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THE IMPACT OF EXERCISE AND COGNITIVE STIMULATION THERAPY ON INTRINSIC CAPACITY COMPOSITE SCORE IN PREFRAIL OLDER ADULTS: A PRE-POST INTERVENTION STUDY

 

R.A. Merchant1,2, Y.H. Chan3, D. Anbarasan2, J. Woo4

 

1. Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore; 2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 3. Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong

Corresponding Author: Associate Professor Reshma Merchant, Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore 119228, Email: reshmaa@nuhs.edu.sg, Telephone number: +65 6779 5555, ORCID iD: 0000-0002-9032-0184

J Frailty Aging 2024;in press
Published online February 15, 2024, http://dx.doi.org/10.14283/jfa.2024.16

 


Abstract

Intrinsic capacity(IC) is a measure of physical, cognitive, vitality, psychological, and sensory abilities which determines functional ability. Decline in IC has been shown to accelerate the trajectory of frailty. We aim to show the impact of exercise (Ex) and cognitive stimulation therapy (CST) on (i) IC domains and composite score (ii) frailty and functional ability in pre-frail older adults. Secondary analysis of data from a pre-post intervention study of pre-frail older adults ≥ 65 years attending primary care clinic. Control (CON) and 2 intervention groups ((i) Ex 6 months (ii) CST 3 months with Ex 6 months (Ex+CST)) were recruited. Pre-frailty was determined using the FRAIL scale. Questionnaires (on demographics, functional ability, and depression) were administered and physical function assessment (gait speed (GS), short physical performance battery (SPPB) test, handgrip strength, five times sit-to-stand (5x-STS)) was conducted at 0, 3, 6 and 12 months. Four domains of IC were evaluated: locomotion (GS and 5x-STS), vitality (nutrition and muscle mass), cognition (MoCA and subjective cognitive decline) and psychological (depression and anxiety). Each domain was scored from 0 to 2 (no decline) with total IC score ranging from 0 to 8. 187 participants completed baseline and 3 months assessments, 109 (58.3%) were allocated to CON, 37 (19.8%) to Ex and 41 (21.9%) to Ex + CST groups. At 3 months, both Ex and Ex +CST showed improvement in IC composite scores, locomotion, and psychological domain scores but improvement in cognition domain only in Ex + CST group. At 6 months, there were improvements in total IC score, locomotion, vitality, and psychological domain in both Ex and Ex + CST groups. At 12 months, significant improvement was evident in total IC score for Ex and Ex+CST groups, vitality when fatigue (in addition to muscle mass and nutrition) was added and instrumental activities of daily living. Multidomain intervention incorporating exercise and CST resulted in significant improvement in IC composite scores, locomotion, vitality, cognition, and psychological domains.

Key words: Intrinsic capacity, vitality, pre-frailty, exercise, cognitive stimulation therapy, physical function.


 

