Open Access
Specific multimorbidity patterns modify the impact of an exercise intervention in older hospitalized adults
(SAGE, 2022) Martínez Velilla, Nicolás; Galbete Jiménez, Arkaitz; Roso Llorach, Albert; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Izquierdo Redín, Mikel; Vetrano, Davide L.; Calderón Larrañaga, Amaia; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: Different multimorbidity patterns present with different prognoses, but it is unknown to what extent they may influence the effectiveness of an individualized multicomponent exercise program offered to hospitalized older adults. Methods: This study is a secondary analysis of a randomized controlled trial conducted in the Department of Geriatric Medicine of a tertiary hospital. In addition to the standard care, an exercise-training multicomponent program was delivered to the intervention group during the acute hospitalization period. Multimorbidity patterns were determined through fuzzy c-means cluster analysis, over 38 chronic diseases. Functional, cognitive and affective outcomes were considered. Results: Three hundred and six patients were included in the analyses (154 control; 152 intervention), with a mean age of 87.2 years, and 58.5% being female. Four patterns of multimorbidity were identified: heart valves and prostate diseases (26.8%); metabolic diseases and colitis (20.6%); psychiatric, cardiovascular and autoimmune diseases (16%); and an unspecific pattern (36.6%). The Short Physical Performance Battery (SPPB) test improved across all patterns, but the intervention was most effective for patients in the metabolic/colitis pattern (2.48-point difference between intervention/control groups, 95% CI 1.60-3.35). Regarding the Barthel Index and the Mini Mental State Examination (MMSE), the differences were significant for all multimorbidity patterns, except for the psychiatric/cardio/autoimmune pattern. Differences concerning quality of life were especially high for the psychiatric/cardio/autoimmune pattern (16.9-point difference between intervention/control groups, 95% CI 4.04, 29.7). Conclusions: Patients in all the analyzed multimorbidity patterns improved with this tailored program, but the improvement was highest for those in the metabolic pattern. Understanding how different chronic disease combinations are associated with specific functional and cognitive responses to a multicomponent exercise intervention may allow further tailoring such interventions to older patients’ clinical profile.
Open Access
Tailored prevention of functional decline through a multicomponent exercise program in hospitalized oncogeriatric patients: study protocol for a randomized clinical trial
(Elsevier, 2023) Martínez Velilla, Nicolás; Arrazubi, Virginia; Zambom Ferraresi, Fabíola; Morilla Ruiz, Idoia; López Sáez de Asteasu, Mikel; Ramírez Vélez, Robinson; Zambom Ferraresi, Fabrício; Casa Marín, Antón de la; Ollo Martínez, Iranzu; Gorospe-García, Itziar; Gurruchaga Sotés, Ibon; Galbete Jiménez, Arkaitz; Cedeño Veloz, Bernardo Abel; Martín-Nevado, L.; Izquierdo Redín, Mikel; Vera García, Ruth; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika
BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.
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
Effect of long-term physical exercise and multidomain interventions on cognitive function and the risk of mild cognitive impairment and dementia in older adults: a systematic review with meta-analysis
(Elsevier, 2024-09-01) Reparaz Escudero, Imanol; Izquierdo Redín, Mikel; Bischoff-Ferrari, Heike A.; Martínez-Lage, Pablo; López Sáez de Asteasu, Mikel; Ciencias de la Salud; Osasun Zientziak
Introduction: Recent studies have suggested that sustained multidomain interventions, including physical exercise, may be beneficial in preventing cognitive decline. This review aims to assess the impact of prolonged physical exercise and multidomain strategies on overall cognitive faculties and dementia risk among community-dwelling older adults without dementia. Methods: We systematically searched PubMed, Web of Science, PsychInfo, and CINHAL databases from inception until April 1, 2024, for randomized controlled trials that investigated the effects of long-term (≥ 12 months) physical exercise or multidomain interventions on non-demented, community-dwelling older adults. The primary outcomes assessed were changes in global cognition and the risk of mild cognitive impairment (MCI) or dementia. Standardized mean differences (SMD) and risk ratios (RR) with 95 % confidence intervals were computed using a random-effects inverse-variance method with the Hartung-Knapp-Sidik-Jonkman adjustment for effect size calculation. The Cochrane Risk-of-Bias-2 tool (RoB-2) was used for bias assessment, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was applied to evaluate the certainty of evidence. Results: Sixteen trials, including 11,402 participants (mean age 73.2 [±5.5] years; 62.3 % female) were examined. The risk of bias was low. Moderate-certainty evidence indicated that physical exercise interventions had modest to no effect on cognitive function (k= 9, SMD: 0.05; 95 % CI: −0.04–0.13; p = 0.25), whereas multidomain interventions were significantly impactful (k=7, SMD: 0.09; 95 % CI: 0.04–0.15; p < 0.01). Physical exercise interventions did not alter MCI risk (k= 4, RR: 0.98; 95 % CI: 0.73–1.31; p = 0.79) or dementia onset (k= 4, RR: 0.61; 95 % CI: 0.25–1.52; p = 0.19), with very low-to low-certainty evidence, respectively. Conclusions: Integrative multidomain strategies incorporating physical exercise may benefit the global cognitive function of older adults. However, long-term physical exercise alone did not yield any cognitive gains. The effectiveness of such exercise interventions to mitigate the overall risk of incident MCI and dementia warrants further research.
