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The cost effectiveness of a multidomain intervention on physical, cognitive, vascular, dietary and psychosocial outcomes among community dwelling older adults with cognitive frailty in Malaysia: The AGELESS Trial

Alzheimer's Research & Therapy volume 17, Article number: 101 (2025) Cite this article

Abstract

Background

Cognitive frailty (CF) in older adults is a potentially reversible syndrome that may benefit from lifestyle-based multidomain interventions. This study assessed the AGELESS intervention’s impact on cognitive, physical, vascular, dietary, and psychosocial outcomes, along with its cost-effectiveness, in a Low-Middle-Income Country (LMIC).

Methods

The AGELESS randomized controlled trial recruited 106 older adults (above 60 years) from Klang Valley, Malaysia, with (pre)-CF (≥ 1 Fried’s criteria and Clinical Dementia Rating scale = 0.5). Participants were randomly assigned to a 24-month multidomain intervention (physical activity, cognitive training, nutritional and psychological counselling, cardiovascular care) or control group (educational module). Primary outcomes, assessed at baseline, 12 and 24 months, included the modified Neuropsychological Tests Battery (mNTB) and physical performance measures. Intervention costs were calculated to determine Incremental Cost-Effectiveness Ratios (ICERs). An intention-to-treat analysis was conducted to account for attrition.

Results

The trial occurred during the COVID-19 pandemic. Despite a 50% dropout rate, adherence among remaining participants was over 50% for all intervention components (range 53%-91%). The intervention led to significant improvements in selected parameters of cognitive function, physical performance, anthropometry, and dietary patterns (for all parameters, p < 0.05 for interaction time*group in repeat-measures ANOVA). The cost per participant was RM 1592.74 (≈USD 355.05) in the multidomain arm, and RM 488.21 (≈USD 108.83) in the control arm. The ICER computation indicated the 2-min step test as the most cost-effective measure (ICER RM 149.19 ≈USD33.26).

Conclusion

The AGELESS trial demonstrates that a multidomain, lifestyle-based intervention can improve cognitive and physical function in older adults with (pre)-CF. This cost-effective approach highlights CF as a modifiable health condition and supports its potential inclusion in health policy to promote healthy aging and reduce health risks in LMICs, where there is a larger prevention potential due to prevalent lifestyle-related risk factors.

Introduction

Alongside the rapid, global growth of the ageing population, frailty has become a common issue among older individuals [1]. Cognitive impairment is another common syndrome in advanced age [2]. The coexistence of frailty and cognitive impairment, conceptualized as 'cognitive frailty' (CF), has been identified as a precursor to dementia [3].

Several modifiable factors have been linked to CF. Older persons with lower socioeconomic status are at higher risk of frailty due to factors such as poor nutrition and physical inactivity, and they are also more prone to poor cognitive health [4]. Particularly, poor diet has been classified as an indicator of frailty and cognitive impairment due to oxidative damage and harmful neuroinflammation [5, 6]. Poor health outcomes and increased risk of frailty are also affected by psychosocial well-being such as lack of support [7]. In Malaysia, the prevalence of CF is reported to be 39.6% [8]. Increasing age, reduced niacin intake, lack of social support, lower functional status, and depression have been identified to increase risk of CF in the Malaysian older adults aged 60 years and above [8].

CF is described as a condition with potential for reversibility through appropriate measures. Physical exercise has been identified as crucial for improving frailty and cognitive symptoms, as well as delaying the progression of cognitive impairments [9]. Cognitive abilities in older individuals could also be enhanced through task-specific training that involves multisensory integration [10].

Compared with single-domain interventions, multidomain interventions can align with the multifactorial nature of CF, promoting synergistic benefits. While evidence on interventions specifically targeting CF is limited, there are studies suggesting that multidomain interventions can improve physical performance and cognition in older adults, such as the seminal Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). This study demonstrated that implementing a 2-year multidomain intervention including exercise, diet, cognitive training, social stimulation, and good control of cardiometabolic disorders, resulted in improved cognitive function and maintained daily functioning in older adults at higher risk of dementia [11, 12]. A more recent analysis from the FINGER trial showed that the 2-year intervention could reverse the first signs of frailty among older men, but not in women [13].

A feasibility study in Malaysia, WE-RISE, included a multidomain intervention for people with CF and lower socioeconomic status, reporting a cost of approximately RM 194.74 (≈USD 43.39) per participant for 48 sessions over 24 weeks [14]. WE-RISE showed improvements in cognition, physical function, body composition, and quality of life, but it did not include vascular or psychosocial parameters [14]. Knowledge gaps remain, on the benefit of multidomain interventions on the CF phenotype, particularly regarding the scalability and long-term impact of multidomain interventions, their cost-effectiveness, and their applicability in low- and middle-income countries (LMICs) such as Malaysia.

Addressing CF aligns with Malaysia’s national health priorities, which emphasize "healthy aging" and the reduction of non-communicable diseases (NCDs) to ease the burden on the healthcare system and promote healthy longevity among elderly people [15].

Building on the FINGER and WE-RISE results, the Multidomain Intervention to Reverse Cognitive Frailty among Community Dwelling Older Adults (AGELESS Trial) tested a multidomain intervention in the Malaysian population with CF. As part of the World-Wide FINGERS (WW-FINGERS) Network of multidomain trials for risk reduction and prevention of dementia [12], the AGELESS trial aimed to develop and deliver culturally appropriate interventions comprising of physical activity, cognitive training, dietary, psychosocial counselling and vascular management, to assess their effectiveness in improving physical and cognitive function (primary outcomes), and several secondary outcomes among older adults with CF. Additionally, the trial assessed cost-effectiveness to inform scalable health interventions for CF management in Malaysia and other LMICs, supporting national goals of promoting healthy lifestyles and extending life expectancy among aging populations.

Methodology

Study design

The AGELESS study protocol, baseline characteristics of participants, and preliminary findings have been described earlier [16,17,18]. Some minor discrepancies exist between the earlier publications and the current report, due to extensive data cleaning processes conducted after the study completion and for this analysis. The AGELESS Trial began recruitment in November 2019, but the onset of the COVID-19 pandemic soon required adjustments to the recruitment process, which was conducted in phases to adapt to lockdown restrictions, with participants being gradually enrolled as conditions allowed. A full intervention schedule was only initiated after lockdowns ended, which led to a revised timeline for intervention delivery and follow-up assessments. Ethical approval was obtained from the Research Ethics Committee of Universiti Kebangsaan Malaysia with approval number UKM PPI/111/8/JEP-2020–347. The study was registered with the National Medical Research Register (NMRR) and the International Standard Randomized Controlled Trial Registry (Trial ID: ISRCTN75429638, dated 1st June 2021). The AGELESS Trial comprised of 2 phases as depicted in Fig. 1. Phase 1 aimed to develop a culturally relevant multidomain intervention module, and phase 2 was the randomized controlled trial to determine the effectiveness of the developed module.

