- Email: [email protected]
Effects of a Multicomponent Frailty Prevention Program in Prefrail Community-Dwelling Older Persons: A Randomized Controlled Trial
JAMDA xxx (2019) 1.ee1.e9
JAMDA journal homepage: www.jamda.com
Original Study
Effects of a Multicomponent Frailty Prevention Program in Prefrail Community-Dwelling Older Persons: A Randomized Controlled Trial Ruby Yu PhD a, b, *, Cecilia Tong MSc a, Florence Ho MSc c, Jean Woo MD a, b a
Jockey Club Institute of Ageing, Chinese University of Hong Kong, Hong Kong SAR, China Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China c Jockey Club Cadenza Hub, Hong Kong SAR, China b
a b s t r a c t Keywords: Frailty multicomponent randomized controlled trial
Objective: To examine the effects of a multicomponent frailty prevention program in communitydwelling older persons with prefrailty. Design: A randomized controlled trial. Setting: A community elderly center in Hong Kong. Participants: Persons aged 50 years who scored 1-2 on a simple frailty questionnaire (FRAIL) Methods: Participants (n ¼ 127) were randomly assigned to a 12-week multicomponent frailty prevention program (exercise, cognitive training, board game activities) or to a wait-list control group. The primary outcomes were FRAIL scores, frailty status, and a combined frailty measure including subjective (FRAIL total score) and objective (grip strength, muscle endurance, balance, gait speed) measures. The secondary outcomes were verbal fluency assessed by dual-task gait speed, attention and memory assessed by digit span task, executive function assessed by the Frontal Assessment Battery, self-rated health, and life satisfaction. Assessments were conducted at baseline and at week 12. Results: The mean age of the participants was 62.2 years, and 88.2% were women. At week 12, the FRAIL score had decreased in the intervention group (1.3, P < .001) but had increased in the control group (0.3, P < .01) (between-group differences P < .001). In addition, 83.3% and 1.6% of the intervention and control groups, respectively, had reversed from prefrailty to robust phenotype (between-group differences P < .001). Participants in the intervention group also had a greater reduction in the combined frailty score and greater improvements in muscle endurance, balance, verbal fluency, attention and memory, executive function, and self-rated health than those in the control group (all P < .05). There were no significant differences between the groups with respect to grip strength, gait speed, and life satisfaction. Conclusions and implications: The multicomponent frailty prevention program reduced frailty and improved physical and cognitive functions, and self-rated health in community-dwelling older persons with prefrailty. Findings can provide insights into the consideration of incorporating frailty prevention programs into the routine practice of community elderly services. Ó 2019 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
With population ageing, the number of persons with frailty is expected to increase. Frailty is a geriatric syndrome resulting from multisystem declines in physiological reserves. Hence, older persons living with frailty are more vulnerable to increased risks of falls,
This work was supported by The Hong Kong Jockey Club Charities Trust. The authors declare no conflicts of interest. * Address correspondence to Ruby Yu, PhD, Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China. E-mail address: [email protected] (R. Yu). https://doi.org/10.1016/j.jamda.2019.08.024 1525-8610/Ó 2019 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
disability, hospitalization or institutionalization, and death when exposed to stress.1 The World Health Organization has emphasized prevention as a key element to counteract the problems associated with healthy ageing, especially in the area of frailty.2 In England, identification of frailty was also made a contractual requirement for all primary care practices since 2017.3-5 For those with frailty, relevant interventions should be provided6 where recommendation is based on studies that had demonstrated frailty is reversible.7 Findings from single-domain prevention trials for frailty have shown positive results. For example, interventions with strength training and protein supplementation have been consistently shown to be an effective strategy to
1.e1
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
reduce frailty and improve functional capacity in older persons.8 Educational or health promotion activities have also been shown to confer favorable effects on frailty.9 A limited number of preliminary studies indicate that cognitive training improved or maintained balance,10,11 gait speed,12 and daily functioning of older persons.13 Nevertheless, frailty is a multifactorial disorder. Hence, multicomponent interventions involving physical exercise, cognitive training, and psychosocial activities simultaneously could be needed for optimum preventive effects. However, relatively few randomized controlled trials (RCTs) of multicomponent interventions have been performed on persons with frailty. An individualized, multifactorial interdisciplinary intervention conducted in Australia found that physical, nutritional, and educational interventional approaches were effective in reversing frailty.14 More recently, a multicomponent RCT has been conducted among persons living with prefrailty or frailty in Singapore, with positive results.15 In Hong Kong, the prevalence of frailty is estimated at 5.1% for adults aged 65 to 69 years and increases to 16.8% for those aged 75 and older.16 A recent analysis of data from multiple birth cohorts also estimated that the levels of frailty among Hong Kong Chinese were increasing.17 Therefore, it remains critically important to study the effects of multicomponent interventions, especially for at-risk persons in Hong Kong. In this study, we examined the effects of a 12-week, 24-session multicomponent intervention on frailty, physical and cognitive functions, self-rated health, and life satisfaction in community-dwelling older persons with prefrailty. Methods Study Design and Participants A single-center randomized, open-label, controlled trial among older persons with prefrailty was conducted in Hong Kong. Potential participants were identified through community screening. Eligible participants were 50 years or older, prefrail (met specified cut-offs for 1-2 of the 5-item simple frailty questionnaire, FRAIL), and not living in an institution. The study has been approved by the Clinical Research Ethics Committee of the University, which operates according to the principles of the Declaration of Helsinki. The study was registered with the Australian New Zealand Clinical Trials Registry (Trial ID: ACTRN12617001036303). Randomization After consent and completion of the baseline assessment, participants were randomly assigned to the intervention or control group by computer-generated random numbers with block sizes of 4. Block randomization was undertaken in order to achieve equal sample sizes within each treatment group during the study period. The group allocation schedule was generated and managed by an investigator independent of participant recruitment and assessment. Intervention The 12-week multicomponent intervention is a combined program of exercise, computer-assisted cognitive training, and board game activities (Table 1). Exercise The intervention group performed 60 minutes of exercise, 2 days per week for 12 weeks, in a group of around 10 participants with a trained exercise coach and a trained exerise assistant. Each exercise session consisted of a warm-up routine, an aerobic circuit training, a resistance training, and a cool-down routine. TheraBands were used for the resistance training to train muscle groups in both the upper
and lower body. The program comprised 4 stages of which the intensity of the exercise increased such as the number of repetitions, sets, and the resistance of the TheraBands as assessed by the exercise coach. Cognitive training After the exercise session, the intervention group performed 30 minutes of computer-assisted cognitive training (Brainastic) developed by Mindvivid Limited (Hong Kong Science Park, Hong Kong). The program consisted of 15 interactive touchscreen minivideo games that were designed to train 5 specific cognitive domains: memory, attention, executive function, flexibility, and visuospatial ability. During each session, participants had access to only 1 prescribed track of games related to the same cognitive domain. The difficulty of each game gradually increased according to each individual’s performance from the previous session. A facilitator was available to assist participants who had trouble accessing the program. Board game activities A 30-minute board game session was held after the session for computer-assisted cognitive training. There were 6 board games throughout the intervention, with each played consecutively for 4 sessions. These board game activities aimed to enhance interactions and friendships between participants. Measurements Outcome assessments were performed at baseline and week 12 by trained research assistants who were blinded to the participants’ group allocation and independent of interventional researchers (including the exercise coach and the exercise assistant) who administered treatments. Frailty was measured based on both subjective and objective aspects. Frailty Subjective measures The FRAIL scale was used to measure frailty. It includes 5 components: fatigue, resistance, ambulation, illnesses, and loss of weight. FRAIL scores range from 0 to 5 (ie, 1 point for each component) with 0 representing robust, 1 to 2 prefrail, and 3 to 5 frail status.18 The FRAIL scale has been validated for populations of African American patients,18 Chinese,19 and other Asian populations20 and has been shown to predict disability and mortality.19,21 Objective measures Hand-grip strength was measured using a digital grip dynamometer (T.K.K.5401 GRIP-D; Takei Scientific Instruments Co, Ltd, Niigata, Japan) where the participants stood upright with feet shoulder-width apart and facing forward with elbow fully extended.22 Two readings were taken from both hands and the maximum value was used for analysis. Low muscle strength was defined by a grip strength of <26 kg for men and <18 kg for women.23 Chair stands were used to evaluate muscle endurance in the lower extremities. The participant was required to rise from a chair for a total of 5 times, as quickly as they could, with arms across their chest. The amount of time required to complete all 5 repetitions was used for analysis. There is no consensus concerning the cut-off point for chair stands. Values ranging from 10 to 15 seconds have been used in different studies.24-26 In this study, low muscle endurance was defined by the time to complete 5 chair stands of 13 seconds.27 Balance tests were performed to evaluate the ability to maintain a stable posture for maximum time with minimal body sway. The participant was required to stand with different postures (tandem and
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
1.e2
Table 1 Description of the Components of the Intervention Exercise Warm up and cool down Aerobic exercise (Circuit training)
Resistance training
Cognitive training Memory card, Catch the star, Color light bulb Conveyor belt, Insect, Films Ice, From small to big, Switch and match Piet Mondrian Mansion, Color shape, Save the Daruma Pairing detective, Most color, Dance in the rain Board games Blockers 3D bricks puzzle series
Mathable Rummikub Dixit (Chinese) Splendor
Description The 5-minute warm-up included a range of motions for different joints of the body from head to toe such as wrist rotation, shoulder rotation, upper body twist, lifting foot up and down, neck, chest and back stretching. The 25-minute circuit training included 15 exercises such as marching, squatting, swinging arms, raising arms out and to the side and up while marching on the spot, while raising each knee alternately, and stepping up and down using a 15-cm platformdcompleting one exercise after another. The target heart rate and rating of perceived exertion increased throughout the program. The 25-minute progressive resistance training involved 8-10 different exercises such as knee extension, chest stretching, torso stretching, lifting legs up and down, squatting, arm and shoulder stretching, standing on both feet or on one leg and balance for 20 s performed using TheraBands. The intensity of exercise increased throughout the program. These games involved memorizing and identifying objects that appeared on the screen and the order in which they appeared. The cognitive domain being trained was “memory.” These games involved identifying objects that appeared to be different or same (eg, color, shape, and pattern). The cognitive domain being trained was “attention.” “Ice” and “From small to big” involved solving simple mathematics calculations or problems. For “Switch and match,” participants needed to group objects with the same color but different pattern into one area. The cognitive domain being trained was “executive function.” These games involved matching objects in accordance to certain rules, eg, color and shapes. The cognitive domain being trained was “flexibility.” These games involved identifying correct shapes (puzzle solving), colors, and patterns of objects. The cognitive domain being trained was “visuospatial.” The goal of this game was to create connected groups of your own tiles (like-color) on the board, while not to capture too many tiles of the same color, played in groups of 4. Each participant received blocks of one color to construct shapes one block at a time, and the goal was to place their blocks to prevent opponents from having visible colored blocks (3D). The participant with the most blocks visible at the end is the winner, played in groups of 4. The aim of this game was to solve simple mathematical equations to score points by placing number tiles on the board, played in groups of 4. The aim of the game was to be the first participant to eliminate all the tiles from his or her rank by forming them into sets of runs (same suit and consecutive values) and groups (same value and different suits), played in groups of 5 The goal of this game was to guess which card the “storyteller” selected from a pile of cards. The “storyteller” will give a title or phrase that matches the image card for the participants to guess, played in groups of 10. The goal of this board game was to build the most prestigious jewelry business and the participant that earned the most prestige points wins the game, played in groups of 5.
