Motoric cognitive risk (MCR) syndrome is featured by subjective cognitive complaints and slow gait among older individuals (Verghese et al., 2019) and is considered to be a pre-dementia syndrome resemble mild cognitive impairment (MCI). However, while the diagnosis of MCI requires a time-consuming comprehensive neuropsychological assessment, diagnosis of MCR does not. This permits easier detection of members of the older population who are at risk for dementia. Previous studies have associated MCR syndrome with a wide range of adverse events, including dementia (Chhetri et al., 2017), frailty (Sathyan et al., 2019), falls (Callisaya et al., 2016), disability (Doi et al., 2017), and all-cause mortality (Ayers and Verghese, 2016; Beauchet et al., 2019; Maggio and Lauretani, 2019). Considering that effective treatment methods for dementia are still lacking, it is critically important to focus on pre-dementia syndromes and their modifiable risk factors to identify opportunities for early interventions to reduce the incidence of dementia.

China is the world’s most populous country. It is estimated that the number of Chinese people aged 80 years or older will quadruple over the next 35 years from 22.6 million in 2013 to 90.4 million in 2050 (Hu et al., 2018; Jia et al., 2020). The prevalence of dementia will increase in parallel to the population age. Dementia imposes heavy burdens on families, the healthcare system, and society (Jia et al., 2020). Several studies in different countries have reported the prevalence of and risk factors associated with MCR syndrome. An MCR prevalence study conducted across 17 countries reported a pooled prevalence of 9.7% globally (Verghese et al., 2014), and a cross-sectional study among Japanese older adults reported a prevalence of 6.4% (Doi et al., 2015). To date, only two studies have researched the prevalence and risk factors associated with MCR in China, examining a province-level and a city-level cohort, respectively. A full-scale picture of the epidemiology of MCR syndrome in China would help identify subgroups of older Chinese adults among whom MCR syndrome occurs more frequently than in the general population, thereby enhancing our understanding of potential risk factors for MCR syndrome among the Chinese elderly population.

In the present study, China Health and Retirement Longitudinal Study (CHARLS), a nationally representative prospective study of the community-dwelling Chinese population aged 45 years and over was used to determine the prevalence of MCR in China and to examine associated factors, such as lifestyle factors, physical function, and biomarker correlates, of MCR.

Of the 5,725 subjects (50.1% male, mean age: 67.9 years), the overall prevalence of MCR was 7.29% (95% CI: 6.62–7.96%). There was a lower prevalence of MCR within the male population (4.85%) compared to the female population (9.73%, p < 0.001). Participants aged 75 years or older had a higher prevalence of MCR than those aged below 75 years (7.85 vs 5.23%, p < 0 0.001). Figure 2 presents MCR prevalence by sex and age. Table 1 presents the characteristics and its comparison between groups. Marital status, BMI, and history of diabetes were not significantly different between groups. All other selected characteristics differed significantly between groups (p < 0.05). The characteristics of excluded participants due to incomplete data were shown in Supplementary Table S1: they were older, had lower prevalence of hypertension (27.87 vs 30.55%), lower proportion of married status (78.46 vs 80.87%) and current smoker (28.63 vs 32.28%), and had slower gait speed (0.75 vs 0.78) than the included participants.

In this large, nationally representative sample of Chinese community-dwelling older adults, we found that 7.3% of Chinese adults aged 60 years or older have MCR syndrome. We found lower or upper extremity functional limitations, ADL disabilities, weaker grip strength, exhaustion, and history of hypertension to be significantly associated with higher odds of MCR syndrome. Further analysis of clinical measures showed that CRP and cystatin C were significantly correlated with MCR.

Our study estimated that the overall prevalence of MCR syndrome was 7.3% among Chinese community-dwelling older adults, which is lower than the prevalence found by The Ningbo Community Study on Aging (12.7%) (Zhang et al., 2020) and The Beijing Longitudinal Study of Ageing II (9.6%) (Chhetri et al., 2020). The differences might be due to the age distribution, size, and representativeness of samples, the definition of low gait speed, and the regional health disparities in China (Mu, 2014; Miao and Wu, 2016). Previous studies among Japanese elders (Nakamura et al., 2013; Doi et al., 2017) have revealed a higher prevalence of MCR among participants recruited from memory clinics (13%), and a lower prevalence of MCR among community-based respondents (6.4%). The source of the population sample may, therefore, impact the recorded prevalence of MCR. Another global epidemiological study based on responses from 22 cohorts from 17 countries reported a pooled prevalence of 9.7% with a variance of between 2 and 16% across cohorts (Verghese et al., 2014). Some single-center studies in Mexico (Aguilar-Navarro et al., 2019) and Malaysia (Lau et al., 2019) have reported the prevalence of MCR syndrome to be 14.3 and 3.4%, respectively. These differences in prevalence may potentially result from differences in the sociodemographic characteristics of the studied populations, and differences in ethnicity, behavior, and lifestyle.