Open Access
Functional and cognitive impairment prevention through early physical activity for geriatric hospitalized patients: study protocol for a randomized controlled trial
(BioMed Central, 2015) Martínez Velilla, Nicolás; Casas Herrero, Álvaro; Zambom Ferraresi, Fabrício; Suárez, Nacho; Alonso Renedo, Javier; Cambra Contin, Koldo; López Sáez de Asteasu, Mikel; Fernández Echeverría, Nuria; Gonzalo Lázaro, María; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 2186/2014
Background: Frail older adults have reduced functional and physiological reserves, rendering them more vulnerable to the effects of hospitalization, which frequently results in failure to recover from the pre-hospitalization functional loss, new disability or even continued functional decline. Alternative care models with an emphasis on multidisciplinary and continuing care units are currently being developed. Their main objective, other than the recovery of the condition that caused admission, is the prevention of functional decline. Many studies on functional decline have discussed the available evidence regarding the effectiveness of acute geriatric units. Despite the theoretical support for the idea that mobility improvement in the hospitalized patient carries multiple benefits, this idea has not been fully translated into clinical practice. Methods/design: This study is a randomized clinical trial conducted in the Department of Geriatrics of a tertiary public hospital with 35 beds allocated. Hospitalized patients who meet the inclusion criteria will be randomly assigned to the intervention or control group. The intervention will consist of a multicomponent exercise training programme, which will be composed of supervised progressive resistance exercise training, balance-training, and walking for 5–7 consecutive days. During the training period, patients will be trained in 20 min sessions twice a day (morning and evening). Discussion: Functional and cognitive impairment after and during acute hospitalization in older adults is a major determinant of the later need for health resources. If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise programme provides effective therapy for improving the functional capacity of acute elderly patients hospitalized for medical pathology versus conventional care, a change of the current system of hospitalization of elderly patients with medical conditions may be justified.
Open Access
Effect of exercise intervention on functional decline in very elderly patients during acute hospitalization: a randomized clinical trial
(American Medical Association, 2018) Martínez Velilla, Nicolás; Casas Herrero, Álvaro; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Lucía, Alejandro; Galbete Jiménez, Arkaitz; García Baztán, Agurne; Alonso Renedo, Javier; González Glaría, Belén; Gonzalo Lázaro, María; Apezteguía Iráizoz, Itziar; Gutiérrez Valencia, Marta; Rodríguez Mañas, Leocadio; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Importance: Functional decline is prevalent among acutely hospitalized older patients. Exercise and early rehabilitation protocols applied during acute hospitalization can prevent functional and cognitive decline in older patients. Objective: To assess the effects of an innovative multicomponent exercise intervention on the functional status of this patient population. Design, Setting, and Participants: A single-center, single-blind randomized clinical trial was conducted from February 1, 2015, to August 30, 2017, in an acute care unit in a tertiary public hospital in Navarra, Spain. A total of 370 very elderly patients undergoing acute-care hospitalization were randomly assigned to an exercise or control (usual-care) intervention. Intention-to-treat analysis was conducted. Interventions: The control group received usual-care hospital care, which included physical rehabilitation when needed. The in-hospital intervention included individualized moderate-intensity resistance, balance, and walking exercises (2 daily sessions). Main Outcomes and Measures: The primary end point was change in functional capacity from baseline to hospital discharge, assessed with the Barthel Index of independence and the Short Physical Performance Battery (SPPB). Secondary end points were changes in cognitive and mood status, quality of life, handgrip strength, incident delirium, length of stay, falls, transfer after discharge, and readmission rate and mortality at 3 months after discharge. Results: Of the 370 patients included in the analyses, 209 were women (56.5%); mean (SD) age was 87.3 (4.9) years. The median length of hospital stay was 8 days in both groups (interquartile range, 4 and 4 days, respectively). Median duration of the intervention was 5 days (interquartile range, 0); there was a mean (SD) of 5 (1) morning and 4 (1) evening sessions per patient. No adverse effects were observed with the intervention. The exercise intervention program provided significant benefits over usual care. At discharge, the exercise group showed a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the SPPB scale and 6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index over the usual-care group. Hospitalization led to an impairment in functional capacity (mean change from baseline to discharge in the Barthel Index of -5.0 points (95% CI, -6.8 to -3.2 points) in the usual-care group, whereas the exercise intervention reversed this trend (1.9 points; 95% CI, 0.2-3.7 points). The intervention also improved the SPPB score (2.4 points; 95% CI, 2.1-2.7 points) vs 0.2 points; 95% CI, -0.1 to 0.5 points in controls). Significant intervention benefits were also found at the cognitive level of 1.8 points (95% CI, 1.3-2.3 points) over the usual-care group. Conclusions and Relevance: The exercise intervention proved to be safe and effective to reverse the functional decline associated with acute hospitalization in very elderly patients. Trial Registration: ClinicalTrials.gov identifier: NCT02300896.
