Abstract
Introduction
The World Health Organisation recently defined the construct of intrinsic capacity (IC), a function-based marker of older adult’s health encompassing all mental and physical capacities of the individual. Multicomponent physical exercise (MCE) is a potential intervention capable to maintain/increase IC at older age; however, evidence is scarce on the effects of MCE on IC in cognitively impaired pre-frail/frail older adults.
Methods
Secondary analyses of a randomised clinical trial. One hundred and eighty-eight older outpatients (age = 84.06 ± 4.77, 70.2% women) presenting with pre-frailty/frailty (according to Fried Criteria) and mild cognitive impairment (MCI)/mild dementia were recruited in the Geriatric clinics of three tertiary hospitals in Spain. Subjects were randomised to participate in the 12-week home-based individualised Vivifrail MCE or usual care. An IC index was created based on the z-score of the locomotion (Short Physical Performance Battery), cognitive (Montreal Cognitive Assessment), psychology (15-item Geriatric Depression Scale Yesavage) and vitality (handgrip strength) domains.
Results
After the 3-month intervention, linear mixed models showed significant between-group differences in the evolution of the IC composite score (β=0.48; 95% confidence interval [CI] = 0.24, 0.74; P < 0.001), IC Locomotion (β = 0.42; 95% CI = 0.10, 0.74; P < 0.001), IC Cognition (β = 0.45; 95% CI = 0.03, 0.87; P < 0.05) and IC Vitality domains (β = 0.50; 95% CI = 0.25, 0.74 at 3-month) favouring the MCE group.
Conclusions
The 12-week Vivifrail multicomponent exercise program is an effective strategy to enhance IC, especially in terms of locomotion, cognition and vitality IC domains in community-dwelling older adults with pre-frailty/frailty and MCI/mild dementia, compared to usual care.
Keywords: exercise, intrinsic capacity, functional ability, older adults, community-dwelling, older people
Key Points
Experts emphasise the need to promote healthy ageing (understood as the process of developing and maintaining the functional ability that enables well-being in older age) as the central objective and focus of all health systems and policies for older populations.
In this scope, World Health Organisation coined the term intrinsic capacity to refer to the composite of physical and mental attributes of the individual. Intrinsic capacity interacts with the environment to determine late-life functional ability.
Despite older adults at risk of disability onset might benefit the most from intrinsic capacity promotion, evidence around potential interventions for intrinsic capacity maintenance/increase in this population group remains very scarce.
Individualised multicomponent exercise has been suggested as a fundamental intervention for healthy ageing, but no study has evaluated the effects of exercise on global intrinsic capacity and its domains.
Our study shows that, compared to usual care, the 12-week Vivifrail multicomponent exercise program improved the composite intrinsic capacity score of community-dwelling older adults with pre-frailty/frailty and mild cognitive impairment/mild-dementia, in particular the domains of locomotion, cognition and vitality.
Introduction
Population ageing is an ongoing worldwide occurrence, which implies the existence of a growing share of the population living with chronic diseases and functional limitations [1]. Overt expansions in the life expectancy have not been accompanied by concurrent increases in healthspan [2], with dramatic implications from the healthcare and societal perspective [3, 4]. Secondary to this demographic transition, the prevailing biomedical strategy has evolved from a disease-based one focused on increasing longevity, to a function-centred perception of older adult’s health [5, 6], in which maintenance of function constitutes the priority, as a mean of guaranteeing free-of-disability late-life [7].
The World Health Organisation (WHO) recently defined healthy ageing as the process of fostering and maintaining the functional ability that enables well-being in older age [8, 9]. Under this framework, functional ability of the individual relies on the individual physical and mental capacities (intrinsic capacity [IC]) and their interactions with the environment [9]. Lately, an IC operationalisation has been proposed based on five domains (locomotion, cognitive, psychological, vitality and sensory) [10, 11], and recent research has shown that it is a measurable construct related to function-related outcomes, supporting its validity [12–14].
The concept of IC provides new opportunities for identifying proactive interventions oriented to healthy ageing promotion in those at high risk of presenting with physical/cognitive limitations [15]. Among them, frail and cognitively impaired community-dwellers might be the target of interventions oriented at prospectively increasing/maintaining IC. They represent older adults at risk of imminent disability, offering a window for intervention and halting or even reverting of the disability cascade [16, 17]. However, evidence around potential interventions for IC maintenance/increase remains scarce [18]. Multicomponent physical exercise (MCE) (comprising strength, aerobic, gait and balance and flexibility exercises), given its proven benefits on several proposed markers of individual domains of IC (locomotion [19, 20], cognitive [21], psychology [22]), has been suggested as a fundamental intervention for healthy ageing in different populations of older adults [23].
Vivifrail (www.vivifrail.com) is a MCE program tailored to the individual, designed to ease prescription of evidence-based exercise interventions in older people (https://vivifrail.com/es/inicio/) [24]. It has been included in the Integrated Care for Older People (ICOPE) guidelines developed by WHO as the treatment of choice for those at risk of mobility limitations [25]. So far, it has shown to promote benefits in terms of functional ability (single markers of physical and cognitive function) and fall risk reduction among institutionalised and community-dwelling older adults [26–29] but no study has explored the effects of the Vivifrail exercise program on IC. Especially appealing may be the potential benefits of the Vivifrail MCE program on the cognitive domain of older adults with mild cognitive impairment (MCI). Despite previous research has shown that exercise might be an effective intervention to cognition in healthy older adult populations [30], so far, its effectiveness in MCI/dementia populations is less clear [31].
This secondary analysis of a randomised clinical trial aims to explore the effects of Vivifrail individualised MCE program on IC and its operational domains among pre-frail/frail community-dwelling older adults with MCI/mild dementia, compared to usual care. Secondarily, we aimed to explore intervention effects according to baseline frailty status (pre-frailty vs. frailty) [32]. We hypothesise that the Vivifrail exercise program will promote increases on IC, specially driven by improvements in the physical and cognitive domains. Given the uncertainty around potential differential effects of exercise across frailty levels, this aspect was explored in the present work without any a priori hypothesis.
Methods
Study design
This is a secondary analysis of a multicentre randomised clinical trial (NCT03657940), aiming to explore between-group differences in an IC composite score and its operational domains. The original study aimed to explore the effectiveness of Vivifrail exercise program on functional capacity of physically pre-frail/frail older individuals diagnosed with MCI/mild dementia. Detailed description of the study can be found elsewhere [33]. The study was conducted between 1 September 2017 and 31 May 2020 in the outpatient clinics of the Geriatrics Department of three tertiary hospitals in Spain (Hospital de Navarra in Pamplona, Matia Fundazioa in San Sebastian and Hospital de Getafe in Getafe). Present analyses were not planned when the original study was conceived.
