Nutritional management interventions and multi-dimensional outcomes in frail and pre-frail older adults: A systematic review and meta-analysis.

BACKGROUND: Frailty, a prevalent geriatric syndrome, presents challenges exacerbated by malnutrition. Nutritional Management Interventions (NMIs) offer hope in frailty reversal, necessitating exploration of their multi-dimensional outcomes. OBJECTIVES: Assess NMIs' impact on frail and pre-frail older adults across diverse outcomes. METHODS: A systematic review and meta-analysis of 13 studies (2012-2023) evaluated NMIs' effects on physical, dietary, psychological, and frailty aspects. Literature quality was assessed, and data analyzed with Review Manager 5.3. RESULTS: A total of 13 studies involving participants were included in the analysis. Participants numbered 968, with the intervention group averaging 77.05±0.77 years and the control group 78.75±0.8 years. Compared to control groups,NMIs significantly increased body weight (SMD = 0.26, P = 0.03) and improved gait speed (SMD = 0.18, P = 0.03). Protein intake showed significance for interventions≤12 weeks (SMD = 1.04, P < 0.001). No significant differences in energy intake (SMD = 0.20, P = 0.60), but >12 weeks NMIs reduced energy intake (SMD = -0.73, P = 0.006). No significant differences in depressive symptoms, frailty scores, BMI, TUG, Handgrip Strength, or SPPB. CONCLUSION: This meta-analysis underscores NMIs' potential benefits for frail and pre-frail older adults. Personalized, multidimensional interventions are recommended despite study limitations, emphasizing extended interventions and diverse assessments for holistic care.

Effects of physical training on depression and related quality of life in pre-frail and frail older adults: a systematic review and meta-analysis.

OBJECTIVES: To investigate the effects of physical training on depression and related quality of life in pre-frail and frail individuals. DESIGN: A systematic review and meta-analysis. PARTICIPANTS: Pre-frail and frail older adults. METHODS: Five electronic databases, including PubMed, Cochrane, Medline, CINAHL, and Wiley were searched through December 2023. Randomized controlled trials (RCT) comparing physical training with usual care, health education, or light-intensity exercise were included. Outcomes included depression and depression-related quality of life. The quality of the included studies was assessed using Physiotherapy Evidence Database (PEDro) score, and the Cochrane Risk of Bias Tool was used to assess the risk of bias. Meta-analysis was performed using the RevMan5.4. The certainty of the evidence was evaluated by The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Ten articles with 589 participants met the inclusion criteria and were included. The pooled analysis indicated that depression (SMD = -0.55, 95%CI = -0.92, -0.17, p = 0.004) and mental health status in life (SMD = 1.05, 95%CI = 0.59, 1.50, p < 0.00001) improved significantly in the experimental group. The results of subgroup analysis revealed that the beneficial effects of physical training were significant only in frail older adults but not in pre-frail older adults. CONCLUSION: This meta-analysis showed that the positive effects of physical training on depression and related quality of life were evident for people with frailty. However, no positive results were observed in pre-frail older adults, indicating the need for further investigation in this subgroup.

Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. METHODS: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. RESULTS: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. CONCLUSIONS: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; 24: 554-562.

Association of intrinsic capacity with functional ability, sarcopenia and systemic inflammation in pre-frail older adults.

Background: Decline in intrinsic capacity (IC) has been shown to accelerate progression to disability. The study aims to explore association of IC composite score with functional ability, sarcopenia and systemic inflammation in pre-frail older adults. Methods: Cross-sectional study of pre-frail older adults ≥60 years old recruited from the community and primary care centers. Composite scores of four domains of IC were measured: locomotion, vitality, cognition and psychological. FRAIL scale was used to define pre-frailty. Muscle mass was measured using the bioelectrical impedance analysis. Systemic inflammation biomarkers [Interleukin-6 (IL-6), Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), and Growth differentiated factor 15 (GDF-15)] were measured. Participants in the lowest tertile (T1) exhibited greater decline in IC. Results: A total of 398 pre-frail older adults were recruited, mean age was 72.7 ± 5.8 years, 60.1% female, education level 7.8 years, and 85.2% were of Chinese ethnicity. A total of 75.1% had decline in locomotion, 40.5% in vitality, 53.2% in cognition and 41.7% in psychological domain. A total of 95% had decline in at least one domain. T1 was significantly associated with ADL impairment (aOR 3.36, 95% CI 1.78-6.32), IADL impairment (aOR 2.37, 95% CI 1.36-4.13), poor perceived health (aOR 0.96, 95% CI 0.95-0.98), fall (aOR 1.63, 95% CI 1.05-2.84), cognitive impairment (aOR 8.21, 95% CI 4.69-14.39), depression (aOR 101.82, 95% CI 33.62-308.37), and sarcopenia (aOR 2.40, 95% CI 1.60-5.45). T1 had significant associations with GDF-15, IL-10, and IL-10 to TNF-α ratio. Conclusion: Decline in IC composite score among pre-frail older adults was associated with functional limitation, sarcopenia, and systemic inflammation.

