The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty

Background: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 (“mild”) or 6 (“moderate”), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

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Effectiveness of Community-Delivered Functional Power Training Program for Frail and Pre-frail Community-Dwelling Older Adults: a Randomized Controlled Study

Prevention Science ◽

10.1007/s11121-021-01221-y ◽

2021 ◽

Author(s):

Nien Xiang Tou ◽

Shiou-Liang Wee ◽

Wei Ting Seah ◽

Daniella Hui Min Ng ◽

Benedict Wei Jun Pang ◽

...

Keyword(s):

Older Adults ◽

Muscle Strength ◽

Controlled Trial ◽

Community Dwelling ◽

Controlled Study ◽

Power Training ◽

Frail Older Adults ◽

Frailty Status ◽

Randomized Controlled ◽

Community Dwelling Older Adults

AbstractTranslation of community-based functional training for older adults to reduce frailty is still lacking. We evaluated the effectiveness and implementation of a community-delivered group-based functional power training (FPT) program for frail older adults within their neighborhoods. A two-arm, multicenter assessor-blind stratified randomized controlled trial was conducted at four local senior activity centers in Singapore. Sixty-one community-dwelling older adults with low handgrip strength were randomized to intervention (IG) or control (CG) group. The IG underwent the FPT program (power and balance exercises using simple equipment) delivered by a community service provider. The 12-week program comprised 2 × 60 min sessions/week. CG continued usual activities at the centers. Functional performance, muscle strength, and frailty status were assessed at baseline and 3 months. Program implementation was evaluated using RE-AIM framework. The program was halted due to Coronavirus Disease 2019-related suspension of senior center activities. Results are reported from four centers, which completed the program. IG showed significantly greater improvement in the Short Physical Performance Battery test as compared to CG (p = 0.047). No effects were found for timed up and go test performance, muscle strength, and frailty status. The community program exhibited good reach, effectiveness, adoption, and implementation. Our study demonstrated that FPT was associated with greater improvement in physical function in pre-frail/frail participants as compared to exercise activities offered at local senior activity centers. It is a feasible intervention that can be successfully implemented for frail older adults in their neighborhoods. Trial registration ClinicalTrials.gov, NCT04438876. Registered 19 June 2020–retrospectively registered.

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Brain Training and Sulforaphane Intake Interventions Separately Improve Cognitive Performance in Healthy Older Adults, Whereas a Combination of These Interventions Does Not Have More Beneficial Effects: Evidence from a Randomized Controlled Trial

Nutrients ◽

10.3390/nu13020352 ◽

2021 ◽

Vol 13 (2) ◽

pp. 352

Author(s):

Rui Nouchi ◽

Qingqiang Hu ◽

Toshiki Saito ◽

Natasha Yuriko dos Santos Kawata ◽

Haruka Nouchi ◽

...

Keyword(s):

Older Adults ◽

Active Control ◽

Processing Speed ◽

Cognitive Functions ◽

Controlled Trial ◽

Memory Performance ◽

Brain Training ◽

Beneficial Effects ◽

Before And After ◽

Double Blinded

Background: Earlier studies have demonstrated that a single-domain intervention, such as a brain-training (BT) game alone and a sulforaphane (SFN) intake, positively affects cognition. This study examined whether a combined BT and SFN intake intervention has beneficial effects on cognitive function in older adults. Methods: In a 12-week double-blinded randomized control trial, 144 older adults were randomly assigned to one of four groups: BT with SFN (BT-S), BT with placebo (BT-P), active control game (AT) with SFN (AT-S), and active control game with placebo (AT-P). We used Brain Age in BT and Tetris in AT. Participants were asked to play BT or AT for 15 min a day for 12 weeks while taking a supplement (SFN or placebo). We measured several cognitive functions before and after the intervention period. Results: The BT (BT-S and BT-P) groups showed more improvement in processing speed than the active control groups (AT-S and AT-P). The SFN intake (BT-S and AT-S) groups recorded significant improvements in processing speed and working memory performance unlike the placebo intake groups (BT-P and AT-P). However, we did not find any evidence of the combined intervention’s beneficial effects on cognition. Discussion: We discussed a mechanism to improve cognitive functions in the BT and SFN alone interventions.

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The EX-FRAIL CKD trial: a study protocol for a pilot randomised controlled trial of a home-based EXercise programme for pre-frail and FRAIL, older adults with Chronic Kidney Disease

BMJ Open ◽

10.1136/bmjopen-2019-035344 ◽

2020 ◽

Vol 10 (6) ◽

pp. e035344

Author(s):

Andrew Christopher Nixon ◽

Theodoros M Bampouras ◽

Helen J Gooch ◽

Hannah M L Young ◽

Kenneth William Finlayson ◽

...

