Open Access
Comment on 'Effects of Vivifrail multicomponent intervention on functional capacity' by Casas-Herrero et al.-The authors reply.
(Wiley, 2024) Sánchez Sánchez, Juan Luis; Izquierdo Redín, Mikel; López Sáez de Asteasu, Mikel; Antón Rodrigo, Iván; Galbete Jiménez, Arkaitz; Álvarez Bustos, Alejandro; Casas Herrero, Álvaro; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Institute of Smart Cities - ISC
In this response letter, we would like to clarify some aspects related to the methodology and inferences derived from our work entitled 'Effects of Vivifrail multicomponent intervention on functional capacity', which was aimed at investigating the effects of a home-based multicomponent individualized exercise programme (Vivifrail) on the functional capacity of frail older adults with mild cognitive impairment/dementia. Yan et al.2 raised concerns related to the amount of data missingness and methods used to handle it in our study. Although we addressed this issue as a limitation of the Discussion section of the original report, we now take the opportunity to further discuss its implications.
Open Access
Effectiveness of a multimodal intervention in functionally impaired older people with type 2 diabetes mellitus
(Wiley, 2019) Rodríguez Mañas, Leocadio; Laosa, Olga; Vellas, Bruno; Paolisso, Giuseppe; Topinkova, Eva; Oliva Moreno, Juan; Bourdel Marchasson, Isabelle; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Background: Type 2 diabetes, a highly prevalent chronic disease, is associated with increasing frailty and functional decline in older people. We aimed to evaluate the effectiveness of a multimodal intervention on functional performance in frail and pre-frail participants aged ≥70 years with type 2 diabetes mellitus. Methods: The MID-Frail study was a cluster-randomized multicenter clinical trial conducted in 74 trial sites across seven European countries. The trial recruited 964 participants who were aged >70 years [mean age in intervention group, 78.4 (SD 5.6) years, 49.2% male and 77.6 (SD 5.29) years, 52.4% male in usual care group], with type diabetes mellitus and determined to be frail or pre-frail using Fried's frailty phenotype. Participants were allocated by trial site to follow either usual care (UCG) or intervention procedures (IG). Intervention group participants received a multimodal intervention composed of (i) an individualized and progressive resistance exercise programme for 16 weeks; (ii) a structured diabetes and nutritional educational programme over seven sessions; and (iii) Investigator-linked training to ensure optimal diabetes care. Short Physical Performance Battery (SPPB) scores were used to assess change in functional performance at 12 months between the groups. An analysis of the cost-effectiveness of the intervention was undertaken using the incremental cost-effectiveness ratio (ICER). Secondary outcomes included mortality, hospitalization, institutionalization, quality of life, burden on caregivers, the frequency and severity of hypoglycaemia episodes, and the cost-effectiveness of the intervention. Results: After 12 months, IG participants had mean SPPB scores 0.85 points higher than those in the UCG (95% CI, 0.44 to 1.26, P < 0.0001). Dropouts were higher in frail participants and in the intervention group, but significant differences in SPPB between treatment groups remained consistent after sensitivity analysis. Estimates suggest a mean saving following intervention of 428.02 EUR (2016) per patient per year, with ICER analysis indicating a consistent benefit of the described health care intervention over usual care. No statistically significant differences between groups were detected in any of the other secondary outcomes. Conclusions: We have demonstrated that a 12 month structured multimodal intervention programme across several clinical settings in different European countries leads to a clinically relevant and cost-effective improvement in the functional status of older frail and pre-frail participants with type 2 diabetes mellitus.
Open Access
Long-term frailty and physical performance transitions in older people with type-2 diabetes: the MIDFRAIL randomized clinical study
(Elsevier, 2025-02-14) Laosa, Olga; Topinkova, Eva; Bourdel Marchasson, Isabelle; Vellas, Bruno; Izquierdo Redín, Mikel; Paolisso, Giuseppe; Hardman, Timothy C.; Zeyfang, Andrej; Pedraza, Laura; Carnicero Carreño, José Antonio; Rodríguez Mañas, Leocadio; Sinclair, Alan J.; Ciencias de la Salud; Osasun Zientziak
Aims: Type 2 diabetes (T2D) is associated with frailty in older people. We aim to explore changes in frailty status after 18 months of intervention. Methods: 298 community-dwelling older adults (>70 years) participating in MIDFRAIL followed-up for 18–24 months were randomly allocated by trial site (cluster) to intervention IG (16-weeks resistance exercise program, nutritional-educational sessions, optimization of diabetes care), or usual care group (UCG). Frailty status was assessed by the Fried Frailty Phenotype criteria at baseline and final visit. Functional status was assessed by the SPPB in every visit. We used multivariate linear and logistic regression for continuous and dichotomous outcomes. This study was registered at Clinicaltrials.gov (NCT01654341). Results: Mean age was 77.7 (SD 5.54), 47% were male, 32.9% frail and 67.1% prefrail. The probability of improving the frailty status and decreasing the number of Fried’s frailty criteria was higher in the IG than in the UCG (OR 2.6, 95%CI 1.3–5.4; p = 0.009 and OR 1.9; 95%CI 1.1 3.1; p = 0.02, respectively). IG participants more frequently improved 1 point in SPPB score (OR 1.85; 95%CI 1.09–3.12; p = 0.022). These benefits were mainly accounted for the prefrail participants. Conclusions: The MIDFRAIL intervention improved frailty status and physical function at long-term follow-up in older people with T2D.