Association between different skeletal muscle mass indices, physical function, and inflammation in obese pre-frail older adults.

OBJECTIVES: There is lack of consensus on measurement of muscle mass and quality in obese older adults. We aim to evaluate the association of four muscle mass indices (appendicular skeletal muscle mass (ASM) over height2(ASMIht), ASM/weight (ASMwt), ASM/body fat percentage (ASMbfp)and ASM/body mass index (BMI) ASMIbmi) with physical function and inflammation in pre-frail obese older adults. METHODS: Cross-sectional study of 407 community dwelling pre-frail older adults. Data on demographics, cognition, and physical function(gait speed, handgrip strength (HGS) and Short Physical Performance Battery (SPPB) test), body composition and inflammation biomarkers were collected. Participants were analysed based on BMI tertiles(T1 lowest,T3 highest). RESULTS: The mean age was 72.67 years, mean BMI 25.42 kg/m2 and 59.5 % were females. Participants in T3 had a mean BMI of 30.75 kg/m2, younger with lower education levels, multimorbidity, polypharmacy and lower prevalence of sarcopenia. In BMI T3, ASMIbmi was significantly associated with EQ-5D index (ß 0.53, 95 % CI 0.04 to 1.03, p = 0.033),HGS (ß 5.28, 95 % CI 0.27 to 10.29, p = 0.039), SPPB (ß 2.19, 95 % CI 0.47 to 3.91, p = 0.013) and IL-6 (ß -4.13, 95 % CI -7.46 to -0.81, p = 0.017). ASMIwt was associated with EQ-5D index (ß 0.17, 95 % CI 0.02 - 0.33, p = 0.047). ASMbfp was associated with HGS (ß 6.97, 95 % CI 0.051 to 13.92, p = 0.049). There was significant association of HGS with all muscle mass indices in BMI T2, and ASMbfpin BMI T1. CONCLUSION: ASMIbmi was significantly associated with SPPB, HGS, EQ-5D index and IL-6 in BMI T3. ASMbfp was associated with HGS in all the tertiles. Our results need further validation at population level.

Impact of Exercise Interventions on Sustained Brain Health Outcomes in Frail Older Individuals: A Comprehensive Review of Systematic Reviews.

Several systematic review studies highlight exercise's positive impact on brain health outcomes for frail individuals. This study adopts a Comprehensive Review of reviews (CRs) approach to amalgamate data from existing reviews, focusing on exercise's influence on brain health outcomes in older frail and pre-frail adults. The methodology involves a thorough search of Portuguese, Spanish, and English-indexed databases (i.e., Ebsco Health, Scielo, ERIC, LILACS, Medline, Web of Science, SportDiscus) from 1990 to 2022, with the AMSTAR-2 tool assessing evidence robustness. The search terms "physical exercise", "elderly frail", and "systematic review" were employed. Results: Out of 12 systematically reviewed studies, four presented high-quality (with metanalyses), while eight exhibit critically low quality. Positive trends emerge in specific cognitive and neuromotor aspects, yet challenges persist in psychosocial domains, complex cognitive tasks, and ADL outcomes. This study yields reasonable and promising evidence regarding exercise's influence on quality of life and depression in frail older individuals. However, the impact on biochemical markers remains inconclusive, emphasizing the need for standardized methodologies. Conclusions: The findings highlight the importance of acknowledging methodological nuances for clinicians and policymakers when translating these results into impactful interventions for aging populations. This emphasizes the necessity for a comprehensive and customized approach to exercise interventions aimed at fostering the sustainability of overall well-being in older individuals, aligning with United Nations Sustainable Development Goal 3.

Pro-Inflammatory Diets Are Associated with Frailty in an Urban Middle-Aged African American and White Cohort.

