Participants

This study protocol was approved by the Institutional Human Research Ethics Committee of National Yang-Ming University. The approved protocol was followed throughout the study period. This trial was registered at http://www.clinicaltrials.in.th/ (TCTR20180531001 on 24-May-2018) and conformed to the CONSORT checklist(supplementary information). Participants were recruited from daycare centers for the elderly in Taiwan. All participants met the following inclusion criteria: (1) age between 65 to 90 years old and (2) the presence of at least one of the 5 following physical characteristics defined by Fried: unintentional body weight loss, exhaustion, weakness, slow gait speed, and low physical activity level5.

1. Unintentional body weight loss was defined as having unintentionally lost more than 1.5 kg in the past 3 months. In the present study, weight loss of 4.5 kg was modified to 1.5 kg because our intervention duration was only 3 months. 2. Exhaustion was defined as the participant agreeing with one of the following two statements: “I felt too tired to do anything” or “I lacked the motivation to do anything”, for at least 3 days in the past week. 3. Weakness was defined as the grip strength of the dominant hand (mean of three measurements) using a hand-held dynamometer. The cutoff grip strengths were as follows: for males with BMIs ≤ 24, grip strength ≤ 29 kg; for males with BMIs 24.1–28, grip strength ≤ 30 kg; for males with BMIs > 28, grip strength ≤ 32 kg; for females with BMIs ≤ 23, grip strength ≤ 17 kg; for females with BMIs 23.1–26, grip strength ≤ 17.3 kg; for females with BMIs 26.1–29, grip strength ≤ 18 kg; for females with BMIs > 29, grip strength ≤ 21 kg. 4. Slow walking speed was defined by a cutoff value for the time it took the participant to walk 4.57 m at a usual pace. For males taller than 173 cm, the cutoff time was 6 seconds; for males shorter than 173 cm, the cutoff time was 7 seconds; for females shorter than 159 cm, the cutoff time was 7 seconds; and for females taller than 159 cm, the cutoff time was 6 seconds. 5. A low physical activity level was defined as burning fewer than 594 kcal per week for men and 295 kcal per week for women, and the calories burned were calculated according to the Taiwan short form of the International Physical Activity Questionnaire (IPAQ) modified for the elderly.

The exclusion criteria were as follows: (1) the presence of unstable medical conditions, such as neurological or cardiopulmonary diseases, that may interfere with participation in the exercise intervention and (2) severe visual impairment that may interfere with the exercise intervention. All participants provided signed informed consent before participation.

Experimental procedures

This study was a single-blinded (assessor) parallel-randomized controlled trial. Participants meeting the criteria were randomly assigned to either the experimental group or the control group via a sealed envelope. The study was performed in accordance with the Declaration of Helsinki. Participants in the experimental group participated in a Kinect-based exergaming exercise program for 60 minutes sessions, three times a week for 12 weeks (EXER group). Those in the control group participated in a combined exercise program for 60 minutes sessions, three times a week for 12 weeks (CE group). Exercise training was supervised by an experienced physical therapist in a small group (3–4 people) for both the EXER and CE groups. The outcomes were measured at baseline and after completing the 36 exercise sessions by the same assessor who was blinded to the group assignment.

Intervention

Combined exercise (CE) group

The exercise program followed the guidelines suggested for older populations by the American College of Sports Medicine. This program included 20 minutes of resistance exercises, 20 minutes of aerobic exercises, and 20 minutes of balance exercises.

1. Resistance exercise: The resistance exercises focused on both the upper and lower extremities. Upper extremity resistance training emphasized shoulders (abductors, adductors and rotators), elbows (flexors and extensors), and wrists and fingers (flexors and extensors). Lower extremity resistance training emphasized muscles that are important for balance and gait control. TheraBands were used during exercise, starting with 1.1 kg of resistance (yellow TheraBand) and then gradually increasing to 3.1 kg (green TheraBand). Participants performed 3 sets of 10 to 15 repetitions for each activity with natural breathing during the exercises.

2. Aerobic exercise: The aerobic program was a sequence of whole-body activities, including stepping exercises in the seated and standing positions, stepping on and off of a stool, and standing up from and sitting in a chair. The training intensity was set to 50–75% of the maximal heart rate (220−age), and the perceived exertion rates were recorded during the exercises to modify the intensity. The ideal perceived exertion was a score of 13 to 14 (“somewhat hard”).

3. Balance exercise: The balance exercises combined dynamic and static balance training. The dynamic balance exercises included slow and fast symmetric weight shifting, catching and throwing balls, walking in a straight line, walking sideways, walking backwards, and figure of eight walking. Static balance training included standing with various materials and bases for support, and single leg standing with eyes open and closed.

Exergaming (EXER) group

Kinect systems (Microsoft Corporation, Redmond, WA, USA) were used for the exergaming group. The Kinect sensors incorporate infrared light and capture and track changes in limb segment motion during exercise to create a virtual 3D full-body map.