Fig. 1
figure 1

The AGELESS trial flowchart

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Study participants

Participants in the AGELESS trial were registered members of the Activity Centers for Older Persons (PAWE), strategically located in low-cost housing areas across the Klang Valley in the center of Malaysia (Kuala Lumpur and Selangor) and a rural area of Seremban (further South of Klang Valley). A team of researchers conducted screenings at these centers to identify individuals aged 60 and above who exhibited cognitive frailty (CF). The operational definition of CF followed the criteria outlined by the IANA/IAGG international consensus group [3] and has been previously published [16, 18]. Briefly, CF was based on the Fried´s phenotype for frailty [19], consisting of 5 components—unintentional weight loss, exhaustion, low physical activity, weak hand grip strength and slow gait speed – and the Clinical Dementia Rating (CDR) scale for the cognitive aspect [20]. People were eligible for the trial if they had score 19–25 on the Mini Mental State Examination (MMSE) [21], 0.5 on the CDR, and had ≥ 1 Fried’s criteria. Participants were classified either as having pre-CF (1–2 Fried’s criteria and CDR = 0.5) or with CF (≥ 3 Fried’s criteria and CDR = 0.5) [3]. The exclusion criteria included major depression, other major psychiatric disorders, severe cognitive impairment or dementia, malignant diseases, or other conditions that would prevent safe participation in the study as judged by the researcher, or concurrent participation in any intervention trial.

The trial sample size initially calculated [16] was reassessed, due to pandemic-related challenges in recruitment, to ensure a sufficient number of participants, and accounting also for new data from ongoing WW-FINGERS trials [22, 23]. Additionally, only participants from the urban area were selected for the intervention due to logistic reasons that allowed the intervention programme to be effectively conducted, due to pandemic-related travel restrictions [18]. The sample size was determined using G-Power Statistical power analysis, incorporating a medium effect size (Cohen’s d = 0.38), which is recommended for detecting medium effects in gerontology studies [24]. Anticipating a dropout rate of 40%, a total of 106 participants were initially recruited: 53 in the intervention group and 53 in the control group.

Randomization and intervention

Participants were randomly assigned to the intervention or control group using Research Randomizer software by a trial manager, employing a simple randomization approach. The group receiving the intervention underwent a multidomain 24-month program, which was adapted from the FINGER trial protocol, as well as the local WE-RISE trial [11, 14, 16]. To facilitate adherence, the multidomain intervention was introduced in a stepwise manner, commencing with vascular management, nutritional and psychological counselling, followed by exercise and cognitive training (Fig. 2). Vascular management sessions were conducted every 6 months, with physician consultations based on blood test results. Dietary and psychological counseling sessions were held monthly in groups for the first 12 months, transitioning to once every three months thereafter, with 8–10 participants per group. Dietary consultations were led by a dietitian and nutritionist, addressing healthy eating among older adults, based on the Malaysian Dietary Guidelines for Older Adults [25] and Malaysian Recommended Nutrient Intake for individuals aged 60 years and above [26]. Psychological counseling was delivered through group sessions and individual sessions, focusing on stress, coping mechanisms, social support, self-efficacy, and depression. The exercise was carried out as a multi component group exercise that included progressive resistance, endurance, flexibility, coordination and balance training. Whereas the cognitive training was administered as paper and pencil routines that were designed specifically to enhance the cognitive domains such as memory, executive function, processing speed, language, visuospatial reasoning and attention. Both exercise and cognitive training were conducted 2 to 3 times a week for a stretch of 24 months.

Fig. 2
figure 2

Intervention Protocol of the AGELESS Trial (adapted and modified from [16])

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Control group

Participants in the control group attended a series of structured health talks every five months over the 24-month study period, totaling five sessions. These health talks were designed to provide general health information, covering topics relevant to aging populations but without the personalized, multidomain focus of the intervention group. Each session lasted approximately 60 min and was led by a healthcare professional or guest speaker with expertise in the respective topic (Fig. 3). This design ensured that control participants received some general health support without the interactive components central to the AGELESS intervention.

Fig. 3
figure 3

Health talks received by the control group

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Outcome measures

The primary outcome included cognitive and physical function [16]. Cognitive function comprised of tests which are part of the modified Neuropsychological Tests Battery (mNTB), including the digit span forward, digit span backward, digit span overall, verbal paired associates (immediate and delayed recall), visual paired associates (immediate and delayed recall), Ray Auditory Verbal Learning Test (RAVLT), and Categorical Fluency Test. Physical function comprised of chair sit and react test, back scratch test, timed up and go test, 30 s sit to stand, 6 min walk test and 2 min step test. The secondary outcomes were anthropometry and body composition measures, vascular measures, psychosocial variables, dietary intake, and functional magnetic resonance imaging (fMRI). We also examined changes in CF status. The outcomes were measured at baseline, 6th month, 12th month and 24th month.

fMRI Assessment

The fMRI assessment involved a subsample that was calculated using the formula proposed by Zhong (2009) [27] and was based on findings from Lau (2020) [28], which reported a mean difference in brain activation of 0.7 between the control and intervention groups, with a pooled standard deviation of 0.26. Using these data, the required sample size was estimated to be 13 participants per group, accounting for a 40% dropout rate, 80% statistical power, and a 95% confidence interval. Participants were screened for eligibility at baseline, and those with claustrophobia or metal implants were excluded from the fMRI assessment. A total of 28 eligible participants provided consent to participate, 14 from the intervention group and 14 from the control group. The fMRI scans were conducted at the Department of Radiology, UKM Specialist Children's Hospital, at baseline, 12th month and 24th month.

Task-based fMRI was employed in relation to cognitive function assessment, using the N-back task and the Stroop Colour Word Task (SCWT). Imaging was performed using a 3.0 Tesla MRI scanner (Magnetom Skyra, Siemens, Erlangen, Germany). High-resolution T1-weighted anatomical images were acquired with a repetition time (TR) of 1,900 ms (ms), an echo time (TE) of 2.27 ms, a voxel size of 1.0 × 1.0 × 1.0 mm (mm), 176 slices, and a slice thickness of 1 mm. Functional scans for the N-back task were obtained using T2*-weighted imaging with a TR of 3,000 ms, a TE of 30 ms, 3-mm isotropic voxels, 29 slices, and a slice thickness of 4 mm. For the SCWT, the acquisition parameters included a TR of 2,000 ms, a TE of 30 ms, a flip angle of 90°, and a slice thickness of 4 mm, using an interleaved sequence with 29 slices per volume.