Open Access
Exercise as therapeutic agent to improve intrinsic capacity in older adults
(Asociación Española de Ciencias del Deporte, 2018) Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Frailty has emerged as one of the most relevant clinical syndromes, due to its direct relationship with adverse health effects such as physical and functional decline and institutionalization. Physical inactivity has been argued to be a key factor contributing to the onset of muscle mass and function decline (i.e. sarcopenia), which in turn appears to be a vital aspect related to frailty. Deterioration in muscular strength and mass, cardiovascular resistance and balance leads to a decrease in daily life activities, a higher risk of falling and a loss of independence, among other consequences. The effects of exercise are potentially similar to those that can be achieved with medication and are even better, with barely any adverse effects when aiming to prevent cardiovascular disease, decrease the risk of death, prevent diabetes and obesity and improve muscular function and quality of life. Multicomponent physical exercise programs and, in particular, strength training are the most effective interventions for delaying disability and other adverse events. Likewise, their use has been proven in other fields which are frequently associated with this syndrome such as falls, cognitive deterioration and depression.
Open Access
Ejercicio físico como intervención eficaz en el anciano frágil
(Gobierno de Navarra, 2012) Casas Herrero, Álvaro; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
El síndrome de la fragilidad define a los ancianos vulnerables que tienen un riesgo elevado de sufrir eventos adversos. Su fisiopatología y etiopatogenia es compleja, pero actualmente disponemos de medidas sencillas de capacidad funcional para su evaluación. La inactividad física, que frecuentemente asocia el envejecimiento, es uno de los factores fundamentales que contribuye a la aparición de sarcopenia, aspecto central de la fragilidad. Los programas de ejercicio físico multicomponente y, particularmente el entrenamiento de la fuerza, constituyen las intervenciones más eficaces para retrasar la discapacidad y otros eventos adversos. Así mismo, han demostrado su utilidad en otros dominios frecuentemente asociados a este síndrome como las caídas, el deterioro cognitivo y la depresión. Sin embargo, es necesario investigar cuáles son los componentes óptimos de un programa de fuerza en el frágil, así como la óptima relación dosis-respuesta que permita desarrollar guías clínicas específicas de actividad física para este grupo poblacional.
Open Access
Lipidomic signatures from physically frail and robust older adults at hospital admission
(Springer, 2022) Ramírez Vélez, Robinson; Martínez Velilla, Nicolás; Correa Rodríguez, María; López Sáez de Asteasu, Mikel; Zambom Ferraresi, Fabrício; Palomino Echeverría, Sara; García Hermoso, Antonio; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 2186/2014; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa, 420/2019
Identifying serum biomarkers that can predict physical frailty in older adults would have tremendous clinical value for primary care, as this condition is inherently related to poor quality of life and premature mortality. We compared the serum lipid profile of physically frail and robust older adults to identify specific lipid biomarkers that could be used to assess physical frailty in older patients at hospital admission. Forty-three older adults (58.1% male), mean (range) age 86.4 (78–100 years) years, were classified as physically frail (n = 18) or robust (n = 25) based on scores from the Short Physical Performance Battery (≤ 6 points). Non-targeted metabolomic study by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. Area under receiver-operating curve (AUROC) analysis was used to test the discriminatory ability of lipid biomarkers for frailty based on the Short Physical Performance Battery. We identified a panel of five metabolites including ceramides Cer (40:2), Cer (d18:1/20:0), Cer (d18:1/23:0), cholesterol, and hosphatidylcholine (PC) (14:0/20:4) that were significantly increased in physically frail older adults compared with robust older adults at hospital admission. The most interesting in the physically frail metabolome study found with the KEGG database were the metabolic pathways, vitamin digestion and absorption, AGE-RAGE signaling pathway in diabetic complications, and insulin resistance. In addition, Cer (40:2) (AUROC 0.747), Cer (d18:1/23:0) (AUROC 0.720), and cholesterol (AUROC 0.784) were identified as higher values of physically frail at hospital admission. The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission. Also, we propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults.