1-legged balance) and maintain balance for 10 seconds each. The number of completed postures was used for analysis.23 Gait speed was measured on a flat walkway of 6 meters. Participants were asked to walk twice at their usual pace. The average of 2 usual walking pace trials was used for analysis. Low gait speed was defined as <0.8 m/s.28 Combined measure of frailty A combined frailty measure including both the subjective and objective measures was developed to give a score ranging from 0 to 5, with 1 point scored for the presence of either prefrailty or frailty (FRAIL total score 1), low grip strength (<26 kg for men and <18 kg for women), low muscle endurance (time 13 seconds to complete 5 chair stands), poor tandem and 1-legged balance (either of which could not be maintained for 10 seconds), and low gait speed (<0.8 m/s). Cognitive functions Dual-task gait speed was used to assess verbal fluency. Participants walked twice at their usual pace while naming animals aloud, which relies on semantic memory. Dual-task gait speed was calculated as the average of 2 usual walking pace trials.29 Wechsler digit span task was used to assess attention and working memory. This test required the interviewer to verbally present digits at a rate of 1 per second. The forward test required the participant to repeat the digits verbatim. The backward test required the participant to repeat the digits in reverse order.30 The Frontal Assessment Battery was used to assess executive function which is a short instrument comprising 6 subtests that are related to the functions of the frontal lobe.31
Self-rated health and life satisfaction Self-rated health was assessed by the participants’ response to the question “Generally speaking, how is your health: excellent, very good, good, fair, or poor?” Life satisfaction was assessed by the participants’ response to the question “Are you satisfied with life?” using a 0- to 10-point linear scale. Covariates, adherence, and adverse events Demographic (age, sex, marital status, education level, employment, living arrangement, disposable income) and lifestyle (physical activity, smoking habits, alcohol intake) data was collected using a standardized questionnaire. Anthropometric measurements were done using standardized methods. Body mass index was calculated as body weight (in kilograms) divided by height-squared (in meters). Adherence and adverse events were recorded. Data Analysis Comparisons across treatment groups were performed by t tests for continuous variables or chi-squared (c2) or Fisher tests for categorical variables. The effects of intervention over 12 weeks on outcome measures were investigated based on the modified intention-to-treat (mITT) analysis, including all randomly assigned participants with complete baseline and week 12 assessments. The change in outcome measures from baseline to week 12 were performed by paired t tests for continuous variables or McNemar or Wilcoxon signed ranks tests for categorical variables. The mean differences of outcome measures between the intervention and the
1.e3
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
234 had been assessed for eligibility
134 had completed baseline assessments 100 were excluded (84 noneligible, 16 not willing to participate)
134 were randomly assigned
72 to intervention
66 had completed follow-up assessments at week 12
62 to control
6 had discontinued intervention (3 for health-related reasons, 2 were unable to participate in the intervention, and 1 could not participate in the postassessment
66 were included in mITT analysis
61 had completed follow-up assessments at week 12
1 had discontinued intervention because of a full-time job
61 were included in mITT analysis
Fig. 1. Flow chart of the frailty prevention program. mITT, modified intention to treat.
control groups were examined using linear regression, whereas the percentage differences were examined using Fisher exact tests or ordinal regression. Regression models were adjusted for baseline values of the outcome measures analyzed and significant variables assessed in the baseline characteristics comparisons. The model for gait speed was further adjusted for height. All analyses were carried out using the Windows-based SPSS Statistical Package (v. 25.0; IBM Corp, Armonk, NY) and P values of less than .05 were considered statistically significant. Results Between November 8, 2017 and September 7, 2018, a total of 134 older persons with prefrailty were randomly assigned to the intervention (n ¼ 72) or the control group (n ¼ 62). After exclusion of 7 of 134 (5.2%) participants (intervention 6, control 1) who had dropped out from the study, 66 participants in the intervention group and 61 in the control group were included in the analysis (Figure 1). The mean age of the participants (n ¼ 127) was 62.2 years, and 88.2% were women. Frailty syndromes were predominantly fatigue (90.6%) and resistance (31.5%), followed by loss of weight (11.0%), illnesses (4.7%), and ambulation (0.8%). No major adverse events specifically attributable to the intervention were evident. Comparison of the baseline characteristics and the outcome measures did not show any statistical differences in age, sex, marital status, education level, employment, living arrangement, disposable income, physical activity, smoking, alcohol intake, body mass index, frailty and physical measures (FRAIL component subscores, grip strength, muscle endurance, balance, gait speed), cognitive measures (verbal fluency, attention and working memory, executive function), self-rated health, and life satisfaction between the intervention and
the control groups, although the FRAIL total score tended to show a difference (intervention group, 1.5 0.5, vs control group, 1.3 0.4, P < .05). At week 12, the FRAIL total score had reduced (1.3, P < .01) in the intervention group but had increased (0.3, P ¼ .001) in the control group. There was a decrease in the FRAIL component subscores (fatigue P < .001, resistance P < .001, and loss of weight P < .05) and the combined frailty score (P < .001) in the intervention group and an increase in the FRAIL resistance subscore (P < .001) in the control group. In addition, 83.3% of the intervention group had reversed from prefrailty phenotype to robust phenotype, whereas the corresponding figure was 1.6% of the control group. Improvements in muscle endurance (P < .001), balance (P < .001), attention and working memory (P < .05), executive function (P < .001), and self-rated health (P < .01) were also found in the intervention but not in the control group. Life satisfaction improved in both treatment groups (P < .01) (Table 2; Figures 2-4). Compared with those in the control group, participants in the intervention group had more reductions in the FRAIL total score (P < .001) and its component subscores (all P < .01 for fatigue, resistance, illnesses, and loss of weight), frailty status (P < .001), and the combined frailty score (P < .001); had more improvements in muscle endurance (P < .001), balance (P < .05), verbal fluency (P < .05), attention and working memory (P < .05), and executive function (P < .001); and were 3 times more likely to report having an improved self-rated health (odds ratio 3.5, 95% CI 1.6-7.9) at week 12, after adjusting for baseline values of the outcome measures analyzed (for all outcome variables) and the FRAIL total score (for all outcome measures except for FRAIL scores and frailty status). However, there were no differences between the groups with respect to grip strength, gait speed, and life satisfaction (Table 3).
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
1.e4
Table 2 Outcome Variables at Baseline and Week 12 Among Participants in the Intervention Group and the Control Group Intervention (n ¼ 66)
Frailty Subjective measures FRAIL scale, subscore Component 1: Fatigue Component 2: Resistance Component 3: Ambulation Component 4: Illnesses Component 5: Loss of weight FRAIL scale, total score Frailty group Robust Prefrail Frail Objective measures Grip strength, kgy Grip strengthy 26 kg for men and 18 kg for women <26 kg for men and <18 kg for women Muscle endurance, chair stand, sy Muscle endurance, chair standy Completed in <13 s Completed in 13 s Tandem and one-legged balance Complete (held for 10 s) Incomplete (held for <10 s) Gait speed, sec Gait speed 0.8 m/s <0.8 m/s Combined measure of frailty The combined frailty scorey Cognitive functions Verbal fluency, gait speed within dual tasks, s Attention and working memory, digit span score Attention and working memory, digit sequence score Executive function, FAB score Self-rated health and life satisfaction Self-rated health Poor or fair Excellent, very good, or good Life satisfaction, score
P*
Control (n ¼ 61)
P*
Baseline
Week 12
Baseline
Week 12
Mean SD or n (%)
Mean SD or n (%)
Mean SD or n (%)
Mean SD or n (%)
0.9 0.4 0.0 0.1 0.2 1.5
0.3 0.5 0.1 0.2 0.4 0.5
0.1 0.0 0.0 0.0 0.0 0.2
0.3 0.1 0.0 0.0 0.2 0.4
0 (0) 66 (100.0) 0 (0)
55 (83.3) 11 (16.7) 0 (0)
23.1 6.3
23.8 6.3
50 (82.0) 11 (18.0) 11.8 4.6
54 (88.5) 7 (11.5) 9.4 2.8
39 (61.9) 24 (38.1)
56 (88.9) 7 (11.1)
47 (71.2) 19 (28.8) 6.4 1.3
64 (97.0) 2 (3.0) 6.4 1.0
55 (83.3) 11 (16.7)
57 (86.4) 9 (13.6)
3.3 0.8 8.6 14.5 13.8 14.5
2.3 2.2 2.4 2.7
46 (69.7) 20 (30.3) 7.1 1.2
<.001 <.001 .321 .083 .010 <.001 <.001
0.3 0.4 0.0 0.2 0.3 0.4
0.8 0.5 0.1 0.1 0.2 1.6
0.4 0.5 0.2 0.3 0.4 0.7
.051 <.001 .083 .103 .058 .001
0 (0) 61 (100.00) 0 (0)
1 (1.6) 53 (86.9) 7 (11.5)
.034
.072
22.3 6.2
22.2 5.6
.717
.344
43 (76.8) 13 (23.2) 12.2 3.6
42 (75.0) 14 (25.0) 13.5 4.6
1.000
<.001
35 (62.5) 21 (37.5)
29 (51.8) 27 (48.2)
.238
<.001
44 (72.1) 17 (27.9) 6.6 1.1
47 (77.0) 14 (23.0) 6.7 1.1
.549
51 (83.6) 10 (16.4)
50 (82.0) 11 (18.0)
1.000
<.001
.525 .774
2.1 0.6
<.001
1.7 2.5 2.3 2.1
.076 .005 .013 <.001
30 (45.5) 36 (54.5) 7.6 1.1
.005
8.1 15.2 14.4 16.5
0.9 0.3 0.0 0.1 0.1 1.3
<.001
3.2 0.8 8.2 13.9 13.1 14.2
2.4 2.0 2.0 2.8
49 (80.3) 12 (19.7) 6.9 1.2
.003
.572
3.3 0.8
.735
2.1 2.1 2.3 3.1
.219 .287 .405 .964
45 (73.8) 16 (26.2) 7.3 1.4
.454
8.6 13.7 13.3 14.2
.006
FAB, Frontal Assessment Battery. *The P value indicates statistical difference between baseline and week 12 within intervention or control groups using paired t test, McNemar test, or the Wilcoxon signed ranked test. y Missing data: grip strength (intervention n ¼ 5; control n ¼ 5); muscle endurance (intervention n ¼ 3; control n ¼ 5); the combined frailty score (intervention n ¼ 6; control n ¼ 8).