Ethical disclosure
All patients provided written informed consent. No financial compensation was offered for participating in the present study. The study followed the principles of Declaration of Helsinki and was approved by the Hospital de Navarra Clinical Research Ethics Committee.
Study population
Eligibility criteria comprised: ≥75 years, Barthel Index ≥60, being able to communicate and ambulate, presenting with MCI or mild dementia according to Diagnostic and Statistical Manual of Mental Disorders (DSM) V criteria (Global Deterioration Scale [Reisberg classification] = 4 [34]), pre-frailty or frailty according to Fried’s criteria and the assistance of a relative/caregiver for exercise monitoring [35]. Subjects were not included if presenting with any contraindication for physical exercising or testing (see [33] for a detailed list).
Settings and study procedures
Volunteers were recruited in the outpatient clinics of the three participating centres. Those who agreed to participate (n = 188) were randomised in a 1:1 ratio to an individualised home-based exercise program (Vivifrail group—VG) or usual care (Control group—GC). A simple randomisation list was generated by an independent statistician using an online instrument (www.randomizer.org) for each hospital. Outcome assessors were blinded to participants’ allocation; subjects were explicitly encouraged not to disclose their group membership during the study. No double-blind strategy was possible due to the behavioural nature of the intervention.
Standard sociodemographic data (age, sex, sociodemographic characteristics and clinical data), as well as endpoints of the study, were assessed by trained staff at baseline and 1 and 3 months later.
Intervention
Subjects in the CG received usual care, including rehabilitation when needed, and were instructed to continue their activities as usual. Besides usual care, subjects randomised to the VG received a 12-week intervention based on Vivifrail, which is a home-based individualised multicomponent (thrice-a-week resistance, balance, flexibility sessions and five walking sessions per week) exercise program tailored to individual’s physical function (assessed the Short Physical Performance Battery (SPPB): Level A-Disability (0–3 points), Level B-Frailty (4–6), Level C-Pre-frailty (7–9) and Level D-Robustness (10–12)) [36]. Subjects in the VG and their caregivers were instructed to follow their specific exercise protocol and progress in terms of intensity, frequency and volume according to Vivifrail guidelines [28] (see Supplementary Table 1 or visit www.vivifrail.com for a detailed description). Booklets and adherence logs were delivered and explained at the start of the interventions. Correct execution and safety were supervised by relatives and caregivers. In addition, in order to monitor adherence and performance, the research physiotherapist scheduled a face-to-face interview at week 4 as well as phone calls at weeks 2 and 8. After completion of the program, no further follow-up was performed.
Intrinsic capacity
Endpoints of present study were assessed at baseline and 1-month and 3-month follow-up visits. Different domains of IC proposed by WHO [11] were evaluated upon data availability by creating z-scores of the IC domains: (i) Locomotion was assessed by the SPPB; (ii) Cognition was evaluated by the Montreal Cognitive Assessment (MOCA), a cognitive impairment screening tool that evaluates global cognition (values ranging 0–30, lower is worse) [37]. (iii) The psychological domain was evaluated by the Yesavage 15-item Geriatric Depression Scale (GDS-15), whose values range between 0 and 15 (higher is worse) [36]. (iv) The vitality domain was evaluated by handgrip strength values (in kg) [10]. (v) Additionally, the sensory domain of IC was assessed through self-reporting of visual and hearing impairments. Specifically, a score was built based on the presence of hypoacusia (yes = 1, no = 0) and reduced visual acuity (yes = 1, no = 0), yielding a total score ranging 0–2.
A composite IC z-score was constructed as the sum of the individual z-scores of locomotion, cognition, psychology and vitality domains divided by 4 to create an IC composite score. GDS score was weighted as −1 (because greater scores indicate worse performance in this domain). The sensory domain score was not included in the composite score, given the categorical nature of the scale used for its assessment. Instead, worsening of the IC sensory domain was characterised as a one-point increase in the sensory domain score.
Statistical analysis
Descriptive statistics (mean and standard deviation and frequency and percentages were provided for continuous and categorical variables, respectively).
Mixed-effect linear models (MELMs) were used to explore the longitudinal evolution of IC domains according to randomisation group over 3 months, except for the worsening of IC sensory domain, for which logistic regression was used. In MELM, fixed terms were group allocation, time, time-by-group interaction and covariates (age, sex, educational level and baseline IC level); random terms were the participants. A random slope on time was assumed. Time was used as a categorical variable. In the logistic regression, we included the same covariates as in MELM. An intention-to-treat approach was used in analyses.
Using similar adjusted models, we investigated differences on the effectiveness of the intervention by baseline frailty levels by including a three-way interaction (group × time × frailty status) in the fixed effects, in addition to the main effects and the two-way interactions between these variables. In the case of a statistically significant interaction, analyses stratified by frailty status were run.
Statistical significance was set at an alpha value of 0.05. All analyses were performed using STATA 14.0 software (Stata Corporation, College Station, TX).
Results
Characterisation of the sample
One hundred and eighty-eight subjects were included in the present study (mean age [SD] = 84.06 ± 4.77; 70.2% [n = 132] women). Demographic and clinical characteristics of the sample are displayed in Table 1. Mean adherence to the intervention in the VG was 79% in the first month and 68% in the following 2 months. No adverse effects were reported by the participants nor their proxies during the follow-up.
Table 1.