Tano and LongGood software packages, due to their various games, were integrated into the Kinect hardware for the present study. Through avatar technology, a virtual environment was presented on a screen (size: 230 cm × 230 cm) in front of the participants. Participants adjusted their own movements instantaneously according to feedback from the virtual character on the screen. Each session included 20 minutes of Tai-Chi, 20 minutes of resistance and aerobic combination training and 20 minutes of balance training. The details of this program are as follows:

1. Tai-chi exercise: The movement form Tai-chi was adopted from the traditional “Yang style Tai Chi” and was simplified to 24 forms. In this study, the Tai-chi started with a warm-up session, consisting of simple motions to help the elderly relax their muscles and joints. Then, the exercise session emphasized moving the arm and leg in circular motions with low speed and focusing on breathing and muscle coordination. It also emphasized weight shifting and squatting to improve balance, stability, and muscle strength.

2. Resistance and aerobic exercises: The PAPAMAMA program was used for upper/lower extremity strengthening and endurance exercises. The principle of adjusting the intensity followed the same rules as the program used in the CE group.

3. Balance game: In this study, we chose window cleaning, firework hitting, and goldfish grasping games for balance training. When playing these games, participants interacted with the virtual objects on the screen. Participants needed to shift their center of mass with upper/lower extremity movements to reach toward a target in a given location quickly and accurately. In addition, we also chose obstacle crossing and stair stepping games for balance training. During these games, participants needed to lift their legs to cross obstacles or to climb up and down steps at a predetermined speed.

Outcome measures

Primary outcomes

The frailty score, frailty status, frailty reversal rate, and frailty phenotype reversal rate were our primary outcomes. The frailty score has been validated in different populations in Taiwan39,40. The frailty score corresponds to the number of the five characteristics of the frail phenotype (unintentional body weight loss, exhaustion, slow walking speed, weakness, and low activity level) an individual displays. One point is allocated if the participant displays one physical characteristic of the frailty phenotype, with the total score ranging from 0 to 5. Frailty status is classified into one of the following 3 statuses: robust (score 0), prefrailty (score 1–2), and frailty (score 3–5), according to the frailty scores. Both the number of participants in each frailty status category and the number of participants displaying each characteristic of the frailty phenotype were calculated. The frailty reversal rate was defined as the fraction of individuals in the frailty status at baseline who improved to the robust or prefrailty status18. The equation is expressed as follows: (the number of individuals who were in the frailty status at baseline and improved to the prefrailty or robust status/the total number of individuals in the frailty status at baseline) * 100%.

To investigate the effect of training on each frailty phenotype, the frailty phenotype reversal rate was also defined as the fraction of participants displaying each frailty phenotype at baseline who no longer displayed it after the intervention18. The equation is expressed as follows: (the number of participants who displayed each frailty phenotype at baseline and no longer displayed it after intervention/the total number of participants who displayed that frailty phenotype at baseline) *100%.

Secondary outcomes

The relationship between physical performance and physical frailty has been established41. For example, the Short Physical Performance Battery (SPPB), which is a composite index for testing physical performance, has good concurrent validity and reliability to other measures of physical frailty42. Therefore, we chose the following common physical performance indicators as secondary outcomes: (1) back scratch, (2) chair sit and reach, (3) 30-second sit-to-stand, (4) 2-minute step, (5) single leg stance, (6) functional reach, (7) timed up and go, (8) walking speed, and (9) grip strength. The Falls Efficacy Scale International (FES-I), which assesses the fear of fall during daily activities and social-related activities, was also included as a secondary outcome43.

Data analysis

All analyses were performed using SPSS 20.0 software (SPSS Inc. Chicago, IL, USA). Descriptive statistics, including the distribution of variables, were generated for all variables in the form of the mean ± standard deviation or the number (%). Independent t-tests or Chi-square tests were applied to examine the baseline differences in various characteristics between the CE and EXER groups. Two-way analysis of variance (ANOVA) with repeated measures was used to determine the effects of the intervention on frailty scores, physical performance and FES-I. The model effects were group (CE, EXER), time (pre, post), and their interaction. The between-group comparison was the group (CE, EXER), and the within-group comparison was the change over time (pre, post). The post-hoc Tukey test was used for those variables with group × time interaction effects. Chi-square and McNemar tests were used to perform the intergroup and intragroup comparisons of the categorical variables. Effect size (sum of squares between/sum of squares total) was also calculated for the variables with significant group differences. The effect size is presented as the odds ratio (OR) for categorized variables and Cohen’s d for continuous variables.

Sample size

G*power 3.0 was used to determine the sample size needed for the present study. The frailty score was the primary outcome in this study, and we set the effect size to 0.25, with an alpha level of 5%, power of 80% and a repeated measures ANOVA model. The calculation indicated that 66 participants in total were necessary to achieve sufficient power. However, after recruiting 61 participants, 52 of which completed the study, the effect size η2 was 0.85 and the power was 99% for the 27 participants in the EXER group, and the effect size η2 was 0.66 and the power was 94% for the 25 participants in the CE group. Finally, a total of 52 participants were included in our study because this number was sufficient to achieve statistical power.