Introduction

The world population is aging rapidly especially in countries like Singapore where 41.5% of the population will be above 65 years old by 2050 with associated increased prevalence of geriatric syndromes such as frailty and dementia (1). Recognising the need to move from disease based approach to function based approach, the World Health Organization (WHO) released the World Report on Ageing and Health in 2015 and reframed the definition of healthy aging as “the process of developing and maintaining the functional ability that enables wellbeing in older age”(2). In 2017, the WHO published the Integrated Care of Older People (ICOPE) guidelines (3) on five steps from screening for decline in intrinsic capacity (IC), assessment, person-cantered care plan to getting involved in the community. Functional ability is determined by the interaction of environment with IC (4). IC is a positive attribute and a measure of physiological reserve adopting a life course approach which includes five interrelated domains: locomotion, cognition, psychological, vitality and sensory (vision and hearing) (5). The multidimensional nature of IC has been validated in many countries and shown to be associated with activity of daily living (ADL) and instrumental activity of daily living (IADL) impairment, poor perceived health, cardiovascular disease incidence, frailty, disability, participation restriction and mortality (6-11).
IC decline and frailty can co-exist in the same person (5, 9). Frailty is a dynamic construct defined by a decline in physiological reserve predisposing older adults to negative outcomes when exposed to stressors (12). Pre-frailty is a transition phase between healthy and frail, and maybe reversible before the onset of disability (12). Between one third to half of the population are pre-frail depending on the population studied and screening tools used (13, 14). The prevalence of at least one IC domain decline in pre-frail older adult is 83.3% (15). Decline in IC has shown to accelerate trajectory of frailty in longitudinal studies (15, 16). Chhetri et al recommended monitoring of IC trajectory to allow for early intervention before the onset of frailty (17).
Most prior intervention studies have focussed on improvements in individual measures such as gait speed, nutrition, social isolation, and cognition instead of functional ability which is one of the key outcome measure for the Decade of Healthy Aging (4, 18, 19). IC domains are interrelated, share common biological pathways and it is the dynamical interrelationship which determines overall improvement in functional ability and frailty status (20, 21). Although the measurement tools remain an ongoing debate especially for the vitality domain and there is no defined gold standard measurement for the composite score, it is increasingly evident through longitudinal studies that IC composite score could serve as a good surrogate for functional ability and mortality (6, 7, 22).
Multidomain interventions have shown to improve gait speed, cognition, and quality of life in pre-frail older adults but there are limited studies on its impact on IC composite score especially in pre-frail older adults (19, 23-25). We aim to show the impact of exercise and cognitive stimulation therapy on intrinsic capacity domains and composite score in pre-frail older adults. In addition, we also analyzed mean changes in FRAIL scores and functional ability from baseline.

 

Methods

Study Participants

This is a secondary analysis of data from a pre-post intervention study in pre-frail older adults ≥ 65 years old recruited from the primary care clinics in the Western region of Singapore from June 2019 to January 2022. Recruited participants should be at least pre-frail, as measured by the 5-item FRAIL scale (Fatigue, Resistance, Aerobic, Illness, and Loss of Weight) where scores of 1 to 2 were considered pre-frail (26). In addition, they should be able to provide consent and follow instructions. Participants with a pacemaker or a defibrillator, liver or gastro-intestinal disease, end stage lung disease, cardiac disease, undergoing active cancer treatment, gout, underlying psychiatric conditions and nursing home residents were excluded. The detailed recruitment and study procedures are outlined in our previous publication (27). Control groups were recruited from the Choa Chu Kang and intervention groups from the Bukit Batok National University Polyclinics (NUP) five kilometres apart in the Western region of Singapore. In Bukit Batok NUP, allocation to exercise (Ex) or exercise with cognitive stimulation therapy (CST) (Ex + CST) groups were not randomised and was dependent on which of the two research staff who recruited them (27). Participants and outcome assessors were not blinded and there was no concealment. Recruitment for intervention groups were affected by Covid-19 restrictions.
This study conformed to the principles of the Declaration of Helsinki and was approved by The National Healthcare Group Domain Specific Review Board (Reference: 2019/00017). Informed consent was obtained from all participants involved in the study.

Intervention

Participants were allocated to either the CON, Ex or Ex + CST groups. The study lasted for 12 months, with 6 months of intervention and another 6 months of observation. The control group received general health education advice which included types of exercises, frequency, and advice on protein enriched nutrition. In addition to health education advice, both intervention groups received 60 minutes of group based multicomponent exercise program, consisting of aerobic training, resistance training, dual task, and balance training twice a week. The exercises were led by trained health coaches and were of moderate intensity. The Ex + CST group received 30 minutes of CST twice a week for a total of 3 months in addition to the exercise, followed by 3 more months of exercise only. CST was conducted after the exercise and participants were divided into Mandarin and English-speaking groups, with a maximum of five in each group. The training modules were adapted from the CST manual which included food, word association, games, current affairs, and art (28). All participants were assessed at baseline, 3 months, 6 months, and 12 months after baseline.