Discussion The frailty prevention program delivers a multicomponent intervention to persons aged 50 years and older in a community setting. Findings from this study demonstrated that a multicomponent frailty prevention program reduced frailty level and improved physical and cognitive functions as well as self-rated health in communitydwelling older persons with prefrailty. Although many RCTs have shown how exercise programs reduce frailty,32 few such trials have assessed the effect of multicomponent interventions on frailty prevention. Our study points to a significant effect in reversing a prefrail status to a robust status in the intervention group compared with the wait-list control group on follow-up at week 12. These are consistent with those reported by the few RCTs that have shown multicomponent interventions can reduce frailty in older persons with prefrailty or frailty. For example, a 12-month multifactorial intervention conducted in Australia found that physical, nutritional, and educational interventional approaches were effective in reversing frailty.14 A 5-month intervention conducted in
Singapore combining nutritional supplementation, physical training, and cognitive training had a significant effect in reducing frailty.15 Our findings also indicated that the program had positive effects on some FRAIL components, including fatigue, resistance, and loss of weight, but not on ambulation or illnesses, probably because of the low prevalence rates of ambulation (0.8%) and illnesses (4.7%). In addition, the program had positive effects on muscle endurance (as measured by a chair stand test) and balance (as measured by the balance tests), which are consistent with another study that had shown that a 24-week multicomponent exercise intervention (65 minutes/d, 5 days/wk) can benefit muscle strength and balance in older persons with frailty.8 However, our program showed limited effects on grip strength or gait speed. The lack of intervention effects on grip strength or gait speed may be related to the types of exercise in the program. Most of the exercises in the program focused on training the core and the lower body muscles compared with the upper body extremity, although arm and shoulder stretch using TheraBand were performed with increased intensity. This could help explain why grip strength did not improve after intervention as training for the upper
1.e5
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
A
B
FRAIL scale, Fatigue 0.9
1
0.9
0.8
0.6
Score
Score
0.8
0.4
***
0
C
D
Score 0
0
0
Intervention Baseline
F 0.2
0.1
FRAIL scale, total score 1.6
1.5
1.3
1 0.5
* 0 Intervention Baseline
Week 12
H
80 60 40 1.6
0
***
Intervention Baseline
*
Control
Week 12
120 100 80 60 40 20 0
J
5 0
86.9
* Control Week 12
Grip strength 23.5
Kilogram
10
23.8 23.1
23 22.3 22.2
22.5 22 21.5
*
Control Week 12
16.7
***
24 11.5
Intervention
100
Baseline
15
0
100
Intervention
(FRAIL total score ≥ 3)
Baseline
Control
Frailty group, Pre-frail
Week 12
Frailty group, Frail
0
**
Intervention
(FRAIL total score = 1-2)
83.3
0
0.2
*** Baseline
(FRAIL total score = 0)
100
0
Control
Frailty group, Robust
Control Week 12
2
Score
Score
Baseline
0.1
0.1
0 Intervention
Control
0.15
0
Percentage
0.1
0.05
1.5
0.05
Percentage
0.1
Week 12
0.2
0.2
0.1
0
FRAIL scale, Loss of weight 0.25
0
Week 12
FRAIL scale, Illnesses
0
Perecentage
Score
0.05
I
*** Control
0.15 0.1
0.1
0
*** 0
Baseline
0.15
E
0.3
Intervention
Control Week 12
FRAIL scale, Ambulation
0.5 0.4
0.2 0
Intervention Baseline
20
0.4
0.1
0.2
G
FRAIL scale, Resistance 0.6
21 Intervention Baseline
Control Week 12
Fig. 2. Changes in frailty measures from baseline to week 12, by treatment groups. (A) Changes in fatigue subscore from baseline to week 12. (B) Changes in resistance subscore from baseline to week 12. (C) Changes in ambulation subscore from baseline to week 12. (D) Changes in illnesses subscore from baseline to week 12. (E) Changes in loss of weight subscore from baseline to week 12. (F) Changes in FRAIL total score from baseline to week 12. (G) Changes in the proportion of robust older persons from baseline to week 12. (H) Changes in the proportion of prefrail older persons from baseline to week 12. (I) Changes in the proportion of frail older persons from baseline to week 12. (J) Changes in grip strength from baseline to week 12. (K) Changes in the proportion of older persons with low grip strength from baseline to week 12. (L) Changes in muscle endurance from baseline to week 12. (M) Changes in the proportion of older persons with low muscle endurance from baseline to week 12. (N) Changes in the proportion of older persons with poor balance from baseline to week 12. (O) Changes in gait speed from baseline to week 12. (P) Changes in the proportion of older persons with low gait speed from baseline to week 12. (Q) Changes in the combined frailty score from baseline to week 12. *P < .05; **P < .01; ***P < .001.
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
L
Low grip strength (Grip strength < 26 kg for men and < 18 kg for women)
30 25 20 15 10 5 0
23.2
25
13
18 11.5
13.5
Baseline
11
9.4
9
5
Control
Intervention
Week 12
Baseline
N
Low muscle endurance
Poor balance
23
3
*** Intervention Baseline
P
Control Week 12
Low gait speed (Gait speed < 0.8 m/s)
6.7
20
6.6 6.4
Percentage
6.6 6.4
6.3
15
16.7
16.4
18
13.6
10
6.2
5 0
Intervention Baseline
Q
27.9
10
Week 12
6.7
6.4
28.8
20
Control
Gait speed
6.5
30
0
6.8
Seconds
Percentage
Percentage
11.1
***
Baseline
O
40
37.5
Intervention
Control Week 12
(Hold times < 10 s)
48.2 38.1
**
***
(Time to complete 5 chair stands ≥ 13 s)
60 50 40 30 20 10 0
12.2
11.8
7 Intervention
M
Muscle endurance, Chair stand 15
Seconds
Percentage
K
1.e6
Control
Intervention
Week 12
Baseline
Control Week 12
The combined frailty score 3.5
3.3
3.2
3.3
Score
3 2.5
2.1
2 1.5 1
*** Intervention Baseline
Control Week 12
Fig. 2. (continued).
limbs were less emphasized on. Another reason to explain why grip strength or gait speed did not improve may possibly be due to the length of the intervention, as other studies had demonstrated that a longer period of intervention (5-6 months) may be needed to improve these outcomes.15,33 This study also demonstrated beneficial effects on verbal fluency, attention, working memory, and executive function, as measured by dual-task gait speed, digit span test, and the Frontal Assessment Battery. These effects were probably partly due to an improvement in physical activity. Several meta-analyses of trials in older persons indicate that physical exercise can improve cognitive measures,34,35 in which physical exercise induced structural and functional changes in
brain functioning.36 In addition, the computer-assisted cognitive training in the present study may improve cognitive function. A previous meta-analysis of trials of computerized cognitive training on cognitive function has shown small to moderate effect sizes for nonverbal and verbal memory, working memory, processing speed, and visuospatial skills but not for attention and executive functions.37 However, these studies targeted mainly healthy older persons and only a few focused on multiple cognitive domains. The games in this present study targeted different cognitive domains, allowing participants to develop cognitive abilities to manage and coordinate the various components of the tasks, which may have enhanced the participant’s executive function.
1.e7
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
8.8
8.6
8.6
Seconds
B
Verbal fluency, Gait speed within dual tasks 8.6
8.4
8.2
8.1
8.2
Score
A
8 7.8 Intervention Baseline
Score
14
14.5 13.9
Baseline
D
13.7
** Intervention
Control Week 12
Executive function, FAB score 17
14.4
16.5
16
13.8
13.5
13.1
13.3
13 12.5
15.2
Week 12
Attention and working memory, Digit sequence score 14.5
15.5 15 14.5 14 13.5 13 12.5
Control
Score
C
Attention and working memory, Digit span score
15
14.5
14.2 14.2
14
*
***
12
13 Intervention Baseline
Control Week 12
Intervention Baseline
Control Week 12
Fig. 3. Changes in cognitive functions from baseline to week 12, by treatment groups. FAB, Frontal Assessment Battery. (A) Changes in verbal fluency from baseline to week 12. (B) Changes in attention and working memoryddigit span score from baseline to week 12. (C) Changes in attention and working memoryddigit sequence score from baseline to week 12. (D) Changes in executive function from baseline to week 12. *P < .05; **P < .01; ***P < .001.
Exposure to board games may also contribute to the observed results in cognitive function. A few longitudinal studies have shown that playing board games was associated with a reduced risk of incident dementia in healthy older persons.38,39 More importantly, playing board games could promote social networks, social interaction, and exchange with peers, which can impart reserved age-related cognitive decline.40 Our findings also showed a significant intervention effect on selfrated health. This effect was partly due to an improvement in physical and cognitive functions, which may have enhanced the participant’s perceived health benefits and sense of capability in their daily life. Furthermore, the social component of the intervention (ie, playing board games) may have had positive effects on self-rated health. Many studies have shown how social participation improves self-rated health.41 However, this study failed to demonstrate an improvement in life satisfaction. The lack of an effect on life satisfaction may be due to a ceiling effect since, at baseline, the life satisfaction score was optimal in most of the participants (mean life satisfaction score 7.0). Given the promising results of the present study, the multicomponent frailty prevention program should be adopted in communitylevel elderly services. The program also appears to be acceptable to older persons because dropout rates (5.2%) were low and adherence to intervention sessions (completed 80% of the sessions 92.1%) was high, 2 reasonable proxies for acceptability. In fact, this program is already part of the activities of a community center (Jockey Club Cadenza Hub, http://www.jcch.org.hk), where it is self-financed and oversubscribed, with participants continuing to participate after each 12-week cycle. However, we do not yet know what factors were related to program adherence. A separate paper is planned to detail participants’ perceptions of program characteristics and factors relating to their intention to participate in the program as well as program adherence. Our study has several strengths. Both subjective and objective measures of frailty were collected. This approach increased the robustness of our models. In addition, cognitive functions were included in addition to frailty and physical functions as the outcome
measures, whereas few studies have examined the effect of multicomponent interventions on cognitive outcomes. However, this study has some limitations. First, only persons with prefrailty were eligible for this study; study findings may not be generalizable to persons with frailty. Second, this study was open-label therefore may potentially introduce biases. The use of block randomization during recruitment may also increase the risk of selection bias and is likely to have inflated the size of the intervention effect. Furthermore, the FRAIL scores that had decreased in the intervention group were self-reported. It is therefore possible that the decreases in FRAIL scores may be partly explained by the unblinding of group assignment and the use of block randomization. Nevertheless, significant intervention effects were obtained in multivariate analysis for objective measures, including muscle endurance and balance as well as the combined frailty score after adjusting for the baseline FRAIL total score. Third, only a verbal fluency task (ie, enumerating out loud as many animal names as possible) but not an arithmetic task (eg, counting backwards out loud) was used in the dual tasks gait assessment. It has been suggested that these 2 tasks involve different cognitive domains.42 Fourth, the effect of each intervention component (exercise, cognitive training, board game activities) compared with the multicomponent intervention (ie, a combination of all components) was not studied. Nevertheless, in a study of community-dwelling older persons with prefrailty and frailty receiving nutritional, physical cognitive, and combination interventions, those who used the combination intervention had higher odds of frailty reduction.15 Furthermore, nutrition aspects were not examined in this study. However, majority of studies did not demonstrate positive effects on physical performance and functional outcomes for older persons at risk of malnutrition.15,43 Fifth, the small study size may have limited the ability to detect changes in lowfrequency outcomes (eg, FRAIL components ambulation and illnesses). In addition, the study population was predominantly female; the results cannot be generalized to male. Finally, although our study showed that the frailty prevention program with duration of twice a week appears to be sufficient in reversing frailty and improving physical and cognitive functions as well as self-rated health, the
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
A 100
60
80.3
69.7
73.8
45.5
40 20 0
** Intervention Baseline
Life satisfaction score
Score
80
Percentage
B
Poor/fair self - rated health
1.e8
7.8 7.6 7.4 7.2 7 6.8 6.6 6.4
Control
7.6 7.3 7.1 6.9
***
**
Intervention
Control
Baseline
Week 12
Week 12
Fig. 4. Changes in self-rated health and life satisfaction from baseline to week 12, by treatment groups. (A) Changes in the proportion of older persons with poor or fair self-rated health from baseline to week 12. (B) Changes in life satisfaction score from baseline to week 12. **P < .01; ***P < .001.
duration may not be sufficient to produce considerable improvements in grip strength and gait speed. We do not know if the intervention leads to improvements in frailty status, cognitive functions, and selfrated health that can be sustained over time. It is expected that some older persons will experience functional decline after initial improvements following the program, because they are more prone to
episodes (eg, severe health conditions) leading to training interruption or have less adherence to the program. Therefore, it is important in future research to evaluate the efficacy of the intervention on longterm effect. A frailty prevention program that incorporates a maintenance intervention may also help participants to be more successful at maintaining robustness and independent longer living.
