Associations of sarcopenia and its defining components with cognitive function in community-dwelling oldest old

Sarcopenia, the age-related decline in skeletal muscle mass concomitant with decreased muscle function [1], has been formally recognized as a geriatric disease with an ICD-10-CM diagnosis code. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP2) updated the operational definition and clinical algorithm of sarcopenia by recommending using low muscle strength and low muscle mass to diagnose sarcopenia. Although the newest 2019 consensus of the Asian Working Group for Sarcopenia (AWGS) also contended that diagnosing sarcopenia required both the measurement of muscle mass, muscle strength and gait speed (GS) [2]. An increasing number of studies have indicated that single or multiple components, like muscle strength, is the key element in sarcopenia [3] in recent years. Growing evidence has shown that greater levels of handgrip strength (HS) is associated with lower risks of cardiovascular disease, all-cause and cardiovascular mortality, physical function, and frailty [4‐6]. Therefore, muscle strength is emphasized as the trigger for further assessment and interventions by the introduction of the “probable sarcopenia” concept in the EWGSOP2 definition [7].

As the most prevalent cause of physical impairment, sarcopenia has repeatedly been associated with adverse outcomes such as frailty, hospitalization and increased mortality [7, 8]. Although some basic science and epidemiological studies have suggested a possible shared pathophysiology related to inflammatory markers and the hormonal pathway between sarcopenia and cognitive impairment [9, 10], evidence of this association among different populations remains controversial. The large variability was attributed to the methods of defining sarcopenia (based on single or multiple components), the age scope of the studied population and the usage of different detections for cognitive function. For instance, a prospective follow-up study with 555 older adults aged 85 years at baseline reported that poor HS predicted accelerated dependency in activities of daily living (ADL) and global cognitive decline using Mini-Mental State Examination (MMSE) in oldest old [11]. Studies among a population aged 60 years and over also found that low HS was associated with cognitive decline in information processing speed using measures of Digit Symbol Substitution Test (DSST) [12‐14]. By contrast, another study included 14,775 Americans at least 50 years old reported that muscle strength capacity and cognitive function may parallel each other [15]. Results from the Tasmanian Study of Cognition and Gait (TASCOG) showed that decline in GS was associated with impairment in executive function, but not other cognitive domains among participants aged 60–85 years [16], while study on Canadians aged older than 65 years old showed no significant association between slower GS and poorer cognitive function detected by MMSE [17]. Moreover, no association was observed between decreased muscle mass and cognitive dysfunction detected by MMSE and the Peterson criteria after 7 y of follow-up in the EPIDOS-Toulouse group [18]. Although MMSE is the most widely used tool when assessing cognitive impairment, some studies report that the Montreal Cognitive Assessment (MoCA) is superior to the MMSE in differentiating mild cognitive impairment (MCI) patients from a healthy control group [19, 20].

Aging is an essential risk factor for sarcopenia and decline of cognitive function [21], and has been associated with a reduced activity tolerance attributed to changes in this skeletal muscle blood flow [22]. MCI is the abnormality of cognitive functions in populations matched for age and education levels, but without loss of functional abilities and skills in everyday social and occupational life [23], and it is associated with increased risk of developing dementia. In 2030, there are predicted to be 16.5 million people age 60 or older with dementia, 6.9 million males and 9.6 million females in China [24]. Identifying risk factors associated with MCI among the oldest old may help to develop early assessment tools for detection of MCI, enabling multi-domain lifestyle interventions at an early phase of dementia [25].

Previous studies showed that associations between handgrip strength, gait speed and cognition were not consistent among oldest-old individuals born in different decades [26], and the associations between blood pressure and cognition were contradictory among young and middle-aged subjects and oldest old subjects [27]. There is scarcity of information on the relationship between components of sarcopenia and different domains of cognitive function among the oldest old in China [28]. Therefore, in this study, we aimed to investigate the association of sarcopenia defined according to the updated 2019AWGS criteria and each of its defining components with performance of whole and multiple cognitive domains in community-dwelling oldest old (over 80 years old) in China.

This study demonstrated that sarcopenia and its defining component HG and GS, were significantly associated with MCI in a sample of community-dwelling oldest old in China. This study also showed that low HS was associated with performance on global and several domains of cognitive function assessed by MoCA, including visuospatial and executive function, naming and delayed recall ability.

In our study, the prevalence of sarcopenia among community-dwelling oldest old was 35.5%, which was higher than people older than 60 (28.8%) in east China [36] and people over 50 (19.31%) in western China [37]. We found that AWGS-based sarcopenia was associated with higher risk of MCI. However, evidence from previous studies about the association between sarcopenia and cognitive function of older adults were controversial, which may be partly due to the different assessment tools of cognitive function and study population. A group study among British older men over 65 reported that no significant association was evidenced between FNIH-defined sarcopenia and mild or severe cognitive impairment assessed by MMSE [38]. Another cross-sectional analysis among 3025 women aged 75 years and older also demonstrated no significant associations between different operative sarcopenia definitions and cognitive impairment (measured by short portable mental status questionnaire) [39]. By comparison, our findings were consistent with previous studies in Asian populations [4, 37, 40]. In a cross-sectional analysis of 201 community-dwelling Korean women with the mean age of 74 years old, sarcopenia was inversely associated with MMSE and CES-D scores [41]. Also, in a prospective study with 131 adults aged 65 years and older in Japan, sarcopenia was founded to be an independent risk factor of cognitive deterioration assessed by MMSE during the 1-year study period [40]. However, the aforementioned studies were not conducted among the oldest old population and failed to examine the relationship between individual defining components of sarcopenia and different domains of cognitive function. Our study used MoCA to detect the mild stages of the cognitive impairment, which was able to differentiate between distinct clinical dementia syndromes at early stages of disease with high sensitivity and specificity [42]. Additionally, in this study, we found that sarcopenia was not associated with global and different domains of cognitive function after adjustment for multiple confounder. This result was conflicting, since most of the previous studies reported that sarcopenia-related cognitive impairment was mainly in the language and executive function using MMSE and Phonemic Verbal Fluency Test. (VFT) [38, 43] The discrepancy may be due to the smaller age range of our study population. Future longitudinal studies are still needed to clarify the association between sarcopenia and cognitive subdomains among populations in this age group.