Characteristics of included participants according to randomisation groups
| Characteristics | Whole sample total (n = 188) | Control group (n = 100) | Vivifrail group (n = 88) |
|---|---|---|---|
| Women, No. (%) | 120 (72.29) | 60 (68.18) | 60 (76.92) |
| Age, y | 84.06 ± 4.77 | 83.99 ± 4.80 | 84.15 ± 4.76 |
| Weight, kg | 66.66 ± 10.98 | 66.49 ± 11.41 | 66.86 ± 10.54 |
| BMI, kg/m2, a | 27.04 ± 3.97 | 27.02 ± 4.31 | 27.06 ± 3.57 |
| Years of schooling | 8.14 ± 4.47 | 8.15 ± 4.31 | 8.13 ± 4.67 |
| Barthel Index (0–100) | 91.43 ± 9.77 | 91.79 ± 10.23 | 91.13 ± 9.27 |
| MCI, No. (%) | 99 (58.93) | 33 (37.50) | 35 (44.30) |
| Dementia, No. (%) | 68 (40.72) | 44 (44.00) | 34 (38.63) |
| Fried Frailty phenotype | |||
| Pre-frailty (1–2 items), No. (%) | 121 (64.36) | 64 (64.00) | 57 (64.77) |
| Frailty (>2 item), No. (%) | 67 (35.64) | 36 (36.00) | 31 (35.23) |
| Polypharmacy (≥5 drugs), No. (%) | 138 (75.82) | 79 7 (79.80) | 59 (71.08) |
| GDS Yesavage score (0–15) | 3.62 ± 2.92 | 3.36 ± 2.91 | 3.92 ± 2.92 |
| Gait speed, m/s | 0.63 ± 0.19 | 0.64 ± 0.19 | 0.61 ± 0.18 |
| 5-STS, s | 19.18 ± 13.39 | 18.38 ± 13.18 | 20.12 ± 13.64 |
| SPPB score (0–12) | 7.31 ± 2.59 | 7.73 ± 2.47 | 6.85 ± 2.66 |
| Handgrip strength, kg | 19.37 ± 7.23 | 19.21 ± 7.70 | 19.56 ± 6.69 |
| MoCA score (0–30) | 15.55 ± 5.20 | 15.37 ± 5.24 | 15.81 ± 14.30 |
| MNA-SF score (0–14) | 12.07 ± 2.09 | 12.06 ± 1.98 | 12.08 ± 2.23 |
| IC Composite Score | 0.06 ± 0.53 | 0.08 ± 0.55 | 0.04 ± 0.48 |
MoCA, Montreal Cognitive Assessment; BMI, body mass index.
aBody mass index calculated as weight in kilograms divided by height in meters squared.
Evolution on IC and IC domains according to randomisation group
After the 3-month intervention, we found significant differences in the evolution of the IC composite score favouring the VG (β = 0.48; 95% confidence interval [CI] = 0.24, 0.74; P < 0.001). Regarding the analyses on the individual IC domains, a better evolution in the IC Locomotion (both at 1- [β = 0.36; 95% CI = 0.21, 0.51; P < 0.001] and 3-month time-points [β = 0.42; 95% CI = 0.10, 0.; P < 0.001]), IC Cognition (at 1- [β = 0.33; 95% CI = 0.01, 0.65; P < 0.05] and 3-month time-points [β = 0.45; 95% CI = 0.03, 0.87; P < 0.05]) and IC Vitality domains (β = 0.50; 95% CI = 0.25, 0.74 at 3-month time-points) was displayed by the VG compared to subjects in the CG. No significant differences were found in the evolution of the IC Psychology domain between the VG and the CG. The sensory domain logistic regression analyses did not reveal differences on the risk of increasing 1 point in the IC Sensory domain score (odds ratio [OR] = 0.21; 95%CI = −0.02, 2.07). Between- and within-group effects of the intervention on endpoints are shown in Table 2.
Table 2.
Mixed-effects linear models analyses for 3-month evolution from baseline in IC domains and the IC composite score according to randomisation groups
| Intrinsic capacity domain | Time-point | Vivifrail group N = 88 β (95% CI) | Control group N = 100 β (95% CI) | Between-group differences β (95% CI) | P-value |
|---|---|---|---|---|---|
| IC Locomotion domain z-score | 1 month | 0.25 (0.13, 0.39) | −0.10 (−0.23, 0.02) | 0.36 (0.21, 0.51) | <0.001 |
| 3 months | 0.24 (−0.01, 0.49) | −0.18 (−0.40, 0.04) | 0.42 (0.10, 0.74) | 0.01 | |
| SPPB score | 1 month | 0.64 (0.29, 0.99) | −0.27 (−0.58, 0.05) | 0.91 (0.52, 1.30) | <0.001 |
| 3 months | 0.54 (−0.12, 1.21) | −0.46 (−1.01, 0.09) | 1.00 (0.18, 1.83) | 0.02 | |
| IC Cognition domain z-score | 1 month | 0.43 (0.12, 0.74) | 0.10 (−0.06, 0.26) | 0.33 (0.01, 0.65) | 0.05 |
| 3 months | 0.39 (0.02, 0.77) | −0.06 (−0.29, 0.17) | 0.45 (0.03, 0.87) | 0.03 | |
| MoCA score | 1 month | 2.24 (0.61, 3.87) | 0.51 (−0.31, 1.33) | 1.73 (0.03, 3.43) | 0.05 |
| 3 months | 2.04 (0.09, 3.99) | −0.31 (−1.49, 0.86) | 2.35 (0.17, 4.54) | 0.03 | |
| IC Vitality domain z-score | 1 month | 0.44 (0.21, 0.68) | 0.02 (−0.07, 0.12) | 0.42 (0.18, 0.66) | 0.001 |
| 3 months | 0.40 (0.16, 0.63) | −0.10 (−0.19, −0.01) | 0.50 (0.25, 0.74) | <0.001 | |
| Handgrip Strength (kg) | 1 month | 3.22 (1.54, 4.91) | 0.18 (−0.51, 0.86) | 3.04 (1.33, 4.75) | 0.001 |
| 3 months | 2.86 (1.14, 4.59) | −0.73 (−1.44, −0.01) | 3.59 (1.83, 5.35) | <0.001 | |
| IC Psychology domain z-score | 3 months | −0.04 (−0.40, 0.33) | −0.28 (−0.48, −0.08) | 0.24 (−0.15, 0.63) | 0.22 |
| GDS Yesavage | 3 months | 0.11 (−0.96, 1.18) | 0.82 (0.23, 1.41) | −0.71 (−1.86, 0.43) | 0.22 |
| IC Composite Score | 3 months | 0.29 (0.06, 0.52) | −0.10 (−0.33, −0.06) | 0.48 (0.24, 0.74) | <0.001 |
Significant associations are in bold. Models were adjusted by age, sex, educational level and baseline IC level. β (95%CI), β-coefficients and 95% confidence interval; 5-STS, 5-times Sit-to-Stand Test; MoCA, Montreal Cognitive Assessment; BMI, body mass index.
Stratified analyses by frailty status
The time-by-group-by-frailty interaction was significant in models with IC Locomotion (β = 0.48; 95% CI = 0.10, 0.85; P = 0.01), IC Cognition (β = 0.85; 95% CI = 0.20, 1.51; P = 0.01), IC Vitality (β = 0.48; 95% CI = 0.20, 0.77; P < 0.001) and IC Composite score (β = 0.48; 95% CI = 0.06, 0.88; P = 0.024) as dependent variables, indicating that frailty levels might modulate the effects of the multicomponent exercise program on these domains.
