This study is the first to analyze the connection between sarcopenia and various types of cognitive dysfunction. The findings indicate a higher prevalence of sarcopenia in individuals with cognitive dysfunction, with varying levels of prevalence at different stages of the disease. Furthermore, the study examines factors related to both conditions, offering novel insights into preventing muscle impairment in patients with aMCI and AD.
To investigate the prevalence of cognitive dysfunction, including different types, and its possible correlation. Based on an analysis of 3975 studies in the 12 included studies, the proportion of MCI with sarcopenia was 10.24% and that of AD with sarcopenia was 21.09% (95% CI: 0.131–0.299). Furthermore, our study revealed a noteworthy correlation between sarcopenia and both mild cognitive impairment (MCI) and Alzheimer's disease (AD). Additionally, we identified significant associations among various subgroups, including country, age, and other study characteristics.
Despite extensive research, the risk factors and predictors for cognitive dysfunction and sarcopenia remain incompletely understood. Our study demonstrated variations in prevalence across diverse ethnic groups, levels of cognitive dysfunction, and age categories. Notably, these results suggest that age alone cannot solely account for the significant link between these two conditions.
Multiple studies have indicated a correlation between sarcopenia and cognitive dysfunction, and researchers have put forth several possible mechanisms to explain this association. One possible explanation is that individuals with cognitive dysfunction are more likely to engage in reduced physical activity compared to the general population. This reduction in physical activity can lead to a decline in muscle mass and contribute to the diagnosis of sarcopenia in older adults[24]. Furthermore, low-grade inflammation, frequently associated with both sarcopenia and cognitive dysfunction, may play a role. Inflammatory markers like interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have been recognized as influential factors in the development of these diseases. [25, 26]. Moreover, adequate and varied nutrition has a distinct impact on the health and function of muscle cells and neurons. Deficiencies in nutrient intake or an inappropriate diet can lead to cognitive dysfunction and sarcopenia[27, 28]. Lastly, cognitive dysfunction can exacerbate neuronal changes in the central nervous system, resulting in alterations in neurotransmitter levels and activity. When combined with inadequate oxygen supply to the brain, this can lead to diminished motor units and impaired muscle activation, potentially contributing to the development of sarcopenia[29]. Therefore, there is a strong connection between sarcopenia and cognitive dysfunction, and they share several common underlying mechanisms.
Our findings also indicate that the proportion of MCI with sarcopenia is lower compared to that of AD with sarcopenia. Generally, MCI is considered as a precursor stage of AD[30]. The prolonged presence of oxidative stress, which is closely linked to chronic diseases, is a significant contributor to age-related muscle wasting. This oxidative stress disrupts the delicate equilibrium between protein synthesis and breakdown, leading to impaired functioning of the mitochondria, initiation of apoptosis, and ultimately contributes to the varying incidence of sarcopenia between different conditions[31]. Additionally, the accumulation of oxidative and nitrosative stress products over time is a significant risk factor for cognitive decline[32]. In addition, MCI and AD are different types of cognitive dysfunction and differ in severity, which may lead to different attitudes, attention, care, and medication approaches to both disorders by healthcare providers and patients, so the results should be interpreted with greater caution.
Our subgroup meta-analysis showed significant heterogeneity in rating scales, diagnostic criteria for sarcopenia, and population. The EWGSOP diagnostic approach reports a lower prevalence of sarcopenia diagnostic methods compared to the guidelines defined by AWGS, and it may be argued that this approach objectively takes into account low muscle mass and low muscle strength and is more rigorous than the single-measure approach. In addition, for the measurement of sarcopenia, previous studies have shown that BIA and DXA have different diagnostic rates in Asian and non-Asian populations. Similarly, assessment tools for cognitive dysfunction also influenced our results, as these questionnaires may introduce subjective bias associated with self-reported responses.
Finally, in our analysis of sarcopenia and MCI and AD, the sensitivity analysis revealed no significant heterogeneity among the main studies, despite variations in subgroup analysis related to ethnicity, diagnostic methods, and age.
Our study has a number of limitations. Firstly, we only included studies written in English, which may introduce a selective bias in our findings. Secondly, most of the studies we reviewed were of cross-sectional design, and not all literature met high standards of quality. Additionally, the subjects included in the studies were mainly elderly individuals living in the community, which could lead to selection bias. Lastly, while we consider MCI and AD to represent different levels of severity, the choice of scale used for diagnosis may influence the outcomes. In summary, we recommend interpreting the results of this study with caution.