Intrinsic Capacity

Four domains of intrinsic capacity (IC) were evaluated in this study – locomotion, vitality, cognition and psychological. The IC domain composite scores were defined and calculated based on prior study by Tay et al where higher scores represented greater IC (21). Four metre gait speed (<1m/s) and 5x sit-to-stand (5x STS)( <12s ) were used to define impaired locomotion (29). Nutrition and muscle mass were used to define vitality domain. Nutritional status was assessed using the Mini Nutritional Assessment-Short Form (MNA-SF) and low appendicular skeletal muscle index (ASMI) using the InBody S10 multi-frequency bioelectrical impedance analyser. MNA-SF has a maximum score of 14, <8 indicates malnourished and 8-11 at risk of malnutrition (30). ASMI was calculated by dividing appendicular skeletal mass with height squared. Low ASMI was defined as <7.0 kg/m2 for males and <5.7 kg/m2 for females based on the Asia Working Group for Sarcopenia (AWGS) 2019 consensus criteria (29). As definition of vitality remains an area of research, we included changes in various definitions of vitality (A: fatigue only; B: fatigue and malnutrition / at risk; C: fatigue, malnutrition / at risk and low ASMI; D: fatigue, malnutrition / at risk, low ASMI and low handgrip strength (HGS)) in Supplementary Table 2.
Impaired cognition domain was based on Montreal Cognitive Assessment (MoCA) score of < 26 out of 30 and/or and self-reported subjective cognitive decline (SCD) (31). SCD was defined based on a question “do you feel that you have more problems with memory than most?” (32). Psychological domain impairment was based on 15-item Geriatric Depression Scale (GDS-15) score >5 out of 15 , and a single question from the EuroQol-5 Dimensions (EQ-5D) question on anxiety/ depression where moderate to extreme anxiety/depression was scored as 1 point (32, 33). Each domain was scored from 0 to 2, with a higher score indicating greater IC. Participants were then given a total IC score, ranging from 0 to 8. Participants scoring < 2 for any domain were considered to have a decline in the respective domains.

Co-variates

Trained research assistants administered the study protocol gathering information on demographics, medications, chronic diseases, cognition, falls, sarcopenia, functional ability (ADL and IADL), pain, and perceived health. Polypharmacy was defined as taking ≥ 5 medications daily and multimorbidity as ≥ 2 chronic diseases. Perceived health was assessed using the EuroQoL Visual Analogue Scale (33). The Rapid Physical Assessment (RAPA) was used to assess physical activity (34). ADL was evaluated using Katz’s ADL questionnaire and IADL using the Lawton and Brody’s IADL questionnaire (35, 36).
Maximum handgrip strength was measured in a seated position using the Jamar hand dynamometer on with elbow flexed at 90º. Low HGS was defined as < 28kg for males and < 18kg for females (37). The Short Physical Performance Battery (SPPB) was measured with maximum score of 12 points across 3 components – balance, gait, and 5x-STS. SPPB < 9 was considered poor performance (37). Diagnosis of sarcopenia was based on the 2019 AWGS criteria (29).

Statistical Analysis

All analyses were performed using SPSS 28.0 with statistical significance set at 2-sided 5%. Descriptive analyses for categorical and continuous variables were presented as frequencies with percentages and mean ± standard deviation, respectively. The primary unit of analysis was to compare the change in intrinsic capacity scores of Ex & Ex + CST over CON. Change in FRAIL score and IADL improvements of Ex & Ex + CST over CON was also compared. General Linear Model (GLM) was performed adjusted for age, gender, ethnicity, education, hypertension, hyperlipidaemia, diabetes, physical activity, polypharmacy, intervention compliance and corresponding baseline values. McNemar test was performed to compare changes in intrinsic capacity decline proportions within the 3 groups. Participants who did not complete the 3 months assessment were excluded from this analysis.

