The relationship between sarcopenia and cognition is reflected in physical mobility and brain function.

Sarcopenia is an aging-related, progressive and generalized skeletal muscle loss disorder characterized by decreased muscle mass, decreased muscle strength, and/or reduced somatic functions (Cesari and Kuchel, 2020), and it is associated with frailty (Gielen et al., 2023), heart disease (Sasaki and Fukumoto, 2022), diabetes (Guerrero et al., 2016; Umegaki et al., 2017), and many other chronic conditions. The definition and diagnosis of sarcopenia continues to evolve, in 2019 the Asian Working Group for Sarcopenia (AWGS) proposed defining muscular dystrophy as “sarcopenia” as well (Chen et al., 2020), which means that sarcopenia is no longer a disease in the traditional sense, but rather a state of muscle atrophy that accompanies aging. Similarly, cognitive decline is a pathological condition that includes a range of cognitively related symptoms. Frailty is a multidimensional syndrome including physical, social, and cognitive aspects, among which physical and cognitive decline are fundamental dimensions (Arai et al., 2018; Kelaiditi et al., 2013).

Current findings in Asia and Europe have found that sarcopenia was associated with the incidence of neurological disorders such as cognitive dysfunction, Alzheimer’s disease and depression (Yang et al., 2022; Lee et al., 2018), and was even a predictor of Alzheimer’s disease, mild cognitive impairment (MCI) and cognitive decline (Beeri et al., 2021). Sarcopenia and cognitive dysfunction not only share many common pathogenic mechanisms of myokines, endocrine and inflammatory markers, but also have some external influencing factors such as lifestyle of lack of physical activity and poor nutritional habits (Cannataro et al., 2021; Sui et al., 2020). Evidence suggests that muscle loss increases the risk of cognitive decline, such as reduced handgrip strength and gait speed (Basile and Sardella, 2021; Chou et al., 2019).

The diagnosis of sarcopenia in early stages has positive implications for the prevention of cognitive dysfunction (Peng et al., 2020). The presence of early motor dysfunction has been suggested as a potential predictor of further cognitive impairment, such as the motoric cognitive risk syndrome (MCR)(Basile and Sardella, 2021). At the same time, separate diagnostic indicatorss of sarcopenia have been associated with cognitive dysfunction (McGrath et al., 2020). Better cognition was associated with a lower risk of developing sarcopenia and could explain some of the potential pathways contributing to sarcopenia (Hu et al., 2024). Studies in the US, Spain, Brazil, Saudi Arabia, and Japan reported a range of MCI prevalence between 6.5 and 38.6% (Lu et al., 2021), compared with 20.8% reported by the Chinese National Centre for Prevention and Control of Chronic and Non-communicable Diseases (Jia et al., 2014), that early recognition of cognitive deterioration is essential to prevent further deterioration of cognitive impairment, especially to prevent MCI turning into dementia. A study based on the China Health and Retirement Longitudinal Study (CHARLS) showed that the incidence of MCI in non-sarcopenia, possible sarcopenia, and sarcopenia groups was 10.1%, 16.5%, and 24.2%, this not only confirms the cross-sectional association between the two, but also suggests the progression of muscle atrophy will accelerate cognition decline.

Although several studies have been conducted to assess potential associations, most of them focused on cognition in general and did not analyze subdomains in detail, and previous studies have demonstrated significant differences in age (Hu et al., 2022; Salinas-Rodriguez et al., 2021; Sugimoto et al., 2022). Considering whether sarcopenia contributes to cognitive decline, we delve into the cognitive profiles of individuals with sarcopenia, with particular emphasis on specific cognitive domains. Subsequently, we assess the evolution of muscle atrophy and cognitive abilities over a 12-week period to explore whether the process of muscle atrophy is accompanied by cognitive function decline.

Through a cross-sectional and longitudinal study, we validated the correlation between sarcopenia and cognitive function, revealing changes in several cognitive subdomains. We demonstrated a moderate positive relationship between cognitive scores and grip strength in older males, suggesting grip strength as a reliable predictor of cognitive impairment. However, no significant differences were observed with calf circumference and muscle mass. Individuals with sarcopenia exhibited lower total MoCA cognitive, particularly in executive function, fluency, calculation and delayed recall. Cognitive ability further declined with increasing severity of muscle atrophy. The progression of muscle atrophy was associated with significant deterioration in cognitive functions, such as fluency.

More research confirmed that cognitive function was related to muscle strength rather than muscle mass (Moon et al., 2016; Menant et al., 2017), while cross-sectional studies have shown an association between overall cortical atrophy and low skeletal muscle mass in patients with cognitive impairment (Abellan van Kan et al., 2012). Both the AWGS and the Chinese Expert Consensus emphasize grip strength as an important indicator for screening and diagnosing sarcopenia (Chen et al., 2020). Grip strength was reliable and consistent with MCI and dementia, making it a useful tool for exploring the sarcopenia-cognition relationship (McGrath et al., 2020; Dudzińska-Griszek et al., 2017). A systematic evaluation revealed that six out of seven studies documented a significant correlation between grip strength, hand dexterity, and cognitive function in older adults (Kobayashi-Cuya et al., 2018). Recent research by Vancampfort et al. (2019) reported that lower grip strength in middle-aged and older adults was associated with an increased likelihood of MCI. Others have shown correlations between grip strength and cognitive subdomains such as MMSE (Dudzińska-Griszek et al., 2017), information processing speed and executive function (Hooghiemstra et al., 2017), stroop task performance and 6-item cognition test scores (Ramnath et al., 2018). This suggests that delaying cognitive decline is just as important as maintaining physical mobility. Therefore, we suggest that perhaps more attention should be paid to muscle work and daily mobility than to musculature.