Open Access
Strength and endurance training prescription in healthy and frail elderly
(International Society on Aging and Disease (ISOAD), 2014) Lusa Cadore, Eduardo; Pinto, Ronei Silveira; Bottaro, Martim; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Aging is associated with declines in the neuromuscular and cardiovascular systems, resulting in an impaired capacity to perform daily activities. Frailty is an age-associated biological syndrome characterized by decreases in the biological functional reserve and resistance to stressors due to changes in several physiological systems, which puts older individuals at special risk of disability. To counteract the neuromuscular and cardiovascular declines associated with aging, as well as to prevent and treat the frailty syndrome, the strength and endurance training seems to be an effective strategy to improve muscle hypertrophy, strength and power output, as well as endurance performance. The first purpose of this review was discuss the neuromuscular adaptations to strength training, as well as the cardiovascular adaptations to endurance training in healthy and frail elderly subjects. In addition, the second purpose of this study was investigate the concurrent training adaptations in the elderly. Based on the results found, the combination of strength and endurance training (i.e., concurrent training) performed at moderate volume and moderate to high intensity in elderly populations is the most effective way to improve both neuromuscular and cardiorespiratory functions. Moreover, exercise interventions that include muscle power training should be prescribed to frail elderly in order to improve the overall physical status of this population and prevent disability.
Open Access
Valoración de la capacidad funcional en el ámbito domiciliario y en la clínica. Nuevas posibilidades de aplicación de la acelerometría para la valoración de la marcha, equilibrio y potencia muscular en personas mayores
(Gobierno de Navarra, 2008) Izquierdo Redín, Mikel; Martínez Ramírez, Alicia; Larrión, J. L.; Irujo Espinosa, M.; Gómez Fernández, Marisol; Matemáticas; Matematika
Dentro de cualquier población de individuos mayores de 65 años, una proporción sustancial (entre el 6% y el 25%) sufre diferentes síntomas del síndrome de fragilidad. A pesar de la complejidad del termino fragilidad y de las imprecisiones en cuanto a su definición existe un consenso sobre sus síntomas y signos. Las personas que poseen este síndrome presentan pérdidas de fuerza muscular, fatiga, disminución de la actividad física, con un aumento del riesgo de padecer anorexia-pérdida de peso, delirium, hospitalización, declive funcional, deterioro cognitivo, mortalidad, ingreso en residencias, caídas e inestabilidad. Bajo este contexto, surge la necesidad de desarrollar tests que sean capaces de predecir de la forma más precoz posible la fragilidad y la discapacidad. La acelerometría es una herramienta adecuada para la monitorización de movimientos humanos de una forma objetiva y fiable, aplicable en la vida diaria de los sujetos sin implicar grandes costes. Los acelerómetros están siendo utilizados en la monitorización de diferentes movimientos. Se pueden obtener una amplio abanico de medidas como: clasificación de movimientos, valoración del nivel de actividad física, estimación del gasto de energía metabólica, medida del equilibrio, ritmo de marcha y control al levantarse-sentarse. Combinando la acelerometría con giróscopos y magnetómetros se podrá añadir información relacionada con la orientación y los cambios de posición. Esta revisión analiza las herramientas y tecnologías existentes que puedan llegar a detectar de manera precoz posibles signos y síntomas de la fragilidad y permitan a los individuos vivir autónomamente de forma más prolongada y en condiciones de mayor seguridad.