Table 3 Comparison of Changes of Outcome Variables Among Participants in the Intervention Group and the Control Group Change From Baseline, Mean SD or n (%)
Frailty Subjective measures FRAIL scale, sub-score Component 1: Fatigue Component 2: Resistance Component 3: Ambulation Component 4: Illnesses Component 5: Loss of weight FRAIL scale, total score Frailty group Improved No change Declined Objective measures Grip strength, kgx Muscle endurance, chair stand, sx Tandem and one-legged balance Improved No change or declinedk Gait speed, s Combined measure of frailty The combined frailty scorex Cognitive functions Verbal fluency, gait speed within dual tasks, s Attention and working memory, digit span score Attention and working memory, digit sequence score Executive function, FAB score Self-rated health and life satisfaction Self-rated health Improved No change Declined Life satisfaction, score
Intervention (n ¼ 66)
Control (n ¼ 61)
0.8 0.4 0.0 0.0 0.1 1.3
0.1 0.2 0.0 0.1 0.1 0.3
0.4 0.5 0.1 0.2 0.4 0.6
0.5 0.5 0.2 0.3 0.3 0.7
Unstandardized B
0.67 0.48 0.05 0.11 0.14 1.45
P*
OR (95% CI) Control Group as Reference
P
<.001 <.001 .071 .003 .004 <.001
d d d d d d
d d d d d d
55 (83.3) 11 (16.7) 0 (0)
1 (1.6) 53 (86.9) 7 (11.5)
d
d
d
<.001y
0.6 2.7 2.4 3.4
0.1 2.5 1.4 3.3
0.94 4.07
.052 <.001
d d
d d
17 (25.8) 49 (74.2) 0.1 1.1
7 (11.5) 54 (88.6) 0.1 1.0
0.22
.185
d
d
1.3 1.0
0.0 0.8
1.21
<.001
d
d
0.62 1.08 0.68 2.12
.039 .001 .031 <.001
d d d d
d d d d
d
d
3.5 (1.6 -7.9)
0.5 0.7 0.6 2.0
2.2 1.9 1.9 3.2
22 (33.3) 38 (57.6) 6 (9.1) 0.5 1.1
0.3 0.2 0.2 0.0
1.9 1.6 1.7 2.8
10 (16.4) 45 (73.8) 6 (9.8) 0.4 1.1
d
0.25
.181
d
.044y
.002z
d
FAB, Frontal Assessment Battery. *P value of linear regression for FRAIL component subscores (adjusted for baseline values of the same component), FRAIL total score (adjusted for baseline FRAIL total score), frailty group (adjusted for baseline frailty group), gait speed with or without dual tasks (adjusted for baseline gait speed with or without dual tasks, FRAIL total score, and height), and other outcomes variables (adjusted for baseline values of the same outcome and the FRAIL total score). y P value of c2 (Fisher exact) test for frailty group (adjusted for baseline FRAIL total score) and tandem and one-legged balance (adjusted for baseline value of balance and the FRAIL total score). z P value of ordinal logistic regression for self-rated health (adjusted for baseline value of self-rated health and the FRAIL total score). x Missing data: grip strength (intervention n ¼ 5; control n ¼ 5); muscle endurance (intervention n ¼ 3; control n ¼ 5); and the combined frailty score (intervention n ¼ 6; control n ¼ 8). k “No change” and “declined” groups were collapsed.
1.e9
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
Conclusions and Implications Our findings indicate that a multicomponent intervention including aerobic and resistance exercise, computer-assisted cognitive training, and board game activities is effective in reducing frailty, and improving physical and cognitive functions and selfrated health among community-dwelling persons with prefrailty. This study can provide evidence of the effectiveness of a multicomponent intervention for older persons with prefrailty as well as insights into the consideration of incorporating frailty prevention programs into the routine practice of community elderly services. Strategies to mitigate detraining effects should be identified to prevent the return to preintervention conditions, because some older persons will continue to experience functional decline, despite focused interventions. Acknowledgments We wish to thank The Hong Kong Jockey Club Charities Trust in supporting the frailty prevention program. We also wish to extend our thanks to the Jockey Club Cadenza Hub, St. James Settlement, The Hong Kong Society for Rehabilitation, Mindvivid Limited, and Mr. Osbert Cheung and Ms. MC So of CUHK Jockey Club Institute of Ageing. References 1. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146eM156. 2. World Health Organization. WHO Clinical Consortium on Healthy Ageing Topic Focus: Frailty and Intrinsic Capacity. Report of Consortium Meeting 1e2 December 2016 in Geneva, Switzerland. Geneva: World Health Organization; 2017. 3. Moody D, Lyndon H, Stevens G. Toolkit for General Practice in Supporting Older People Living With Frailty. London: NHS England; 2017. 4. National Health Service England. Supporting routine frailty identification through the GP contract 2017/18. Available at: https://www.england.nhs.uk/ wp-content/uploads/2017/04/supporting-guidance-on-frailty-update-sept2017.pdf. Accessed March 12, 2018. 5. National Health Service England. NHS England standard general medical services contract. Available at: https://www.england.nhs.uk/wp-content/uploads/ 2018/01/17-18-gms-contract.pdf. Accessed March 12, 2018. 6. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 7. Lee JSW, Auyeung TW, Leung J, et al. Transitions in frailty states among community-living older adults and their associated factors. J Am Med Dir Assoc 2014;15:281e286. 8. Tarazona-Santabalbina FJ, Gomez-Cabrera MC, Perez-Ros P, et al. A multicomponent exercise intervention that reverses frailty and improves cognition, emotion, and social networking in the community-dwelling frail elderly: A randomized clinical trial. J Am Med Dir Assoc 2016;17:426e433. 9. Salem BE, Ma-Pham J, Chen S, et al. Impact of a community-based frailty intervention among middle-aged and older prefrail and frail homeless women: A pilot randomized controlled trial. Community Ment Health J 2017;53: 688e694. 10. Li KZ, Roudaia E, Lussier M, et al. Benefits of cognitive dual-task training on balance performance in healthy older adults. J Gerontol A Biol Sci Med Sci 2010;65:1344e1352. 11. Smith-Ray RL, Hughes SL, Prohaska TR, et al. Impact of cognitive training on balance and gait in older adults. J Gerontol B Psychol Sci Soc Sci 2015;70: 357e366. 12. Verghese J, Mahoney J, Ambrose AF, et al. Effect of cognitive remediation on gait in sedentary seniors. J Gerontol A Biol Sci Med Sci 2010;65:1338e1343. 13. Willis SL, Tennstedt SL, Marsiske M, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA 2006;296: 2805e2814. 14. Cameron ID, Fairhall N, Langron C, et al. A multifactorial interdisciplinary intervention reduces frailty in older people: Randomized trial. BMC Med 2013; 11:65. 15. Ng TP, Feng L, Nyunt MSZ, et al. Nutritional, physical, cognitive, and combination interventions and frailty reversal among older adults: A randomized controlled trial. Am J Med 2015;128:1225e1236.e1.
16. Woo J, Yu R, Wong M, et al. Frailty screening in the community using the FRAIL Scale. J Am Med Dir Assoc 2015;16:412e419. 17. Yu R, Wong M, Chong KC, et al. Trajectories of frailty among Chinese older people in Hong Kong between 2001 and 2012: An age-period-cohort analysis. Age Ageing 2018;47:254e261. 18. Morley JE, Malmstrom TK, Miller DK. A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. J Nutr Health Aging 2012;16:601e608. 19. Woo J, Leung J, Morley JE. Comparison of frailty indicators based on clinical phenotype and the multiple deficit approach in predicting mortality and physical limitation. J Am Geriatr Soc 2012;60:1478e1486. 20. Jung HW, Yoo HJ, Park SY, et al. The Korean version of the FRAIL scale: Clinical feasibility and validity of assessing the frailty status of Korean elderly. Korean J Intern Med 2016;31:594e600. 21. Malmstrom TK, Miller DK, Morley JE. A comparison of four frailty models. J Am Geriatr Soc 2014;62:721e726. 22. Mathiowetz V, Kashman N, Volland G, et al. Grip and pinch strength: Normative data for adults. Arch Phys Med Rehabil 1985;66:69e74. 23. Chen LK, Liu LK, Woo J, et al. Sarcopenia in Asia: Consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 2014;15:95e101. 24. Makizako H, Shimada H, Doi T, et al. Predictive cutoff values of the Five-Times Sit-to-Stand Test and the Timed “Up & Go” Test for disability incidence in older people dwelling in the community. Phys Ther 2017;97:417e424. 25. Lusardi MM, Fritz S, Middleton A, et al. Determining risk of falls in community dwelling older adults: A systematic review and meta-analysis using posttest probability. J Geriatr Phys Ther 2017;40:1e36. 26. Buatois S, Miljkovic D, Manckoundia P, et al. Five Times Sit to Stand Test is a predictor of recurrent falls in healthy community-living subjects aged 65 and older. J Am Geriatr Soc 2008;56:1575e1577. 27. Nishimura T, Arima K, Okabe T, et al. Usefulness of chair stand time as a surrogate of gait speed in diagnosing sarcopenia. Geriatr Gerontol Int 2017;17: 668e669. 28. Cesari M, Kritchevsky SB, Penninx BW, et al. Prognostic value of usual gait speed in well-functioning older peopledResults from the Health, Aging and Body Composition Study. J Am Geriatr Soc 2005;53:1675e1680. 29. Montero-Odasso M, Bergman H, Phillips NA, et al. Dual-tasking and gait in people with mild cognitive impairment. The effect of working memory. BMC Geriatr 2009;9:41. 30. Wechsler D. Wechsler Adult Intelligence ScaleeThird Edition: Administration and Scoring Manual. San Antonio, TX: The Psychological Corporation; 1997. 31. Mok V, Wong A, Wong KS. The validity and reliability of Chinese Frontal Assessment Battery in evaluating executive dysfunction among Chinese patients with small subcortical infarcts. J Neurol Sci 2005;229:310e311. 32. de Labra C, Guimaraes-Pinheiro C, Maseda A, et al. Effects of physical exercise interventions in frail older adults: A systematic review of randomized controlled trials. BMC Geriatr 2015;15:154. 33. Chan DD, Tsou HH, Chang CB, et al. Integrated care for geriatric frailty and sarcopenia: A randomized control trial. J Cachexia Sarcopenia Muscle 2017;8: 78e88. 34. Smith PJ, Blumenthal JA, Hoffman BM, et al. Aerobic exercise and neurocognitive performance: A meta-analytic review of randomized controlled trials. Psychosom Med 2010;72:239e252. 35. Kelly ME, Loughrey D, Lawlor BA, et al. The impact of exercise on the cognitive functioning of healthy older adults: A systematic review and meta-analysis. Ageing Res Rev 2014;16:12e31. 36. Thomas AG, Dennis A, Bandettini PA, Johansen-Berg H. The effects of aerobic activity on brain structure. Front Psychol 2012;3:86. 37. Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: A systematic review and meta-analysis of effect modifiers. PLoS Med 2014;11:e1001756. 38. Fabrigoule C, Letenneur L, Dartigues JF, et al. Social and leisure activities and risk of dementia: A prospective longitudinal study. J Am Geriatr Soc 1995;43: 485e490. 39. Dartigues JF, Foubert-Samier A, Le Goff M, et al. Playing board games, cognitive decline and dementia: A French population-based cohort study. BMJ Open 2013;3:e002998. 40. Kelly ME, Duff H, Kelly S, et al. The impact of social activities, social networks, social support and social relationships on the cognitive functioning of healthy older adults: A systematic review. Syst Rev 2017;6:259. 41. Leone T, Hessel P. The effect of social participation on the subjective and objective health status of the over-fifties: Evidence from SHARE. Ageing Soc 2016;36:968e987. 42. Beauchet O, Aminian K, Gonthier R, Kressig RW. Dual-task-related gait changes in the elderly: Does the type of cognitive task matter? J Motor Behav 2005;37: 259e264. 43. Rosendahl E, Lindelof N, Littbrand H, et al. High-intensity functional exercise program and protein-enriched energy supplement for older persons dependent in activities of daily living: A randomised controlled trial. Aust J Physiother 2006;52:105e113.
