The Effects of Mind-Body Exercise on Cognitive Performance in Elderly: A Systematic Review and Meta-Analysis

Background: As the situation of cognitive aging is getting worse, preventing or treating cognitive decline through effective strategies is highly important. This systematic review aims to investigate whether mind-body exercise is an effective approach for treating cognition decline. Methods: Searches for the potential studies were performed on the eight electronic databases (MEDLINE, Scopus, Web of Science, SPORTDiscus, CINAHL, PsycArtilces, CNKI, and Wanfang). Randomized controlled trials (RCTs) examining the effect of mind-body exercise on cognitive performance in older adults were included. Data were extracted and effect sizes were pooled with 95% confidence intervals (95% CI) using random-effects models. The Physiotherapy Evidence Database Scale was employed to examine the study quality. Results: Nineteen RCTs including 2539 elders (67.3% female) with fair to good study quality were identified. Mind-body exercise, relative to control intervention, showed significant benefits on cognitive performance, global cognition (Hedges’g = 0.23), executive functions (Hedges’g = 0.25 to 0.65), learning and memory (Hedges’g = 0.37 to 0.49), and language (Hedges’g = 0.35). In addition, no significant adverse events were reported. Conclusion: Mind-body exercise may be a safe and effective intervention for enhancing cognitive function among people aged 60 years or older. Further research evidence is still needed to make a more conclusive statement.


Introduction
Aging is thought to be the time-based progressive deterioration of physiological functions in organs and tissue that influences human survival and fertility [1]. To date, aging-related health problems (e.g., cardiovascular disease, hypertension, arthritis, and Alzheimer's disease) have become a serious and global issue, along with the growing of aging and life expectancy. Among these health problems, cognitive aging, which can affect a wide range of cognitive functions such as memory, processing speed, learning, understanding and decision making, is becoming a public health concern [2]. Thus, preventing or treating cognitive decline through effective strategies is highly urgent and critical.
In an effort to address this issue, scholars have focused on preventing or alleviating the rate of cognitive decline using different approaches (e.g., memory training [3], music therapy [4], and exercise therapy [5][6][7]). In the meantime, growing evidence suggests that aerobic exercise is associated with enhanced cognition [8][9][10][11]. Previous studies have shown that aerobic exercise improves the cognitive function at three levels: the systemic level (attention and learning), the molecular level (neurotrophins), and the cellular level (synaptic plasticity) [12]. For instance, research has demonstrated that aerobic exercise could prevent hippocampal volume loss among older adults because of the high level of Brain-Derived Neurotrophic Factor (BDNF) [13]. Another study found that aerobic exercise has a positive effect on cognition for people with mild cognitive impairment (MCI) through elevating the neurotrophic factors levels and decreasing the concentration of inflammatory parameters [14].
Similar to other types of physical exercise, mind-body exercise (i.e., Tai Chi, Qigong, Yoga, and Pilates) involves a variety of actions such as stretching and relaxation of skeletal muscles, as well as coordinated body and regular breathing movements. Additionally, meditative states are also involved in mind-body exercise to regulate attention and consciousness [15]. Recently, mind-body exercise has attracted scholars' attention because of its effectiveness in treating diseases and secondary conditions such as mental illness, mood disorder, balance problems and ill-being [16][17][18][19]. However, no review study has investigated the impact of mind-body exercise on cognitive performance, and only few reviews have been independently carried out that have focused on the efficacy of Tai Chi, Yoga or Pilates on cognitive function in older adults [20,21]. Moreover, as several recent empirical studies have been performed to examine the effect of mind-body exercise on cognitive performance, there is a need to update existing meta-analyses. Finally, despite Tai Chi and Qigong originating in China, previous reviews did not include articles in the Chinese language. Therefore, this systematic review aims to examine the effects of mind-body exercise on cognitive performance among the elderly. It is hoped that the findings of this review will provide practitioners with evidence for the design of programs for the prevention of cognitive decline, as well as identifying some gaps for future research.