 

Results

Participant Characteristics and Demographics

Out of 190 participants, 187 participants completed at least the baseline and 3 months assessments with complete IC data. Amongst them, 109 (58.3%) were allocated to CON, 37 (19.8%) to Ex and 41 (21.9%) to Ex + CST groups (Table 1). There were significant differences in gender distribution, education level and physical activity between the groups. CON had the greatest proportion of males (54.1% vs 40.5% vs 31.7%). Education level was significantly higher in Ex and lowest in the CON groups (9.4 ± 3.6 years vs 7.4 ± 3.8 years). Participants in the Ex group had the lowest physical activity level followed by Ex+CST and CON group (2.7 ± 1.5 vs 3.6 ± 1.6 vs 3.7 ± 1.5). The CON group had significantly lower MoCA scores compared with Ex+CST or Ex groups (25.4 ± 3.4 vs 27.4 ± 3.4 vs 27.2 ± 2.6) respectively. Nevertheless, no differences in total IC score or decline in IC domains were observed between the groups.

Table 1. Baseline Characteristics

Values presented as n (%) or mean ± SD; Bold indicates significance (p < 0.05); ab Values with common superscript are significantly different. Abbreviations: BMI, Body Mass Index; ADL; Activities of Daily Living; MoCA; Montreal Cognitive Assessment; MNA-SF, Mini Nutritional Assessment-Short Form; SPPB, Short Physical Performance Battery; ASMI, Appendicular Skeletal Muscle Index. 1. Based on Asian Working Group for Sarcopenia (AWGS) 2019’s definition; 2 Adjusted for gender

 

Outcome Measures

Changes in Intrinsic Capacity

At 3 months, when compared with CON (β 0.24, 95% CI -0.07 to 0.55), both Ex (β 0.96, 95% CI 0.45 to 1.47) and Ex + CST (β 1.15, 95% CI 0.45 to 1.85) groups had significant improvements in IC total scores. Similarly, locomotion domain scores improved in the Ex (β 0.36, 95% CI 0.15 to 0.57) and Ex+CST (β 0.40, 95% CI 0.21 to 0.60) groups compared with CON (β 0.09, 95% CI -0.04 to 0.21) and psychological domain score in Ex (β 0.48, 95% CI 0.25 to 0.71) and Ex+CST (β 0.33, 95% CI 0.12 to 0.55) compared with CON groups (β 0.05, 95% CI -0.09 to 0.18). Only Ex + CST group had significant improvement in cognitive domain score (β 0.37, 95% CI 0.19 – 0.55).
At 6 months, when compared to CON, both Ex and Ex + CST groups saw improvements in total IC score (β -0.03, 95% CI -0.42 to 0.37 vs β 0.90, 95% CI 0.03 to 1.76 vs β 1.02, 95% CI 0.26 to 1.77), locomotion domain score (β -0.02, 95% CI -0.20 to 0.16 vs β 0.46, 95% CI 0.13 to 0.79 vs β 0.52, 95% CI 0.15 – 0.88), vitality domain score (β -0.09, 95% CI -0.27 to 0.90 vs β 0.37, 95% CI 0.10 to 0.74 vs β 0.49, 95% CI 0.07 to 0.69) and psychological domain score (β -0.14, 95% CI -0.33 to 0.06 vs β 0.30, 95% CI -0.05 to 0.65 vs β 0.43, 95% CI 0.05 to 0.82). At 12 months, significant improvement was only evident in total IC score for Ex (β 1.06, 95% CI 0.27 to 1.85) and Ex+CST (β 0.91, 95% CI 0.17 to 1.66) compared to CON (β -0.01, 95% CI -0.34 to 0.33). Significant improvements were seen in the vitality domains incorporating fatigue, nutrition and ASMI at 6 months and 12 months in both the Ex and Ex+CST groups (Supplementary Table 1).
Figure 1 reflects the proportion of participants with decline for each IC domain at baseline, 3 months, and 6 months. There was significant reduction in decline in locomotion domain in both Ex and Ex+CST groups from baseline to 3 months (Ex: 75.7% vs 48.6%, Ex+CST 73.2% vs 43.9%) respectively. Similar trends were seen in psychological domain at 3 months (Ex: 40.5% vs 24.3%; Ex + CST: 36.6% vs 26.8%). Significant decline in participants with impaired cognition domain was seen at 3 months only in the Ex + CST group (51.2% vs 30.0%).

