Open Access
Effect of an exercise intervention on functional decline in very old patients during acute hospitalizations: results of a multicenter, randomized clinical trial
(American Medical Association, 2022) Martínez Velilla, Nicolás; Abizanda, Pedro; Gómez-Pavón, Javier; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Fiatarone Singh, Maria; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
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
Relative handgrip strength diminishes the negative effects of excess adiposity on dependence in older adults: a moderation analysis
(MDPI, 2020) Ramírez Vélez, Robinson; Pérez Sousa, Miguel A.; García Hermoso, Antonio; Zambom Ferraresi, Fabrício; Martínez Velilla, Nicolás; López Sáez de Asteasu, Mikel; Cano Gutiérrez, Carlos Alberto; Rincón Pabón, David; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
The adverse effects of fat mass on functional dependence might be attenuated or worsened, depending on the level of muscular strength. The aim of this study was to determine (i) the detrimental effect of excess adiposity on dependence in activities of daily living (ADL), and (ii) whether relative handgrip strength (HGS) moderates the adverse effect of excess adiposity on dependence, and to provide the threshold of relative HGS from which the adverse effect could be improved or worsened. A total of 4169 participants (69.3 +/- 7.0 years old) from 244 municipalities were selected following a multistage area probability sampling design. Measurements included anthropometric/adiposity markers (weight, height, body mass index, waist circumference, and waist-to-height ratio (WHtR)), HGS, sarcopenia 'proxy' (calf circumference), and ADL (Barthel Index scale). Moderation analyses were performed to identify associations between the independent variable (WHtR) and outcomes (dependence), as well as to determine whether relative HGS moderates the relationship between excess adiposity and dependence. The present study demonstrated that (i) the adverse effect of having a higher WHtR level on dependence in ADL was moderated by relative HGS, and (ii) two moderation thresholds of relative HGS were estimated: 0.35, below which the adverse effect of WHtR levels on dependency is aggravated, and 0.62, above which the adverse effect of fat on dependency could be improved. Because muscular strength represents a critically important and modifiable predictor of ADL, and the increase in adiposity is inherent in aging, our results underscore the importance of an optimal level of relative HGS in the older adult population.
Open Access
Effects of exercise on DNA methylation: a systematic review of randomized controlled trials
(Springer, 2024-06-05) Etayo Urtasun, Paula; López Sáez de Asteasu, Mikel; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Background: regular exercise reduces chronic disease risk and extends a healthy lifespan, but the underlying molecular mechanisms remain unclear. DNA methylation is implicated in this process, potentially altering gene expression without changing DNA sequence. However, previous findings appear partly contradictory. Objective: this review aimed to elucidate exercise effects on DNA methylation patterns. Methods: PubMed, Scopus and Web of Science databases were searched following PRISMA 2020 guidelines. All articles published up to November 2023 were considered for inclusion and assessed for eligibility using the PICOS (Population, Intervention, Comparison, Outcomes and Study) framework. Randomized controlled trials that assessed the impact of exercise interventions on DNA methylation in previously inactive adults were included. We evaluated the methodological quality of trials using the PEDro scale. Results: a total of 852 results were identified, of which 12 articles met the inclusion criteria. A total of 827 subjects were included in the studies. Intervention lengths varied from 6 weeks to 12 months. Most trials indicated that exercise interventions can significantly alter the DNA methylation of specific genes and global DNA methylation patterns. Conclusions: the heterogeneity of results may arise from differences in participant demographics, intervention factors, measurement techniques, and the genomic contexts examined. Future research should analyze the influences of activity type, intensity, and duration, as well as the physical fitness outcomes on DNA methylation. Characterizing such dose¿response relationships and identifying genes responsive to exercise are crucial for understanding the molecular mechanisms of exercise, unlocking its full potential for disease prevention and treatment.
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
Tailored exercise is safe and beneficial for acutely hospitalised older adults with COPD
(European Respiratory Society, 2020) Martínez Velilla, Nicolás; Valenzuela, Pedro L.; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Ramírez Vélez, Robinson; García Hermoso, Antonio; Lucía, Alejandro; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Open Access
Comparison of hospitalisation settings and exercise interventions in acute care: a systematic review and meta-analysis
(Oxford University Press, 2025-02-21) Etayo Urtasun, Paula; López Sáez de Asteasu, Mikel; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Background: Inpatient hospitalisation is associated with adverse outcomes in older adults, including hospital-associated deconditioning. The hospital-at-home (HaH) model may promote physical activity. This systematic review and meta-analysis compares functional outcomes between inpatient and HaH settings and evaluates the efficacy of exercise interventions in both settings. Methods: Systematic searches of PubMed, Scopus, Web of Science and ScienceDirect were conducted on 27 April 2024. T hreedistinct searches were performed: (i) studies comparing HaHandinpatienthospitalisation, (ii) trials evaluating inpatient exercise interventions and (iii) research on HaH exercise interventions. Two reviewers independently selected studies published from 2014 onwards using the PICOS framework and they assessed quality using PEDro scale. A meta-analysis was performed using a random effects model to analyse exercise interventions. This systematic review with meta-analysis was conducted according to PRISMA 2020 guidelines and was registered on PROSPERO (CRD42024598286). Results: Among the 9470 studies identified, nine studies comparing acute-care settings and 21 studies on exercise interventions (one in HaH) were included. Findings suggest that HaH may positively affect functional and cognitive outcomes. Inpatient exercise interventions significantly improved physical performance [standardised mean difference (SMD)=0.42, 95%confidence interval (CI)=0.12–0.72] and functional independence (SMD=0.45, 95% CI=0.14–0.77) at discharge. Conclusion: HaH may contribute to preserving physical and cognitive status. Supervised exercise interventions during inpatient hospitalisation are safe and effective for improving older adults’ functional status, although further research in the HaH model is needed.
