Possible Sarcopenia and Impact of Dual-Task Exercise on Gait Speed, Handgrip Strength, Falls, and Perceived Health

Background: Sarcopenia is defined as a progressive age-related loss in muscle mass and strength affecting physical performance. It is associated with many negative outcomes including falls, disability, cognitive decline, and mortality. Protein enriched diet and resistance training have shown to improve muscle strength and function but there is limited evidence on impact of dual-task exercise in possible sarcopenia. Objective: To evaluate impact of community-based dual-task exercise on muscle strength and physical function in possible sarcopenia defined by either slow gait (SG) or poor handgrip strength (HGS). The secondary aims include effect on cognition, frailty, falls, social isolation, and perceived health. Methods: Community-dwelling older adults ≥60 years old were recruited from screening program intended to identify seniors at risk, and invited to participate in dual-task exercise program called HAPPY (Healthy Aging Promotion Program for You). One hundred and eleven participants with possible sarcopenia completed 3 months follow-up. Questionnaire was administered on demographics, frailty, sarcopenia, falls, perceived health, social network, functional, and cognitive status. Physical performance included assessment of HGS, gait speed, and Short Physical Performance Battery test (SPPB). Results: The mean age of the Exercise group was 75.9 years old and 73.0% were women. The Exercise group had more female (73.0 vs. 47.5%), were older (75.9 vs. 72.5 years old), had higher prevalence of falls (32.4 vs. 15.0%), lower BMI (23.7 vs. 25.8), and education (4.0 vs. 7.2 years). The gait speed of the Exercise group increased significantly with significant reduction in the prevalence of SG and poor HGS. All components of SPPB as well as the total score increased significantly while the prevalence of pre-frailty and falls dropped by half. The risk of social isolation reduced by 25% with significant improvement in perceived health and cognition in the Exercise group. Significant impact on improvement gait speed and SPPB persisted after adjustment for baseline factors. Conclusion: Dual-task exercise program is effective in improving gait speed, SPPB score, and reducing the prevalence of poor HGS with significant improvement in perceived health, cognition, and reduction in falls and frailty. Future prospective randomized control trials are needed to evaluate the effectiveness of dual-task interventions in reversing sarcopenia.


INTRODUCTION
The world's older population ≥ 65 years old is projected to increase from 703 million in 2019 to 1.5 billion in 2050 causing an exponential increase in people with sarcopenia, frailty, cognitive impairment, and associated disability (1). Similarly, older persons ≥ 80 years old is projected to triple between 2019 and 2050 to 426 million (1). Sarcopenia is defined as a progressive age-related loss in muscle mass and strength affecting physical performance (2). It is classified as a disease under the World Health Organization (WHO)'s International Statistical Classification of Diseases and Related Health Problems (ICD) (3). The prevalence of sarcopenia ranges between 9 and 51%, and probable or possible sarcopenia between 26.3 and 73.3% depending on the case finding approach, population subgroup, and definitions used (4)(5)(6)(7)(8). Aging is a known risk factor for sarcopenia and the number of individuals with sarcopenia is projected to increase by 72.4% in Europe between 2016 and 2045 (9,10).
Sarcopenia is associated with many negative health outcomes such as falls, fractures, functional decline, fear of falling, cognitive decline, depression, and mortality (2,11). It is the precursor for physical frailty (9). While sarcopenia is a target for drug development, most drug therapeutic trials have been unsuccessful (12). The European Working Group on Sarcopenia in Older People recently updated the clinical definition and consensus diagnostic criteria for sarcopenia in 2018 incorporating low muscle mass, strength, and low physical performance (13). In recent years, there has been increasing emphasis on muscle quality where low muscle strength and poor performance rather than muscle mass are considered as principal determinants of adverse outcomes. The Sarcopenia Definition and Outcomes Consortium proposed for weakness defined by low handgrip strength (HGS) and slowness defined by low gait speed to be included in the definition of sarcopenia as both individually or in combination are associated with poor health outcomes (14).
Sarcopenia is often overlooked and undertreated in a busy clinical practice where a practical and effective screening tool like SARC-F can be used (15,16). Slow gait (SG), prolonged chairstand test, and/or poor HGS are included in many guidelines to diagnose possible sarcopenia to enable earlier case finding, assessment, and implement interventions to delay the decline or reverse the condition (13,17).
Various studies have shown that muscle strength and function can be improved with protein enriched diet and resistance training exercise with variable impact on muscle mass (18). Gait and cognition share a common neural pathway, and dual-task exercise of varying intensity has shown to improve cognition and gait speed (19,20). There is limited evidence on impact of dual task exercise on muscle strength and muscle function, and the type, intensity, and frequency of exercise in older adults with differing functional status is an emerging area of research (21). The aim of our study is to evaluate impact of community-based dual-task exercise on muscle strength and physical function in participants with possible sarcopenia. The secondary aims include effect on cognition, frailty, falls, social isolation, and overall perceived health.