Diet quality is a modifiable risk factor for frailty, but research on the association of frailty with dietary inflammatory potential is limited. The objective was to determine associations between diet quality assessed by the dietary inflammatory index (DII) with frailty status over time. Participants with both dietary and frailty data from the longitudinal Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used (n = 2901, 43.5% male, 43.8% African American, 48.5 y mean baseline age, with a mean 8.7 y of follow-up). Group-based trajectory modeling identified two frailty (remaining non-frail or being pre-frail/frail over time) and three diet quality trajectory groups (high or medium pro-inflammatory and anti-inflammatory potentials). Multiple logistic regression found both medium pro-inflammatory and anti-inflammatory DII trajectory groups, compared to the high pro-inflammatory group, were positively associated with being non-frail over time for the overall sample, both sexes and races. Kaplan-Meier curves and log-rank test revealed anti-inflammatory DII scores were associated with lower risk for being pre-frail or frail. No longitudinal relationship existed between frailty status at baseline and annualized DII change, a check on reverse causality. This study contributes to our current knowledge providing longitudinal evidence of the link between anti-inflammatory DII score with lower frailty risk.

Impact of exercise and leucine-enriched protein supplementation on physical function, body composition, and inflammation in pre-frail older adults: a quasi-experimental study.

Background: Exercise and a protein-enriched diet are essential for muscle protein synthesis, cellular growth, mitochondrial function, and immune function. The U.S. Food and Nutrition Board's current guideline on recommended dietary allowance for protein in older adults is 0.8 g/kg per day, which may not be sufficient in vulnerable pre-frail older adults. Aims: This study aimed to evaluate the impact of leucine-enriched protein supplementation with or without exercise over 3 months in pre-frail older adults who consumed ≤1 g/kg/day of protein on improving (i) physical function, (ii) body composition measures, and (iii) inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Methods: A non-randomized cluster quasi-experimental study guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist of 178 pre-frail older adults [112 control, 44 nutrition (Nu), and 22 in the nutrition with exercise (Nu+Ex) group] comparing the effect of Nu+Ex and Nu on physical function, body composition, and inflammation. At 0, 3, and 6 months, questionnaires on demographics, depression, perceived health, and cognition were administered. Physical function assessment (short physical performance battery [SPPB] test, gait speed, handgrip strength, 5× sit-to-stand [STS]) was conducted, and body composition analysis was performed using a bioelectrical impedance analysis machine. IL-6 and TNF-α were measured at 0 and 3 months. Results: At 3 months, there were significant improvements in gait speed, 5× STS, SPPB scores, depression, perceived health, fat-free mass, and appendicular skeletal muscle mass indices in the Nu+Ex group. Both Nu+Ex and Nu groups had improvements in body cell mass and reductions in IL-6 and TNF-α. The improvements were not sustained after 6 months. Conclusion: Our study results need to be validated in future longitudinal randomized studies with a larger sample size focusing on populations at risk.

Vitamin D Levels in Pre-frail Older Adults and Its Correlation with Hand Grip Strength.

BACKGROUND: Vitamin D deficiency is frequent in older adults and associated with poor musculoskeletal function. The prevalence of pre-frailty is also high in older persons, who may proceed to a frail state. This study aimed to determine the vitamin D levels in pre-frail older adults and its correlation with hand grip strength. METHODS: A cross-sectional study was conducted on older adults (age > 60 years) with a pre-frail condition who were visiting the outpatient geriatric clinic at Cipto Mangunkusumo Hospital in Jakarta, Indonesia. Serum levels of vitamin D, measured as 25(OH)D, were determined by enzyme-linked immunosorbent assay (ELISA), and hand grip strength was measured using a Jamar hydraulic dynamometer. Correlations between vitamin D levels and hand grip strength were evaluated by Spearman's rank correlation coefficient. Multiple linear regression analysis was carried out to assess contribution of variables that influence hand grip strength. RESULTS: Of 95 pre-frail older adults (mean age 70.08 ± 5.35 years), 67.4% were female,  and the median vitamin D level was 17.91 (interquartile range/IQR 13.68-26.36) ng/mL. Overall, 11.6% of the participants had normal vitamin D levels, whereas 34.7% and 53.7% had insufficient and deficient levels, respectively. Females were more likely to have inadequacy of vitamin D than males.  Those with vitamin D deficiency tended to have a higher body mass index (BMI) and lower vitamin D intake than normal levels. A significant correlation between serum vitamin D levels and hand grip strength was observed (r = 0.283; P = 0.006). After adjusting for age, comorbidities, nutritional status, functional status, BMI, protein intake, and sun exposure score, regression analysis between hand grip strength and vitamin D levels gave standard coefficient beta = 0.255 (P = 0.013). CONCLUSION: In this study, pre-frail older adults had a high proportion of deficient and insufficient vitamin D levels, and a significant correlation was found between serum vitamin D levels and hand grip strength.