This study found that low HS was not only associated with higher risk of MCI, but also associated with less scores in global cognitive function, visuospatial and executive function, and delayed recall in adjusted models, which indicated that low HS might be used as an early clinical screening tool for cognitive impairment among the oldest old population. Our findings are consistent with those of previous studies [11, 39, 44, 45]. Diana et.al found that poor HS is a predictor of accelerated cognitive decline using total scores of MMSE in the oldest old (> 85 years old) in Leiden [11]. Kim et.al also reported that baseline HS of 2378 Korean adults aged 65 or older was found to be positively associated with MMSE scores at baseline and over 8 years’ time [46]. Similar to our results, one cross-sectional analysis in Brazil also showed that low muscle strength was associated with poorer performance in all assessed cognitive domains [43], while Taekema et al. only found an association with MMSE changes and not with other cognitive variables, such as memory, attention, and processing speed [47]. Whether HS could be a predictive value for cognitive decline and its exact mechanism needed to be further explored in longitudinal studies.

Also, similar to previous findings [48‐51], we found that low GS was associated with MCI after adjusting for all confounders. The associations between low GS and different domains of cognitive function were not fully studied in previous studies. Our study found that GS was positively associated with global cognitive function, visuospatial and executive function and abstraction in crude analysis. However, no associations were found after full adjustment, which was inconsistent with previous studies. Annika et al. reported that low GS was associated with impairment in executive function among community-dwelling older people with CI [52]. The heterogeneity of results may be due to differences in study populations and diagnosis criteria of low GS.

The associations between low skeletal muscle mass and incidence of MCI, as well as cognitive subdomains were also analyzed in our study. We found that low muscle mass was only associated with poorer performance in orientation in crude analysis, and no association was observed between low muscle mass and risk of MCI. Results among previous studies regarding the association between cognitive impairment and low skeletal muscle mass have been inconsistent: Won et al. found that skeletal muscle mass of elders older than 60 years old detected by bioelectrical impedance analysis (BIA) was linked with cognitive function [53], while Moon et al. showed that low muscle mass of Korean older adults was not associated with progression to cognitive impairment after 5 years of follow-up in the prospective study [54]. The cross-sectional analysis in Brazil also showed that low muscle mass was associated with poorer performance in the VFT [43] According to one systematic review, controversies among studies in the association of muscle mass with cognitive impairment were mainly due to differences of body composition devices [55], since the association might be stronger with use of BIA to measure body composition versus DEXA [56].

The possible mechanism between sarcopenia, low HS, low GS and cognitive function lies in that inflammations, oxidative stress, and hormonal changes share a common pathological role [57]. Several possible mechanisms may reinforce our conclusions that the association of sarcopenia and cognitive function is probably driven by alterations in muscle strength and not in muscle mass. First, muscle strength could reflect the change of brain-aging processes, such as the functioning of the central nervous system or white matter integrity [46]. Secondly, low HS and cognitive impairment may share common pathophysiological pathways such as systemic inflammation, insulin resistance and oxidative stress, all of which may contribute to both weak muscle strength and cognitive impairment [58]. Additionally, some studies also reported that changes in cognition and walking speed interact to predict future dementia [59]. It is thought that walking and cognition rely on similar brain regions, predominantly in the prefrontal cortex [60]. Neurodegeneration is a possible underlying mechanism linking declines in physical and cognitive function, with lower GS associated with changes in subcortical white matter and cortical gray matter volumes [61]. Another potential mechanism is neuroinflammation, which is thought to lead to impaired neuroplasticity in the brain areas controlling motor and cognitive function [60]. High concentrations of inflammatory markers are predictive of new-onset dementia and have also been implicated in mobility impairment [62].

The present study has many strengths. First, this is the first study to investigate the associations between sarcopenia and its defining components with different cognitive domains among Chinese community-dwelling oldest old, which provided extra support in addition to composite sarcopenia and global cognition function [63]. Our findings may have important implications in the early recognition of sarcopenia and cognitive impairment. Second, we used the MoCA scale as an early manifestation of MCI, which was more comprehensive and sensitive than other cognition measures with good test-retest reliability [64]. Third, our participants were a reliable group of community-dwelling oldest old coming from the real world, who had electronic health records from long-run medical centers. Our interview took place in these medical centers, which guaranteed reliability and were more representative of the real world.

There are several limitations in the present study. First, we used cross-sectional models so that causality could not be proved. Longitudinal studies will be required to illustrate the relationship between sarcopenia and MCI among adults older than 80 years old. Second, this study was done using a relatively small number of cases at one retirement community. However, our data can be considered as relatively valid because it was collected using standardized methods. Third, we only used MoCA to assess cognitive performance, which has no validated subscales in several cognitive domains. Therefore, other neuropsychological testing batteries are needed to have a more comprehensive assessment of cognitive abilities in future studies.

The present results showed that sarcopenia was significantly associated with MCI among community-dwelling oldest old. Furthermore, our findings suggested that low HS may be useful to identify cognitive impairment, decreased visuospatial and executive function, naming and delayed recall at an earlier stage in non-disabled older adults living in the community. Additional longitudinal studies are needed to clarify associations between sarcopenia and its defining components and different domains of cognitive function.