Search Strategy
Searches for the potential studies were performed on the eight electronic databases (MEDLINE, Scopus, Web of Science, SPORTDiscus, CINAHL, PsycArticles, CNKI, and Wanfang) from inception until 29 August, 2018. Three groups of search terms, including "elderly" OR "older people" OR "older adults" OR "aging" OR "senior" AND "cognitive function" OR "cognition" OR "recall" OR "processing" OR "awareness" OR "comprehension" OR "attention" OR "memory" OR "verbal fluency" OR "executive function" OR "language" AND "Tai Chi" OR "Taiji" OR "Qigong" OR "Baduanjin" OR "Yoga" OR "Pilates" OR "mind body exercise" were combined for search. Furthermore, hand searches were used to identify the extra studies from published reference lists. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline [22].

Study Selection Criteria
The inclusion criteria for eligible studies were as follows: (1) randomized controlled trial (RCT); (2) participants aged 60 or older; (3) the mind-body intervention included Tai Chi, Qigong, Yoga, and/or Pilates; (4) at least one cognitive outcome was reported and corresponding data were available for effect size calculation; and (5) publications in either English or Chinese language. Studies were excluded if: (1) they were non-randomized controlled trails, case reports, published abstracts, conference proceedings or reviews; (2) the intervention group included training components (e.g., medication, health education) that are not parts of mind-body exercise; or (3) cognitive outcomes were not reported.

Data Extraction and Collection
To obtain the eligible studies in this meta-analysis, two reviewers (Y.Z. and C.X.) independently screened the titles, abstracts and full texts according to the predetermined standards. In the same way, two reviewers (YZ and CX) also extracted the following data: author and year, study design, participant characteristics (sample size, age, gender distribution), intervention program (training type, training time, duration of intervention), and outcomes. In the case of discrepancies, a consensus would be reached by consulting a third reviewer (L.Y.).

Study Quality Assessment
The methodology quality of the included studies was independently assessed by two reviewers (YZ and CX) using the Physiotherapy Evidence Database (PEDro) scale [23]. The scale consists of 11 items: eligibility criteria (not scored), random allocation, concealed allocation, groups similar at baseline, blinding of therapist, blinding of assessors, less than 15% dropouts, intention-to-treat analysis, between-group statistical comparisons, and point measures and variability data. Studies were classified as having excellent (9-10), good (6)(7)(8), fair (4)(5) or poor (<4) quality, respectively.

Statistical Analysis
The Comprehensive Meta-Analysis software was used to perform the meta-analysis. The standardized mean difference or effective size (Hedges'g) was computed. Of note, the original study with two control groups led to 2 effect sizes. Effect sizes across individual trials were synthesized for each outcome using the random-effects model with 95% confidence intervals (CI) and p value. The magnitudes of effect size were classified as small (0.2-0.49), medium (0.5-0.79), and large (0.8 or more), respectively. I 2 statistic was used to estimate the heterogeneity across studies. The I 2 values were divided into three levels: small (25%), moderate (50%), and high (75%). Additionally, to examine potential variables that may account for the effect of mind-body exercise on cognitive performance, moderator analysis was conducted according to either the categorical (cognitive status) or continuous predictor (total training time). Publication bias was assessed using the Egger's test and a significant p value indicates publication bias. Figure 1 describes the process of study selection. Electronic and manual searches returned 1201 records. Duplicates (n = 274) were firstly removed. Secondly, 65 potential studies were retained after screening the titles and abstracts. Finally, 46 studies were further excluded after reading through full texts and 19 eligible studies met the inclusion criteria were included in this review.

Mind-Body Exercise and Language
Eight trials [24,30,35,36,41] measured the language ability for older adults in Table 3. When compared to the control group, a small positive effect as compared with the control was detected after receiving the mind-body intervention (Hedges'g = 0.35, 95% CI 0.14 to 0.56, p = 0.001, I 2 = 48.30%). Egger's test suggested that there was no publication bias (p = 0.20).