Impact of Exercise and Cognitive Stimulation Therapy on Physical Function, Cognition and Muscle Mass in Pre-Frail Older Adults in the Primary Care Setting: A Cluster Randomized Controlled Trial.

OBJECTIVES: Multicomponent exercise program have shown to improve function and cognition in older adults but studies on pre-frail older adults in the primary care setting are limited. This study aimed i) to evaluate impact of 6 months exercise (Ex) versus complementary effect of 3 months of cognitive stimulation therapy (CST) to 6 months of Ex (Ex+CST) on physical function, muscle mass and cognition versus control group at 3, 6 and 12 months ii) inflammatory biomarkers such as Interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α). DESIGN: Cluster randomised control trial. SETTING AND INTERVENTION: Pre-frail older adults ≥ 65 years attending primary care clinic. Two intervention groups i) Ex 6 months ii) CST 3 months with Ex 6 months. MEASUREMENTS: At 0, 3, 6 and 12 months, questionnaires (on demographics, physical function, cognition, and depression) were administered and physical function assessment (gait speed, short physical performance battery (SPPB) test, handgrip strength, five times sit-to-stand (5x-STS)) was conducted. Muscle mass and its surrogates such as phase angle and body cell mass were measured using bioelectrical impedance analysis machine. Inflammatory biomarkers were measured at 0 and 3 months. RESULTS: Data from 190 participants was analysed at 3 months (111 control, 37 Ex and 41 Ex+CST). At 3 months, significant improvement in cognition was seen only in the Ex+CST group whereas improvements in depression, gait speed, SPPB and 5x-STS were seen in both the Ex and Ex+CST groups. At 6 months, the Ex+CST group improved in cognition and depression whereas improvement in frailty and muscle mass indices were seen in both the interventions groups. At 12 months, both the interventions groups had better perceived health, gait speed and less decline in muscle mass compared with control groups. Both the Ex and Ex+CST had significant association with TNF-α at 3 months (ß -2.71 (95% CI -4.80 - -0.62); p = 0.012 and ß -1.74 (95% CI -3.43 - -0.06); p = 0.043 respectively). CONCLUSION: Combined Ex+CST had significant improvement in cognition whereas the intervention groups improved in depression, physical function, muscle mass, frailty, perceived health and TNF-α levels. With growing evidence of the benefits of multicomponent interventions at primary care level, incorporating it into mainstream care with action plans on long-term sustainability and scalability should be a priority for every country.

Mortality Risks after Two Years in Frail and Pre-Frail Older Adults Admitted to Hospital.

BACKGROUND: Frailty is characterized by a progressive decline in the physiological functions of multiple body systems that lead to a more vulnerable condition, which is prone to the development of various adverse events, such as falls, hospitalization, and mortality. This study aims to determine whether frailty increases mortality compared to pre-frailty and to identify variables associated with a higher risk of mortality. MATERIALS: Two cohorts, frail and pre-frail subjects, are evaluated according to the Fried phenotype. A complete examination of frailty, cognitive status, comorbidities and pharmacology was carried out at hospital admission and was extracted through electronic health record (EHR). Mortality was evaluated from the EHR. METHODS: Kaplan-Meier estimates of survival probability functions were calculated at two years censoring time for frail and pre-frail cohorts. The log-rank test assessed significant differences between survival probability functions. Significant variables for frailty (p < 0-05) were extracted by independent sample t-test. Further selection was based on variable significance found in multivariate logistic regression discrimination between frail and pre-frail subjects. Cox regression over univariate t-test-selected variables was calculated to identify variables associated with higher proportional hazard risks (HR) at two years. RESULTS: Frailty is associated with greater mortality at two years censoring time than pre-frailty (log-rank test, p < 0.0001). Variables with significant (p < 0.05) association with mortality identified in both cohorts (HR 95% (CI in the frail cohort) are male sex (0.44 (0.29-0.66)), age (1.05 (1.01-1.09)), weight (0.98 (0.96-1.00)), and use of proton-pump inhibitors (PPIs) (0.60 (0.41-0.87)). Specific high-risk factors in the frail cohort are readmission at 30 days (0.50 (0.33-0.74)), SPPB sit and stand (0.62 (0.45-0.85)), heart failure (0.67 (0.46-0.98)), use of antiplatelets (1.80 (1.19-2.71)), and quetiapine (0.31 (0.12-0.81)). Specific high-risk factors in the pre-frail cohort are Barthel's score (120 (7.7-1700)), Pfeiffer test (8.4; (2.3-31)), Mini Nutritional Assessment (MNA) (1200 (18-88,000)), constipation (0.025 (0.0027-0.24)), falls (18,000 (150-2,200,000)), deep venous thrombosis (8400 (19-3,700,000)), cerebrovascular disease (0.01 (0.00064-0.16)), diabetes (360 (3.4-39,000)), thyroid disease (0.00099 (0.000012-0.085)), and the use of PPIs (0.062 (0.0072-0.54)), Zolpidem (0.000014 (0.0000000021-0.092)), antidiabetics (0.00015 (0.00000042-0.051)), diuretics (0.0003 (0.000004-0.022)), and opiates (0.000069 (0.00000035-0.013)). CONCLUSIONS: Frailty is associated with higher mortality at two years than pre-frailty. Frailty is recognized as a systemic syndrome with many links to older-age comorbidities, which are also found in our study. Polypharmacy is strongly associated with frailty, and several commonly prescribed drugs are strongly associated with increased mortality. It must be considered that frail patients need coordinated attention where the diverse specialist taking care of them jointly examines the interactions between the diversity of treatments prescribed.