Open Access
Inter-individual variability in response to exercise intervention or usual care in hospitalized older adults
(Wiley, 2019) López Sáez de Asteasu, Mikel; Martínez Velilla, Nicolás; Zambom Ferraresi, Fabrício; Casas Herrero, Álvaro; Lusa Cadore, Eduardo; Ramírez Vélez, Robinson; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 2186/2014
Background: Exercise protocols applied during hospitalization can prevent functional and cognitive decline in older adults. The purpose of this study was to examine the individual response of acutely hospitalized patients to usual care and to physical exercise on functional capacity, muscle strength, and cognitive function and to assess the relationship with mortality at 1 year post-discharge. Methods: In a single-blind randomized clinical trial, 370 hospitalized patients [56.5% women; mean age (standard deviation) 87.3 (4.9) years] were allocated to an exercise intervention group (IG, n = 185) or a control group (CG, n = 185). The participants were older adults aged 75 years or older in an acute care unit in a tertiary public hospital in Navarra, Spain. The usual care group received habitual hospital care, which included physical rehabilitation when needed. The in-hospital intervention included individualized multicomponent exercise training programme performed during 5–7 consecutive days (two sessions/day). Functional capacity was assessed with the Short Physical Performance Battery (SPPB) test and the Gait Velocity Test (GVT). Handgrip strength and cognitive function were also measured at admission and discharge. Patients in both groups were categorized as responders (Rs), non-responders (NRs), and adverse responders (ARs) based on the individual response to each treatment during hospitalization. Results: The prevalence of Rs was higher and the prevalence of NRs and ARs was lower in the intervention group than in the control group for functional capacity (SPPB IG: Rs 85.3%, NRs 8.7%, ARs 6.0% vs. CG: Rs 37.9%, NRs 28.8%, ARs 33.3% and GVT IG: Rs 51.2%, NRs 47.3, ARs 1.6% vs. CG: Rs 18.0%, NRs 67.7%, ARs 14.3%), muscle strength (IG: Rs 62.3%, NRs 26.5%, ARs 11.3% vs. CG: Rs 20.0%, NRs 38.0%, ARs 42.0%), and cognition (IG: Rs 41.5%, NRs 57.1%, ARs 1.4% vs. CG: Rs 13.8%, NRs 76.6%, ARs 9.7%) (all P < 0.001). The ARs for the GVT in the control group and the ARs for the SPPB in the intervention group had a significantly higher rate of mortality than the NRs and Rs in the equivalent groups (0.01 and 0.03, respectively) at follow-up. Conclusions: Older patients performing an individualized exercise intervention presented higher prevalence of Rs and a lower prevalence of NRs and ARs for functional capacity, muscle strength, and cognitive function than those who were treated with usual care during acute hospitalization. An adverse response on functional capacity in older patients to physical exercise or usual care during hospitalization was associated with mortality at 1 year post-discharge.
Open Access
Effects of Vivifrail multicomponent intervention on functional capacity: a multicentre, randomized controlled trial
(Wiley Open Access, 2022) Casas Herrero, Álvaro; López Sáez de Asteasu, Mikel; Antón Rodrigo, Iván; Sánchez Sánchez, Juan Luis; Montero Odasso, Manuel; Marín Epelde, Itxaso; Ramón Espinoza, Fernanda; Zambom Ferraresi, Fabrício; Petidier Torregrosa, Roberto; Elexpuru Estomba, Jaione; Álvarez Bustos, Alejandro; Galbete Jiménez, Arkaitz; Martínez Velilla, Nicolás; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: physical exercise is an effective strategy for preserving functional capacity and improving the symptoms of frailty in older adults. In addition to functional gains, exercise is considered to be a cornerstone for enhancing cognitive function in frail older adults with cognitive impairment and dementia. We assessed the effects of the Vivifrail exercise intervention for functional capacity, cognition, and well-being status in community-dwelling older adults. Methods: in a multicentre randomized controlled trial conducted in three tertiary hospitals in Spain, a total of 188 older patients with mild cognitive impairment or mild dementia (aged >75 years) were randomly assigned to an exercise intervention (n = 88) or a usual-care, control (n = 100) group. The intervention was based on the Vivifrail tailored multicomponent exercise programme, which included resistance, balance, flexibility (3 days/week), and gait-retraining exercises (5 days/week) and was performed for three consecutive months (http://vivifrail.com). The usual-care group received habitual outpatient care. The main endpoint was change in functional capacity from baseline to 1 and 3 months, assessed with the Short Physical Performance Battery (SPPB). Secondary endpoints were changes in cognitive function and handgrip strength after 1 and 3 months, and well-being status, falls, hospital admission rate, visits to the emergency department, and mortality after 3 months. Results: the Vivifrail exercise programme provided significant benefits in functional capacity over usual-care. The mean adherence to the exercise sessions was 79% in the first month and 68% in the following 2 months. The intervention group showed a mean increase (over the control group) of 0.86 points on the SPPB scale (95% confidence interval [CI] 0.32, 1.41 points; P < 0.01) after 1 month of intervention and 1.40 points (95% CI 0.82, 1.98 points; P < 0.001) after 3 months. Participants in the usual-care group showed no significant benefit in functional capacity (mean change of −0.17 points [95% CI −0.54, 0.19 points] after 1 month and −0.33 points [95% CI −0.70, 0.04 points] after 3 months), whereas the exercise intervention reversed this trend (0.69 points [95% CI 0.29, 1.09 points] after 1 month and 1.07 points [95% CI 0.63, 1.51 points] after 3 months). Exercise group also obtained significant benefits in cognitive function, muscle function, and depression after 3 months over control group (P < 0.05). No between-group differences were obtained in other secondary endpoints (P > 0.05). Conclusions: the Vivifrail exercise training programme is an effective and safe therapy for improving functional capacity in community-dwelling frail/prefrail older patients with mild cognitive impairment or mild dementia and also seems to have beneficial effect on cognition, muscle function, and mood status.