Keyword(s):

Older Adults ◽

Chronic Kidney Disease ◽

Randomised Controlled Trial ◽

Kidney Disease ◽

Outcome Measures ◽

Controlled Trial ◽

Exercise Programme ◽

Frailty Status ◽

Home Based ◽

Randomised Controlled

IntroductionFrailty is highly prevalent in adults with chronic kidney disease (CKD) and is associated with adverse health outcomes including falls, poorer health-related quality of life (HRQOL), hospitalisation and mortality. Low physical activity and muscle wasting are important contributors to physical frailty in adults with CKD. Exercise training may improve physical function and frailty status leading to associated improvements in health outcomes, including HRQOL. The EX-FRAIL CKD trial aims to inform the design of a definitive randomised controlled trial (RCT) that investigates the effectiveness of a progressive, multicomponent home-based exercise programme in prefrail and frail older adults with CKD.Methods and analysisThe EX-FRAIL CKD trial is a two-arm parallel group pilot RCT. Participants categorised as prefrail or frail, following Frailty Phenotype (FP) assessment, will be randomised to receive exercise or usual care. Participants randomised to the intervention arm will receive a tailored 12-week exercise programme, which includes weekly telephone calls to advise on exercise progression. Primary feasibility outcome measures include rate of recruitment, intervention adherence, outcome measure completion and participant attrition. Semistructured interviews with a purposively selected group of participants will inform the feasibility of the randomisation procedures, outcome measures and intervention. Secondary outcome measures include physical function (walking speed and Short Physical Performance Battery), frailty status (FP), fall concern (Falls Efficacy Scale-International tool), activities of daily living (Barthel Index), symptom burden (Palliative care Outcome Scale-Symptoms RENAL) and HRQOL (Short Form-12v2).Ethics and disseminationEthical approval was granted by a National Health Service (NHS) Regional Ethics Committee and the NHS Health Research Authority. The study team aims to publish findings in a peer-reviewed journal and presents the results at relevant national and international conferences. A summary of findings will be provided to participants, a local kidney patient charity and the funding body.Trial registration numberISRCTN87708989.

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Effects of Resistance Training Intervention along with Leucine-Enriched Whey Protein Supplementation on Sarcopenia and Frailty in Post-Hospitalized Older Adults: Preliminary Findings of a Randomized Controlled Trial

Journal of Clinical Medicine ◽

10.3390/jcm11010097 ◽

2021 ◽

Vol 11 (1) ◽

pp. 97

Author(s):

Maria Amasene ◽

Cristina Cadenas-Sanchez ◽

Iñaki Echeverria ◽

Begoña Sanz ◽

Cristina Alonso ◽

...

Keyword(s):

Older Adults ◽

Resistance Training ◽

Controlled Trial ◽

Protein Supplementation ◽

Training Intervention ◽

Resistance Training Program ◽

Frailty Status ◽

Appendicular Skeletal Muscle ◽

Protein Group ◽

Hospitalized Older Adults

Resistance training and protein supplementation are expected to exert the greatest effect in counteracting muscle-wasting conditions. Myokines might play a key role, but this remains to be elucidated. The aim of this study (NCT03815201) was to examine the effects of a resistance training program with post-exercise leucine-enriched protein supplementation on sarcopenia and frailty status and on the plasma myokine concentrations of post-hospitalized older adults. A total of 41 participants were included in this 12-week resistance training intervention and randomized either to the placebo group or the protein group. Sarcopenia, frailty, body composition and blood-based myokines were measured at baseline and after 12 weeks. Both groups improved in terms of physical performance (p < 0.005) and frailty (p < 0.07) following the resistance training intervention, but without any difference between groups. Myokine concentrations did not change after the intervention in either group. Changes in myostatin concentrations were associated with greater improvements in appendicular skeletal muscle mass at the end of the intervention (p < 0.05). In conclusion, the implementation of resistance training programs after hospitalization in older adults should be prioritized to combat sarcopenia and frailty immediately. The results regarding myostatin should be taken as preliminary findings.