Association of physical function and body composition with falls in pre-frail older adults with poor physical performance: A cross-sectional study.

BACKGROUND: Falls in pre-frail older adults is often attributed to poor physical performance, lower muscle quality and quantity. The aims of our study were to determine (i) demographics, physical function, and body composition in pre-frail older adults with poor physical performance (ii) characteristics of fallers amongst those with poor physical performance and (iii) association of physical function and body composition measures with falls in pre-frail older adults with poor physical performance. METHODS: Cross-sectional study of 328 pre-frail community-dwelling older adults ≥ 60 years. Data was collected on demographics, cognition, short physical performance battery (SPPB) and gait speed. Poor physical performance was defined by SPPB ≤ 9, 5x chair-stand time ≥12 s or gait speed <1 m/s. InBody S10 used to measure body composition. RESULTS: Mean age 72.51 years, 185(56.4%) females, 276(84.1%) of Chinese ethnicity and 257 (78.4%) had poor physical performance. Within the poor performers, SPPB balance (OR 0.50; 95% CI 0.27-0.92; p = 0.025) and 5x-chair-stand (OR 1.09; 95% CI 1.01-1.18; p = 0.038) in addition to higher body fat percentage, fat mass index, fat mass to fat free mass ratio, all segmental lean masses except for left leg and body cell mass were significantly associated with falls. CONCLUSIONS: Longer chair-stand time, lower balance, low muscle and high fat mass are associated with falls in poor performers and could serve as screening tools for those at increased risk of falls. The findings from our study need to be validated prospectively in a larger population study.

Protein-Added Healthy Lunch-Boxes Combined with Exercise for Improving Physical Fitness and Vascular Function in Pre-Frail Older Women: A Community-Based Randomized Controlled Trial.

Purpose: Preventive or therapeutic interventions are key to maintaining independence in pre-frail and/or frail elderly. Therefore, we investigated whether multi-component interventions were effective in physical fitness levels and vascular functions in pre-frail older women. Patients and Methods: Sixty participants aged ≥ 65 years (81.5 ± 4.3 yrs) were divided equally into control group, diet group, aerobic exercise and diet group, and aerobic exercise with electromyostimulation and diet group. For 8 weeks, the participants received a set of protein-added meals twice daily on weekdays. The aerobic exercise groups performed 45 mins of stepping exercise at 50-70% of the maximal heart rate for 3 days/week, and the aerobic exercise with electromyostimulation was applied on each limb in 8 weeks. Blood pressure, physical fitness, cardiovascular biomarkers, pulse wave velocity, and flow-mediated dilation were measured before and after the 8-week. Results: There were no group differences in age, height, weight, body mass index, free fat mass, and %body fat at baseline. The right grip strength significantly increased in the diet group, aerobic exercise and diet group, and aerobic exercise with electromyostimulation and diet group (p < 0.05). Short physical performance battery, 6-min walking distance, and flow-mediated dilation significantly increased in the aerobic exercise and diet group and aerobic exercise with electromyostimulation and diet group (p < 0.05). Blood pressure and pulse wave velocity did not differ between interventions. High-density lipoprotein-cholesterol levels significantly increased after 8 weeks in all intervention groups (p < 0.05). There were no significant differences in glucose, HbA1c, total cholesterol, low-density lipoprotein-cholesterol, triglyceride, insulin, Homeostatic Model Assessment for Insulin Resistance, nitric oxide, and C-reactive protein levels. Conclusion: These results show that multi-component interventions appear to improve physical fitness and vascular function in pre-frail older women. Thus, possible strategies to prevent early frailty including proper nutrition and exercise may be needed.