METHODS
Community-dwelling older adults ≥ 60 years old in Singapore were recruited from population screening program intended to identify seniors at risk, e.g., pre-frail, frail, and those with cognitive impairment between August 2017 and December 2018. The publicity was through network of grassroots volunteers, senior activity centers, and words of peers. Phase 1 of the screening program was for general population, and those screened to be high risk were invited to participate in phase 2 screening and dual-task exercise program called HAPPY (Healthy Aging Promotion Program for You) conducted once or twice weekly within the neighborhood setting. The HAPPY program is adapted from "Cognicise, " a multi-component program designed by the National Center for Geriatrics and Gerontology (NCGG) in Nagoya, Japan (20). There are more than 80 different dual-task exercises of increasing complexity and intensity. The 60 min exercise sessions led by trained health coaches comprise of 20 min of stretching, warming up, and cooling down with 40 min of personalized dual-task training incorporating resistance, balance, aerobic, and cognitive tasks (e.g., marching, clapping, with step-up/down movement on the step-board with simultaneous naming/recalling tasks, subtracting, adding, and remembering the steps on the numbered colorful ladder). The implementation and types of exercises are described in a recently published paper (20).
Exclusion criteria were diagnosis of dementia (Chinese Mini-Mental State Examination <18 or known diagnosis of dementia), wheelchair or bedbound, and living in a nursing home. A total of 569 seniors attended phase 1 screening, 296 participants were enrolled in phase 2 and complete follow up data was available for 197 participants at 3 months where 111 participants had either poor HGS or SG (Figure 1).
Multi-morbidity was defined as presence of 2 or more of the following comorbidities: hypertension, hyperlipidemia, diabetes mellitus, heart disease, cancer, stroke, and lung disease.
Physical performance test comprised assessment of HGS, gait speed, and Short Physical Performance Battery test (SPPB). HGS was measured on the dominant arm using Jamar hand dynamometer in the seated position with elbow flexed at 90 • . Maximum HGS was taken from two trials. Cut-offs of 28 kg for males and 18 kg for females were used to define poor HGS according to the Asian Working Group for Sarcopenia criteria (17). The SPPB was scored out of a total of 12 points and included components on balance, gait speed over 4 m, and five continuous chair-stand with a maximum of 4 points awarded for each component.
The controls aged ≥ 65 years old were recruited from a primary care practice in Singapore between October 2019 and December 2020. This group of participants did not participate in any intervention except being treated for their chronic diseases by their primary care physician and led their usual lifestyle.
Possible sarcopenia was defined as either having poor HGS or SG (<1 m/s) according to the Asian Working Group  for Sarcopenia recommendations (17). Both the Exercise and Control groups had baseline assessments at 0 and 3 months. Ethics approval was obtained from Domain-Specific Review Board of National Healthcare Group, Singapore. All participants provided written informed consent.

Statistical Analysis
Descriptive statistics were presented as mean values (standard deviation) for continuous variables and frequencies (percentages) for categorical variables. Differences in baseline characteristics between the Exercise and Control group were analyzed using

RESULTS
A total of 111 participants with either poor HGS or SG, participated in the HAPPY Program and completed assessment at 3rd month (Figure 1). The mean age of the Exercise group was 75.9 years old and 73.0% were women. The participants attended an average of 13 sessions over 3 months. Data of 40 participants recruited from the primary care practices with either HGS or SG, and did not participate in any intervention was used as "Control". Comparison of baseline characteristics between the Exercise and Control groups are shown in When comparing differences between the Exercise and Control groups, the Exercise group showed significantly greater improvement in cMMSE (Unstandardized β = 1.11, 95% CI = 0.13-2.10, p = 0.027) before adjustment ( Table 2). Model 1 was adjusted for age, education level, and number of sessions attended and model 2 was further adjusted for corresponding baseline scores/measurements, physical activity level and presence of multi-morbidities. Improvement in maximum gait speed and total SPPB score were significantly greater in the Exercise group both in Model 1 (Unstandardized β = 0.15, 95% CI = 0.03-0.26, p = 0.017 and Unstandardized β = 1.31, 95% CI = 0.35-2.26, P < 0.01) and Model 2 (Unstandardized β = 0.17, 95% CI = 0.05-0.30, p < 0.01 and Unstandardized β = 1.13, 95% CI = 0.23-2.03, P = 0.014).