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Depression Screening and Rates of Mood Disorder Diagnosis and Suicide in Younger and Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.1188 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 369-369

Author(s):

Julie Lutz ◽

Kenneth Conner ◽

Michael Hasselberg ◽

Kathleen Fear ◽

Kim Van Orden

Keyword(s):

Older Adults ◽

Mood Disorder ◽

Large Scale ◽

Medical Center ◽

Severe Depression ◽

Care Physician ◽

Depression Screening ◽

Established Risk Factor ◽

Patient Reported ◽

The University

Abstract Rates of suicide are elevated among older adults in the U.S. and around the world, with the highest rates in older men (CDC, 2019; WHO, 2014). More than half of older adults who die by suicide were in contact with a primary care physician within the month prior to death, and almost one-third within the prior week (Luoma et al., 2002; Stene-Larsen & Reneflot, 2019), demonstrating the importance of better identification and treatment of mental health issues among older adults across healthcare systems. Depression, a well-established risk factor for suicide, goes under-diagnosed and under-treated, especially among older adults (Bryant, 2010). The University of Rochester Medical Center has led integration of patient-reported outcomes assessment via large-scale implementation of PROMIS measures across multiple departments. We compared results of PROMIS depression screening from 1/1/2015 to 8/31/2019 with mood disorder diagnoses within the year prior and year following screening. Twenty-six percent (39491/154669) of adults under age 65 and 23% (11694/51702) of those age 65 and older screened positive for mild, moderate, or severe depression. Whereas 29.0% of younger adults who screened positive received mood disorder diagnoses, 22.1% of older adults received a diagnosis (χ2(1)=214.69, p<.001). Suicide outcomes using National Death Index data will also be reported. Results confirm depression is underdiagnosed (and, by extension, likely undertreated) at all ages, but show a distinct disparity for older adults, which may put them at greater risk for negative outcomes such as suicide.

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Targeting autonomic flexibility to enhance cognitive training outcomes in older adults with mild cognitive impairment: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05530-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Feng V. Lin ◽

Kathi Heffner ◽

Richard Gevirtz ◽

Zhengwu Zhang ◽

Duje Tadin ◽

...

Keyword(s):

Older Adults ◽

Randomized Controlled Trial ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Training ◽

Medical Center ◽

Controlled Trial ◽

Long Term Effects ◽

Randomized Controlled ◽

Combined Intervention

Abstract Importance Cognitive training with components that can further enhance the transferred and long-term effects and slow the progress of dementia is needed for preventing dementia. Objective The goal of the study is to test whether improving autonomic nervous system (ANS) flexibility via a resonance frequency breathing (RFB) training will strengthen the effects of a visual speed of processing (VSOP) cognitive training on cognitive and brain function, and slow the progress of dementia in older adults with mild cognitive impairment (MCI). Design Stage II double-blinded randomized controlled trial. The study was prospectively registered at ClinicalTrials.gov, with registration approved on 21 August 2020 (No. NCT04522791). Setting Study-related appointments will be conducted on-site at University of Rochester Medical Center locations. Data collection will be conducted from August 2020 to February 2025. Participants Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a IR-only control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility, measured by heart rate variability, and multiple markers of dementia progress. Data will be collected across a 14-month period. Discussion This will be among the first RCTs to examine in older persons with MCI a novel, combined intervention targeting ANS flexibility, an important contributor to overall environmental adaptation, with an ultimate goal for slowing neurodegeneration. Trial registration ClinicalTrials.gov NCT04522791. Registered on 21 August 2020 Protocol version: STUDY00004727; IRB protocol version 2, approved on 30 July 2020.

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Evaluation of the effect of intravenous calcium and magnesium (CaMg) on chronic and acute neurotoxicity associated with oxaliplatin: Results from a placebo-controlled phase III trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4025 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4025-4025

Author(s):

A. Grothey ◽

D. A. Nikcevich ◽

J. A. Sloan ◽

J. W. Kugler ◽

P. T. Silberstein ◽

...

Keyword(s):