JAMDA journal homepage: www.jamda.com
Original Study
Effects of a Multicomponent Frailty Prevention Program in Prefrail Community-Dwelling Older Persons: A Randomized Controlled Trial Ruby Yu PhD a, b, *, Cecilia Tong MSc a, Florence Ho MSc c, Jean Woo MD a, b a
Jockey Club Institute of Ageing, Chinese University of Hong Kong, Hong Kong SAR, China Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China c Jockey Club Cadenza Hub, Hong Kong SAR, China b
a b s t r a c t Keywords: Frailty multicomponent randomized controlled trial
Objective: To examine the effects of a multicomponent frailty prevention program in communitydwelling older persons with prefrailty. Design: A randomized controlled trial. Setting: A community elderly center in Hong Kong. Participants: Persons aged 50 years who scored 1-2 on a simple frailty questionnaire (FRAIL) Methods: Participants (n ¼ 127) were randomly assigned to a 12-week multicomponent frailty prevention program (exercise, cognitive training, board game activities) or to a wait-list control group. The primary outcomes were FRAIL scores, frailty status, and a combined frailty measure including subjective (FRAIL total score) and objective (grip strength, muscle endurance, balance, gait speed) measures. The secondary outcomes were verbal fluency assessed by dual-task gait speed, attention and memory assessed by digit span task, executive function assessed by the Frontal Assessment Battery, self-rated health, and life satisfaction. Assessments were conducted at baseline and at week 12. Results: The mean age of the participants was 62.2 years, and 88.2% were women. At week 12, the FRAIL score had decreased in the intervention group (1.3, P < .001) but had increased in the control group (0.3, P < .01) (between-group differences P < .001). In addition, 83.3% and 1.6% of the intervention and control groups, respectively, had reversed from prefrailty to robust phenotype (between-group differences P < .001). Participants in the intervention group also had a greater reduction in the combined frailty score and greater improvements in muscle endurance, balance, verbal fluency, attention and memory, executive function, and self-rated health than those in the control group (all P < .05). There were no significant differences between the groups with respect to grip strength, gait speed, and life satisfaction. Conclusions and implications: The multicomponent frailty prevention program reduced frailty and improved physical and cognitive functions, and self-rated health in community-dwelling older persons with prefrailty. Findings can provide insights into the consideration of incorporating frailty prevention programs into the routine practice of community elderly services. Ó 2019 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
With population ageing, the number of persons with frailty is expected to increase. Frailty is a geriatric syndrome resulting from multisystem declines in physiological reserves. Hence, older persons living with frailty are more vulnerable to increased risks of falls,
This work was supported by The Hong Kong Jockey Club Charities Trust. The authors declare no conflicts of interest. * Address correspondence to Ruby Yu, PhD, Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China. E-mail address: [email protected] (R. Yu). https://doi.org/10.1016/j.jamda.2019.08.024 1525-8610/Ó 2019 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
disability, hospitalization or institutionalization, and death when exposed to stress.1 The World Health Organization has emphasized prevention as a key element to counteract the problems associated with healthy ageing, especially in the area of frailty.2 In England, identification of frailty was also made a contractual requirement for all primary care practices since 2017.3-5 For those with frailty, relevant interventions should be provided6 where recommendation is based on studies that had demonstrated frailty is reversible.7 Findings from single-domain prevention trials for frailty have shown positive results. For example, interventions with strength training and protein supplementation have been consistently shown to be an effective strategy to
1.e1
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
reduce frailty and improve functional capacity in older persons.8 Educational or health promotion activities have also been shown to confer favorable effects on frailty.9 A limited number of preliminary studies indicate that cognitive training improved or maintained balance,10,11 gait speed,12 and daily functioning of older persons.13 Nevertheless, frailty is a multifactorial disorder. Hence, multicomponent interventions involving physical exercise, cognitive training, and psychosocial activities simultaneously could be needed for optimum preventive effects. However, relatively few randomized controlled trials (RCTs) of multicomponent interventions have been performed on persons with frailty. An individualized, multifactorial interdisciplinary intervention conducted in Australia found that physical, nutritional, and educational interventional approaches were effective in reversing frailty.14 More recently, a multicomponent RCT has been conducted among persons living with prefrailty or frailty in Singapore, with positive results.15 In Hong Kong, the prevalence of frailty is estimated at 5.1% for adults aged 65 to 69 years and increases to 16.8% for those aged 75 and older.16 A recent analysis of data from multiple birth cohorts also estimated that the levels of frailty among Hong Kong Chinese were increasing.17 Therefore, it remains critically important to study the effects of multicomponent interventions, especially for at-risk persons in Hong Kong. In this study, we examined the effects of a 12-week, 24-session multicomponent intervention on frailty, physical and cognitive functions, self-rated health, and life satisfaction in community-dwelling older persons with prefrailty. Methods Study Design and Participants A single-center randomized, open-label, controlled trial among older persons with prefrailty was conducted in Hong Kong. Potential participants were identified through community screening. Eligible participants were 50 years or older, prefrail (met specified cut-offs for 1-2 of the 5-item simple frailty questionnaire, FRAIL), and not living in an institution. The study has been approved by the Clinical Research Ethics Committee of the University, which operates according to the principles of the Declaration of Helsinki. The study was registered with the Australian New Zealand Clinical Trials Registry (Trial ID: ACTRN12617001036303). Randomization After consent and completion of the baseline assessment, participants were randomly assigned to the intervention or control group by computer-generated random numbers with block sizes of 4. Block randomization was undertaken in order to achieve equal sample sizes within each treatment group during the study period. The group allocation schedule was generated and managed by an investigator independent of participant recruitment and assessment. Intervention The 12-week multicomponent intervention is a combined program of exercise, computer-assisted cognitive training, and board game activities (Table 1). Exercise The intervention group performed 60 minutes of exercise, 2 days per week for 12 weeks, in a group of around 10 participants with a trained exercise coach and a trained exerise assistant. Each exercise session consisted of a warm-up routine, an aerobic circuit training, a resistance training, and a cool-down routine. TheraBands were used for the resistance training to train muscle groups in both the upper
and lower body. The program comprised 4 stages of which the intensity of the exercise increased such as the number of repetitions, sets, and the resistance of the TheraBands as assessed by the exercise coach. Cognitive training After the exercise session, the intervention group performed 30 minutes of computer-assisted cognitive training (Brainastic) developed by Mindvivid Limited (Hong Kong Science Park, Hong Kong). The program consisted of 15 interactive touchscreen minivideo games that were designed to train 5 specific cognitive domains: memory, attention, executive function, flexibility, and visuospatial ability. During each session, participants had access to only 1 prescribed track of games related to the same cognitive domain. The difficulty of each game gradually increased according to each individual’s performance from the previous session. A facilitator was available to assist participants who had trouble accessing the program. Board game activities A 30-minute board game session was held after the session for computer-assisted cognitive training. There were 6 board games throughout the intervention, with each played consecutively for 4 sessions. These board game activities aimed to enhance interactions and friendships between participants. Measurements Outcome assessments were performed at baseline and week 12 by trained research assistants who were blinded to the participants’ group allocation and independent of interventional researchers (including the exercise coach and the exercise assistant) who administered treatments. Frailty was measured based on both subjective and objective aspects. Frailty Subjective measures The FRAIL scale was used to measure frailty. It includes 5 components: fatigue, resistance, ambulation, illnesses, and loss of weight. FRAIL scores range from 0 to 5 (ie, 1 point for each component) with 0 representing robust, 1 to 2 prefrail, and 3 to 5 frail status.18 The FRAIL scale has been validated for populations of African American patients,18 Chinese,19 and other Asian populations20 and has been shown to predict disability and mortality.19,21 Objective measures Hand-grip strength was measured using a digital grip dynamometer (T.K.K.5401 GRIP-D; Takei Scientific Instruments Co, Ltd, Niigata, Japan) where the participants stood upright with feet shoulder-width apart and facing forward with elbow fully extended.22 Two readings were taken from both hands and the maximum value was used for analysis. Low muscle strength was defined by a grip strength of <26 kg for men and <18 kg for women.23 Chair stands were used to evaluate muscle endurance in the lower extremities. The participant was required to rise from a chair for a total of 5 times, as quickly as they could, with arms across their chest. The amount of time required to complete all 5 repetitions was used for analysis. There is no consensus concerning the cut-off point for chair stands. Values ranging from 10 to 15 seconds have been used in different studies.24-26 In this study, low muscle endurance was defined by the time to complete 5 chair stands of 13 seconds.27 Balance tests were performed to evaluate the ability to maintain a stable posture for maximum time with minimal body sway. The participant was required to stand with different postures (tandem and
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
1.e2
Table 1 Description of the Components of the Intervention Exercise Warm up and cool down Aerobic exercise (Circuit training)
Resistance training
Cognitive training Memory card, Catch the star, Color light bulb Conveyor belt, Insect, Films Ice, From small to big, Switch and match Piet Mondrian Mansion, Color shape, Save the Daruma Pairing detective, Most color, Dance in the rain Board games Blockers 3D bricks puzzle series
Mathable Rummikub Dixit (Chinese) Splendor
Description The 5-minute warm-up included a range of motions for different joints of the body from head to toe such as wrist rotation, shoulder rotation, upper body twist, lifting foot up and down, neck, chest and back stretching. The 25-minute circuit training included 15 exercises such as marching, squatting, swinging arms, raising arms out and to the side and up while marching on the spot, while raising each knee alternately, and stepping up and down using a 15-cm platformdcompleting one exercise after another. The target heart rate and rating of perceived exertion increased throughout the program. The 25-minute progressive resistance training involved 8-10 different exercises such as knee extension, chest stretching, torso stretching, lifting legs up and down, squatting, arm and shoulder stretching, standing on both feet or on one leg and balance for 20 s performed using TheraBands. The intensity of exercise increased throughout the program. These games involved memorizing and identifying objects that appeared on the screen and the order in which they appeared. The cognitive domain being trained was “memory.” These games involved identifying objects that appeared to be different or same (eg, color, shape, and pattern). The cognitive domain being trained was “attention.” “Ice” and “From small to big” involved solving simple mathematics calculations or problems. For “Switch and match,” participants needed to group objects with the same color but different pattern into one area. The cognitive domain being trained was “executive function.” These games involved matching objects in accordance to certain rules, eg, color and shapes. The cognitive domain being trained was “flexibility.” These games involved identifying correct shapes (puzzle solving), colors, and patterns of objects. The cognitive domain being trained was “visuospatial.” The goal of this game was to create connected groups of your own tiles (like-color) on the board, while not to capture too many tiles of the same color, played in groups of 4. Each participant received blocks of one color to construct shapes one block at a time, and the goal was to place their blocks to prevent opponents from having visible colored blocks (3D). The participant with the most blocks visible at the end is the winner, played in groups of 4. The aim of this game was to solve simple mathematical equations to score points by placing number tiles on the board, played in groups of 4. The aim of the game was to be the first participant to eliminate all the tiles from his or her rank by forming them into sets of runs (same suit and consecutive values) and groups (same value and different suits), played in groups of 5 The goal of this game was to guess which card the “storyteller” selected from a pile of cards. The “storyteller” will give a title or phrase that matches the image card for the participants to guess, played in groups of 10. The goal of this board game was to build the most prestigious jewelry business and the participant that earned the most prestige points wins the game, played in groups of 5.