  • a. N-back

A qualified radiologist explained the N-back task procedures to the participants, ensuring that they understood the task by providing diagrams and a detailed explanation of the protocol. The task was designed and displayed using SuperLab 5 (Cedrus, Los Angeles, CA, United States) and included two conditions: 0-back and 1-back [29].

In the 0-back condition, participants were required to respond to a stimulus by determining whether it matched a predefined target presented at the beginning of the block. In the 1-back condition, participants had to decide whether the current stimulus matched the one immediately before it. Each condition consisted of four blocks, with each block lasting 30 s, followed by a 30-s rest interval. The total duration of the task was 510 s. Before beginning the task, participants underwent a 5.42-min anatomical brain scan, which was followed by approximately 9.11 min of N-back task performance.

  • b. Stroop Colour Word Task (SCWT)

The Stroop Colour Word Task (SCWT) was implemented using E-PRIME 3.0 (Psychological Software Tools, Inc., Sharpsburg, Philadelphia). During the fMRI scan, participants were presented with a continuous series of colour-related stimuli designed to assess cognitive control. The task began with a neutral baseline condition in which the symbol “XXXX” was displayed in different colours, and participants were required to respond based on the colour shown. This was followed by the congruent condition, where colour words were displayed in matching ink colours, such as the word “red” appearing in red ink. Finally, the task progressed to the incongruent condition, where colour words were presented in mismatched ink colours, such as the word “red” displayed in yellow ink. Four colours; red, blue, yellow, and green were used in various congruent and incongruent combinations, following the approach of [29].

Adherence

Participants´ adherence was calculated by dividing their total number of attended intervention sessions by the total number of sessions offered, and then multiplying the result by 100 to determine the percentage.

Cost effectiveness

The costs of various components for the multidomain intervention were determined using Activity-Based Costing (ABC), a method designed to provide a detailed understanding of costs associated with specific activities and processes [30]. In this study, expenses were categorized into materials (including printed materials, stationery, cognitive stimulation tools, and exercise equipment), logistics (such as meals and participant honorariums), and fieldworker costs (encompassing wages, transportation, and telecommunication charges).

The calculations were based on a structured schedule where 53 participants attended 168 sessions of exercise and cognitive training, 24 sessions of dietary and psychological training, and 4 sessions of vascular consultation each. Since exercise and cognitive training sessions were held consecutively on the same day, transportation costs were combined for both domains. A similar approach was applied to vascular, psychosocial, and dietary consultation sessions. The cost for control group comprised of the expenditure for the 5 sessions of health talk including transportation and charges for the speaker. Total costs were computed by aggregating expenses across all sessions conducted during the trial period.

The costing analysis of the AGELESS trial utilized the Incremental Cost-Effectiveness Ratio (ICER), which allows for a comprehensive comparison of the economic value of a healthcare intervention relative to an alternative. ICER is determined by dividing the difference in costs between the intervention and control groups by the difference in their outcomes (Costintervention − Costcontrol)/(Outcomeintervention − Outcomecontrol). Only primary outcomes that showed significant differences between groups were included in the ICER calculation to ensure a meaningful assessment of cost-effectiveness.

Statistical analysis

All analyses were performed using IBM Statistical Package for the Social Sciences (IBM SPSS), version 23.0 (SPSS Inc., Chicago, IL, USA). A significance level of alpha < 0.05 was used for all tests. Descriptive and frequency analyses were conducted to report characteristics of the participants, including CF status (pre-CF and CF). To compare sociodemographic profiles between control and multidomain groups, chi-squared (χ2) tests were used for categorical variables, and independent t-tests were used for continuous variables. Repeat measures ANOVA was employed to examine the within-group effect (time effect), between-group effect (group effect), and interaction effect (time x group). We based the primary efficacy analysis on the intention-to-treat population (ITT).

Results

Recruitment

A total of 957 community-dwelling older adults from urban (n = 764) and rural (n = 193) areas were screened for eligibility across Klang Valley and Seremban, respectively. However, only participants screened in urban area in Klang Valley proceeded with the intervention trial due to commuting restrictions to rural areas at that time. Among the 764 individuals screened in Klang Valley, 650 completed the screening process, of whom 275 met the eligibility criteria for CF. Ultimately, 106 participants (36.1%) consented to participate in the trial (Fig. 4). The majority were classified as pre-CF (n = 91, 85.9%), while the remaining 15 participants (14.1%) met the criteria for CF. People were randomly assigned to either intervention (n = 53) or control group (n = 53). Throughout the 24-month intervention period, an average of 50% participants dropped out from the trial due to various reasons, such as health issues and medical appointments (n = 10), loss of contact (n = 15), personal commitments (n = 7), relocated (n = 6), family did not grant permission (n = 1), work commitments (n = 3) and withdrawn without reason (n = 11). Therefore, the study conducted an intention-to-treat analysis to account for these dropouts.

Fig. 4
figure 4

Consort Flow Diagram for AGELESS Multidomain Intervention Trial Recruitment

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Participant characteristics

As shown in Table 1, majority of the participants were aged between 60 to 69 years old (63.2%), predominantly female (58.5%), of Malay ethnicity (83%), living with others (85.8%), unmarried or widowed (52.8%), and no longer working (87.74%). Many participants also exhibited multimorbidity (59.4%), with hypertension (66%), hypercholesterolemia (56.6%) and diabetes (56.6%) as the most common chronic diseases reported. There were no significant disparities between the intervention and control groups in terms of sociodemographic or clinical profiles (p > 0.05 for all parameters). Most of the participants (85.9%) were classified as pre-CF, with no significant differences between the multidomain and control group.

Table 1 Sociodemographic and clinical characteristics of participants stratified by intervention and control groups (presented as n (%) or mean ± standard deviation)
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The adherence rate of participants towards the multidomain intervention was satisfactory (> 50% for all domains) throughout the 24 months (Fig. 5). The adherence rate was the highest for vascular consultation (91%) and was the lowest for exercise and cognitive training (53%).

Fig. 5
figure 5

Adherence rate of participants based on intervention domains

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Primary outcomes

As tabulated in Table 2, a significant intervention effect on cognitive change (time*group interaction) was observed for most of neuropsychological tests, including digit span forward (p < 0.05, n2 = 0.18), digit span overall (p < 0.005, n2 = 0.16), visual paired immediate recall ((p < 0.05, n2 = 0.10), visual paired delayed recall (p < 0.05, n2 = 0.15) verbal paired immediate recall (p < 0.001, n2 = 0.23) verbal paired delayed recall (p < 0.05, n2 = 0.29). Though no significant interaction effect was noted for category fluency test and RAVLT (delay), but significant effect of time within group effect was observed (p < 0.05). Mean score of the cognitive tests in the intervention group showed improvement at 6th and 12th month, and a reduction in mean score at 24th month.