Controlled Trial ◽

Acute Effect ◽

Patient Reported Outcome ◽

Phase Iii ◽

Muscle Cramps ◽

Patient Reported ◽

Blinded Manner ◽

Acute Neurotoxicity ◽

Double Blinded ◽

Dose Limiting Toxicity

4025 Background: Cumulative sNT is the dose-limiting toxicity of oxaliplatin which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant setting. We recently demonstrated the protective effect of CaMg against oxaliplatin-induced sNT as assessed by NCI-CTC (Nikcevich ASCO 2008). It is unclear, though, if CaMg reduced acute and/or chronic, cumulative sNT. Methods: 104 pts with colon cancer undergoing adjuvant therapy with FOLFOX were randomized to IV CaMg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo (PL) in a double-blinded manner. NCI-CTC, an oxaliplatin-specific sNT scale and patient-reported outcome (PRO) questionnaires were used to differentially assess the effect of CaMg on acute (effect on sNT on days 1–4 after oxaliplatin) and chronic sNT (area between curves over whole course of therapy). Results: A total of 102 pts (50 CaMg, 52 PL; 96 mFOLFOX6, 6 FOLFOX4) were available for analysis. Apart from a strong reduction in muscle cramps with CaMg (p=0.002), no difference was found between CaMg and PL in PRO with regard to items reflecting acute sNT (e.g. sensitivity to cold, swallowing of cold liquids, throat discomfort) on days 1–4 after oxaliplatin of any treatment cycle. In contrast, CaMg was able to significantly reduce cumulative sNT in form of numbness in fingers (p=0.02), impaired ability to button shirts (p=0.05), tingling in fingers (p=0.06), and muscle cramps over the course of therapy (p=0.01). Conclusions: In our phase III, placebo-controlled trial, CaMg was able to significantly reduce chronic, cumulative sNT related to oxaliplatin as evaluated by specific PRO questionnaires. No effect was noted on phenomena associated with acute sNT. CaMg can be recommended as neuroprotectant against oxaliplatin-related chronic sNT, oxaliplatin's dose-limiting toxicity. [Table: see text]

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Identifying patient-reported anxiety and depression in older adults with cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.11556 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 11556-11556

Author(s):

Reena Jayani ◽

Can-Lan Sun ◽

Kemeberly Charles ◽

Enrique Soto Perez De Celis ◽

Leana Chien ◽

...

Keyword(s):

Mental Health ◽

Older Adults ◽

Controlled Trial ◽

Well Being ◽

Anxiety And Depression ◽

High Anxiety ◽

Cut Points ◽

Cut Point ◽

Patients With Cancer ◽

Patient Reported

11556 Background: Anxiety and depression are associated with decreased quality of life, treatment adherence, and survival in patients with cancer. Mental Health Inventory (MHI-17) is a validated screening tool for psychological well-being, but cut points for older adults with cancer are unknown. The goal of this study is to identify cut points on MHI-17 Anxiety (MHI-A) and Depression (MHI-D) subscales which correlate with patient-reported anxiety and depression in older adults with cancer. Methods: This is a secondary analysis of baseline data from a randomized controlled trial in adults aged 65+ with solid tumors starting chemotherapy. At baseline, patients completed MHI-17. MHI-A and MHI-D were calculated (range 0-100; higher scores represent better mental health). Self-reported anxiety was obtained from single-item Linear Analog Scale Assessment (0-5 = low, 6-10 = high). Self-reported depression was obtained from Yale Depression Screen, “Do you often feel sad or depressed?” The association of MHI-A and MHI-D with the patient-reported outcomes was analyzed using logistic regression. Youden’s index was used to determine the optimal cut points for MHI-A and MHI-D for identifying patients with high anxiety and depression. Results: 458 patients (median age 71 (range 65-91), 57% female, 55% non-Hispanic white) were included in this analysis. The most common cancer types were: GI (31%), breast (19%), GU (18%), and pulmonary (16%); 75% had stage IV cancer. Twenty-four percent (N = 110) reported high anxiety and 21% (N = 97) depression. Median scores for MHI-A and MHI-D were 75 (range 0-100) and 80 (range 0-100). The optimal cut point for high anxiety on MHI-A was 65; this had an accuracy of 76.1%, a sensitivity of 71.8%, and a specificity of 77.5%. The optimal cut point for depression on MHI-D was 70; this had an accuracy of 80.1%, a sensitivity of 80.4%, and a specificity of 79.8%. Conclusions: The current study identified optimal cut points for MHI-Anxiety and MHI-Depression subscales to identify older adults with cancer starting chemotherapy with self-reported anxiety and depression. In the absence of patient-reported anxiety and depression, these cut points could be used to identify older patients with cancer at risk for poor mental health.