1-legged balance) and maintain balance for 10 seconds each. The number of completed postures was used for analysis.23 Gait speed was measured on a flat walkway of 6 meters. Participants were asked to walk twice at their usual pace. The average of 2 usual walking pace trials was used for analysis. Low gait speed was defined as <0.8 m/s.28 Combined measure of frailty A combined frailty measure including both the subjective and objective measures was developed to give a score ranging from 0 to 5, with 1 point scored for the presence of either prefrailty or frailty (FRAIL total score 1), low grip strength (<26 kg for men and <18 kg for women), low muscle endurance (time 13 seconds to complete 5 chair stands), poor tandem and 1-legged balance (either of which could not be maintained for 10 seconds), and low gait speed (<0.8 m/s). Cognitive functions Dual-task gait speed was used to assess verbal fluency. Participants walked twice at their usual pace while naming animals aloud, which relies on semantic memory. Dual-task gait speed was calculated as the average of 2 usual walking pace trials.29 Wechsler digit span task was used to assess attention and working memory. This test required the interviewer to verbally present digits at a rate of 1 per second. The forward test required the participant to repeat the digits verbatim. The backward test required the participant to repeat the digits in reverse order.30 The Frontal Assessment Battery was used to assess executive function which is a short instrument comprising 6 subtests that are related to the functions of the frontal lobe.31
Self-rated health and life satisfaction Self-rated health was assessed by the participants’ response to the question “Generally speaking, how is your health: excellent, very good, good, fair, or poor?” Life satisfaction was assessed by the participants’ response to the question “Are you satisfied with life?” using a 0- to 10-point linear scale. Covariates, adherence, and adverse events Demographic (age, sex, marital status, education level, employment, living arrangement, disposable income) and lifestyle (physical activity, smoking habits, alcohol intake) data was collected using a standardized questionnaire. Anthropometric measurements were done using standardized methods. Body mass index was calculated as body weight (in kilograms) divided by height-squared (in meters). Adherence and adverse events were recorded. Data Analysis Comparisons across treatment groups were performed by t tests for continuous variables or chi-squared (c2) or Fisher tests for categorical variables. The effects of intervention over 12 weeks on outcome measures were investigated based on the modified intention-to-treat (mITT) analysis, including all randomly assigned participants with complete baseline and week 12 assessments. The change in outcome measures from baseline to week 12 were performed by paired t tests for continuous variables or McNemar or Wilcoxon signed ranks tests for categorical variables. The mean differences of outcome measures between the intervention and the
1.e3
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
234 had been assessed for eligibility
134 had completed baseline assessments 100 were excluded (84 noneligible, 16 not willing to participate)
134 were randomly assigned
72 to intervention
66 had completed follow-up assessments at week 12
62 to control
6 had discontinued intervention (3 for health-related reasons, 2 were unable to participate in the intervention, and 1 could not participate in the postassessment
66 were included in mITT analysis
61 had completed follow-up assessments at week 12
1 had discontinued intervention because of a full-time job
61 were included in mITT analysis
Fig. 1. Flow chart of the frailty prevention program. mITT, modified intention to treat.
control groups were examined using linear regression, whereas the percentage differences were examined using Fisher exact tests or ordinal regression. Regression models were adjusted for baseline values of the outcome measures analyzed and significant variables assessed in the baseline characteristics comparisons. The model for gait speed was further adjusted for height. All analyses were carried out using the Windows-based SPSS Statistical Package (v. 25.0; IBM Corp, Armonk, NY) and P values of less than .05 were considered statistically significant. Results Between November 8, 2017 and September 7, 2018, a total of 134 older persons with prefrailty were randomly assigned to the intervention (n ¼ 72) or the control group (n ¼ 62). After exclusion of 7 of 134 (5.2%) participants (intervention 6, control 1) who had dropped out from the study, 66 participants in the intervention group and 61 in the control group were included in the analysis (Figure 1). The mean age of the participants (n ¼ 127) was 62.2 years, and 88.2% were women. Frailty syndromes were predominantly fatigue (90.6%) and resistance (31.5%), followed by loss of weight (11.0%), illnesses (4.7%), and ambulation (0.8%). No major adverse events specifically attributable to the intervention were evident. Comparison of the baseline characteristics and the outcome measures did not show any statistical differences in age, sex, marital status, education level, employment, living arrangement, disposable income, physical activity, smoking, alcohol intake, body mass index, frailty and physical measures (FRAIL component subscores, grip strength, muscle endurance, balance, gait speed), cognitive measures (verbal fluency, attention and working memory, executive function), self-rated health, and life satisfaction between the intervention and
the control groups, although the FRAIL total score tended to show a difference (intervention group, 1.5 0.5, vs control group, 1.3 0.4, P < .05). At week 12, the FRAIL total score had reduced (1.3, P < .01) in the intervention group but had increased (0.3, P ¼ .001) in the control group. There was a decrease in the FRAIL component subscores (fatigue P < .001, resistance P < .001, and loss of weight P < .05) and the combined frailty score (P < .001) in the intervention group and an increase in the FRAIL resistance subscore (P < .001) in the control group. In addition, 83.3% of the intervention group had reversed from prefrailty phenotype to robust phenotype, whereas the corresponding figure was 1.6% of the control group. Improvements in muscle endurance (P < .001), balance (P < .001), attention and working memory (P < .05), executive function (P < .001), and self-rated health (P < .01) were also found in the intervention but not in the control group. Life satisfaction improved in both treatment groups (P < .01) (Table 2; Figures 2-4). Compared with those in the control group, participants in the intervention group had more reductions in the FRAIL total score (P < .001) and its component subscores (all P < .01 for fatigue, resistance, illnesses, and loss of weight), frailty status (P < .001), and the combined frailty score (P < .001); had more improvements in muscle endurance (P < .001), balance (P < .05), verbal fluency (P < .05), attention and working memory (P < .05), and executive function (P < .001); and were 3 times more likely to report having an improved self-rated health (odds ratio 3.5, 95% CI 1.6-7.9) at week 12, after adjusting for baseline values of the outcome measures analyzed (for all outcome variables) and the FRAIL total score (for all outcome measures except for FRAIL scores and frailty status). However, there were no differences between the groups with respect to grip strength, gait speed, and life satisfaction (Table 3).
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
1.e4
Table 2 Outcome Variables at Baseline and Week 12 Among Participants in the Intervention Group and the Control Group Intervention (n ¼ 66)
Frailty Subjective measures FRAIL scale, subscore Component 1: Fatigue Component 2: Resistance Component 3: Ambulation Component 4: Illnesses Component 5: Loss of weight FRAIL scale, total score Frailty group Robust Prefrail Frail Objective measures Grip strength, kgy Grip strengthy 26 kg for men and 18 kg for women <26 kg for men and <18 kg for women Muscle endurance, chair stand, sy Muscle endurance, chair standy Completed in <13 s Completed in 13 s Tandem and one-legged balance Complete (held for 10 s) Incomplete (held for <10 s) Gait speed, sec Gait speed 0.8 m/s <0.8 m/s Combined measure of frailty The combined frailty scorey Cognitive functions Verbal fluency, gait speed within dual tasks, s Attention and working memory, digit span score Attention and working memory, digit sequence score Executive function, FAB score Self-rated health and life satisfaction Self-rated health Poor or fair Excellent, very good, or good Life satisfaction, score
P*
Control (n ¼ 61)
P*
Baseline
Week 12
Baseline
Week 12
Mean SD or n (%)
Mean SD or n (%)
Mean SD or n (%)
Mean SD or n (%)
0.9 0.4 0.0 0.1 0.2 1.5
0.3 0.5 0.1 0.2 0.4 0.5
0.1 0.0 0.0 0.0 0.0 0.2
0.3 0.1 0.0 0.0 0.2 0.4
0 (0) 66 (100.0) 0 (0)
55 (83.3) 11 (16.7) 0 (0)
23.1 6.3
23.8 6.3
50 (82.0) 11 (18.0) 11.8 4.6
54 (88.5) 7 (11.5) 9.4 2.8
39 (61.9) 24 (38.1)
56 (88.9) 7 (11.1)
47 (71.2) 19 (28.8) 6.4 1.3
64 (97.0) 2 (3.0) 6.4 1.0
55 (83.3) 11 (16.7)
57 (86.4) 9 (13.6)
3.3 0.8 8.6 14.5 13.8 14.5
2.3 2.2 2.4 2.7
46 (69.7) 20 (30.3) 7.1 1.2
<.001 <.001 .321 .083 .010 <.001 <.001
0.3 0.4 0.0 0.2 0.3 0.4
0.8 0.5 0.1 0.1 0.2 1.6
0.4 0.5 0.2 0.3 0.4 0.7
.051 <.001 .083 .103 .058 .001
0 (0) 61 (100.00) 0 (0)
1 (1.6) 53 (86.9) 7 (11.5)
.034
.072
22.3 6.2
22.2 5.6
.717
.344
43 (76.8) 13 (23.2) 12.2 3.6
42 (75.0) 14 (25.0) 13.5 4.6
1.000
<.001
35 (62.5) 21 (37.5)
29 (51.8) 27 (48.2)
.238
<.001
44 (72.1) 17 (27.9) 6.6 1.1
47 (77.0) 14 (23.0) 6.7 1.1
.549
51 (83.6) 10 (16.4)
50 (82.0) 11 (18.0)
1.000
<.001
.525 .774
2.1 0.6
<.001
1.7 2.5 2.3 2.1
.076 .005 .013 <.001
30 (45.5) 36 (54.5) 7.6 1.1
.005
8.1 15.2 14.4 16.5
0.9 0.3 0.0 0.1 0.1 1.3
<.001
3.2 0.8 8.2 13.9 13.1 14.2
2.4 2.0 2.0 2.8
49 (80.3) 12 (19.7) 6.9 1.2
.003
.572
3.3 0.8
.735
2.1 2.1 2.3 3.1
.219 .287 .405 .964
45 (73.8) 16 (26.2) 7.3 1.4
.454
8.6 13.7 13.3 14.2
.006
FAB, Frontal Assessment Battery. *The P value indicates statistical difference between baseline and week 12 within intervention or control groups using paired t test, McNemar test, or the Wilcoxon signed ranked test. y Missing data: grip strength (intervention n ¼ 5; control n ¼ 5); muscle endurance (intervention n ¼ 3; control n ¼ 5); the combined frailty score (intervention n ¼ 6; control n ¼ 8).