Among individuals classified as pre-frail according to Fried’s definition at baseline (n = 121 [64.36% of the whole sample], mean age = 84.09 ± 4.68, 70.75% women), subjects randomised to the VG (n = 57) showed significant differential prospective evolution in the IC Locomotion (β = 0.29; 95%CI = 0.02, 0.55; P < 0.001) and Vitality (β = 0.42; 95%CI = 0.12, 0.73; P < 0.001) domains compared to the CG (n = 64) (Figure 1 and Table 3).
Figure 1.
Between-group 3-month change in IC and its domains by randomisation group in pre-frail and frail individuals. β-coefficients were estimated by linear mixed models with group, time, its interaction and covariates (age, sex, educational level and baseline IC level) as fixed effects. A random slope on time was assumed. IC computed by the average of four available IC domains: IC Locomotion (average of the z-score of SPPB, GS and 5-STS), IC Cognition (assessed through the MoCA test), IC Vitality (evaluated through the HS) and IC Psychology (by the 15-item GDS). β (95%CI), β-coefficients and 95% confidence interval; 5-STS, 5-times Sit-to-Stand Test; MoCA, Montreal Cognitive Assessment.
Table 3.
Within-group evolution from baseline in IC domains and the IC Composite Score by frailty status
| Pre-frail individuals (n = 121) | Frail individuals (n = 67) | |||||
|---|---|---|---|---|---|---|
| IC domain | Time-point | Vivifrail group N = 57 β (95% CI)a | Control group N = 64 β (95% CI) | Time-point | Vivifrail group N = 31 β (95% CI)a | Control group N = 36 β (95% CI) |
| IC Locomotion domain z-score | 1 month | 0.17 (0.01, 0.33)* | −0.08 (−0.23, 0.07) | 1 month | 0.37 (0.15, 0.60) | −0.20 (−0.39, −0.01) |
| 3 months | 0.42 (0.15, 0.69)** | −0.13 (−0.35, 0.10) | 3 months | 0.47 (0.07, 0.87)* | −0.18 (−0.50, 0.15) | |
| IC Cognition domain z-score | 1 month | 0.52 (−0.03, 1.08) | 0.10 (−0.10, 0.31) | 1 month | 0.64 (−0.07, 1.35) | 0.06 (−0.20, 0.33) |
| 3 months | 0.44 (−0.17, 1.05) | −0.09 (−0.40, 0.20) | 3 months | 0.79 (0.03, 1.55)* | −0.01 (−0.33, 0.30) | |
| IC Vitality domain z-score | 1 month | 0.41 (0.12, 0.70)** | 0.06 (−0.05, 0.18) | 1 month | 0.47 (0.08, 0.86)* | −0.05 (−0.21, 0.11) |
| 3 months | 0.38 (0.08, 0.67)* | −0.05 (−0.16, 0.07) | 3 months | 0.42 (0.02, 0.83)* | −0.20 (−0.38, −0.02)* | |
| IC Psychology domain z-score | 3 months | −0.29 (−0.72, −0.07)* | −0.17 (−0.38, 0.04) | 3 months | 0.21 (−0.48, 0.91) | −0.49 (−0.91, −0.09) |
| IC Composite Score | 3 months | 0.11 (−0.16, 0.38) | −0.16 (−0.33, 0.004) | 3 months | 0.28 (−0.09, 0.65) | −0.56 (−0.84, −0.28) |
Significant associations are in bold. Models were adjusted by age, sex, educational level and baseline IC level. β (95%CI), β-coefficients and 95% confidence interval.
* P < 0.05, **P < 0.01.
When analyses were restricted to frail individuals (≥3 Fried’s criteria), the VG (n = 31) showed significant increases in the IC Locomotion (β = 0.37; 95%CI = 0.15, 0.60 at 1-month; β = 0.47; 95%CI = 0.07, 0.87 at 3-month visit) and IC Cognitive (β = 0.79; 95%CI = 0.03, 1.55 at 3-month visit) domains. Between-group difference analyses showed significant benefits in the IC Locomotion (β = 0.46; 95%CI = 0.20, 0.72; P < 0.001 at 1-month visit; β = 0.66; 95%CI = 0.15, 1.17; P < 0.001 at 3-mont visit), IC Vitality (β = 0.62; 95%CI = 0.20, 1.05; P < 0.001 at 3-mont visit) and the IC Cognition domains (only at 3-month time-points: β = 0.80; 95%CI = 0.03, 1.57; P < 0.05) of VG compared to usual care (CG, n = 36). Finally, VG showed to positively impact the IC Composite score compared to CG among frail individuals (between-group difference β-coefficient = 0.83; 95%CI = 0.42, 1.25; P < 0.001) (Figure 1).
Discussion
The present study showed that, among community-dwelling older adults with pre-frailty/frailty and MCI/mild-dementia, a 12-week Vivifrail MCE program exerted benefits on IC composite score and its domain evolution compared to usual care. These benefits were mainly driven by improvements on the locomotion, cognitive and vitality IC domains. In addition, we showed the effects of greater magnitude among frail individuals compared to pre-frail counterparts. Our study expands evidence from the primary study from which data were used in present analyses, which showed that Vivifrail MCE was able to positively impact independent measures of physical and cognitive functions [28]. Our study shows how these benefits observed fragmentedly translate to a novel overall marker of capacities, IC, recently incorporated as functional-based indicator of older adults’ health [11]. Sadly, given the distribution-based nature of our main endpoint (dimensionless IC composite score based on z-scores of the different domains), our results are not clinically straightforwardly interpretable in terms of effect of size. But notably, effects on the individual domains capturing cognition and mobility represent a substantial positive short-term change. In addition, if changes in the IC composite score (z-score = 0.5) were translated into individual domains, these would clearly pose a clinically meaningful change. Our study constitutes one of the first pieces of evidence on the effects of interventions, and specifically Vivifrail MCE, on the IC of community-dwelling individuals at risk of disability. Present analyses contribute to reinforce the role of individualised Vivifrail MCE as an effective intervention for healthy ageing promotion in older adults at risk of disability [23, 38, 39].