Figure 1. Changes in proportion of participants with decline in intrinsic capacity domains. (A) Locomotion (B) Vitality (C) Psychological (D) Cognition

* Indicates significant change from baseline (p < 0.05).

Table 2. Mean changes in intrinsic capacity and respective domains from baseline to 3 months, 6 months, and 12 months respectively

Values present as mean (95% confidence interval); Bold indicates significance (p < 0.05); ab Values with common superscript alphabet are significantly different; IC, Intrinsic Capacity. Adjusted for Age, Gender, Ethnicity, Education, HTN, HLD, DM, Physical Activity, Polypharmacy, Intervention Compliance, and Baseline Values

 

Changes in Frailty and Functional Ability

Mean changes in FRAIL scores and its domains including fatigue, and resistance (ability to climb 1 flight of stairs) were seen in Ex and Ex+CST groups at 3 and 6 months (Table 3). In addition, both the Ex and Ex+CST groups also improved in aerobic component (ability to walk 50m) at 6 months. There was significant improvement in IADL but not FRAIL score at 12 months.

Table 3. Mean changes in FRAIL scores, ADL and IADL from baseline to 3 months, 6 months, and 12 months respectively

Values present as mean (95% confidence interval); Bold indicates significance (p < 0.05); ab Values with common superscript alphabet are significantly different. Adjusted for Age, Gender, Ethnicity, Education, HTN, HLD, DM, Physical Activity, Polypharmacy, Intervention Compliance, and Baseline Values.

 