DISCUSSION
With population aging, maintaining functional and cognitive ability, improving quality of life, and reducing social isolation should be every country's priority. The Decade of Healthy Aging Report has highlighted on the need to design national programs on age-friendly cities and community to add life to years (32). Many countries are focusing on multi-strategic cost-effective population programs to maintain functional and cognitive ability (21,33,34). Older adults are heterogenous and may not be able to participate in high intensity resistance exercise. Determining the threshold and optimal levels of physical activity that are necessary for healthy aging or disease management is crucial for older persons with declining intrinsic capacity. The Healthy Aging Promotion Program for You (HAPPY) is a communitybased tailored dual-task exercise program for older adults led by health coaches (HC) to promote healthy aging has shown to improve function and cognition in at risk older adults (20). Three months of dual-task exercise program for older adults with possible sarcopenia defined by poor HGS or SG showed significant improvement in gait speed, balance, chair-stand, frailty status, cognition, perceived health, and reduction in falls compared with control. The significant improvement in gait speed and total SPPB scores persisted even after adjusting for confounding factors such as age, education, multimorbidity, and physical activity.
Various guidelines have defined possible or probable sarcopenia as the presence of weakness or slowness as a reflection of muscle quality to enable upstream interventions before the onset of sarcopenia or severe sarcopenia (13,14,17). SARC-F which has a very high specificity, fast, and practical has been used as a case-finding tool in the community and hospital setting (35,36). HGS is a good surrogate for muscle strength and gait speed for physical performance where both are well-established markers of biological aging and intrinsic capacity (37). Various studies have found that higher gait speed, HGS, and shorter time to complete chair-stand test are associated with independent aging (38). HGS is reproducible, reliable, and can be measured easily using inexpensive portable device. Low HGS is a known predictor of poor health outcomes such as falls, mobility limitation, functional impairment, and mortality in community dwelling older adults. The various guidelines on diagnosis of sarcopenia have different cut-point for poor HGS depending on gender, age, ethnicity, and population. Poor HGS can also be affected by occupation, depression, motivation, pain, and arthritis of the hands which were not evaluated in our study (17,39).
Sarcopenia and cognition are closely related, both associated with aging and still an area of ongoing research. Sarcopenia is a risk factor for metabolic syndrome as skeletal muscle plays a crucial role in body's glucose metabolism, and both  conditions either in isolation or together are associated with increased prevalence of cognitive impairment (40). Brain-derived neurotrophic factor released by contracting skeletal muscles is responsible for synapse and structural connectivity. The individual components of sarcopenia such as SG and muscle strength are known to be associated with cognitive impairment. In a study by Buchman et al. there was 9% increased risk of AD with each 1-lb annual decline in HGS (41). Gait speed is a well-recognized predictor of dementia especially in those with underlying cognitive impairment (42). Gait is a complex activity which involves planning and interplay between the central and peripheral nervous system, body systems e.g., cardiovascular, respiratory and musculoskeletal systems, fitness, and vision. Gait and cognition share similar neural pathway involving the corpus callosum, prefrontal, parietal, and temporal areas. SG is associated with impairment in many cognitive domains including attention, executive function, language, construction, abstraction, and orientation (43). More than one third male and one-half female ≥ 80 years old have SG (43). Strength training and aerobic exercises between 10 and 24 weeks have shown to improve cognition in prior studies (44). Dual-task exercise incorporating cognitive task and physical exercise showed increased activation in Broca's area, corresponding area on right hemisphere, widespread cortical activation across fronto-temporo-parietal areas and prefrontal cortex (45,46). The participants in the dual-task exercise group in our study did improve in gait speed, cognition, balance, and chair-stand after 3 months. Previous studies have shown that dual-task exercises

