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ObjectiveAgeing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty.DesignWe profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet).ResultsAdherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks.ConclusionCollectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.

The efficacy of exercise to reverse frailty in the aging population has not been extensively investigated. This study aimed to investigate the effectiveness of a multicomponent exercise program (MCEP) on frailty, physical performance (handgrip strength, Berg Balance Scale (BBS), Timed Up and Go test (TUG), and VO2Max), blood biomarkers (Interleukin-6 (IL-6) and C-reactive protein (CRP)) in frail older adults. A randomized controlled trial using an allocation concealment method, included 64 older adults (77.78 ± 7.24 years), were divided into two parallel groups using block randomization: an MCEP group (n = 32) and a control group (n = 32). The combined center- and home-based MCEP training consisted of chair aerobic, resistance, and balance, which was carried out 3 days per week for 24 weeks. A mixed model repeated measure ANOVA demonstrated significant interaction effects of group x time for BBS, TUG and frailty scores (p < 0.001). Additionally, the post-hoc analysis revealed that the MCEP group showed significantly improved BBS, TUG, and frailty scores (p < 0.01), at both 12- and 24-weeks. When compared with controls at 12-weeks, the MCEP group decreased IL-6 and CRP levels (p < 0.05). The combined center- and home-based MCEP were effective in reversing frailty to pre-frailty and improving physical performance especially balance in the older population.

Cognitive frailty is defined as the presence of both physical frailty and cognitive impairment (clinical dementia rating score = 0.5), in the absence of dementia. It is characterized by concurrent physical frailty and potentially reversible cognitive impairment. In this study, we sought to elucidate the effects of high-speed resistance exercise training on cognitive function and physical performance in older adults with cognitive frailty. We conducted a parallel-group, randomized controlled trial involving community-living older adults with cognitive frailty. The participants' mean age was 73.9 (± 4.3 SD) years, and 69.8% (n=30) were female. Two different 4-month interventions included high-speed resistance exercise training group (n=22) and a control group (balance and band stretching, n=23). Frailty score, cognitive function (memory, processing speed, cognitive flexibility, working memory, executive function), physical function (SPPB, TUG, gait speed), and muscle strength (grip strength, knee extension strength) were assessed at baseline, 8 weeks, and 16 weeks. Statistical analysis showed that exercise improved performance significantly in the tests for cognitive function (processing speed and executive function, both p < 0.05), physical function (SPPB, TUG, gait speed, both p < 0.05), and muscle strength (grip strength, knee extension strength, both p < 0.05). However, no significant changes in frailty score were observed between intervention and either control group (p < 0.05). In conclusion, our findings indicate that high-speed resistance exercise training approaches are effective in improving cognitive function and physical performance in older adults with cognitive frailty. This study shows that it is feasible to identify older adults with cognitive frailty in the community and primary care setting for effective intervention to reduce their level of frailty and cognitive impairment.

Background Once older persons become frail, the risk of falls, bone fractures, and other problems increases. Exercise intervention is a form of prevention that has a high degree of evidence. Objective We investigated the effectiveness of frailty prevention consisting of exercise intervention by community pharmacists at 11 pharmacies operated by Osaka Pharma Plan. Methods In total, 103 older persons between 70 and 79 years of age (53 males and 50 females) who were suffering from chronic conditions and who visited one of 11 pharmacies between January and March 2021 were enrolled. They were then randomly assigned to either the Intervention group (IG: 6 pharmacies, 61 patients) who were subjected to intervention by a pharmacist, or the Usual Care group (UG: 5 pharmacies, 42 patients) who were not subjected to intervention. At the beginning of the trial and 6 month after, their muscle mass, etc. were measured using a body composition meter, and their Five-Times Sit-To-Stand Test results were also measured. Patients in the IG were provided with information by way of leaflets during the time they were guided regarding taking their medication for a period of one to six months that encouraged exercising at home. Those in the UG were given the standard guidance related to taking their medication. Results The amount of change in muscle mass was 1.08 ± 7.83% (95%CI: -1.24-3.41) in IG and − 0.43 ± 2.73% (95%CI:-1.58-0.72) in UG, indicating that there was a trend toward an increase in IG. The percent change in the Five Times Sit-To-Stand Test times at + 6 M was − 0.002 ± 0.24% (95%CI: -0.09-0.05) in IG and − 0.04 ± 0.21% (95%CI:-0.13-0.07) in UG, but in cases in which the second measured time was faster than the first measured time, the results were 65.2% for IG and 29.2% for UG, indicating a significant difference (p = 0.00563). Conclusion Despite the fact that the amount of time community pharmacists can devote to providing guidance on taking medications is limited, it has been previously reported that providing information to patients causes a change in patient behavior. The results of the present study are highly significant as they suggest the possibility that this may hold true even when used to prevent frailty, based on the evidence obtained. Trial registration This trial was registered at UMIN-CRT on 1st of January, 2021. The registration number is UMIN000042571.