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The effectiveness of Kinesio Taping® for mobility and functioning improvement in knee osteoarthritis: a randomized, double-blind, controlled trial

Clinical Rehabilitation ◽

10.1177/0269215520916859 ◽

2020 ◽

Vol 34 (7) ◽

pp. 877-889 ◽

Cited By ~ 1

Author(s):

Venta Donec ◽

Raimondas Kubilius

Keyword(s):

Knee Osteoarthritis ◽

Controlled Trial ◽

Intervention Group ◽

Outpatient Rehabilitation ◽

Control Group ◽

Double Blind ◽

Kinesio Taping ◽

Patient Reported ◽

Double Blinded

Objective: To evaluate the effectiveness of the Kinesio Taping® method for mobility and functioning improvement for patients with knee osteoarthritis (KO). Design: Randomized, double-blinded, controlled trial. Setting: Outpatient rehabilitation department. Subjects: A total of 187 subjects with symptomatic I–III grade KO participated; of these, 157 subjects were included in the analyses (intervention group, n = 81 (123 knees); control group, n = 76 (114 knees). Intervention: The intervention group received a specific Kinesio Taping application, and the control group received non-specific knee taping for a month. Main measures: Changes in Knee injury and Osteoarthritis Outcome Scores (KOOS), knee active range of motion, 10-Meter Walk, and the five times sit to stand tests (5xSST) were assessed at baseline, after four weeks of taping, and a month post taping intervention. Subjective participants’ experiences and opinions on the effect of knee taping were evaluated. The chosen level of significance was p < 0.05. Results: The mean age of participants was 68.7 ± 9.9 in intervention group and 70.6 ± 8.3 in control group ( p > 0.05). The change from baseline in gait speed in the intervention group after taping month was +0.04 ± 0.1 m/s, at follow-up +0.06 ± 0.1 m/s; in control group +0.07 ± 0.1 m/s, and +0.09 ± 0.1 m/s; the change in time needed to accomplish 5xSST was –2.2 ± 3.2 seconds, at follow-up –2.4 ± 3.1 seconds; in control group –2.8 ± 3.6 seconds, and –2.4 ± 4 seconds. Improved knee flexion and enhancement in functioning assessed by KOOS were noticed in both groups, with lasting improvement to follow up. No difference in the change in the above-mentioned outcomes was found between groups ( p > 0.05). Fewer subjects (6.2% (5) vs. 21.1% (16), χ2 = 7.5, df = 2, p = 0.024) from Kinesio Taping group were unsure if taping alleviated their mobility and more intervention group patients indicated higher subjective satisfaction with the effect of knee taping to symptom and mobility alleviation than control group ( p < 0.005). Conclusion: Investigated Kinesio Taping technique did not produce better results in mobility and functioning improvement over non-specific knee taping; however, it had higher patient-reported subjective value for symptom attenuation and experienced mobility enhancement.

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Limited formal education is strongly associated with lower cognitive status, functional disability and frailty status in older adults

Dementia & Neuropsychologia ◽

10.1590/1980-57642018dn13-020011 ◽

2019 ◽

Vol 13 (2) ◽

pp. 216-224 ◽

Cited By ~ 6

Author(s):

Allan Gustavo Brigola ◽

Tiago da Silva Alexandre ◽

Keika Inouye ◽

Monica Sanches Yassuda ◽

Sofia Cristina Iost Pavarini ◽

...

Keyword(s):

Older Adults ◽

Formal Education ◽

Functional Disability ◽

Negative Impact ◽

Later Life ◽

Cognitive Status ◽

Functional Abilities ◽

Cognitive Screening ◽

Cross Sectional ◽

Frailty Status

ABSTRACT. Limited formal education is still common in ageing populations. Although limited formal education seems to be independently and negatively associated with cognition, functional abilities and frailty in ageing, no studies have examined whether the gradient of limited formal education has an impact on health in later life. Objective: to examine the relationship of limited formal education with cognitive status, functional abilities, and frailty status. Methods: a cross-sectional study was conducted involving 540 older adults stratified into groups: no formal education, 12-24 months of education, and 25-48 months of education. Cognitive screening (MMSE), functional abilities (Lawton Index), and frailty (CHS criteria) were measured. Regression analyses were performed. Results: 27% had no formal education, 21% had 12-24 months of formal education, and 55% had 25-48 months of formal education. Limited formal education has a clear gradient of negative impact: No formal education was associated with scoring below MMSE cut-off scores (OR = 7.9), being totally/partially dependent for IADLs (OR = 2.5) and frail (OR = 2.0). Having 12-24 months of education was associated with scoring below MMSE cut-off scores (OR = 5.2) and with being frail (OR = 2.0). The No formal education group was 10.1 times more likely to have worse cognitive scores, worse functional abilities and frailty/pre-frailty status concomitantly (CCoFF), while older adults who had 12-24 months of education had a 4.6 times greater chance of having CCoFF. Conclusion: limited education had a gradient association with cognitive performance, functional disability and frailty. These findings clearly emphasize the importance of prevention through education from childhood to older age.

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