking speed (OR=1.023, 95%CI: 1.004-1.043, P=0.014), but not on fat-free mass or grip strength. Sensitivity analyses indicated some heterogeneity but no horizontal pleiotropy. The findings suggest a causal relationship between sarcopenia and cognitive impairment, indicating that sarcopenia may serve as a predictor for cognitive impairment, providing a theoretical basis for early clinical screening. This study, based on international public databases, offers new evidence for the association between sarcopenia and cognitive impairment in Chinese populations and has important reference value for early screening and prevention of both diseases.
1. Introduction
In the context of accelerating global population aging, cognitive impairment has become a major public health issue that urgently needs to be addressed [1]. Cognitive impairment is a clinical syndrome characterized by progressive multidimensional cognitive dysfunction, including memory decline, slowed thinking, and language impairment, with its global prevalence continuously rising [2-4]. Given the significant limitations of current clinical treatments, in-depth research on modifiable risk factors for this condition is of great practical significance for optimizing disease prevention and treatment systems.
Sarcopenia (SP) is a geriatric syndrome characterized by progressive loss of skeletal muscle mass and significant decline in muscle function [5]. The 2019 revised diagnostic criteria of the European Working Group on Sarcopenia in Older People (EWGSOP) clearly state that the diagnosis of sarcopenia requires meeting three core indicators: reduced muscle mass, decreased muscle strength, and impaired physical performance [6]. Epidemiological surveys show that the global prevalence of sarcopenia in the elderly is 10%-16% [7], and with the acceleration of population aging, the total number of patients worldwide is expected to exceed 200 million by 2060 [8]. Therefore, early intervention on controllable risk factors is crucial for the prevention and treatment of sarcopenia.
Sarcopenia and cognitive impairment share multiple common risk factors in their pathogenesis. Studies have shown that both sarcopenia and cognitive impairment can significantly increase the risk of adverse health outcomes such as falls, disability, dementia, and death [9-11]. Furthermore, clinical observations have found that patients with sarcopenia often have varying degrees of cognitive impairment, suggesting that sarcopenia may serve as an important biological marker for early identification of cognitive impairment [12]. However, existing evidence indicates that age alone cannot fully explain the association between sarcopenia and cognitive impairment [13]. In recent years, the 'muscle-brain axis' theory has provided a new perspective for understanding the link between sarcopenia and cognitive impairment [14]. This theory posits that skeletal muscle, as an endocrine organ, participates in bidirectional regulation between muscle and brain by secreting myokines (such as interleukin-6, brain-derived neurotrophic factor, irisin, etc.).
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Yin Xingxiao, Peng Hao, Song Yanping, Yao Na, Shen Zhen, Jiang Yang, Chen Hongbo, Huang Li, Song Yueyu, Li Yanqi, Chen Qigang (2026). Sarcopenia and cognitive impairment: a data analysis based on European population databases. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21355
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Frequently Asked Questions
What is the causal relationship between sarcopenia and cognitive impairment?
The study found that sarcopenia-related traits (fat-free mass, grip strength, walking speed) are positively causally associated with cognitive function, suggesting that sarcopenia may be a risk factor for cognitive impairment.
Which sarcopenia indicator has the strongest causal effect on cognitive function?
Walking speed showed the strongest positive causal effect on cognitive function (OR=3.069, 95%CI: 1.997-4.717, P<0.001), indicating that slower walking speed is strongly associated with worse cognitive function.
Does cognitive function causally affect sarcopenia?
Reverse Mendelian randomization analysis showed that cognitive function only had a significant positive causal effect on walking speed (OR=1.023, 95%CI: 1.004-1.043, P=0.014), but not on fat-free mass or grip strength.
What is the 'muscle-brain axis' theory?
The 'muscle-brain axis' theory suggests that skeletal muscle acts as an endocrine organ, secreting myokines (e.g., IL-6, BDNF, irisin) that mediate bidirectional communication between muscle and brain, potentially explaining the link between sarcopenia and cognitive impairment.
How can these findings be applied in clinical practice?
The findings suggest that sarcopenia, particularly low walking speed, could serve as a predictor for cognitive impairment, enabling early screening and intervention to prevent or delay cognitive decline.
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