Table 2 Effectiveness of the AGELESS Multidomain Intervention on Cognitive and Physical Function (Primary Outcomes) (Presented as mean ± SD)
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Physical measures that showed significant intervention effects were chair sit and reach test (p < 0.005, n2 = 0.01), 6-min walk test (p < 0.05, n2 = 0.01), and 2-min step test (p < 0.05, n2 = 0.11). Whereas, for timed up and go, there was a significant time effect observed (p < 0.05, n2 = 0.05).

Post hoc analysis was done to determine mean differences in change between groups from baseline to 6, 12 and 24 months (Appendix A, Table S1). Most of the physical and cognitive variables showed significant changes from baseline to 6th and 12th month (p < 0.05), while some outcomes were also significantly different at 24th months between intervention and control.

Secondary outcomes

The secondary measures of the AGELESS Trial included anthropometry, body composition, dietary intake, food groups, fMRI behavioral performance and psychosocial measures. Table 3 represents the effectiveness of the AGELESS trial on anthropometry and body composition. Waist circumference (p < 0.005, n2 = 0.07), body fat mass (p < 0.05, n2 = 0.03) and skeletal muscle mass (p < 0.05, n2 = 0.03) showed significant time*group interaction effects. No significant intervention effect was found for blood parameters assessment of vascular function (Table 3) and psychosocial parameters (data not shown).

Table 3 Effectiveness of the AGELESS Multidomain Intervention on Secondary outcome (Anthropometry and Body Composition) (Presented as mean ± SD)
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In terms of dietary intake (Table 4), significant interaction effect was observed for energy intake (p < 0.05, n2 = 0.03), protein (p < 0.001, n2 = 0.12), niacin (p < 0.05, n2 = 0.03), calcium (p < 0.001, n2 = 0.07), vegetables intake (p < 0.001, n2 = 0.32), fruit intake (p < 0.001, n2 = 0.14), fish intake (p < 0.005, n2 = 0.07), legume intake (p < 0.001, n2 = 0.15) and milk intake (p < 0.05, n2 = 0.04).

Table 4 Effectiveness of the AGELESS Multidomain Intervention on Secondary Outcomes (Dietary intake and food group) (Presented as mean ± SD)
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The 24 months of multidomain intervention showed significant intervention effect on the behavioral performances measured through fMRI (Table 5). Left Dorsolateral Prefrontal Cortex (DLPFC) activation and Right DLPFC showed significant time*group interaction for 1 back and Stroop colour (p < 0.05, n2 = 0.13), and word test (SCWT) (p < 0.05, n2 = 0.17) respectively. No other significant group*time interactions were found for fMRI measures (data not shown).

Table 5 Effectiveness of multidomain intervention on fMRI behavioural performance (Presented as mean ± SD)
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Cognitive frailty status

Approximately 34.0% (n = 18) were no longer (pre-) CF after 12 months of intensive intervention (transitioned to pre-physical frailty, or Mild cognitive Impairment (MCI) or robust phenotype). However, the percentage dropped to 28.3% (n = 15) in 24 months (Fig. 6). The control group showed 39.7% (pre-)CF reversal at 12 months and 32.1% (pre-)CF reversal at 24 months. Nevertheless, there was no significant difference between the groups. Reversal rate did not differ significantly between the control and the intervention group (p > 0.05). Also, 3.8% (n = 2) of older adults in the control group progressed to dementia after 24 months and such an occurrence was not observed in the intervention group.

Fig. 6
figure 6

Reversibility of cognitive frailty at 6th month, 12.th month and 24th month. CF: Cognitive frailty; MCI: Mild cognitive Impairment. Operationalization of definitions: Pre-CF (1–2 Fried’s criteria and CDR = 0.5), CF (≥ 3 Fried’s criteria and CDR = 0.5), Pre-Physical (1–2 Fried’s criteria), Physical Frailty (≥ 3 Fried’s criteria), MCI (CDR = 0.5), Dementia (CDR = 1), Robust (< 1 Fried’s criteria and CDR = 0)

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Cost effectiveness

The total cost of the AGELESS intervention for 24 months and control was RM 1592.74 (≈USD 355.05) per subject (Appendix B, Table S2) and RM 488.21 (≈USD 108.83) (Appendix C, Table S3), respectively. The ICER computation showed that 2-min step test was the most cost effective (RM149.19; ≈USD 33.26), followed by chair sit and reach (RM 280.08; ≈USD 62.40) and verbal paired associates immediate recall (RM 457.06; ≈USD 112.57) (Table 6).

Table 6 Incremental cost effectiveness ratio (ICER) based on statistically significant primary outcomes
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Discussion

This study marks one of the initial investigations into the effects of multidomain interventions on groups experiencing cognitive frailty among aging population from a LMIC. Significant intervention effects were observed after 2 years, in both primary outcomes including verbal memory (assessed via verbal paired associates), visual memory (assessed via visual paired associates), attention and working memory (evaluated using the digit span test), lower body flexibility (chair sit and reach), walking speed (6 m walk test), cardiovascular endurance (2 min step test), as well as in secondary outcomes such as anthropometric measures, body composition, and dietary intake.

Significant trends observed during the first 12 months of assessment provide encouraging evidence of the intervention’s impact within a shorter timeframe. These early improvements in cognitive and physical outcomes highlight the intervention’s potential to initiate positive health changes relatively quickly. The findings suggest that the AGELESS intervention can facilitate meaningful health improvements within the first year of implementation, emphasizing the potential for short-term benefits even before completing the full 24-month period. However, most variables did not show significant maintenance of this change at 24th month, possibly due to the reduced intensity of the psychosocial and dietary components (once every three months) compared to the first 12 months (once every month). Also, the high drop-out rate (50%) could have limited the possibility of detecting significant changes.

Overall, the experimental group showed higher mean scores across all cognitive tests compared to the control group. Previous research has demonstrated that cognitive training, when administered alone, significantly impacts executive function, stimulates cognitive reserve, and compensates for age-related neurological damage [31,32,33]. Combining physical exercise with cognitive training has been suggested to enhance neurogenesis, a critical factor in maintaining cognitive function and repairing aging and neurological damage to brain cells. This combination may also increase cerebral blood flow, basal levels of brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1), potentially strengthening memory [34, 35]. Additionally, improvements in physical fitness resulting from exercise training can influence brain plasticity and contribute to enhancements in memory [35].