Mobility and strength training with and without protein supplements for pre-frail or frail older adults with low protein intake: the Maximising Mobility and Strength Training (MMoST) feasibility randomised controlled trial protocol.

Background Frailty is a common syndrome affecting older people and puts them at risk of hospitalisation, needing care or death. First signs of frailty include reduced muscle strength and mobility decline. A key cause of mobility decline as we age is sarcopenia (age related reduction in muscle strength and mass). Poor nutrition contributes to sarcopenia. A shortfall in protein is associated with reduced muscle mass and strength. This may be due to inadequate intake but also because older people have higher protein needs, especially those with multimorbidity. We need to develop effective treatment to reduce or slow the onset of frailty and mobility decline. Exercise is a recommended treatment. Protein supplements to address the shortfall in protein have the potential to enhance the benefit of regular exercise in frail or pre-frail older adults. This has yet to be definitively demonstrated. Aim To establish the feasibility of conducting an RCT evaluating mobility and strength training with or without protein supplements for people over 60 years old who are frail or pre-frail with a low protein intake. Methods A multicentre, parallel, 2-group, feasibility RCT. Participants (recruitment target = 50) with problems walking, low protein intake and classified as frail or pre-frail will be recruited from four NHS Physiotherapy community services. Participants will be randomised (secure computer-generated: 1:1) to receive 24 weeks of mobility and strength training (delivered in 16 group sessions plus home exercises) or 24 weeks of mobility and strength training with daily protein supplements. Primary feasibility objectives are to estimate 1) ability to screen and recruit eligible participants, 2) intervention fidelity, adherence, and tolerance and 3) retention of participants at follow up. Secondary objectives are to 1) test data collection procedures, 2) assess data completeness and 3) confirm sample size calculation for a definitive RCT. Registration ISRCTN Registry (ISRCTN30405954; 18/10/2022).

As people get older, they may become frail and become less able to deal with illness or injury. People with frailty are more likely to fall or need care. We need to find ways to stop people becoming frail or slow the progress of frailty so older people can live independently. Exercise is a treatment for frailty that can improve muscle strength and walking. Including extra protein in an older person's diet may also help. Protein provides the building blocks for muscles, but many older people do not eat enough protein. Taking extra protein while exercising may increase the benefits of exercise, but we do not know if it reduces frailty or improves walking and quality of life. We want to conduct a large clinical trial comparing mobility and strength training plus extra protein to training alone. This study aims to test if it is possible to carry out a large trial by finding out:       â€¢   Can we recruit enough participants with low protein intake?       â€¢   Do participants attend the exercise classes and take the protein supplements?       â€¢   Do participants attend follow-up assessments? We aim to recruit up to 50 older people who are frail/at risk of frailty and have low protein intake. We will identify participants via NHS Community Trusts, from an existing cohort study and by advertising in the community. Participants are randomly allocated to training plus protein or training only. Training involves muscle strengthening, balance, and walking exercises. Participants will attend a weekly exercise class with a physiotherapist for 16 weeks and do exercises at home once/week. They are then asked to exercise at home twice weekly for a further 8 weeks. Half the participants will take extra protein while exercising. At enrolment and 8 months later, we collect information on frailty, walking ability, muscle strength and quality of life.

Effectiveness and usability of the system for assessment and intervention of frailty for community-dwelling pre-frail older adults: A pilot study.

Background: Effective multicomponent interventions in the community targeted at preventing frailty in at-risk older adults can promote healthy ageing. However, there is a lack of studies exploring the effectiveness of technology-enabled autonomous multi-domain community-based interventions for frailty. We developed a novel end-to-end System for Assessment and Intervention of Frailty (SAIF) with exercise, nutrition, and polypharmacy components. This pilot study aimed to explore SAIF's effectiveness in improving frailty status, physical performance and strength, and its usability in pre-frail older adults. Materials and methods: This is a single arm 8-week pilot study in 20 community-dwelling older adults who were pre-frail, defined using the Clinical Frailty Scale (CFS) as CFS 3 + (CFS 3 and FRAIL positive) or CFS 4. For outcomes, we assessed frailty status using the modified Fried Frailty Phenotype (FFP) and CFS; physical performance using Short Physical Performance Battery (SPPB); and Hand Grip Strength (HGS) at baseline and 8-week. User experience was explored using the System Usability Scale (SUS), interest-enjoyment subscale of the Intrinsic Motivation Inventory and open-ended questions. We analyzed effectiveness using repeated-measures tests on pre-post scores, and usability using a convergent mixed-method approach via thematic analysis of open-ended responses and descriptive statistics of usability/interest-enjoyment scales. Results: Sixteen participants (71.8 ± 5.5 years) completed the 8-week study. There was a significant improvement in FFP score (-0.5, p < 0.05, effect size, r = 0.43), but not CFS (-1.0, p = 0.10, r = 0.29). Five (31.3%) improved in frailty status for both FFP and CFS. SPPB (+1.0, p < 0.05, r = 0.42) and HGS (+3.5, p < 0.05, r = 0.45) showed significant improvements. Three themes were identified: "Difficulty in module navigation" (barriers for SAIF interaction); "User engagement by gamification" (facilitators that encourage participation); and "Perceived benefits to physical health" (subjective improvements in physical well-being), which corroborated with SUS (68/100) and interest-enjoyment (3.9/5.0) scores. Taken together, user experience results cohere with the Senior Technology Acceptance and Adoption Model. Conclusion: Our pilot study provides preliminary evidence of the effectiveness of SAIF in improving frailty status, physical performance and strength of pre-frail older adults, and offers user experience insights to plan the follow-up large-scale randomized controlled trial.