Discussion

Our study is one of the first few to show the benefit of exercise and CST on IC composite score, cognition, locomotion, vitality and psychological domains and sustainability after discontinuation of interventions in pre-frail community dwelling older adults. Improvement in overall IC composite score, locomotion and psychological domains was observed in both the Ex and Ex+CST groups at 3 and 6 months. However, improvement in cognition domain was only observed in the Ex+CST group at 3 months possibly due to discontinuation of CST after 3 months. Improvement in vitality scores were seen at 6 months and 12 months only when fatigue in addition to nutrition and muscle mass was included in the definition. At 12 months, significant improvements were seen in the total IC composite scores in the Ex and Ex+CST groups. Similar to our study, a 12-week Vivifrail exercise program amongst frail cognitive impaired older adults showed improvement in IC composite score, locomotion, cognition, and vitality measured using handgrip strength (38).
There are significant variations in the measurement of vitality domains where studies use ASMI, handgrip strength, nutrition, and/or fatigue (9, 10, 22). Improvement in the vitality domain at 12 months in our study population was seen only after inclusion of fatigue to ASMI and nutrition. Improvement in other domains was not sustained after the discontinuation of the intervention. Huang et al similarly showed that impact of aerobic and resistance exercise waned off after discontinuation of exercise in older adults with subjective cognitive concerns (39).
There was no improvement in FRAIL scores or its domains beyond 6 months and improvement in IADL was only seen at 12 months. Lu et al recently showed that participants with higher vitality had fewer IADL impairment on follow up possibly mediated through cognitive, psychological, and locomotive domains which was not evident from our study. In addition to IADL, perceived health, physical activity and gait speed improvement were also seen in the same study population at 12 months in our prior study suggesting IC composite score and vitality (incorporating fatigue) may be a useful measure for self-reported functional ability in pre-frail older adult (22, 27). Tay et al used similar composite score measurements and showed that higher composite IC scores were associated with reduced risk of frailty progression, frailty onset amongst robust older adults, falls and functional decline (21). Liu et al reported that new impairment in the vitality and locomotion domain was associated with transition from non-frail to frail status and 57.9% of older adults with IC impairment deteriorated over two years (15). Jia et al similarly showed that impaired locomotion and vitality at baseline were associated with “kept frail” or “worsened frail” (16). The same study showed that impaired sensory and vitality were associated with transitions of IC and poor IC was associated with functional disability.
Recognising that older adults are heterogenous, and functional ability is determined by multiple interacting factors, there is a need for co-development of multicomponent interventions addressing the individual IC domains. The interventions need to be co-ordinated, and multidisciplinary as impairment in one domain may affect uptake in another such as vision and hearing impairment may affect participation in physical activity or food insecurity (40, 41). We had no information on vision and hearing impairment in our study population. Vision impairment doubles the risk of progression to frailty, and associated with physical, cognitive, and psychological impairment (42, 43). Cataract, glaucoma and under-corrected refractory errors are top three causes of blindness in those above 50 years old globally which may be correctable (44). Similarly, hearing impairment can impact improvement in other IC domains and associated with frailty and dementia (45, 46). Participants in the Ex+CST group improved in cognitive domain at 3 months. Studies on CST have been mainly in persons with dementia and a systematic review reported significant improvement in cognition, quality of life and social interaction (47). Social isolation, depression and malnutrition are also known to be associated with frailty. Our interventions were delivered in a group based setting. Various systematic reviews and studies show that multicomponent exercises delivered in groups had favourable impact on frailty and depression (19, 48-50).
The findings from our study supports the notion of measuring IC composite scores in addition to or instead of individual functional measures for population level intervention as it was associated with better functional ability. To date, there is no global agreement on the measurement of individual domains, especially vitality and IC composite scores. A more recent study by Koivunen et al constructed a composite IC score of 0-100, validated and showed once point higher IC score was associated with a 7% decreased risk of functional decline at 6 years and 2% decreased mortality risk at 10 years (51). There are several limitations which warrants mention. First and most important, we had no information on vision and hearing IC domains which could have impacted the participation in Ex and Ex+CST groups and improvement in the interventions groups. Second, both the participants and assessors were not blinded which could have affected outcomes. However, most outcomes were based on objective measurements such as gait speed, 5x-STS, muscle mass, nutrition and MoCA. There was no randomisation within the intervention groups and enrolment was based on which of the two research staff who recruited them. However, both groups had similar outcomes except for cognition in the Ex+CST group. Third, the result from our study only applies to pre-frail older adults, and the findings need to be validated at population level. In addition, we have no longitudinal data beyond 12 months to show if improved IC composite score impacted on frailty trajectory. Fourth, demographics data such as falls and chronic diseases maybe subject to recall bias. Reporting of subjective cognitive decline may vary between different population and ethnic groups (52). Fifth, the study was conducted during Covid-19 pandemic which resulted in some participants having missing data and lost to follow up. Sixth, there were significant differences in the cognition level between CON and intervention groups which were adjusted for in the final analysis. Lastly, participants in our study were ambulant and able to follow instruction. In prior studies, impact of CST has mainly been observed in participants with cognitive impairment. It is not known if inclusion of participants with cognitive impairment would have affected the cognition domain scores at 6 and 12 months.
Many countries are embarking on transformative pathway to screen for and optimise functional ability building on WHO framework and implementing programs such as the INSPIRE ICOPE-CARE program in Occitania region through multisectoral collaborations (53). While the concept and validity of IC are well established, the measurements of individual domains and cut off points needs to be determined in future research. This topic is still in the infancy stage and yet, there are no studies on systematic assessment and management using IC framework and its impact of functional outcomes at population level.

 

Conclusion

Multidomain intervention incorporating exercise and CST resulted in significant improvement in IC composite scores, locomotion, vitality, cognition, and psychological domains. After discontinuation of interventions at 12 months, improvement in IC composite scores and IADL remained significant. Future longitudinal studies are needed to validate and evaluate the impact IC composite score on overall population health and frailty trajectory.

 

Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author Contributions: RAM obtained funding and designed the study. RAM, YHC, and DA contributed to data analysis and drafting of chart and tables. RAM, YHC, DA and JW contributed to drafting of manuscript. All authors read, edited, and approved the version submitted.

Funding: This work was funded by Ministry of Health of Singapore: Healthy Ageing Innovation Grant under National Innovation Challenge on Active and Confident Ageing (Award No: MOH/NIC/HAIG02/2017).

 

SUPPLEMENTARY MATERIAL

 

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