Open Access
Chronic effects of different intensities of power training on neuromuscular parameters in older people: a systematic review with meta-analysis
(Springer, 2023) Guimarães, Marcelo Bandeira; Blanco‑Rambo, Eduarda; Vieira, Alexandra Ferreira; López Sáez de Asteasu, Mikel; Pinto, Ronei Silveira; Izquierdo Redín, Mikel; Lusa Cadore, Eduardo; Ciencias de la Salud; Osasun Zientziak
Background Power training (PT) has been shown to be an efective method for improving muscle function, includ‑ ing maximal strength, measured by one-repetition maximum (1RM), and power output in older adults. However, it is not clear how PT intensity, expressed as a percentage of 1RM, afects the magnitude of these changes. The aim of this systematic review (International prospective register of systematic reviews—PROSPERO—registration: CRD42022369874) was to summarize the evidence from randomized clinical trials (RCT) assessing the efects of lowintensity (≤49% of 1RM) and moderate-intensity (50–69% of 1RM) versus high-intensity (≥70% of 1RM) PT on maximal power output and maximal strength in older adults. Methods We included RCTs that examined the efects of diferent intensities of power training on maximum strength and power output in older people. The search was performed using PubMed, LILACS, Embase, and Scopus. Methodological quality was assessed using the preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020 statement checklist), and the quality of evidence was determined using the PEDro scale. Data were analyzed using standardized mean diferences (SMD) with a 95% confdence interval (CI), and random efects models were used for calculations. A signifcance level of p≤0.05 was accepted. Results Three RCTs assessing 179 participants, all of high methodological quality, were included. There were no sig‑ nifcant diferences between diferent PT intensities in terms of power output gains for leg press [SMD=0.130 (95% CI −0.19, 0.45), p=0.425] and knee extension exercises [SMD: 0.016 (95% CI −0.362, 0.395), p=0.932], as well as leg press 1RM increases [SMD: 0.296 (95% CI −0.03, 0.62); p=0.072]. However, high-intensity PT (70–80% of 1RM) was sig‑ nifcantly more efective than low-intensity PT in increasing 1RM for knee extension exercise [SMD: 0.523 (95% CI 0.14, 1.91), p=0.008]. Conclusions PT performed at low-to-moderate intensities induces similar power gains compared to high-inten‑ sity PT (70–80% of 1RM) in older adults. Nonetheless, the infuence of PT intensity on lower-limb strength gains seems to be dependent on the assessed exercise. Cautious interpretation is warranted considering the inclusion of only three studies.
Open Access
Effects of game-based interventions on functional capacity in acutely hospitalised older adults: results of an open-label non-randomised clinical trial
(Oxford University Press, 2022-01-23) Cuevas Lara, César; López Sáez de Asteasu, Mikel; Ramírez Vélez, Robinson; Izquierdo Redín, Mikel; Zambom Ferraresi, Fabíola; Antoñanzas Valencia, Cristina; Galbete Jiménez, Arkaitz; Zambom Ferraresi, Fabrício; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Gobierno de Navarra / Nafarroako Gobernua
Background: Hospitalisation-associated disability due to reduced physical activity levels and prolonged bedrest episodes are highly prevalent in older adults. Objective: To assess the effect of gamified interventions on functional capacity in hospitalised older adults. Methods: A three-armed non-randomised controlled trial with two experimental intervention groups and a control group was conducted in a tertiary public hospital in Navarre, Spain. Participants were allocated to a simple gamification group (SGG) (n = 21), a technology-based gamification group (TGG) (n = 23) or a control group (CG) (n = 26). The end points were changes in functional capacity, muscle strength, cognition, mood status and quality of life. Results: Seventy patients (mean age 86.01 ± 4.27 years old) were included in the study; 29 (41.4%) were women. At discharge, compared to CG, a mean increase of 1.47 points (95%CI, 0.15–2.80 points) and 2.69 points (95%CI, 1.32–4.06 points) was observed (SGG and TGG, respectively) in the SPPB test; as well as an increase of 5.28 points (95%CI, 0.70–9.76 points) in the Barthel Index and 2.03 kg (95%CI, 0.33–3.72 kg) in handgrip strength in the TGG. Regression mediation analyses demonstrated that muscle strength changes (β = 1.30; 95%CI, 0.45–2.14; indirect effect 0.864; 95%CI, 0.09–1.90) significantly mediated the TGG effect on the SPPB score. Conclusions: The TGG intervention programme may provide significant benefits in physical and muscle function over usual care and seems to reverse the functional decline frequently associated with acute hospitalisation in older adults.
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.