Research indicates that multicomponent exercises, such as resistance training, balance training integrating physical and cognitive activities, and aerobic training, are associated with overall improvements in cognitive function and short-term memory [36, 37]. Previous studies have also shown that dietary choices and lifestyle factors can enhance cognitive function [38, 39]. In the current study, there was a significant increase in the intake of vegetables, fruits, calcium, legumes, milk, fish, niacin, protein, and total energy over the 24-month intervention period. Diets rich in polyphenols found in vegetables and fruits have been demonstrated to stimulate neurogenesis in animal models [40]. Additionally, higher consumption of fish in the intervention group may have contributed to the enhancement of cognitive function, as marine omega-3 polyunsaturated fatty acids found in fish are known to have a positive impact on cognitive performance [41, 42]. The observed increase in brain activity within the intervention group may also be linked to their higher fish, fruit and vegetables consumption in the same group [43, 44].

In the present study, the fMRI data provides some insight on the possible mechanisms underlying the intervention effects on cognition. Participants in the multidomain intervention group showed increased functional activation in the DLPFC after the intervention. This is in line with previous research suggesting that multidomain interventions can increase brain activation during interference tasks in older adults at high risk of cognitive decline [45]. Although these are exploratory findings, and should thus be interpreted with caution, it is possible that the increased brain activation associated with interference tasks in cognitively high-risk older adults observed in the AGELESS study may indicate that the effects of the intervention on brain activation differ according to the participant’s cognitive level and the type of cognitive task.

Multi-component exercises have shown positive outcomes in terms of strength, endurance, and flexibility among older adults with cognitive impairment [46]. However, our study did not find a significant effect on muscle strength, which could be due to the shorter duration of the strength training component (30 min per session). Research suggests that to effectively improve muscle strength, strength training sessions should ideally exceed 75 min in duration, as duration significantly impacts strength gains [47]. Nonetheless, our intervention did show an effect on skeletal muscle mass. These parameters could have been affected by factors such as the presence of comorbidities triggering age-related declines in muscle strength, and increased protein intake among participants in the active group [48, 49]. These results differ from the FINGER trial, which did not report significant effects on physical function, although there was a significant improvement on the chair rise test in the multidomain intervention compared to the control group [50]. Such discrepancy might be attributed to differences in the target population, as FINGER trial participants were on average more physically fit compared to AGELESS, with only 28.4% of the FINGER population being classified as pre-frail or frail at baseline, based on Fried´s criteria [11]. Additionally, the 2 studies had different outcome measures, as the FINGER trial used a composite score from the Short Physical Performance Battery, while the current study assessed individual scores for each physical test [11].

In the AGELESS trial, we did not observe a significant intervention effect on psychosocial measures and vascular parameters. Notably, the psychosocial module developed in this study is pioneering, given the scarcity of existing evidence on psychosocial interventions, particularly among cognitive frailty groups in LMICs. Despite the absence of a clear direct impact, it is plausible that the psychosocial intervention contributed significantly to enhancing cognitive function within the experimental group [51]. The current study’s’ lack of significant effects on vascular parameters mirrors the findings of the preDIVA study, which may be attributed to participants already receiving high-standard vascular management in primary care settings [52]. However, significant effects were observed in other vascular related parameters, including anthropometry and body composition.

In both the intervention and control group of the study, transitions across different categories of (pre)-CF were observed, based on changes related to physical and cognitive components. Following 24 months of intervention, a small percentage of participants in the experimental group transitioned to a robust state, but results were not statistically significant and must be interpreted with caution, also given the high drop-out rate. Recent data from the FINGER trial indicated a favorable trend in reversing (pre)-frailty among older men, as after the 2-year intervention pre-frail or frail men in the multidomain intervention group had higher probability of being non-frail, compared to pre-frail or frail men in the control group. No effect on frailty status was detected in women [13]. Notably, most of the FINGER study participants defined as frail were pre-frail, with a very low number of people being classified as frail. There are a few studies on the preventative role of multidomain lifestyle-based intervention in pre-frail and cognitively (pre)-frail older adults, and the current study adds to the existing literature indicating the feasibility of a multidomain approach in this target group in LMICs.

The adherence rate among participants was moderate, averaging around 50%, particularly for cognitive and exercise training sessions. We previously reported that adherence during the first year, when intervention was more intense, was not correlated with sociodemographic data, cognition (except performance in the fluency test), depressive symptoms, cardiovascular risk factors, physical fitness test, or psychosocial factors [18]. In a qualitative study among participants from the multidomain arm, we found that caregiving responsibilities, such as caring for grandchildren, limited access to transportation, health and physical limitations, were among the factors cited as hindrances to attending weekly sessions during the 2-year period [53]. Despite these challenges with attendance, participants who did attend each session showed high compliance with the training protocol, which likely contributed to improvements in both cognitive and physical function. In line with this, in the FINGER study the greatest cognitive benefits were reported among those who participated in at least half of all proposed activities [54]. Both AGELESS and FINGER interventions were quite intensive, especially in the first 12 months, suggesting that such an intensity of intervention might be needed to achieve beneficial outcomes. Therefore, efforts should be directed towards supporting adherence.

The AGELESS Trial intervention had an estimated total cost of about RM 1592.74 (≈ USD 355.05) per participant over 24 months. In comparison, a study conducted in Singapore reported a cost of SGD 620 (≈ USD 458) per participant for a multidomain intervention aimed at older adults at risk of cognitive decline over 24 weeks [55]. Despite the longer duration of the AGELESS trial, its cost is relatively low, especially considering that it targeted dual impairments such as CF. A significant portion of the budget was allocated for transportation, as many participants lacked access to transport, which increased the logistical and operational expenses. While the cost-effectiveness of non-pharmacological interventions is less frequently reported, they are generally considered cost-effective due to their potential to reduce healthcare costs for older adults [56].