We found that weakness is significantly associated with higher odds of MCR syndrome, which is in line with previous studies (Zhang et al., 2020). There are several potential pathophysiological mechanisms underlying the association between low handgrip strength and dementia, including production of pro-inflammatory cytokines (Hatabe et al., 2020), serum testosterone level, and white matter hyper-intensities in the brain (McGrath et al., 2020). Moreover, higher handgrip strength may be a proxy for engagement in habitual exercise, which has been found to be a protective factor for dementia (Lamb et al., 2018). We also found exhaustion and ADL disability to be significantly related to MCR syndrome, a result that has not been reported before. Similar to weakness, exhaustion is one of the indicators of frailty (Hatabe et al., 2020), which shares underlying pathogeneses with Alzheimer’s disease, including vascular pathology, dysregulated energy production, and stress (Islamoska et al., 2019). We found that FTSS time was only associated with MCR in the minimally adjusted model; when all potential confounders were adjusted for, this association was not statistically significant. This result is inconsistent with Zhang’s study (Zhang et al., 2020), which showed FTSS time to be significantly associated with MCR syndrome. However, both studies used a cross-sectional design, and this association needs to be further examined by prospective cohort studies in the future. In the present study, lifestyle factors, such as obesity, smoking status, and drinking status, were not associated with MCR after adjusting for all potential confounders. There have been numerous studies on the associations between lifestyle factors and dementia. However, few studies have focused on the associations between lifestyle factors and MCR syndrome. Two previous studies of the Chinese population showed that obesity and MCR syndrome are not correlated (Chhetri et al., 2020; Zhang et al., 2020), which is in line with our results. Notably, a recent meta-analysis indicated that a BMI ≥30 is not linked with an increased risk of all-cause dementia and non-vascular dementia (Lee et al., 2020). Consistent with the work of Chhetri and Zhang, we found no association between MCR and drinking status. However, while their work identified an association between MCR and smoking, we found no such association in the present study. Previous studies have confirmed that smoking, as a major cardiovascular risk factor, is associated with an increased risk of cognitive decline (Baumgart et al., 2015). It is important to note that there may be subtypes of MCR, specifically those that are characterized both by subjective cognitive complaints and objective cognitive decline, and those that have only subjective cognitive complaints without objective cognitive decline. The high proportion of MCR patients without objective cognitive decline might render the association between smoking and MCR insignificant. Moreover, cross-sectional study designs might not be robust enough to accurately capture these associations.

We observed an elevated level of CRP, an important marker of inflammation, among older adults with MCR. The associations between inflammatory markers, cognitive performance, (Baumgart et al., 2015; Chaparro and Suchdev, 2019; Qin et al., 2019), and gait speed (Verghese et al., 2011) have been repeatedly reported. Our study was the first of its kind to link elevated levels of CRP to MCR, which further supports the view that inflammation plays a crucial role in pathological declines in cognitive performance and gait speed. Additionally, we found MCR patients to have higher SBP levels than those without MCR, which agrees with the finding that participants with a history of hypertension have 1.48 times higher odds of having MCR syndrome. Similar findings were reported in a study by Zhang and others (Zhang et al., 2020). Furthermore, in the present study, we found that 20.29% of MCR patients had a hemoglobin concentration below 12 g/dl, the cutoff for anemia defined by the World Health Organization (Chaparro and Suchdev, 2019), as opposed to 14.91% among participants without MCR. This finding is consistent with evidence that anemia is an independent risk factor for cognitive decline (Qin et al., 2019) and frailty (Ruan et al., 2019). Notably, the multivariate analyses showed no statistically significant association between SBP, hemoglobin and MCR. Future studies are still warranted to further investigate these associations. Moreover, compared to the participants without MCR, proportionally more MCR patients had an elevated level of cystatin C (31.88 vs 23.82%, p < 0.001), a marker of kidney function (Jensen et al., 2017). The multivariate analysis also showed that cystatin C were significantly associated with MCR both as continuous and categorical variable. Previous studies have found that patients with chronic kidney disease (CKD) who are treated with dialysis have impaired physical functioning (Painter and Marcus, 2013), and impaired kidney function has been associated with impairments in learning and memory, language, complex attention, executive function, and global cognitive function among elders (Månsson et al., 2019).

Our study has several strengths. First, to our knowledge, this is the first study to examine the prevalence of MCR in a representative cohort of Chinese older adults. Second, our study offers comprehensive insight into the variety of factors associated with MCR syndrome by accounting for physical performance and clinical measures in community-dwelling Chinese older adults. Our findings will further the understanding of the pathophysiological mechanisms underlying MCR syndrome and the development of deep multifactorial interventions for MCR syndrome. However, some limitations of our study should also be noted. Firstly, this analysis is based on cross-sectional data; therefore, we were unable to establish a causal association. Future studies utilizing a prospective design may elucidate a potential dynamic association between these related factors. Second, selection bias may exist in this study since only community dwellers were enrolled in the baseline survey of the CHARLS. Therefore, our estimates of the prevalence of MCR may not generalize to the entirety of the Chinese elderly population. Thirdly, some modifiable associated factors were measured based on self-reported answers, such as ADL disabilities, functional limitations and cognitive function. This might be subject to recall bias and lead to overestimation or underestimation of exposure. Finally, traits associated with MCR were only measured once; these measures may vary over time. Therefore, future research must characterize the trajectories of MCR over time, and further explore their relation to adverse outcomes, including dementia, falls, and mortality.

Our large cohort study reported that 7.3% of Chinese adults aged 60 years or older have MCR syndrome. Additionally, lower or upper extremity functional limitations, ADL disabilities, weaker grip strength, exhaustion, and history of hypertension were observed to be significantly associated with higher odds of MCR syndrome. Our results also showed that clinical measures including cystatin C and CRP were correlated with MCR. Our findings will help improve early detection and develop prevention strategies for dementia in China and other countries, and more longitudinal studies are warranted to further explore the modifiable risk factors of MCR.