The concept of IC has arisen as innovative approach to older adult’s health. Accordingly, there is a need to develop strategies oriented to promote healthy ageing through the maintenance or expansion of IC [40]. Nevertheless, evidence around specific interventions to improve IC are still in its infancy. Exercise has widely shown to be associated with healthier ageing phenotypes, by having been associated with a lower incidence of ageing-related chronic conditions [41, 42] and disability at older age [41–43]. In addition, it has been shown to positively impact individual domains of functional ability such as physical performance [32, 44], cognitive function [45, 46] and depressive symptoms [47] in different older adults’ populations. Given that capacities are understood as overt expressions of integrated functioning of different physiological systems [48], exercise whole-organism benefits such as improved metabolic and cardiovascular health [49, 50], muscle mass and function [51, 52], and neurogenesis at the central nervous system [53, 54] might underlie its effectiveness in reversing frailty [55–57], reducing the risk of late-life adverse events [58, 59] and contributing to improve quality of life [60], even in the most vulnerable populations [61, 62]. Therefore, in accordance with our findings and scarcely available evidence, Vivifrail individualised MCE program might be considered an effective intervention in the development and maintenance of IC at an older age, especially for those presenting with low IC reserves [23].
MCE has been shown to be the most effective approach to improve physical performance among physically frail older adults [63–65], by combining different stimulus. Besides inducing muscle mass and function (strength and power) increases [53, 66], benefits of these programs might positively impact cognitive [28, 67, 68] and psychological domains [56]. Whereas our study contributes to the growing evidence around the role of MCE as an effective intervention to improve cognitive function among older adults [69], it failed at showing benefits on the IC psychology domain, an aspect that remains controversial in the literature [38, 70] There is a need for further research on the role of MCE effects on the psychological sphere.
So far and to our knowledge, no study has explored the effects of a structured exercise program on IC of frail/pre-frail older adults. However, one study by Huang et al. compared the effects of aerobic versus strength exercises on IC in a sample of Japanese older adults with memory complaints (n = 415, mean age = 72.3 ± 4.6, 47% women). They showed that both aerobic and resistance exercise were indistinctly effective in promoting IC improvements over 26 weeks compared to a health education program [71]. Interestingly, in their study, single-domain analyses revealed a differential effect of aerobic exercise (that improved IC locomotion and psychological domains), and resistance training (positively impacting IC locomotion and vitality domains), suggesting a potential maximisation of benefits when combining exercise modalities [71].
Our study further showed greater impact of exercise on the IC composite score and IC domains of frail older adults compared to pre-frail individuals. This observation is compatible with previous research [72, 73], and could be due to the lower reserves of frail individuals, for which similar exercise regimes might constitute a greater physiological insult, and therefore, lead to greater adaptations in the context of their greater trainability [74]. This fact might reinforce the need to adapt and individualise exercise prescription as proposed in Vivifrail, with the objective of optimising gains independently of the baseline frailty status/functional ability. Due to the substantial loss in statistical power in stratified analyses of present work and scarcity of studies around differential effects of exercise in frail versus pre-frail in community-dwelling older adults, this topic deserves more research.
Strengths
Our study presents several strengths, such as its novelty, its multicentre nature and the specific characteristics of included participants, oldest-old (mean age 84.06 ± 4.77) displaying IC declines, that might be the target of preventive strategies as recommended by ICOPE and are usually excluded from clinical trials. In addition, the use of a continuous composite score of IC as the outcome allowed us to monitor the trajectories of the complex construct of IC in response to exercise based on the effect on several domains. This approach allows a more nuanced and powerful analyses compared to categorical outcomes such as disability or mortality [12]. In addition, sub-group analyses allowed us to explore differential effects of the intervention based on frailty baseline levels, responding to the need of better information about how different subpopulation may respond to interventions in the era of precision medicine [75].
As limitations of the study, it should be noted that this is a secondary analysis of a study designed for exploring effects of Vivifrail multicomponent exercise program on functional capacity in frail older patients with MCI/mild dementia. Therefore, our study should be deemed as hypothesis generating—rather than hypothesis—testing. Consequently, IC operationalisation was constrained by data availability and might have slightly deviated from currently available proposed approaches [76]. Especially remarkable is the inability to include the sensory domain in the composite IC score, due to the categorical nature of the available data in this domain in the present study.
Second, the follow-up period was relatively limited. However, potential maintenance or improvement in IC in such an older and vulnerable population even in the short term might constitute a relevant functional achievement for the individual and for the whole society. Additionally, in the present study, evolution in the PA levels during the participation was not evaluated, hampering our ability to investigate to what extent such changes might have affected observed benefits. Finally, we failed at achieving the sample size proposed in the study protocol [33], given that following the coronavirus disease 2019 lockdown, recruitment had to be stopped. The latter limited the possibility of performing further exploratory sub-analyses (such as sex-stratified analysis) that might have been informative.
Conclusions
The Vivifrail MCE program has been proposed as the elective intervention for those presenting with declines in the IC locomotion domain in ICOPE by WHO [25], with potential for positively impacting cognitive, vitality and psychological domains. Our study contributes to this recommendation by demonstrating the ability of the home-based personalised Vivifrail exercise program to boost an overall marker of IC among community-dwelling older adults at risk of disability, through improvements on the physical, cognitive and vitality domain. Therefore, our study supports WHO recommendations on IC declines management. Until a consensus IC operationalisation is reached, and original data from studies primarily designed to explore the effect of interventions on IC, this might serve as a proof of concept. Further research should confirm our results in other clinical scenarios such as primary care, hospitals, nursing homes and in other older adult subpopulations.
Supplementary Material
Acknowledgements
We would like to show our gratefulness to participants and their relatives, as well as to the research personnel of the hospital involved in the study. Data will be made available upon reasonable request. Open access funding provided by Universidad Pública de Navarra.
Contributor Information
Juan Luis Sánchez-Sánchez, Gérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalier Universitaire de Toulouse, 31000 Toulouse, France; MOVE-IT Research Group, Department of Physical Education, Faculty of Education Sciences, University of Cadiz, 11519 Cadiz, Spain; Universidad Pública de Navarra (UPNA), Pamplona, Spain.
Philipe de Souto Barreto, Gérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalier Universitaire de Toulouse, 31000 Toulouse, France; CERPOP, Inserm 1295, Université de Toulouse, UPS, Toulouse, France.
Iván Antón-Rodrigo, Hospital of Eibar, OSI Debabarrena, Osakidetza, Eibar, Gipuzkoa, Spain; Grupo de Investigación en Atención Primaria, Biodonostia Institute of Health Research, San Sebastián, Gipuzkoa, Spain.