Discussion The frailty prevention program delivers a multicomponent intervention to persons aged 50 years and older in a community setting. Findings from this study demonstrated that a multicomponent frailty prevention program reduced frailty level and improved physical and cognitive functions as well as self-rated health in communitydwelling older persons with prefrailty. Although many RCTs have shown how exercise programs reduce frailty,32 few such trials have assessed the effect of multicomponent interventions on frailty prevention. Our study points to a significant effect in reversing a prefrail status to a robust status in the intervention group compared with the wait-list control group on follow-up at week 12. These are consistent with those reported by the few RCTs that have shown multicomponent interventions can reduce frailty in older persons with prefrailty or frailty. For example, a 12-month multifactorial intervention conducted in Australia found that physical, nutritional, and educational interventional approaches were effective in reversing frailty.14 A 5-month intervention conducted in
Singapore combining nutritional supplementation, physical training, and cognitive training had a significant effect in reducing frailty.15 Our findings also indicated that the program had positive effects on some FRAIL components, including fatigue, resistance, and loss of weight, but not on ambulation or illnesses, probably because of the low prevalence rates of ambulation (0.8%) and illnesses (4.7%). In addition, the program had positive effects on muscle endurance (as measured by a chair stand test) and balance (as measured by the balance tests), which are consistent with another study that had shown that a 24-week multicomponent exercise intervention (65 minutes/d, 5 days/wk) can benefit muscle strength and balance in older persons with frailty.8 However, our program showed limited effects on grip strength or gait speed. The lack of intervention effects on grip strength or gait speed may be related to the types of exercise in the program. Most of the exercises in the program focused on training the core and the lower body muscles compared with the upper body extremity, although arm and shoulder stretch using TheraBand were performed with increased intensity. This could help explain why grip strength did not improve after intervention as training for the upper
1.e5
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
A
B
FRAIL scale, Fatigue 0.9
1
0.9
0.8
0.6
Score
Score
0.8
0.4
***
0
C
D
Score 0
0
0
Intervention Baseline
F 0.2
0.1
FRAIL scale, total score 1.6
1.5
1.3
1 0.5
* 0 Intervention Baseline
Week 12
H
80 60 40 1.6
0
***
Intervention Baseline
*
Control
Week 12
120 100 80 60 40 20 0
J
5 0
86.9
* Control Week 12
Grip strength 23.5
Kilogram
10
23.8 23.1
23 22.3 22.2
22.5 22 21.5
*
Control Week 12
16.7
***
24 11.5
Intervention
100
Baseline
15
0
100
Intervention
(FRAIL total score ≥ 3)
Baseline
Control
Frailty group, Pre-frail
Week 12
Frailty group, Frail
0
**
Intervention
(FRAIL total score = 1-2)
83.3
0
0.2
*** Baseline
(FRAIL total score = 0)
100
0
Control
Frailty group, Robust
Control Week 12
2
Score
Score
Baseline
0.1
0.1
0 Intervention
Control
0.15
0
Percentage
0.1
0.05
1.5
0.05
Percentage
0.1
Week 12
0.2
0.2
0.1
0
FRAIL scale, Loss of weight 0.25
0
Week 12
FRAIL scale, Illnesses
0
Perecentage
Score
0.05
I
*** Control
0.15 0.1
0.1
0
*** 0
Baseline
0.15
E
0.3
Intervention
Control Week 12
FRAIL scale, Ambulation
0.5 0.4
0.2 0
Intervention Baseline
20
0.4
0.1
0.2
G
FRAIL scale, Resistance 0.6
21 Intervention Baseline
Control Week 12
Fig. 2. Changes in frailty measures from baseline to week 12, by treatment groups. (A) Changes in fatigue subscore from baseline to week 12. (B) Changes in resistance subscore from baseline to week 12. (C) Changes in ambulation subscore from baseline to week 12. (D) Changes in illnesses subscore from baseline to week 12. (E) Changes in loss of weight subscore from baseline to week 12. (F) Changes in FRAIL total score from baseline to week 12. (G) Changes in the proportion of robust older persons from baseline to week 12. (H) Changes in the proportion of prefrail older persons from baseline to week 12. (I) Changes in the proportion of frail older persons from baseline to week 12. (J) Changes in grip strength from baseline to week 12. (K) Changes in the proportion of older persons with low grip strength from baseline to week 12. (L) Changes in muscle endurance from baseline to week 12. (M) Changes in the proportion of older persons with low muscle endurance from baseline to week 12. (N) Changes in the proportion of older persons with poor balance from baseline to week 12. (O) Changes in gait speed from baseline to week 12. (P) Changes in the proportion of older persons with low gait speed from baseline to week 12. (Q) Changes in the combined frailty score from baseline to week 12. *P < .05; **P < .01; ***P < .001.
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
L
Low grip strength (Grip strength < 26 kg for men and < 18 kg for women)
30 25 20 15 10 5 0
23.2
25
13
18 11.5
13.5
Baseline
11
9.4
9
5
Control
Intervention
Week 12
Baseline
N
Low muscle endurance
Poor balance
23
3
*** Intervention Baseline
P
Control Week 12
Low gait speed (Gait speed < 0.8 m/s)
6.7
20
6.6 6.4
Percentage
6.6 6.4
6.3
15
16.7
16.4
18
13.6
10
6.2
5 0
Intervention Baseline
Q
27.9
10
Week 12
6.7
6.4
28.8
20
Control
Gait speed
6.5
30
0
6.8
Seconds
Percentage
Percentage
11.1
***
Baseline
O
40
37.5
Intervention
Control Week 12
(Hold times < 10 s)
48.2 38.1
**
***
(Time to complete 5 chair stands ≥ 13 s)
60 50 40 30 20 10 0
12.2
11.8
7 Intervention
M
Muscle endurance, Chair stand 15
Seconds
Percentage
K
1.e6
Control
Intervention
Week 12
Baseline
Control Week 12
The combined frailty score 3.5
3.3
3.2
3.3
Score
3 2.5
2.1
2 1.5 1
*** Intervention Baseline
Control Week 12
Fig. 2. (continued).
limbs were less emphasized on. Another reason to explain why grip strength or gait speed did not improve may possibly be due to the length of the intervention, as other studies had demonstrated that a longer period of intervention (5-6 months) may be needed to improve these outcomes.15,33 This study also demonstrated beneficial effects on verbal fluency, attention, working memory, and executive function, as measured by dual-task gait speed, digit span test, and the Frontal Assessment Battery. These effects were probably partly due to an improvement in physical activity. Several meta-analyses of trials in older persons indicate that physical exercise can improve cognitive measures,34,35 in which physical exercise induced structural and functional changes in
brain functioning.36 In addition, the computer-assisted cognitive training in the present study may improve cognitive function. A previous meta-analysis of trials of computerized cognitive training on cognitive function has shown small to moderate effect sizes for nonverbal and verbal memory, working memory, processing speed, and visuospatial skills but not for attention and executive functions.37 However, these studies targeted mainly healthy older persons and only a few focused on multiple cognitive domains. The games in this present study targeted different cognitive domains, allowing participants to develop cognitive abilities to manage and coordinate the various components of the tasks, which may have enhanced the participant’s executive function.
1.e7
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
8.8
8.6
8.6
Seconds
B
Verbal fluency, Gait speed within dual tasks 8.6
8.4
8.2
8.1
8.2
Score
A
8 7.8 Intervention Baseline
Score
14
14.5 13.9
Baseline
D
13.7
** Intervention
Control Week 12
Executive function, FAB score 17
14.4
16.5
16
13.8
13.5
13.1
13.3
13 12.5
15.2
Week 12
Attention and working memory, Digit sequence score 14.5
15.5 15 14.5 14 13.5 13 12.5
Control
Score
C
Attention and working memory, Digit span score
15
14.5
14.2 14.2
14
*
***
12
13 Intervention Baseline
Control Week 12
Intervention Baseline
Control Week 12
Fig. 3. Changes in cognitive functions from baseline to week 12, by treatment groups. FAB, Frontal Assessment Battery. (A) Changes in verbal fluency from baseline to week 12. (B) Changes in attention and working memoryddigit span score from baseline to week 12. (C) Changes in attention and working memoryddigit sequence score from baseline to week 12. (D) Changes in executive function from baseline to week 12. *P < .05; **P < .01; ***P < .001.
Exposure to board games may also contribute to the observed results in cognitive function. A few longitudinal studies have shown that playing board games was associated with a reduced risk of incident dementia in healthy older persons.38,39 More importantly, playing board games could promote social networks, social interaction, and exchange with peers, which can impart reserved age-related cognitive decline.40 Our findings also showed a significant intervention effect on selfrated health. This effect was partly due to an improvement in physical and cognitive functions, which may have enhanced the participant’s perceived health benefits and sense of capability in their daily life. Furthermore, the social component of the intervention (ie, playing board games) may have had positive effects on self-rated health. Many studies have shown how social participation improves self-rated health.41 However, this study failed to demonstrate an improvement in life satisfaction. The lack of an effect on life satisfaction may be due to a ceiling effect since, at baseline, the life satisfaction score was optimal in most of the participants (mean life satisfaction score 7.0). Given the promising results of the present study, the multicomponent frailty prevention program should be adopted in communitylevel elderly services. The program also appears to be acceptable to older persons because dropout rates (5.2%) were low and adherence to intervention sessions (completed 80% of the sessions 92.1%) was high, 2 reasonable proxies for acceptability. In fact, this program is already part of the activities of a community center (Jockey Club Cadenza Hub, http://www.jcch.org.hk), where it is self-financed and oversubscribed, with participants continuing to participate after each 12-week cycle. However, we do not yet know what factors were related to program adherence. A separate paper is planned to detail participants’ perceptions of program characteristics and factors relating to their intention to participate in the program as well as program adherence. Our study has several strengths. Both subjective and objective measures of frailty were collected. This approach increased the robustness of our models. In addition, cognitive functions were included in addition to frailty and physical functions as the outcome
measures, whereas few studies have examined the effect of multicomponent interventions on cognitive outcomes. However, this study has some limitations. First, only persons with prefrailty were eligible for this study; study findings may not be generalizable to persons with frailty. Second, this study was open-label therefore may potentially introduce biases. The use of block randomization during recruitment may also increase the risk of selection bias and is likely to have inflated the size of the intervention effect. Furthermore, the FRAIL scores that had decreased in the intervention group were self-reported. It is therefore possible that the decreases in FRAIL scores may be partly explained by the unblinding of group assignment and the use of block randomization. Nevertheless, significant intervention effects were obtained in multivariate analysis for objective measures, including muscle endurance and balance as well as the combined frailty score after adjusting for the baseline FRAIL total score. Third, only a verbal fluency task (ie, enumerating out loud as many animal names as possible) but not an arithmetic task (eg, counting backwards out loud) was used in the dual tasks gait assessment. It has been suggested that these 2 tasks involve different cognitive domains.42 Fourth, the effect of each intervention component (exercise, cognitive training, board game activities) compared with the multicomponent intervention (ie, a combination of all components) was not studied. Nevertheless, in a study of community-dwelling older persons with prefrailty and frailty receiving nutritional, physical cognitive, and combination interventions, those who used the combination intervention had higher odds of frailty reduction.15 Furthermore, nutrition aspects were not examined in this study. However, majority of studies did not demonstrate positive effects on physical performance and functional outcomes for older persons at risk of malnutrition.15,43 Fifth, the small study size may have limited the ability to detect changes in lowfrequency outcomes (eg, FRAIL components ambulation and illnesses). In addition, the study population was predominantly female; the results cannot be generalized to male. Finally, although our study showed that the frailty prevention program with duration of twice a week appears to be sufficient in reversing frailty and improving physical and cognitive functions as well as self-rated health, the
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
A 100
60
80.3
69.7
73.8
45.5
40 20 0
** Intervention Baseline
Life satisfaction score
Score
80
Percentage
B
Poor/fair self - rated health
1.e8
7.8 7.6 7.4 7.2 7 6.8 6.6 6.4
Control
7.6 7.3 7.1 6.9
***
**
Intervention
Control
Baseline
Week 12
Week 12
Fig. 4. Changes in self-rated health and life satisfaction from baseline to week 12, by treatment groups. (A) Changes in the proportion of older persons with poor or fair self-rated health from baseline to week 12. (B) Changes in life satisfaction score from baseline to week 12. **P < .01; ***P < .001.
duration may not be sufficient to produce considerable improvements in grip strength and gait speed. We do not know if the intervention leads to improvements in frailty status, cognitive functions, and selfrated health that can be sustained over time. It is expected that some older persons will experience functional decline after initial improvements following the program, because they are more prone to
episodes (eg, severe health conditions) leading to training interruption or have less adherence to the program. Therefore, it is important in future research to evaluate the efficacy of the intervention on longterm effect. A frailty prevention program that incorporates a maintenance intervention may also help participants to be more successful at maintaining robustness and independent longer living.