Factors
Unstandardized β-coefficient are better than single-task in improving gait speed, cadence, and other cognitive variables (47). There was significant reduction in falls in the Exercise group at 3 months. Older adults are at higher risk of falls during dual task activities such as talking while walking. Motor control and walking requires intact neural system, attention, and planning. Cognitive impairment affects the planning and multisensory integration processes for gait in turn causing falls. Participation in cognitive activities is effective in improving neuromotor performance and possibly reducing falls with shorter foot reactive time and faster gait speed (48). The Exercise group also had significantly better perceived health at 3 months and reduction of social isolation by 25%.
Decline in physical performance during hospitalization and up to 3 months post discharge has been attributable to loss of muscle mass and muscle strength, and exercise programs in the hospital and post discharge is crucial to reduce the impact of acute illness on physical performance and enhance recovery (21,49,50). Most studies have focused on high intensity resistance training. Based on findings from our study and a recent study by , exercises tailored to individual's functional status can also be introduced in the hospital and post discharge to reduce the impact of post-hospitalization functional decline.
Covid-19 pandemic and associated measures such as social distancing and lockdown has resulted in reduction of physical activity and alteration in dietary habit increasing sarcopenia prevalence (51). While previous studies have emphasized on the need of resistance exercise and protein supplement, our study is the first to document improvement in gait speed, with reduction in the prevalence of SG and poor HGS after 3 months of dualtask exercise. While there are many studies evaluating web-based multi-domain interventions in the home setting, the inclusion of web-based dual-task exercises combined with resistance exercise, and protein enriched diet needs to studied to guide Public Health authorities on measures to prevent sarcopenia during future pandemics and lockdown (52).
There is a constant debate on how do we define outcomes which are meaningful for participants as statistically significant may not necessarily translate into being clinically meaningful and vice versa (53). Improvement in gait speed of 0.07 m/s and SPPB 0.5 points are considered clinically meaningful change based on ICFSR Task Force perspective and our study participants did show improvement of 0.07 m/s in gait speed and 0.6 points in SPPB which were also statistically significant. There was no significant change in HGS between the groups but greater significant reduction in the prevalence of poor HGS in the Exercise group. The possible explanation could be due to higher numbers of male in the Control group whom are known to have higher HGS and higher cut-off for poor HGS, and gender variation between the two groups. It is not known if 3 months is too short to notice any improvement in HGS as other multicomponent studies have shown similar findings (54).
The main strengths of our study are inclusion of community dwelling older adults with either poor HGS or SG, and the increasing complexity dual-task exercises conducted in neighborhood setting by trained health coaches suited to their functional performance. However, there are several limitations. The initial selection criteria to participate in the dual-task exercise were either prefrail, frail, or underlying cognitive impairment (cMMSE ≤ 26). SG and poor HGS is a subgroup analysis and were not the primary inclusion criteria. In addition, our interventions were not homogenous nor fully standardized, conducted twice weekly in slightly more than half of the participants, and the type and intensity of the dual-task exercises varied each week at health coaches discretion. Despite this, there were significant improvements and possibility of greater improvement if the exercises were conducted twice weekly in the Exercise group as shown in the entire group (20). Our study was not a randomized controlled trial but the recruitments were from different sites, and the final results were adjusted for differences between the 2 groups.
Despite the limitations, our study has generated a few interesting findings. Gait speed and cognition are closely associated, and 3 months dual-task exercise of varying intensity and complexity is effective in reducing the prevalence of SG, poor HGS, improving gait speed, frailty, perceived health, cognition, reducing falls, and social isolation. Population level screening with SARC-F with necessary targeted intervention may help reduce prevalence of sarcopenia and associated complications, reduce falls, and improve quality of life (33).
Future prospective randomized studies are needed to compare aerobic, high intensity strength training, and dual-task exercise with or without high protein diet in older people with differing functional status on the effect of muscle strength, performance, and muscle mass.

CONCLUSION
Possible sarcopenia defined by either SG or poor HGS are known to be associated with poor outcomes. High intensity resistance exercise and high protein diet are known to improve muscle strength and performance. Dual-task exercise program of varying type and increasing intensity is useful in improving gait speed, SPPB scores, and reducing the prevalence of poor HGS with significantly improved perceived health. Future prospective randomized control trials are needed to evaluate the effectiveness of dual-task interventions in reversing sarcopenia and associated complications.

DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

ETHICS STATEMENT
The studies involving human participants were reviewed and approved by Domain Specific Review Board of National Healthcare Group. The patients/participants provided their written informed consent to participate in this study.