Fernanda Ramón-Espinoza, Functional Recovery Unit, Hospital San Juan de Dios, Pamplona, Spain.
Itxaso Marín-Epelde, Geriatric Department, Hospital Universitario de Navarra (HUN), Pamplona, Spain.
Marina Sánchez-Latorre, Geriatric Department, Hospital Universitario de Navarra (HUN), Pamplona, Spain.
Débora Moral-Cuesta, Geriatric Department, Hospital Universitario de Navarra (HUN), Pamplona, Spain.
Álvaro Casas-Herrero, Geriatric Department, Hospital Universitario de Navarra (HUN), Pamplona, Spain; Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain; CIBER of Frailty and Healthy Aging (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.
Declaration of Conflicts of Interest
None.
Declaration of Sources of Funding
This study has been funded by a Gobierno de Navarra project grant and FEDER Funds (426/2016, del 30 September 28/16). The funder played no role in the conception or execution of the study, data analyses or results reporting.
References
- 1. United Nations. World Population Prospects 2019: Data Booklet. https://www.un-ilibrary.org/population-and-demography/world-population-prospects-2019-data-booklet_3e9d869f-en (17 March 2020, date last accessed).
- 2. WHO | World Health Statistics 2019: Monitoring health for the SDGs. WHO. http://www.who.int/gho/publications/world_health_statistics/2019/en/ (18 March 2020, date last accessed).
- 3. Brown GC. Living too long: the current focus of medical research on increasing the quantity, rather than the quality, of life is damaging our health and harming the economy. EMBO Rep 2015; 16: 137–41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Mason CN, Miller T. International projections of age specific healthcare consumption: 2015–2060. J Econ Ageing 2018; 12: 202–17. [Google Scholar]
- 5. Seals DR, Kaplon RE, Gioscia-Ryan RA, LaRocca TJ. You’re only as old as your arteries: translational strategies for preserving vascular endothelial function with aging. Physiology (Bethesda) 2014; 29: 250–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. WHO | World Report on Ageing and Health 2015. WHO. http://www.who.int/ageing/events/world-report-2015-launch/en/ (10 February 2021, date last accessed).
- 7. Seals DR, Justice JN, LaRocca TJ. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol (Lond) 2016; 594: 2001–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Michel J-P, Graf C, Ecarnot F. Individual healthy aging indices, measurements and scores. Aging Clin Exp Res 2019; 31: 1719–25. [DOI] [PubMed] [Google Scholar]
- 9. Beard JR, Officer A, Carvalho IAD et al. The world report on ageing and health: a policy framework for healthy ageing. Lancet 2016; 387: 2145–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Cesari M, Araujo de Carvalho I, Amuthavalli Thiyagarajan J et al. Evidence for the domains supporting the construct of intrinsic capacity. J Gerontol A Biol Sci Med Sci 2018; 73: 1653–60. [DOI] [PubMed] [Google Scholar]
- 11. de Carvalho IA, Martin FC, Cesari M, Sumi Y, Thiyagarajan JA, Beard J. Operationalising the concept of intrinsic capacity in clinical settings. 2017; 31. 10.1016/j.bpa.2017.01.003. [DOI] [Google Scholar]
- 12. Beard JR, Jotheeswaran AT, Cesari M, Araujo de Carvalho I. The structure and predictive value of intrinsic capacity in a longitudinal study of ageing. BMJ Open 2019; 9: e026119. 10.1136/bmjopen-2018-026119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Sánchez-Sánchez JL, Rolland Y, Cesari M, de Souto BP. Associations between intrinsic capacity and adverse events among nursing home residents: the INCUR study. J Am Med Dir Assoc 2021; S1525-8610: 00775–1. [DOI] [PubMed] [Google Scholar]
- 14. Charles A, Buckinx F, Locquet M et al. Prediction of adverse outcomes in nursing home residents according to intrinsic capacity proposed by the World Health Organization. J Gerontol A Biol Sci Med Sci 2020; 75: 1594–9. [DOI] [PubMed] [Google Scholar]
- 15. Thiyagarajan JA, Araujo de Carvalho I, Peña-Rosas JP et al. Redesigning care for older people to preserve physical and mental capacity: WHO guidelines on community-level interventions in integrated care. PLoS Med 2019; 16: e1002948. 10.1371/journal.pmed.1002948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Gill TM, Gahbauer EA, Allore HG, Han L. Transitions between frailty states among community-living older persons. Arch Intern Med 2006; 166: 418–23. [DOI] [PubMed] [Google Scholar]
- 17. Dent E, Morley JE, Cruz-Jentoft AJ et al. Physical frailty: ICFSR international clinical practice guidelines for identification and management. J Nutr Health Aging 2019; 23: 771–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Giudici KV, de Souto BP, Beard J et al. Effect of long-term omega-3 supplementation and a lifestyle multidomain intervention on intrinsic capacity among community-dwelling older adults: secondary analysis of a randomized, placebo-controlled trial (MAPT study). Maturitas 2020; 141: 39–45. [DOI] [PubMed] [Google Scholar]
- 19. Giné-Garriga M, Roqué-Fíguls M, Coll-Planas L, Sitjà-Rabert M, Salvà A. Physical exercise interventions for improving performance-based measures of physical function in community-dwelling, frail older adults: a systematic review and meta-analysis. Arch Phys Med Rehabil 2014; 95: 753–769.e3. [DOI] [PubMed] [Google Scholar]
- 20. Jadczak AD, Makwana N, Luscombe-Marsh N, Visvanathan R, Schultz TJ. Effectiveness of exercise interventions on physical function in community-dwelling frail older people: an umbrella review of systematic reviews. JBI Database System Rev Implement Rep 2018; 16: 752–75. [DOI] [PubMed] [Google Scholar]
- 21. Coelho-Junior H, Marzetti E, Calvani R, Picca A, Arai H, Uchida M. Resistance training improves cognitive function in older adults with different cognitive status: a systematic review and meta-analysis. Aging Ment Health 2022; 26: 213–24. [DOI] [PubMed] [Google Scholar]
- 22. Daryanti Saragih I, Yang Y-P, Saragih IS, Batubara SO, Lin C-J. Effects of resistance bands exercise for frail older adults: a systematic review and meta-analysis of randomised controlled studies. J Clin Nurs 2022; 31: 43–61. [DOI] [PubMed] [Google Scholar]
- 23. Izquierdo M, Merchant RA, Morley JE et al. International Exercise Recommendations in Older Adults (ICFSR): expert consensus guidelines. J Nutr Health Aging 2021; 25: 824–53. [DOI] [PubMed] [Google Scholar]
- 24. Izquierdo M, Rodriguez-Mañas L, Sinclair AJ. Editorial: what is new in exercise regimes for frail older people - how does the Erasmus Vivifrail project take us forward? J Nutr Health Aging 2016; 20: 736–7. [DOI] [PubMed] [Google Scholar]
- 25. Integrated care for older people (ICOPE): guidance for person-centred assessment and pathways in primary care. https://www.who.int/publications-detail-redirect/WHO-FWC-ALC-19.1 (11 May 2022, date last accessed).