AbstractBackgroundThe benefits of supplemental vitamin D3, marine omega-3 fatty acids, and a simple home exercise program (SHEP) on frailty prevention in generally healthy community-dwelling older adults are unclear. ObjectiveTo test the effect of vitamin D3, omega-3s, and a SHEP, alone or in combination on incident pre-frailty and frailty in robust older adults over a follow-up of 36 months. MethodsDO-HEALTH is a multi-center, double-blind, placebo-controlled, 2x2x2 factorial randomized clinical trial among generally healthy European adults aged 70 years or older, who had no major health events in the 5 years prior to enrollment, sufficient mobility and intact cognitive function. As a secondary outcome of the DO-HEALTH trial, among the subset of participants who were robust at baseline, we tested the individual and combined benefits of supplemental 2,000 IU/day of vitamin D3, 1 g/day of marine omega-3s, and a SHEP on the odds of being pre-frail and frail over 3 years of follow-up. ResultsAt baseline, 1,137 out of 2,157 participants were robust (mean age 74.3 years, 56.5% women, mean gait speed 1.18 m/s). Over a median follow-up time of 2.9 years, 696 (61.2%) became pre-frail and 29 (2.6%) frail. Odds ratios for becoming pre-frail were not significantly lower for vitamin D3, or omega 3-s, or SHEP, individually, compared to control (placebo for the supplements and control exercise). However, the three treatments combined showed significantly decreased odds (OR 0.61 [95% CI 0.38–0.98; p=0.04) of becoming pre-frail compared to control. None of the individual treatments or their combination significantly reduced the odds of becoming frail. ConclusionRobust, generally healthy and active older adults without major comorbidities, may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP with regard to the risk of becoming pre-frail over 3 years.

BackgroundInterprofessional collaborative practice (ICP) is currently recommended for the delivery of high-quality integrated care for older people. Frailty prevention and management are key elements to be tackled on a multi-professional level.AimThis study aims to develop a consensus-based European multi-professional capability framework for frailty prevention and management.MethodsUsing a modified Delphi technique, a consensus-based framework of knowledge, skills and attitudes for all professions involved in the care pathway of older people was developed within two consultation rounds. The template for the process was derived from competency frameworks collected in a comprehensive approach from EU-funded projects of the European Commission (EC) supported best practice models for health workforce development.ResultsThe agreed framework consists of 25 items structured in 4 domains of capabilities. Content covers the understanding about frailty, skills for screening and assessment as well as management procedures for every profession involved. The majority of items focused on interprofessional collaboration, communication and person-centred care planning.DiscussionThis framework facilitates clarification of professionals’ roles and standardizes procedures for cross-sectional care processes. Despite a lack of evidence for educational interventions, health workforce development remains an important aspect of quality assurance in health care systems.ConclusionsThe multi-professional capability framework for frailty prevention and management incorporated interprofessional collaborative practice, consistent with current recommendations by the World Health Organization, Science Advice for Policy by European Academies and the European Commission.

The recent recognition of the multidimensional features of frailty has emphasised the need for individualised multicomponent interventions. In the context of sub-Saharan Africa, few studies have examined: a) the frailty status of the older population; b) the level of frailty and its health implications and; c) the impact of a nurse-led intervention to reduce frailty. This study aims to design, implement, and evaluate a nurse-led intervention to reduce frailty and associated health consequences among older people living in Ethiopia. The study will be conducted on 68 older persons using a pre-, post-, and follow-up single-group quasi-experimental design. Residents of Ethiopia, ≥60 years and living in the community will be invited to participate in a 24-week program designed to decrease frailty and associated health consequences. Data will be collected at three-time points: baseline, immediately after the intervention, and 12 weeks post-intervention. To determine the effect of the intervention, changes in frailty, nutritional status, activities of daily living, depression and quality of life scores will be measured. To measure the effect of a nurse-led intervention on the level of frailty among older people a generalised linear model (GLM) using repeated measures ANOVA will be used. Statistical significances will be set at p-values < 0.05. The results of this study will determine the impact of a nurse-led intervention to reduce frailty amongst community-dwelling older people living in Ethiopia. The results of this study will inform the development of future interventions designed to reduce frailty in lower-income countries. The trial was registered in ClinicalTrials.gov with the identifier of NCT05754398.