Mind-Body Exercise and Learning and Memory
The immediate recall and delayed recall that are indictors of the learning and memory function were reported in seven and eight trials, respectively (Table 3). In terms of the immediate recall [26,32,35,41], the pooled result demonstrated a small and significant benefit in favor of the mind-body exercise (Hedges'g = 0.37, 95% CI 0.20 to 0.54, p < 0.001, I 2 = 0%). As for delayed recall, the synthesized result from eight trials [25,29,30,32,35,41] suggested that the mind-body exercise was more effective than the control intervention and the effect was close to moderate (Hedges'g = 0.49, 95% CI 0.29 to 0.69, p < 0.001, I 2 = 23.15%). Egger's test suggested that there was no publication bias on both immediate recall (p = 0.26) and delayed recall (p = 0.91).

Moderator Analysis
A sub-group analysis was performed to examine the effects of mind-body exercise on cognitive performance based on the categorical (cognitive status: cognitive impairment including MCI and dementia vs. non-cognitive impairment) and continuous predictor (total training time) in Tables 4  and 5, respectively. Collectively, there were no statistical group differences in cognitive functions except for language (Q = 5.45, df = 1, p = 0.02) ( Table 4). Moreover, mind-body exercise seemed to be more effective for elderly people without cognitive impairment. In term of continuous predictors, the results of meta-regression revealed that total training time is a

Adverse Events
Seventeen out of the 19 studies recorded no adverse events, and there were only two adverse events [26,35] (Table 3). One participant was diagnosed with groin muscle strain while practicing Yoga [26]. Another person felt dizziness during Yoga training [35].

Discussion
Our review summarized the evidence regarding the effects of mind-body exercise on cognitive performance for adults aged 60 years and older. Although different types of mind-body interventions (i.e., Tai Chi, Yoga, Pilates, and Qigong) were used across 19 included studies, all of these exercise programs involved core actions and breathing techniques (e.g., stretching, lying, and abdominal breathing) [15,43,44]. Despite varying exercise programs and participant characteristics (e.g., stroke, MCI, and depression), the findings of this review generally suggested that mind-body exercise could be an effective and safe method in improving older adults' cognitive performance.

Global Cognition
A small effect of mind-body exercise on global cognitive function was detected in the present review. Worthy of noting is that only two out of the ten included studies demonstrated that mind-body exercise significantly benefited to holistic cognition of healthy elders or older adults with MCI [27,37]. The insignificant findings of individual studies may be attributed to the small number of training sessions (e.g., [29]) and/or the inclusion of other types of exercise (e.g., resistance training) in the control group (e.g., [33,36,40,42]). By comparison, the meta-analytic result of mind-body exercise on global cognition was congruent with prior reviews and meta-analysis examining the efficacy of Pilates, Yoga or Tai Chi on global cognitive function [21,45,46]. For example, in Wayne and colleagues' meta-analysis, in which they included 4 RCTs (Tai Chi vs. blanket control) and a small treatment effect was observed among elders [21].

Executive Function
The executive functions involve advanced cognitive processes (e.g., planning, attention, working memory, multitasking, and purposive action), which are deemed necessary for behavioral control in humans [47]. In our review, the TMT [Part A and Part B], Stroop test and digit span (forward, backward) were used to assess executive function [24][25][26]28,[30][31][32]35,36,38,41], and mild to moderate improvements were obtained. This result provides the very first piece of synthesized evidence that mind-body exercise may enhance executive function in senior people. When participating in mind-body exercise, trainees are required to remember the new skills and movement patterns, and to recall the various movements and their sequences. The frontal lobe, as part of the brain areas, may thus regulate the executive function to complete tasks through mind-body exercise [48,49]. Moreover, it is highly possible that there is a reciprocal effect between mind-body movement and executive function [47].