- 26. Courel-Ibáñez J, Pallarés JG, García-Conesa S, Buendía-Romero Á, Martínez-Cava A, Izquierdo M. Supervised exercise (Vivifrail) protects institutionalized older adults against severe functional decline after 14 weeks of COVID confinement. J Am Med Dir Assoc 2021; 22: 217–219.e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Courel-Ibáñez J, Buendía-Romero Á, Pallarés JG, García-Conesa S, Martínez-Cava A, Izquierdo M. Impact of tailored multicomponent exercise for preventing weakness and falls on nursing home residents’ functional capacity. J Am Med Dir Assoc 2022; 23: 98–104.e3. [DOI] [PubMed] [Google Scholar]
- 28. Casas-Herrero Á, Sáez de Asteasu ML, Antón-Rodrigo I et al. Effects of Vivifrail multicomponent intervention on functional capacity: a multicentre, randomized controlled trial. J Cachexia Sarcopenia Muscle 2022; 13: 884–93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Romero-García M, López-Rodríguez G, Henao-Morán S, González-Unzaga M, Galván M. Effect of a multicomponent exercise program (VIVIFRAIL) on functional capacity in elderly ambulatory: a non-randomized clinical trial in Mexican women with dynapenia. J Nutr Health Aging 2021; 25: 148–54. [DOI] [PubMed] [Google Scholar]
- 30. Sáez de Asteasu ML, Martínez-Velilla N, Zambom-Ferraresi F, Casas-Herrero Á, Izquierdo M. Role of physical exercise on cognitive function in healthy older adults: a systematic review of randomized clinical trials. Ageing Res Rev 2017; 37: 117–34. [DOI] [PubMed] [Google Scholar]
- 31. Venegas-Sanabria LC, Cavero-Redondo I, Martínez-Vizcaino V, Cano-Gutierrez CA, Álvarez-Bueno C. Effect of multicomponent exercise in cognitive impairment: a systematic review and meta-analysis. BMC Geriatr 2022; 22: 617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Talar K, Hernández-Belmonte A, Vetrovsky T, Steffl M, Kałamacka E, Courel-Ibáñez J. Benefits of resistance training in early and late stages of frailty and sarcopenia: a systematic review and meta-analysis of randomized controlled studies. J Clin Med 2021; 10: 1630. 10.3390/jcm10081630. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Casas-Herrero A, Anton-Rodrigo I, Zambom-Ferraresi F et al. Effect of a multicomponent exercise programme (VIVIFRAIL) on functional capacity in frail community elders with cognitive decline: study protocol for a randomized multicentre control trial. Trials 2019; 20: 362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Reisberg B, Ferris SH, de Leon MJ, Crook T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry 1982; 139: 1136–9. [DOI] [PubMed] [Google Scholar]
- 35. 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: M146–56. [DOI] [PubMed] [Google Scholar]
- 36. Yesavage JA, Brink TL, Rose TL et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982; 17: 37–49. [DOI] [PubMed] [Google Scholar]
- 37. Nasreddine ZS, Phillips NA, Bédirian V et al. The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 53: 695–9. [DOI] [PubMed] [Google Scholar]
- 38. Herbert P. Promoting exercise in older people to support healthy ageing. Nurs Stand 2022; 37: 46–50. [DOI] [PubMed] [Google Scholar]
- 39. Billot M, Calvani R, Urtamo A et al. Preserving mobility in older adults with physical frailty and sarcopenia: opportunities, challenges, and recommendations for physical activity interventions. Clin Interv Aging 2020; 15: 1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Zhou Y, Ma L. Intrinsic capacity in older adults: recent advances. Aging Dis 2022; 13: 353–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol 2012; 2: 1143–211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Pedersen BK, Saltin B. Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 2015; 25: 1–72. [DOI] [PubMed] [Google Scholar]
- 43. Pahor M, Guralnik JM, Ambrosius WT et al. Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 2014; 311: 2387–96. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Mañas A, Gómez-Redondo P, Valenzuela PL, Morales JS, Lucía A, Ara I. Unsupervised home-based resistance training for community-dwelling older adults: a systematic review and meta-analysis of randomized controlled trials. Ageing Res Rev 2021; 69: 101368. 10.1016/j.arr.2021.101368. [DOI] [PubMed] [Google Scholar]
- 45. Öhman H, Savikko N, Strandberg TE, Pitkälä KH. Effect of physical exercise on cognitive performance in older adults with mild cognitive impairment or dementia: a systematic review. Dement Geriatr Cogn Disord 2014; 38: 347–65. [DOI] [PubMed] [Google Scholar]
- 46. van Uffelen JGZ, Paw MJM CA, Hopman-Rock M, van Mechelen W. The effects of exercise on cognition in older adults with and without cognitive decline: a systematic review. Clin J Sport Med 2008; 18: 486–500. [DOI] [PubMed] [Google Scholar]
- 47. Bigarella LG, Ballotin VR, Mazurkiewicz LF et al. Exercise for depression and depressive symptoms in older adults: an umbrella review of systematic reviews and meta-analyses. Aging Ment Health 2021; 1–11. [DOI] [PubMed] [Google Scholar]
- 48. Lazarus NR, Lord JM, Harridge SDR. The relationships and interactions between age, exercise and physiological function. J Physiol (Lond) 2019; 597: 1299–309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49. Fiuza-Luces C, Santos-Lozano A, Joyner M et al. Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat Rev Cardiol 2018; 15: 731–43. [DOI] [PubMed] [Google Scholar]
- 50. Garatachea N, Pareja-Galeano H, Sanchis-Gomar F et al. Exercise attenuates the major hallmarks of aging. Rejuvenation Res 2015; 18: 57–89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51. Bao W, Sun Y, Zhang T et al. Exercise programs for muscle mass, muscle strength and physical performance in older adults with sarcopenia: a systematic review and meta-analysis. Aging Dis 2020; 11: 863–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52. Cadore EL, Casas-Herrero A, Zambom-Ferraresi F et al. Multicomponent exercises including muscle power training enhance muscle mass, power output, and functional outcomes in institutionalized frail nonagenarians. Age (Dordr) 2014; 36: 773–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53. Fabel K, Wolf SA, Ehninger D, Babu H, Leal-Galicia P, Kempermann G. Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Front Neurosci 2009; 3. 10.3389/neuro.22.002.2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54. Máderová D, Krumpolec P, Slobodová L et al. Acute and regular exercise distinctly modulate serum, plasma and skeletal muscle BDNF in the elderly. Neuropeptides 2019; 78: 101961. 10.1016/j.npep.2019.101961. [DOI] [PubMed] [Google Scholar]