Unlike other multidomain intervention trials, the AGELESS study was specifically designed to be feasible and accessible to cater older adults from low to moderate socioeconomic backgrounds in a LMIC. Main results suggest that the AGELESS model can be cost effective and culturally appropriate to be executed among community dwelling older adults. This study follows a rigorous protocol, with blinded raters assessing comprehensive outcome measures. This trial began amid the COVID-19 pandemic, posing challenges in recruiting participants and maintaining their active involvement in the multidomain intervention [18]. The older population's heightened fear of the disease added to these difficulties [57]. This study faced several limitations that should be acknowledged. First, the limited sample size and the high dropout rate (50%) over the 24-month period may have influenced the results, preventing the possibility to detect beneficial effects. Yet, significant interventions benefits were detected in different parameters. The adherence rate of participants for exercise and cognitive training sessions was indicated as average. While there is no established gold standard for adherence rates, future studies could explore strategies to enhance consistent engagement of older adults in longitudinal studies. Second, the use of self-reported measures for certain outcomes, such as dietary intake and psychosocial variables, introduces the potential for response bias. The generalizability of the findings is limited by the specific demographic and cultural characteristics of the study population. Further research in diverse populations is necessary to confirm the broader applicability of this intervention. Future research should focus on the long-term sustainability of multidomain interventions, particularly in terms of maintaining adherence over extended periods and minimizing dropout rates.

Conclusion

Findings from the 24-month AGELESS trial indicate that this multidomain model can be an effective, feasible and cost-effective non-pharmacological approach to address cognitive and physical components of (pre)-CF, which is potentially reversible. Practitioners in geriatric health may benefit from integrating multidomain interventions that include physical activity, dietary guidance, cognitive training, and psychosocial support to address the complex needs of cognitively frail individuals. For policymakers, the cost-effectiveness of the AGELESS intervention underscores its potential as a scalable public health strategy, particularly in settings with limited healthcare resources and considering the high prevalence of modifiable risk factors for dementia in LMICs [58]. Active involvement in the AGELESS study could enhance public health literacy by spreading awareness of the ideas of "confident ageing in place" and "healthy ageing" across a larger population.

Data availability

No datasets were generated or analysed during the current study.

References

  1. Hoogendijk EO, Afilalo J, Ensrud KE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health. Lancet. 2019;394(10206):1365–75.

    Article  PubMed  Google Scholar 

  2. Grande G, Haaksma ML, Rizzuto D, Melis RJF, Marengoni A, Onder G, Welmer AK, Fratiglioni L, Vetrano DL. Co-occurrence of cognitive impairment and physical frailty, and incidence of dementia: systematic review and meta-analysis. Neurosci Biobehav Rev. 2019;107:96–103. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.neubiorev.2019.09.001. Epub 2019 Sep 3 PMID: 31491474.

    Article  PubMed  Google Scholar 

  3. Kelaiditi E, Cesari M, Canevelli M, Van Kan GA, Ousset PJ, Gillette-Guyonnet S, Ritz P, Duveau F, Soto ME, Provencher V, Nourhashemi F. Cognitive frailty: rational and definition from an (IANA/IAGG) international consensus group. J Nutr Health Aging. 2013;17(9):726–34.

    Article  CAS  PubMed  Google Scholar 

  4. Shahar S, Vanoh D, Mat Ludin AF, Singh DK, Hamid TA. Factors associated with poor socioeconomic status among Malaysian older adults: an analysis according to urban and rural settings. BMC Public Health. 2019;19:1–2.

    Article  Google Scholar 

  5. Apóstolo J, Cooke R, Bobrowicz-Campos E, Santana S, Marcucci M, Cano A, Vollenbroek-Hutten M, Germini F, D’Avanzo B, Gwyther H, Holland C. Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review. JBI Evidence Synthesis. 2018;16(1):140–232.

    Google Scholar 

  6. Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Braveman P, Gottlieb L. The social determinants of health: it’s time to consider the causes of the causes. Public Health Rep. 2014;129:19–31.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Malek Rivan NF, Shahar S, Rajab NF, Singh DK, Din NC, Hazlina M, Hamid TA. Cognitive frailty among Malaysian older adults: baseline findings from the LRGS TUA cohort study. Clin Interv Aging. 2019;25:1343–52.

    Article  Google Scholar 

  9. Teri L, Logsdon RG, McCurry SM. Exercise interventions for dementia and cognitive impairment: the Seattle Protocols. J Nutr Health Aging. 2008;12(6):391–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hirst RJ, Setti A, De Looze C, Kenny RA, Newell FN. Multisensory integration precision is associated with better cognitive performance over time in older adults: a large-scale exploratory study. Aging Brain. 2021;2: 100038.

    Article  Google Scholar 

  11. Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255–63.

    Article  PubMed  Google Scholar 

  12. Kivipelto M, Mangialasche F, Snyder HM, Allegri R, Andrieu S, Arai H, Baker L, Belleville S, Brodaty H, Brucki SM, Calandri I. World-Wide FINGERS Network: a global approach to risk reduction and prevention of dementia. Alzheimers Dement. 2020;16(7):1078–94.

    Article  PubMed  Google Scholar 

  13. Saarela L, Lehtisalo J, Ngandu T, Kyrönlahti S, Havulinna S, Strandberg T, Levälahti E, Antikainen R, Soininen H, Tuomilehto J, Laatikainen T, Kivipelto M, Kulmala J. Effects of multidomain lifestyle intervention on frailty among older men and women - a secondary analysis of a randomized clinical trial. Ann Med. 2025;57(1):2446699.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Murukesu RR, Shahar S, Subramaniam P, Mohd Rasdi HF, Nur AM, Ajit Singh DK. Correction: The WE-RISE™ multi-domain intervention: a feasibility study for the potential reversal of cognitive frailty in Malaysian older persons of lower socioeconomic status. BMC Geriatr. 2024;24(1):991.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ministry of Health Malaysia. National health policy report 2023. Ministry of Health Malaysia; 2023. https://moh.gov.my/.

  16. Ponvel P, Shahar S, Singh DK, Ludin AF, Rajikan R, Rajab NF, Ai-Vyrn C, Din NC, Ibrahim N, Subramaniam P, Haron H. Multidomain intervention for reversal of cognitive frailty, towards a personalized approach (AGELESS Trial): study design. J Alzheimers Dis. 2021;82(2):673–87.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mustafa Khalid N, Ponvel P, Ibrahim AM, Mohd Safien AI, Md Fadzil NH, Singh DK, Mat Ludin AF, Ibrahim N, Subramaniam P, Haron H, Rajikan R. Development and evaluation of content validity and acceptance of a multidomain intervention module for reversal of cognitive frailty among older adults. Clin Interv Aging. 2024;31:1189–202.

    Article  Google Scholar 

  18. Ibrahim AM, Singh DK, Ludin AF, Subramaniam P, Ai-Vyrn C, Ibrahim N, Haron H, Safien AM, Khalid NM, Ponvel P, Fadzil NH. Multidomain intervention for reversal of cognitive frailty, towards a personalised approach (AGELESS Trial): recruitment and baseline characteristics of participants.

  19. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.