Corrigendum: Effectiveness and usability of the system for assessment and intervention of frailty for community-dwelling pre-frail older adults: A pilot study.

[This corrects the article DOI: 10.3389/fmed.2022.955785.].

Frailty is Associated With Frontal Cortex-Related Cognitive Function in Patients With Alzheimer Disease.

OBJECTIVE: We compared the cognitive functions of Alzheimer disease (AD) patients who were robust, frail or pre-frail and hypothesized that declines in frontal cortex-related neuropsychological function would be associated with frailty. METHOD: One hundred and sixty outpatients aged 65 years or older with mild AD were enrolled. Cognitive function was assessed using the Cognitive Ability Screening Instrument and further classified into 4 clusters (recent memory, frontal cortex cluster, posterior cortex cluster, and orientation). Other variables included depressive mood, daily activities, body mass index, handgrip strength (HGS), and normal gait speed (NGS). RESULTS: Performance in daily activities, and slower NGS than robust group. Both the frail and pre-frail groups had lower HGS and more depressive symptoms than robust group. Generalized linear with ordinal logistic analysis showed that increment in age, slowing in NGS, and worse frontal cortex cluster function associated with being in a higher level of frailty. The patients with depression symptoms were the odds of being in a higher level of frailty compared to those without depression symptoms. CONCLUSIONS: In addition to physical and psychological symptoms, frailty is associated with specific cognitive domains in patients with AD. A multidimensional approach should be used to assess the impact of intervention programs focusing on frail patients with AD.

Effects of a short eight Tai Chi-forms for the pre-frail elderly people in senior living communities.

PURPOSE: To investigate effects of a short 8-form Tai Chi exercise on physical function, fear of falling, and depression in pre-frail elderly people living in senior communities. METHODS: This 8-week randomized controlled trial was conducted in senior living communities with qualified pre-frail elderly subjects in a Tai Chi group (TCG, n= 32) and a control group (CG, n = 33). The TCG received TC intervention: three times/week, 60 min each; while the CG did usual care only. Assessments of the 30-s chair rise test (CRT), 4.5-m walking speed (WS), fear of falling (FOF), and Geriatric Depression Scale (GDS), were all applied at baseline, end of 4th week, and end of 8th week. RESULTS: Between-group comparison at the 4th week showed significantly better outcomes in CRT (TCG: 14.56 ± 1.87; CG: 11.48 ± 2.83; P< .001) and WS (TCG: 4.28 ± 0.69; CG: 5.11 ± 1.16; P = .001) in the TCG than those in the CG, but not in FOF (TCG: 0.56 ± 0.56; CG: 0.79 ± 0.89; P = .228) and GDS (TCG: 7.91 ± 5.54; CG: 9.58 ± 6.85; P = .285). However, at the 8th week, significant differences (P< .001) were found in all four assessments: (1) CRT: TCG vs CG: 17.28 ± 2.00 vs 11.36± 2.94; (2) WS: TCG vs CG: 3.94 ± 0.59 vs 5.17 ± 1.22; (3) FOF: TCG vs CG: 0.16 ± 0.37 vs 1.00 ± 0.90; and (4) GDS: TCG vs CG: 3.84 ± 3.60 vs 9.97 ± 6.80, and the intervention effect of 8 weeks was better than at 4 weeks. For within-group comparison of the TCG, significant improvements were identified in CRT (P< .001), WS (P = .008), and FOF (P = .002); but not in GDS, P = .121 at the 4th week, and also in CRT (P< .001), WS (P< .001), FOF (P< .001), and GDS (P< .001) at the 8th week. On the other hand, there were no significant differences in the CG for pre- and post-comparison (CRT: P = .891; WS: P = .984; FOF: P = .636; GDS: P = .822). CONCLUSION: This short-form TC exercise could improve physical function (the lower limbs' strength and gait speed), fear of falling, and depression.