Open Access
Effect of a multicomponent exercise programme (VIVIFRAIL) on functional capacity in frail community elders with cognitive decline: study protocol for a randomized multicentre control trial
(BioMed Central, 2019) Casas Herrero, Álvaro; Antón Rodrigo, Iván; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Martínez Velilla, Nicolás; Elexpuru Estomba, Jaione; Marín Epelde, Itxaso; Ramón Espinoza, Fernanda; Petidier Torregrosa, Roberto; Sánchez Sánchez, Juan Luis; Ibáñez Beroiz, Berta; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: The benefit of physical exercise in ageing and particularly in frailty has been the aim of recent research. Moreover, physical activity in the elderly is associated with a decreased risk of mortality, of common chronic illnesses (i.e. cardiovascular disease or osteoarthritis) and of institutionalization as well as with a delay in functional decline. Additionally, very recent research has shown that, despite its limitations, physical exercise is associated with a reduced risk of dementia, Alzheimer disease or mild cognitive decline. Nevertheless, the effect of physical exercise as a systematic, structured and repetitive type of physical activity, in the reduction of risk of cognitive decline in the elderly, is not very clear. The purpose of this study aims to examine whether an innovative multicomponent exercise programme called VIVIFRAIL has benefits for functional and cognitive status among pre-frail/frail patients with mild cognitive impairment or dementia. Methods/design: This study is a multicentre randomized clinical trial to be conducted in the outpatient geriatrics clinics of three tertiary hospitals in Spain. Altogether, 240 patients aged 75 years or older being capable of and willing to provide informed consent, with a Barthel Index ≥ 60 and mild cognitive impairment or mild dementia, pre-frail or frail and having someone to help to supervise them when conducting the exercises will be randomly assigned to the intervention or control group. Participants randomly assigned to the usual care group will receive normal outpatient care, including physical rehabilitation when needed. The VIVIFRAIL multicomponent exercise intervention programme consists of resistance training, gait re-training and balance training, which appear to be the best strategy for improving gait, balance and strength, as well as reducing the rate of falls in older individuals and consequently maintaining their functional capacity during ageing. The primary endpoint is the change in functional capacity, assessed with the Short Physical Performance Battery (1 point as clinically significant). Secondary endpoints are changes in cognitive and mood status, quality of life (EQ-5D), 6-m gait velocity and changes in gait parameters (i.e. gait velocity and gait variability) while performing a dual-task test (verbal and counting), handgrip, maximal strength and power of the lower limbs as well as Barthel Index of independence (5 points as clinically significant) at baseline and at the 1-month and 3-month follow-up. Discussion: Frailty and cognitive impairment are two very common geriatric syndromes in elderly patients and are frequently related and overlapped. Functional decline and disability are major adverse outcomes of these conditions. Exercise is a potential intervention for both syndromes. If our hypothesis is correct, the relevance of this project is that the results can contribute to understanding that an individualized multicomponent exercise programme (VIVIFRAIL) for frail elderly patients with cognitive impairment is more effective in reducing functional and cognitive impairment than conventional care. Moreover, our study may be able to show that an innovative individualized multicomponent exercise prescription for these high-risk populations is plausible, having at least similar therapeutic effects to other pharmacological and medical prescriptions.