    Article  CAS  PubMed  Google Scholar 

  20. Morris JC. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psychogeriatr. 1997;9(Suppl 1):173–8.

    Article  PubMed  Google Scholar 

  21. Ibrahim NM, Shohaimi S, Chong HT, Rahman AHA, Razali R, Esther E, Basri HB. Validation study of the mini-mental state examination in a Malay-speaking elderly population in Malaysia. Dement Geriatric Cognit Disord. 2009;27(3):247–53.

    Article  Google Scholar 

  22. Tainta M, Ecay-Torres M, de Arriba M, et al. GOIZ ZAINDU study: a FINGER-like multidomain lifestyle intervention feasibility randomized trial to prevent dementia in Southern Europe. Alzheimers Res Ther. 2024;16(1):44 Published 2024 Feb 27.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Röhr S, Arai H, Mangialasche F, et al. Impact of the COVID-19 pandemic on statistical design and analysis plans for multidomain intervention clinical trials: experience from World-Wide FINGERS. Alzheimers Dement (N Y). 2021;7(1):e12143 Published 2021 Mar 11.

    Article  PubMed  Google Scholar 

  24. Brydges CR. Effect size guidelines, sample size calculations, and statistical power in gerontology. Innov Aging. 2019;3(4):igz036.

    Article  PubMed  PubMed Central  Google Scholar 

  25. National Coordinating Committee on Food and Nutrition (NCCFN). Malaysian dietary guidelines for older persons. Ministry of Health; 2023.

  26. Recommended nutrient intakes for Malaysia, National Coordinating Committee on Food and Nutrition, Ministry of Health Malaysia. 2017.

  27. Zhong B. How to calculate sample size in randomized controlled trial? J Thorac Dis. 2009;1(1):51–4.

    PubMed  PubMed Central  Google Scholar 

  28. Lau H, Shahar S, Mohamad M, Rajab NF, Yahya HM, Din NC, Hamid HA. The effects of six months Persicaria minor extract supplement among older adults with mild cognitive impairment: a double-blinded, randomized, and placebo-controlled trial. BMC Complement Medicine and Therapies. 2020;20(1):1–15.

    Article  Google Scholar 

  29. You YX, Shahar S, Mohamad M, Rajab NF, Haron H, Che Din N, Abdul Hamid H. Neuroimaging functional magnetic resonance imaging task-based dorsolateral prefrontal cortex activation following 12 weeks of cosmos caudatus supplementation among older adults with mild cognitive impairment. J Magn Reson Imaging. 2021;54(6):1804–18.

    Article  PubMed  Google Scholar 

  30. Cannavacciuolo L, Illario M, Ippolito A, Ponsiglione C. An activity-based costing approach for detecting inefficiencies of healthcare processes. Bus Process Manag J. 2015;21(1):55–79.

    Article  Google Scholar 

  31. Chapman SB, Aslan S, Spence JS, Keebler MW, DeFina LF, Didehbani N, Perez AM, Lu H, D’Esposito M. Distinct brain and behavioral benefits from cognitive vs. physical training: a randomized trial in aging adults. Front Human Neurosci. 2016;10:338.

    Article  Google Scholar 

  32. Stern C, Munn Z. Cognitive leisure activities and their role in preventing dementia: a systematic review. Int J Evid Based Healthc. 2010;8(1):2–17.

    Article  PubMed  Google Scholar 

  33. Grady C. The cognitive neuroscience of ageing. Nat Rev Neurosci. 2012;13(7):491–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhou B, Wang Z, Zhu L, Huang G, Li B, Chen C, Huang J, Ma F, Liu TC. Effects of different physical activities on brain-derived neurotrophic factor: a systematic review and bayesian network meta-analysis. Front Aging Neurosci. 2022;26(14):981002.

    Article  Google Scholar 

  35. de Sousa Fernandes MS, Ordônio TF, Santos GC, Santos LE, Calazans CT, Gomes DA, Santos TM. Effects of physical exercise on neuroplasticity and brain function: a systematic review in human and animal studies. Neural Plast. 2020;2020(1):8856621.

    PubMed  PubMed Central  Google Scholar 

  36. 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(2):213–24.

    Article  PubMed  Google Scholar 

  37. Kovacevic A, Fenesi B, Paolucci E, Heisz JJ. The effects of aerobic exercise intensity on memory in older adults. Appl Physiol Nutr Metab. 2020;45(6):591–600.

    Article  PubMed  Google Scholar 

  38. Poulose SM, Miller MG, Scott T, Shukitt-Hale B. Nutritional factors affecting adult neurogenesis and cognitive function. Adv Nutr. 2017;8(6):804–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Naomi R, Embong H, Othman F, Ghazi HF, Maruthey N, Bahari H. Probiotics for Alzheimer’s disease: a systematic review. Nutrients. 2022;14(1):20.

    Article  CAS  Google Scholar 

  40. Bensalem J, Dudonné S, Gaudout D, Servant L, Calon F, Desjardins Y, Layé S, Lafenetre P, Pallet V. Polyphenol-rich extract from grape and blueberry attenuates cognitive decline and improves neuronal function in aged mice. J Nutr Sci. 2018;7:e19.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Dighriri IM, Alsubaie AM, Hakami FM, Hamithi DM, Alshekh MM, Khobrani FA, Dalak FE, Hakami AA, Alsueaadi EH, Alsaawi LS, Alshammari S. Effects of omega-3 polyunsaturated fatty acids on brain functions: a systematic review. Cureus. 2022;14(10):e30091.

  42. Cardoso C, Afonso C, Bandarra NM. Dietary DHA and health: cognitive function ageing. Nutr Res Rev. 2016;29(2):281–94.

    Article  CAS  PubMed  Google Scholar 

  43. Scarmeas N, Anastasiou CA, Yannakoulia M. Nutrition and prevention of cognitive impairment. Lancet Neurol. 2018;17(11):1006–15.

    Article  PubMed  Google Scholar 

  44. Freeman LR, Keller JN. Oxidative stress and cerebral endothelial cells: regulation of the blood–brain-barrier and antioxidant based interventions. Biochim Biophys Acta-Mol Basis Dis. 2012;1822(5):822–9.

    Article  CAS  Google Scholar 

  45. Nishiguchi S, Yamada M, Tanigawa T, et al. A 12-week physical and cognitive exercise program can improve cognitive function and neural efficiency in community-dwelling older adults: a randomized controlled trial. J Am Geriatr Soc. 2015;63(7):1355–63.

    Article  PubMed  Google Scholar 

  46. Lam FM, Huang MZ, Liao LR, Chung RC, Kwok TC, Pang MY. Physical exercise improves strength, balance, mobility, and endurance in people with cognitive impairment and dementia: a systematic review. J Physiother. 2018;64(1):4–15.