Background: The aim of this study was to clarify the effects of a theater training program intervention on the physical and cognitive functions in community-dwelling older people. Methods: Of the 59 participants, 30 were the control group, and 29 were the intervention group. We assessed physical and mental/cognitive functions and criteria of physical frailty. Results: Statistical analysis showed that the usual walking speed (UWS) (p < 0.01), grip strength (GS) (p < 0.01), and GDS-15 (p < 0.05) improved significantly in the intervention group, whereas the Geriatric Depression Scale short-form (GDS-15) (p < 0.01) worsened significantly in the control group. Cognitive function was not significantly different between the two groups. Physical frailty was unchanged in the control group but significantly improved in the intervention group (p < 0.05), and a significant interaction was found for GDS-15 in ANOVA (F = 5.76, p < 0.05). Conclusions: The results of this study suggest that a theater intervention for the older adults may be effective in preventing and improving depression and physical frailty in old age.

Key summary points Aim To analyze the effectiveness of different interventions in preventing frailty onset in older adults. Findings In this network meta-analysis, interventions that were based on physical exercise significantly reduced frailty incidence. Message Physical exercise appears to be effective in the prevention of frailty onset in older adults. Purpose Frailty in older adults is associated with multiple adverse health outcomes, while evidence on its successful prevention has been scarce. Therefore, we analyzed the effectiveness of different interventions for the prevention of frailty onset. Methods In this systematic review, eight databases were searched for randomized controlled trials of interventions in non-frail (i.e., robust or pre-frail) adults aged ≥ 60 years that assessed frailty incidence at follow-up. Additive component network meta-analysis (CNMA) was conducted to isolate the effect of different intervention types on the main outcome of frailty incidence, reporting relative risk (RR) with 95% confidence intervals (CI). The effect on gait speed was analyzed as an additional outcome using a classic network meta-analysis and the standardized mean difference (SMD) with 95% CI. Results We screened 24,263 records and identified 11 eligible trials. Nine trials (842 participants, all categorized according to the physical phenotype) in pre-frail (seven RCTs) and robust/pre-frail (two RCTs) older adults were included in the CNMA. Physical exercise significantly reduced frailty incidence at follow-up (RR 0.26, 95% CI 0.08; 0.83), while this was not found for nutritional interventions (RR 1.16, 95% CI 0.33; 4.10). Interventions based on physical exercise also improved gait speed (SMD 1.55, 95% CI 1.16; 1.95). In addition, 22 eligible trial protocols without published results were identified. Conclusion Interventions based on physical exercise appear to be effective in preventing the onset of frailty in older adults. Although the available data are still limited, results from ongoing trials may add to the body of evidence in the foreseeable future.

Background Low serum 25-hydroxyvitamin D [25(OH)D] level is associated with a greater risk of frailty, but the effects of daily vitamin D supplementation on frailty are uncertain. This secondary analysis aimed to examine the effects of vitamin D supplementation on frailty using data from the Study To Understand Fall Reduction and Vitamin D in You (STURDY). Methods The STURDY trial, a two-stage Bayesian, response-adaptive, randomized controlled trial, enrolled 688 community-dwelling adults aged ≥ 70 years with a low serum 25(OH)D level (10–29 ng/mL) and elevated fall risk. Participants were initially randomized to 200 IU/d (control dose; n = 339) or a higher dose (1000 IU/d, 2000 IU/d, or 4000 IU/d; n = 349) of vitamin D3. Once the 1000 IU/d was selected as the best higher dose, other higher dose groups were reassigned to the 1000 IU/d group and new enrollees were randomized 1:1 to 1000 IU/d or control group. Data were collected at baseline, 3, 12, and 24 months. Frailty phenotype was based on number of the following conditions: unintentional weight loss, exhaustion, slowness, low activity, and weakness (≥ 3 conditions as frail, 1 or 2 as pre-frail, and 0 as robust). Cox proportional hazard models estimated the risk of developing frailty, or improving or worsening frailty status at follow-up. All models were adjusted for demographics, health conditions, and further stratified by baseline serum 25(OH)D level (insufficiency (20–29 ng/mL) vs. deficiency (10–19 ng/mL)). Results Among 687 participants (mean age 77.1 ± 5.4, 44% women) with frailty assessment at baseline, 208 (30%) were robust, 402 (59%) were pre-frail, and 77 (11%) were frail. Overall, there was no significant difference in risk of frailty outcomes comparing the pooled higher doses (PHD; ≥ 1000 IU/d) vs. 200 IU/d. When comparing each higher dose vs. 200 IU/d, the 2000 IU/d group had nearly double the risk of worsening frailty status (HR = 1.89, 95% CI: 1.13–3.16), while the 4000 IU/d group had a lower risk of developing frailty (HR = 0.22, 95% CI: 0.05–0.97). There were no significant associations between vitamin D doses and frailty status in the analyses stratified by baseline serum 25(OH)D level. Conclusions High dose vitamin D supplementation did not prevent frailty. Significant subgroup findings might be the results of type 1 error. Trial registration ClinicalTrials.gov: NCT02166333 .