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
Effects of exercise interventions on inflammatory parameters in acutely hospitalized older patients: a systematic review and meta-analysis of randomized controlled trials
(MDPI, 2021) Ramírez Vélez, Robinson; García Hermoso, Antonio; Martínez Velilla, Nicolás; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Recarey Rodríguez, Anel Eduardo; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa; Gobierno de Navarra / Nafarroako Gobernua
The purpose of this systematic review and meta-analysis was to appraise the acute effects of exercise training on inflammatory parameters in hospitalized older adults. We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, Medline and PubMed were searched for studies published until August 2020. The review included all randomized controlled trials (RCTs) that evaluated and compared the effect of exercise versus usual care on inflammatory parameters in acutely hospitalized older adults. Two reviewers independently assessed the studies. The quality of all the included studies was assessed using the DerSimonian–Laird random-effects inverse-variance model. Five studies (275 participants) met the inclusion criteria. The exercise interventions included resistance or multicomponent intervention programs. The results indicate that, compared with usual care, exercise interventions have a positive impact on overall inflammatory parameters, including C-reactive protein (CRP) and insulin-like growth factor-I (IGF-1) (Hedge's g = −0.19, 95% confidence interval [CI] −0.33 to −0.04, p = 0.011, I2 = 0%). However, analyses of individual inflammatory parameters revealed a non-significant trend for reductions in CRP (Hedge's g = −0.20, 95% CI −0.47 to 0.07, p = 0.151, I2 = 31.2%) and IGF-I (Hedge's g = −0.34, 95% CI −0.79 to 0.11, p = 0.138, I2 = 0%). On the basis of this review, we conclude that exercise during acute hospitalization offers a mild improvement in the inflammatory profile over usual care in older patients. Nevertheless, due to limited number of RCTs, our findings must be interpreted with caution and confirmed in future studies.
Open Access
Effects of physical exercise intervention on functional and cognitive decline in geriatric hospitalized patients
(2019) López Sáez de Asteasu, Mikel; Izquierdo Redín, Mikel; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 2186/2014
La actual disertación doctoral gira en torno a los efectos de una intervención de ejercicio físico en la capacidad funcional y función cognitiva en ancianos hospitalizados. Se ha sugerido que las enfermedades médicas agudas y su posterior hospitalización son eventos importantes en el desarrollo de discapacidad en las personas mayores. Una intervención de ejercicio físico puede ser una terapia efectiva para revertir el deterioro funcional y cognitivo asociado a la hospitalización en los pacientes muy mayores. Esta tesis doctoral se basa en seis estudios científicos que han sido publicados o enviados para su publicación en revistas científicas internacionales. En el primer estudio (Capítulo 1) nuestro objetivo fue examinar el papel de diferentes programas de ejercicio físico (aeróbico, fuerza y multicomponente) sobre la función cognitiva en personas mayores sanas. Los datos presentados en los siguientes estudios fueron recogidos en el mismo proyecto de investigación (ClinicalTrials.gov NCT02300896 registrado el 19 de noviembre de 2014). En el segundo estudio (Capítulo 2), el objetivo principal fue evaluar los efectos de una intervención de ejercicio físico multicomponente en la capacidad funcional, función cognitiva y estado de bienestar en pacientes muy mayores admitidos en la Unidad Geriátrica de Agudos. El tercer estudio (Capítulo 3) analiza los efectos del ejercicio físico en la capacidad funcional, fuerza muscular máxima y potencia muscular durante la estancia hospitalaria en las personas mayores. En el cuarto estudio (Capítulo 4) nuestro objetivo fue comparar diferencias en las características de la marcha y variables de rendimiento muscular (es decir, fuerza muscular máxima y potencia muscular) de los pacientes ancianos admitidos en la Unidad Geriátrica de Agudos en base al estado funcional presentado al ingreso, y determinar los mecanismos subyacentes al deterioro de la marcha. En el quinto estudio (Capítulo 5) investigamos la variabilidad inter-individual en la respuesta al ejercicio físico y a la atención habitual (indicado por variables funcionales, fuerza muscular y cognitivas) de las personas mayores, y la relación entre la respuesta a la intervención con la mortalidad al año posterior al alta hospitalaria. En el último estudio (Capítulo 6) el objetivo principal fue evaluar los efectos del programa de ejercicio físico multicomponente en dominios cognitivos específicos como la función ejecutiva y la fluencia verbal en pacientes ancianos hospitalizados.