    Article  PubMed  Google Scholar 

  47. Hauer K, Schwenk M, Zieschang T, Essig M, Becker C, Oster P. Physical training improves motor performance in people with dementia: a randomized controlled trial. J Am Geriatr Soc. 2012;60(1):8–15.

    Article  PubMed  Google Scholar 

  48. de Souza GP, Martini LA. Effect of protein intake on bone and muscle mass in the elderly. Nutr Rev. 2010;68(10):616–23.

    Article  Google Scholar 

  49. Chen L, Nelson DR, Zhao Y, Cui Z, Johnston JA. Relationship between muscle mass and muscle strength, and the impact of comorbidities: a population-based, cross-sectional study of older adults in the United States. BMC Geriatr. 2013;13:1–8.

    Article  Google Scholar 

  50. Kulmala J, Ngandu T, Havulinna S, Levälahti E, Lehtisalo J, Solomon A, Antikainen R, Laatikainen T, Pippola P, Peltonen M, Rauramaa R, Soininen H, Strandberg T, Tuomilehto J, Kivipelto M. The effect of multidomain lifestyle intervention on daily functioning in older people. J Am Geriatr Soc. 2019;67(6):1138–44. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/jgs.15837. Epub 2019 Feb 26 PMID: 30809801.

    Article  PubMed  Google Scholar 

  51. Chow G, Gan JK, Chan JK, Wu XV, Klainin-Yobas P. Effectiveness of psychosocial interventions among older adults with mild cognitive impairment: a systematic review and meta-analysis. Aging Ment Health. 2021;25(11):1986–97.

    Article  PubMed  Google Scholar 

  52. van Charante EP, Richard E, Eurelings LS, van Dalen JW, Ligthart SA, Van Bussel EF, Hoevenaar-Blom MP, Vermeulen M, van Gool WA. Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial. Lancet. 2016;388(10046):797–805.

    Article  Google Scholar 

  53. Ong YQ, Shahar S, Mohd Safien AI, Ibrahim N, Chin AV, Mangialasche F, Kivipelto M, Singh DK. A qualitative study on the impact and participation in the AGELESS multidomain intervention: insights from older adults with cognitive frailty and their caregivers. BMC Public Health. 2025;25(1):7.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ngandu T, Lehtisalo J, Korkki S, Solomon A, Coley N, Antikainen R, Backman L, Hanninen T, Lindstrom J, Laatikainen T, Paajanen T, Havulinna S, et al. The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER). Alzheimer’s Dement. 2022;18:1325–34.

    Article  Google Scholar 

  55. Ng PEM, Nicholas SO, Wee SL, et al. Implementation and effectiveness of a multi-domain program for older adults at risk of cognitive impairment at neighborhood senior centres. Sci Rep. 2021;11(1):3787 Published 2021 Feb 15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lenox-Smith A, Reed C, Lebrec J, Belger M, Jones RW. Potential cost savings to be made by slowing cognitive decline in mild Alzheimer’s disease dementia using a model derived from the UK GERAS observational study. BMC Geriatr. 2018;18:1–6.

    Article  Google Scholar 

  57. Kukreti S, Hsieh MT, Liu CH, Chen JS, Chen YJ, Hsieh MT, Lin CY, Griffiths MD. Fear, stress, susceptibility, and problematic social media use explain motivation for COVID-19 preventive behaviors among patients with stroke and their caregivers. Inquiry. 2024;61:469580231225030.

    Article  PubMed  Google Scholar 

  58. Mukadam N, Sommerlad A, Huntley J, Livingston G. Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data. Lancet Glob Health. 2019;7(5):e596–603. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/S2214-109X(19)30074-9. PMID:31000129;PMCID:PMC7617123.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank the entire research team, including the coresearchers, field workers, enumerators, and participants, as well as their caregivers, for their contribution in this study. This research is a part of the World-Wide FINGERS Network. As such, we would like to thank WW-FINGERS Network and its Global Scientific Coordinating Center (supported by ADDI and DAC), for their contributions to this research. FM and MK are supported by FORTE grant (FINGER-Pro).

Funding

This research was funded by Long Term Research Grant Scheme (LRGS) from the Ministry of Education Malaysia (LRGS/1/2019/UM-UKM/1/4).

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Authors and Affiliations

  1. Center of Wellness and Healthy Aging, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Pavapriya Ponvel, Suzana Shahar, Devinder Kaur Ajit Singh, Arimi Fitri Mat Ludin, Ponnusamy Subramaniam, Norhayati Ibrahim, Hasnah Haron, Hidayah Fadzil, Norhayati Mustafa Khalid, A’isyah Mohammad Safien, Jamilah Mohammad Hanipah & Azyana Ibrahim

  2. Department of Physiotherapy, Faculty of Health and Life Sciences, Inti International University, BBN Putra Nilai, Negeri Sembilan, Malaysia

    Pavapriya Ponvel

  3. Department of Public Health Medicine Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Aniza Ismail

  4. Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

    Chin Ai-Vyrn

  5. Centre for Diagnostic, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Therapeutic & Investigative Studies, Kuala Lumpur, Malaysia

    Mazlyfarina Mohamad

  6. Department of Public Health, Lifestyles and Living Environments Unit, Finnish Institute for Health and Welfare (THL), Helsinki, Finland

    Jenni Lehtisalo

  7. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    Jenni Lehtisalo & Miia Kivipelto

  8. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Alzheimer Research Center, Karolinska Institute, Solna, Sweden

    Miia Kivipelto & Francesca Mangialasche

  9. Theme Inflammation and Aging, Medical Unit Aging, Karolinska University Hospital, Stockholm, Sweden

    Miia Kivipelto & Francesca Mangialasche

  10. Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK

    Miia Kivipelto

  11. FINGERS Brain Health Institute, Stockholm, Sweden

    Miia Kivipelto & Francesca Mangialasche

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Contributions

P.P did the main writing of the manuscript, S.S, D.K.A.S, A.A, P.S, N.I, H.H, A.I, C.AV provided supervision in proofreading and editing the manuscript. A.I, H.F, N.A.K, A.M.S, J.M.H did the data collection and analysis, J.L, F.F and M.K did the final editing.

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Correspondence to Suzana Shahar.

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Ponvel, P., Shahar, S., Singh, D.K.A. et al. The cost effectiveness of a multidomain intervention on physical, cognitive, vascular, dietary and psychosocial outcomes among community dwelling older adults with cognitive frailty in Malaysia: The AGELESS Trial. Alz Res Therapy 17, 101 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13195-025-01722-w

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Alzheimer's Research & Therapy

ISSN: 1758-9193