Table 3 Comparison of Changes of Outcome Variables Among Participants in the Intervention Group and the Control Group Change From Baseline, Mean SD or n (%)
Frailty Subjective measures FRAIL scale, sub-score Component 1: Fatigue Component 2: Resistance Component 3: Ambulation Component 4: Illnesses Component 5: Loss of weight FRAIL scale, total score Frailty group Improved No change Declined Objective measures Grip strength, kgx Muscle endurance, chair stand, sx Tandem and one-legged balance Improved No change or declinedk Gait speed, s Combined measure of frailty The combined frailty scorex Cognitive functions Verbal fluency, gait speed within dual tasks, s Attention and working memory, digit span score Attention and working memory, digit sequence score Executive function, FAB score Self-rated health and life satisfaction Self-rated health Improved No change Declined Life satisfaction, score
Intervention (n ¼ 66)
Control (n ¼ 61)
0.8 0.4 0.0 0.0 0.1 1.3
0.1 0.2 0.0 0.1 0.1 0.3
0.4 0.5 0.1 0.2 0.4 0.6
0.5 0.5 0.2 0.3 0.3 0.7
Unstandardized B
0.67 0.48 0.05 0.11 0.14 1.45
P*
OR (95% CI) Control Group as Reference
P
<.001 <.001 .071 .003 .004 <.001
d d d d d d
d d d d d d
55 (83.3) 11 (16.7) 0 (0)
1 (1.6) 53 (86.9) 7 (11.5)
d
d
d
<.001y
0.6 2.7 2.4 3.4
0.1 2.5 1.4 3.3
0.94 4.07
.052 <.001
d d
d d
17 (25.8) 49 (74.2) 0.1 1.1
7 (11.5) 54 (88.6) 0.1 1.0
0.22
.185
d
d
1.3 1.0
0.0 0.8
1.21
<.001
d
d
0.62 1.08 0.68 2.12
.039 .001 .031 <.001
d d d d
d d d d
d
d
3.5 (1.6 -7.9)
0.5 0.7 0.6 2.0
2.2 1.9 1.9 3.2
22 (33.3) 38 (57.6) 6 (9.1) 0.5 1.1
0.3 0.2 0.2 0.0
1.9 1.6 1.7 2.8
10 (16.4) 45 (73.8) 6 (9.8) 0.4 1.1
d
0.25
.181
d
.044y
.002z
d
FAB, Frontal Assessment Battery. *P value of linear regression for FRAIL component subscores (adjusted for baseline values of the same component), FRAIL total score (adjusted for baseline FRAIL total score), frailty group (adjusted for baseline frailty group), gait speed with or without dual tasks (adjusted for baseline gait speed with or without dual tasks, FRAIL total score, and height), and other outcomes variables (adjusted for baseline values of the same outcome and the FRAIL total score). y P value of c2 (Fisher exact) test for frailty group (adjusted for baseline FRAIL total score) and tandem and one-legged balance (adjusted for baseline value of balance and the FRAIL total score). z P value of ordinal logistic regression for self-rated health (adjusted for baseline value of self-rated health and the FRAIL total score). x Missing data: grip strength (intervention n ¼ 5; control n ¼ 5); muscle endurance (intervention n ¼ 3; control n ¼ 5); and the combined frailty score (intervention n ¼ 6; control n ¼ 8). k “No change” and “declined” groups were collapsed.
1.e9
R. Yu et al. / JAMDA xxx (2019) 1.ee1.e9
Conclusions and Implications Our findings indicate that a multicomponent intervention including aerobic and resistance exercise, computer-assisted cognitive training, and board game activities is effective in reducing frailty, and improving physical and cognitive functions and selfrated health among community-dwelling persons with prefrailty. This study can provide evidence of the effectiveness of a multicomponent intervention for older persons with prefrailty as well as insights into the consideration of incorporating frailty prevention programs into the routine practice of community elderly services. Strategies to mitigate detraining effects should be identified to prevent the return to preintervention conditions, because some older persons will continue to experience functional decline, despite focused interventions. Acknowledgments We wish to thank The Hong Kong Jockey Club Charities Trust in supporting the frailty prevention program. We also wish to extend our thanks to the Jockey Club Cadenza Hub, St. James Settlement, The Hong Kong Society for Rehabilitation, Mindvivid Limited, and Mr. Osbert Cheung and Ms. MC So of CUHK Jockey Club Institute of Ageing. References 1. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146eM156. 2. World Health Organization. WHO Clinical Consortium on Healthy Ageing Topic Focus: Frailty and Intrinsic Capacity. Report of Consortium Meeting 1e2 December 2016 in Geneva, Switzerland. Geneva: World Health Organization; 2017. 3. Moody D, Lyndon H, Stevens G. Toolkit for General Practice in Supporting Older People Living With Frailty. London: NHS England; 2017. 4. National Health Service England. Supporting routine frailty identification through the GP contract 2017/18. Available at: https://www.england.nhs.uk/ wp-content/uploads/2017/04/supporting-guidance-on-frailty-update-sept2017.pdf. Accessed March 12, 2018. 5. National Health Service England. NHS England standard general medical services contract. Available at: https://www.england.nhs.uk/wp-content/uploads/ 2018/01/17-18-gms-contract.pdf. Accessed March 12, 2018. 6. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 7. Lee JSW, Auyeung TW, Leung J, et al. Transitions in frailty states among community-living older adults and their associated factors. J Am Med Dir Assoc 2014;15:281e286. 8. Tarazona-Santabalbina FJ, Gomez-Cabrera MC, Perez-Ros P, et al. A multicomponent exercise intervention that reverses frailty and improves cognition, emotion, and social networking in the community-dwelling frail elderly: A randomized clinical trial. J Am Med Dir Assoc 2016;17:426e433. 9. Salem BE, Ma-Pham J, Chen S, et al. Impact of a community-based frailty intervention among middle-aged and older prefrail and frail homeless women: A pilot randomized controlled trial. Community Ment Health J 2017;53: 688e694. 10. Li KZ, Roudaia E, Lussier M, et al. Benefits of cognitive dual-task training on balance performance in healthy older adults. J Gerontol A Biol Sci Med Sci 2010;65:1344e1352. 11. Smith-Ray RL, Hughes SL, Prohaska TR, et al. Impact of cognitive training on balance and gait in older adults. J Gerontol B Psychol Sci Soc Sci 2015;70: 357e366. 12. Verghese J, Mahoney J, Ambrose AF, et al. Effect of cognitive remediation on gait in sedentary seniors. J Gerontol A Biol Sci Med Sci 2010;65:1338e1343. 13. Willis SL, Tennstedt SL, Marsiske M, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA 2006;296: 2805e2814. 14. Cameron ID, Fairhall N, Langron C, et al. A multifactorial interdisciplinary intervention reduces frailty in older people: Randomized trial. BMC Med 2013; 11:65. 15. Ng TP, Feng L, Nyunt MSZ, et al. Nutritional, physical, cognitive, and combination interventions and frailty reversal among older adults: A randomized controlled trial. Am J Med 2015;128:1225e1236.e1.
16. Woo J, Yu R, Wong M, et al. Frailty screening in the community using the FRAIL Scale. J Am Med Dir Assoc 2015;16:412e419. 17. Yu R, Wong M, Chong KC, et al. Trajectories of frailty among Chinese older people in Hong Kong between 2001 and 2012: An age-period-cohort analysis. Age Ageing 2018;47:254e261. 18. Morley JE, Malmstrom TK, Miller DK. A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. J Nutr Health Aging 2012;16:601e608. 19. Woo J, Leung J, Morley JE. Comparison of frailty indicators based on clinical phenotype and the multiple deficit approach in predicting mortality and physical limitation. J Am Geriatr Soc 2012;60:1478e1486. 20. Jung HW, Yoo HJ, Park SY, et al. The Korean version of the FRAIL scale: Clinical feasibility and validity of assessing the frailty status of Korean elderly. Korean J Intern Med 2016;31:594e600. 21. Malmstrom TK, Miller DK, Morley JE. A comparison of four frailty models. J Am Geriatr Soc 2014;62:721e726. 22. Mathiowetz V, Kashman N, Volland G, et al. Grip and pinch strength: Normative data for adults. Arch Phys Med Rehabil 1985;66:69e74. 23. Chen LK, Liu LK, Woo J, et al. Sarcopenia in Asia: Consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 2014;15:95e101. 24. Makizako H, Shimada H, Doi T, et al. Predictive cutoff values of the Five-Times Sit-to-Stand Test and the Timed “Up & Go” Test for disability incidence in older people dwelling in the community. Phys Ther 2017;97:417e424. 25. Lusardi MM, Fritz S, Middleton A, et al. Determining risk of falls in community dwelling older adults: A systematic review and meta-analysis using posttest probability. J Geriatr Phys Ther 2017;40:1e36. 26. Buatois S, Miljkovic D, Manckoundia P, et al. Five Times Sit to Stand Test is a predictor of recurrent falls in healthy community-living subjects aged 65 and older. J Am Geriatr Soc 2008;56:1575e1577. 27. Nishimura T, Arima K, Okabe T, et al. Usefulness of chair stand time as a surrogate of gait speed in diagnosing sarcopenia. Geriatr Gerontol Int 2017;17: 668e669. 28. Cesari M, Kritchevsky SB, Penninx BW, et al. Prognostic value of usual gait speed in well-functioning older peopledResults from the Health, Aging and Body Composition Study. J Am Geriatr Soc 2005;53:1675e1680. 29. Montero-Odasso M, Bergman H, Phillips NA, et al. Dual-tasking and gait in people with mild cognitive impairment. The effect of working memory. BMC Geriatr 2009;9:41. 30. Wechsler D. Wechsler Adult Intelligence ScaleeThird Edition: Administration and Scoring Manual. San Antonio, TX: The Psychological Corporation; 1997. 31. Mok V, Wong A, Wong KS. The validity and reliability of Chinese Frontal Assessment Battery in evaluating executive dysfunction among Chinese patients with small subcortical infarcts. J Neurol Sci 2005;229:310e311. 32. de Labra C, Guimaraes-Pinheiro C, Maseda A, et al. Effects of physical exercise interventions in frail older adults: A systematic review of randomized controlled trials. BMC Geriatr 2015;15:154. 33. Chan DD, Tsou HH, Chang CB, et al. Integrated care for geriatric frailty and sarcopenia: A randomized control trial. J Cachexia Sarcopenia Muscle 2017;8: 78e88. 34. Smith PJ, Blumenthal JA, Hoffman BM, et al. Aerobic exercise and neurocognitive performance: A meta-analytic review of randomized controlled trials. Psychosom Med 2010;72:239e252. 35. Kelly ME, Loughrey D, Lawlor BA, et al. The impact of exercise on the cognitive functioning of healthy older adults: A systematic review and meta-analysis. Ageing Res Rev 2014;16:12e31. 36. Thomas AG, Dennis A, Bandettini PA, Johansen-Berg H. The effects of aerobic activity on brain structure. Front Psychol 2012;3:86. 37. Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: A systematic review and meta-analysis of effect modifiers. PLoS Med 2014;11:e1001756. 38. Fabrigoule C, Letenneur L, Dartigues JF, et al. Social and leisure activities and risk of dementia: A prospective longitudinal study. J Am Geriatr Soc 1995;43: 485e490. 39. Dartigues JF, Foubert-Samier A, Le Goff M, et al. Playing board games, cognitive decline and dementia: A French population-based cohort study. BMJ Open 2013;3:e002998. 40. Kelly ME, Duff H, Kelly S, et al. The impact of social activities, social networks, social support and social relationships on the cognitive functioning of healthy older adults: A systematic review. Syst Rev 2017;6:259. 41. Leone T, Hessel P. The effect of social participation on the subjective and objective health status of the over-fifties: Evidence from SHARE. Ageing Soc 2016;36:968e987. 42. Beauchet O, Aminian K, Gonthier R, Kressig RW. Dual-task-related gait changes in the elderly: Does the type of cognitive task matter? J Motor Behav 2005;37: 259e264. 43. Rosendahl E, Lindelof N, Littbrand H, et al. High-intensity functional exercise program and protein-enriched energy supplement for older persons dependent in activities of daily living: A randomised controlled trial. Aust J Physiother 2006;52:105e113.