Other Functions
In a normal aging process, there is a decline of language function such as verbal fluency, verbal retrieval and naming tasks [50]. We found that the positive effect of mind-body exercise on language functions was stronger among healthy participants than counterparts with cognitive impairments. The moderation effect is tentative, given only a small number of trials were involved in the analysis. On the other hand, the detected effect may be due to the fact that language functions tend to remain in a better condition among people have no cognitive impairments than those who have cognitive impairments during the aging process [51]. This finding suggests that it would be difficult to reverse or maintain older adults' language function once they are diagnosed with cognitive impairments.
For learning and memory, our findings were consistent with previous clinical trials [29,32,35,41], showing that mind-body exercise significantly improved the performance in immediate and delayed recall. Early research has shown that healthy older volunteers who received Tai Chi and Baduanjin training had greater changes in hippocampus and improvement in memory performance than elderly who did not receive any intervention [52,53]. Given there is a significant relationship between hippocampal volume and memory function [13,54], participants may increase their hippocampus volume after practicing mind-body exercise.
Likewise, the synthesized result indicated that mind-body exercise significantly improved participants' visuospatial ability, which is crucial for independent activities in life. Previous studies have demonstrated that aerobic exercise improved the visuospatial ability through enhancing the functional connectivity [55]. Given mind-body exercise is considered to be one kind of aerobic exercise, it might have a similar effect in enhancing functional connectivity among elderly.

Possible Mechanisms
Some plausible hypotheses may be used for explaining the positive effects of mind-body exercise on cognitive functions among elderly. Mind-body exercise emphasizes the coordination of body movements and rhythmic breathing, attention of feeling, weight shifting as well as the connection between the body and mind [15,25,31]. The characteristics of mind-body exercise have been found to be associated with increased hippocampus volumes and frontal lobes stimulation [53,56]. As such, a body of studies supports the hypothesis that hippocampus and frontal lobes may play a critical role in preserving cognitive function [49,52,53]. Additionally, some evidence demonstrates that physical activity contributes to elevate the levels of plasma biomarkers such as BDNF and tumor necrosis factor-α, which are important for cognitive function enhancement [13,25]. Indeed, practicing mind-body exercise involves skill learning processes such as memorizing skills or imitating others [57,58]. Lots of beneficial effects were gained from this kind of skill-related learning activity [59,60]. For example, an increase in brain regions (e.g., the cingulate cortex, insula, corpus callosum, and sensorimotor cortex) was observed after learning how to dance [60]. Therefore, all this evidence provided us with a better understanding of the mechanistic and molecular basis of how mind-body exercise improves cognitive function.

Limitations
Our review is subject to several limitations. First, several significant heterogeneities were observed in several of the cognitive outcomes. The heterogeneities may be attributed to the use of various assessment tools while evaluating the same cognitive outcome. In addition, the varied participant characteristics may also contribute to heterogeneity. Second, the current review was limited to cognitive outcomes. Other indexes, such as stress and emotion, that are closely associated with cognition among older adults were not evaluated in this review [2]. Finally, different programs were included as a comparison to mind-body exercise interventions, making the interpretation of meta-analytic results difficult.

Conclusions
A relatively large number of studies with fair to good methodological quality have been conducted to evaluate the efficacy of mind-body exercise on cognitive functions among elderly. The findings from this review generally suggest that mind-body exercise could be safe and effective in enhancing cognitive function for people aged 60 years or older. More RCTs with good to excellent research quality assessing different types of cognitive functions are needed to provide additional evidence. In addition, both a short-term and follow-up evaluation should be included in future research to evaluate the lasting effect of mind-body exercise on cognitive outcomes.
Author Contributions: Y.Z. and W.S. contributed to the conception and design of the review. Y.Z. applied the search strategy. Y.Z., C.L., and X.L. applied the selection criteria. Y.Z., C.L., and L.Z. completed assessment of risk of bias. Y.Z. and C.L. analyzed the data and interpreted data. Y.Z. and C.L. drafted this manuscript. L.Z., X.L. and W.S. edited this manuscript.
Funding: This research received no external funding.

Conflicts of Interest:
The authors declare no conflict of interest.