- 55. Tarazona-Santabalbina FJ, Gómez-Cabrera MC, Pérez-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: 426–33. [DOI] [PubMed] [Google Scholar]
- 56. Giné-Garriga M, Guerra M, Pagès E, Manini TM, Jiménez R, Unnithan VB. The effect of functional circuit training on physical frailty in frail older adults: a randomized controlled trial. J Aging Phys Act 2010; 18: 401–24. [DOI] [PubMed] [Google Scholar]
- 57. Castell MV, Gutiérrez-Misis A, Sánchez-Martínez M et al. Effectiveness of an intervention in multicomponent exercise in primary care to improve frailty parameters in patients over 70 years of age (MEFAP-project), a randomised clinical trial: rationale and study design. BMC Geriatr 2019; 19: 25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58. García-Hermoso A, Ramirez-Vélez R, Sáez de Asteasu ML et al. Safety and effectiveness of long-term exercise interventions in older adults: a systematic review and meta-analysis of randomized controlled trials. Sports Med 2020; 50: 1095–106. [DOI] [PubMed] [Google Scholar]
- 59. Sherrington C, Fairhall NJ, Wallbank GK et al. Exercise for preventing falls in older people living in the community. Cochrane Database Syst Rev 2019; 1: CD012424. 10.1002/14651858.CD012424.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60. Campbell E, Petermann-Rocha F, Welsh P et al. The effect of exercise on quality of life and activities of daily life in frail older adults: a systematic review of randomised control trials. Exp Gerontol 2021; 147: 111287. 10.1016/j.exger.2021.111287. [DOI] [PubMed] [Google Scholar]
- 61. Valenzuela PL, Castillo-García A, Morales JS et al. Physical exercise in the oldest old. Compr Physiol 2019; 9: 1281–304. [DOI] [PubMed] [Google Scholar]
- 62. de Souto BP, Morley JE, Chodzko-Zajko W et al. Recommendations on physical activity and exercise for older adults living in long-term care facilities: a taskforce report. J Am Med Dir Assoc 2016; 17: 381–92. [DOI] [PubMed] [Google Scholar]
- 63. Aguirre LE, Villareal DT. Physical exercise as therapy for frailty. Nestle Nutr Inst Workshop Ser 2015; 83: 83–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64. Casas Herrero Á, Cadore EL, Martínez Velilla N, Izquierdo Redin M. Physical exercise in the frail elderly: an update. Rev Esp Geriatr Gerontol 2015; 50: 74–81. [DOI] [PubMed] [Google Scholar]
- 65. Freiberger E, Häberle L, Spirduso WW, Zijlstra GAR. Long-term effects of three multicomponent exercise interventions on physical performance and fall-related psychological outcomes in community-dwelling older adults: a randomized controlled trial. J Am Geriatr Soc 2012; 60: 437–46. [DOI] [PubMed] [Google Scholar]
- 66. Rodriguez-Larrad A, Arrieta H, Rezola C et al. Effectiveness of a multicomponent exercise program in the attenuation of frailty in long-term nursing home residents: study protocol for a randomized clinical controlled trial. BMC Geriatr 2017; 17: 60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67. Cordes T, Bischoff LL, Schoene D et al. A multicomponent exercise intervention to improve physical functioning, cognition and psychosocial well-being in elderly nursing home residents: a study protocol of a randomized controlled trial in the PROCARE (prevention and occupational health in long-term care) project. BMC Geriatr 2019; 19: 369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 68. Huang X, Zhao X, Li B et al. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: a systematic review and network meta-analysis. J Sport Health Sci 2022; 11: 212–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 69. Da Silva JL, Agbangla NF, Le Page C, Ghernout W, Andrieu B. Effects of chronic physical exercise or multicomponent exercise programs on the mental health and cognition of older adults living in a nursing home: a systematic review of studies from the past 10 years. Front Psychol 2022; 13: 888851. 10.3389/fpsyg.2022.888851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70. Caldo-Silva A, Furtado GE, Chupel MU et al. Effect of a 40-weeks multicomponent exercise program and branched chain amino acids supplementation on functional fitness and mental health in frail older persons. Exp Gerontol 2021; 155: 111592. 10.1016/j.exger.2021.111592. [DOI] [PubMed] [Google Scholar]
- 71. Huang CH, Umegaki H, Makino T et al. Effect of various exercises on intrinsic capacity in older adults with subjective cognitive concerns. J Am Med Dir Assoc 2021; 22: 780–786.e2. [DOI] [PubMed] [Google Scholar]
- 72. Takano E, Teranishi T, Watanabe T et al. Differences in the effect of exercise interventions between prefrail older adults and older adults without frailty: a pilot study. Geriatr Gerontol Int 2017; 17: 1265–9. [DOI] [PubMed] [Google Scholar]
- 73. Wakida M, Asai T, Kubota R et al. Longitudinal effects of physical exercise on health-related outcomes based on frailty status in community-dwelling older adults. Geriatr Gerontol Int 2022; 22: 213–8. [DOI] [PubMed] [Google Scholar]
- 74. Vogel O, Niederer D, Vogt L. Multimodal exercise effects in older adults depend on sleep, movement biography, and habitual physical activity: a randomized controlled trial. Front Aging Neurosci 2021; 13: 722799. 10.3389/fnagi.2021.722799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 75. Morley JE, Vellas B. Patient-Centered (P4) medicine and the older person. J Am Med Dir Assoc 2017; 18: 455–9. [DOI] [PubMed] [Google Scholar]
- 76. López-Ortiz S, Lista S, Peñín-Grandes S et al. Defining and assessing intrinsic capacity in older people: a systematic review and a proposed scoring system. Ageing Res Rev 2022; 79: 101640. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.