Use of the Patient-Generated Subjective Global Assessment to Identify Pre-Frailty and Frailty in Hospitalized Older Adults.

OBJECTIVES: The Scored Patient-Generated Subjective Global Assessment (PG-SGA) and Edmonton Frail Scale (EFS) are widely used in acute care settings to assess nutritional and frailty status, respectively. We aimed to determine whether the scored PG-SGA can identify pre-frailty and frailty status, to simultaneously evaluate malnutrition and frailty in clinical practice. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: A convenience sample of 329 consecutive patients admitted to an acute medical unit in South Australia. MEASUREMENTS: Nutritional and frailty status were ascertained with scored PG-SGA and EFS, respectively. Optimal cut-off scores to identify pre-frailty and frailty were determined by calculating the Scored PG-SGA's sensitivity, specificity, positive and negative predictive values, Youden Index (YI), Liu index, Receiver Operator Curves (ROC) and Area Under Curve (AUC). Nutritional status and patient characteristics were analysed according to frailty categories. RESULTS: The optimal cut-off PG-SGA score as determined by the highest YI, to identify both pre-frailty and frailty was >3, with a sensitivity of 0.711 and specificity of 0.746. The AUC was 0.782 (95% CI 0.731-0.833). In this cohort, 64% of the patients were well-nourished, 26% were moderately malnourished and 10% were severely malnourished. Forty-three percent, 24% and 33% of the patients were classified as robust, pre-frail and frail, respectively. Bivariate analysis showed that those robust were significantly younger than those who were pre-frail (-2.8, 95% CI -5.5 to -0.1, p=0.036) or frail (-3.4, 95% CI -5.9 to -1.0, p=0.002). Robust patients had significantly lower Scored PG-SGA than those who were pre-frail (-2.5, 95%CI -3.8 to -1.1, p<0.001) or frail (-4.9, 95% CI -6.1 to -3.7, p<0.001). CONCLUSION: The Scored PG-SGA is moderately sensitive in identifying pre-frailty/frailty in older hospitalized adults and can be useful in identifying both conditions concurrently.

Sex-specific differences in the prevalence of sarcopenia among pre-frail community-dwelling older adults in Saudi Arabia.

OBJECTIVES: To assess sex differences in the prevalence of sarcopenia among pre-frail community-dwelling older adults in Saudi Arabia. METHODS: This was a cross-sectional study conducted at a tertiary-level hospital in Riyadh, Saudi Arabia, in 2019. The study participants were pre-frail community-dwelling older adults, according to the Edmonton Frail Scale. The SARC-F questionnaire was used to diagnose sarcopenia. The Katz Activities of Daily Living (ADL) was used to rank the adequacy of performance in six functions: bathing, dressing, toileting, transferring, continence, and feeding, while the Lawton Instrumental Activities of Daily Living scale was used to assess the more complex ADL necessary for living in the community. RESULTS: In total, 283 community-dwelling older adults were recruited for this study, with a mean (±SD) age of 70.77 (±6.26) years; 72.7% of the total were female participants. The majority (85.5%) of the patients reported that they needed home care assistance. The mean ADL score of the participants was high, indicating high function and independence (KATZ-ADL: M 4.60 SD 1.75; Lawton Brody: 60%). The overall prevalence of sarcopenia among the studied participants was 65.7%, which was significantly higher among females (71.9%) than among males (59.1%), with a P-value of 0.007. Among the demographic characteristics of the participants, there was a significant difference in the need for home care assistance in female sarcopenic and non-sarcopenic participants (74.1% vs. 25.9%, p = 0.017), but without demonstrable difference in males. Additionally, there was a significant difference (P < 0.05) in the prevalence of sarcopenia between male and female participants according to ADL scores. The strongest predictor for sarcopenia prevalence in males was an ADL score <2 according to the Katz index, with an odds ratio of 6.5, while the need for home care was the only significant predictor of sarcopenia among female participants (OR 3.25, CI: 1.14-9.25, p = 0.02). CONCLUSION: Overall, almost two-thirds of the studied pre-frail community-dwelling older adult population were sarcopenic. The prevalence of sarcopenia was significantly higher among females than males. The strongest predictor of sarcopenia was an ADL score <2 based on the Katz index in males and the need for home care assistance in females.