The worsening of sarcopenia has been found to lead to poorer cognitive functioning, particularly in specific dimensions. Previous studies indicate that Chinese elderly with more severe sarcopenia have higher rates of MCI compared to those with possible sarcopenia (Hu et al., 2022). These findings suggest that the severity of sarcopenia increases the likelihood of cognitive impairment and negatively impacts cognitive function. Analyses from the CHARLS database showed associations between sarcopenia and cognitive functions such as orientation, memory, calculation and drawing (Hu et al., 2022). Other studies also reported correlations between sarcopenia and verbal fluency and recall abilities (Salinas-Rodriguez et al., 2021; Szlejf et al., 2019). Similar to these results, fluency and delayed recall were also significantly worse in our results, and we believe that fluency is associated with recall and expression, which explains why dementia and Alzheimer’s disease occur at higher rates in people with sarcopenia (Beeri et al., 2021; Waite et al., 2021). Computational ability and logical agility were related to thought integration, it is thought that people with sarcopenia have reduced responsiveness and poorer executive performance, explaining their motor speed such as poor gait speed and decreased balance (Bahureksa et al., 2017).

The association between sarcopenia and cognitive impairment could be explained from physiological and functional links. Neuromuscular junction dysfunction (Moreira-Pais et al., 2022), neuronal hyperexcitability, dopaminergic dysfunction, muscle-brain axis (Arosio et al., 2023) and brain atrophy are among the regulatory processes associated with the pathophysiology of sarcopenia. Secondly, changes in the structure and function of the neuromuscular system. A prospective study in 2021 found moderate to severe parietal lobe atrophy, overall cortical atrophy, and medial temporal lobe atrophy were more common in the sarcopenia group compared to the non-sarcopenia group (Hsu et al., 2021). In the same year, a Korean longitudinal study involving 1,284 individuals over four years using magnetoencephalography found a greater decrease in gray matter volume in the sarcopenia group (Yu et al., 2021). This finding suggests that sarcopenia accelerates gray matter atrophy, low muscle mass is linked to reduced frontal, parietal, and occipital gray matter volumes, with significant parietal gray matter atrophy in sarcopenic patients. Finally, in terms of functional performance, older individuals with sarcopenia are more prone to falls as they experience a decline in balance, in turn the poorer the muscle control and balance of body, less active and more susceptible to sarcopenia, producing a slower gait speed (Kim and Won, 2019), decreased balance (Basile and Sardella, 2021), and psycho-emotional functioning (Lee et al., 2018; Ohta et al., 2019; Scisciola et al., 2021).

Although the causal relationship have not been confirmed, most studies have shown that the deterioration of physical function precedes cognitive function decline, such as gait speed and suffering from MCR (Basile and Sardella, 2021; Skillbäck et al., 2022). Therefore, strengthen physical activity are commended, which will not only improve muscle performance (Billot et al., 2020), but also affect cognition through the muscle-brain axis, such as L-6, which increases 100-fold during physical exercise (Pedersen and Febbraio, 2008). Post-exercise blood circulation also regulates brain functions and protects neurons from damage, increases neurogenesis and plasticity in the hippocampus, enhances the function of the prefrontal cortex (Scisciola et al., 2021; Nuzum et al., 2020). These can also be maintained through nutritional supplementation, creatine monohydrate supplementation may confer beneficial effects on cognitive function particularly in the domains of memory, attention time, and processing speed (Xu et al., 2024), Vitamin D and the Mediterranean diet can also help prevent dementia when providing the body with adequate nutrition (Cannataro et al., 2021; Psaltopoulou et al., 2013). We propose that sarcopenia aggravates cognitive impairment, lifestyle factors such as exercise and diet may improve the progressive aggravation.

Several limitations are in this study. First, although age and chronic diseases have been controlled, the baseline habitual physical activity of the participants was not assessed. In this study, only diagnostic indicators of sarcopenia were evaluated, using scales for cognitive function rather than objective indicators, such as brain imaging. Second, the causal relationship between muscle atrophy and cognitive impairment is difficult to explain. Last, the number of samples retained during the secondary collection was small. These need to be further refined in subsequent studies.

There is a correlation between sarcopenia and cognitive function, with older individuals in sarcopenia performing worse in overall cognition as well as in executive function, fluency, calculation and delayed recall. Muscle atrophy was accompanied by cognitive decline after the exclusion of intervening factors such as age, chronic diseases and physical activity, particularly affecting verbal fluency. Sarcopenia and decreased muscle function may have dual implications for the exacerbation of cognitive impairment.