Open Access
Biological sex as a tailoring variable for exercise prescription in hospitalized older adults
(Elsevier, 2024-09-27) López Sáez de Asteasu, Mikel; Martínez Velilla, Nicolás; Ramírez Vélez, Robinson; Zambom Ferraresi, Fabrício; Galbete Jiménez, Arkaitz; Lusa Cadore, Eduardo; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Gobierno de Navarra / Nafarroako Gobernua, 2186/2014
Background. Sex-based differences in the clinical presentation and outcomes are well-established in patients hospitalized for geriatric syndromes. We aimed to investigate sex differences in response to in-hospital exercise on function, strength, cognition, and quality of life in acute care admissions. Methods. 570 patients (mean age 87 years, 298 females [52.3%]) admitted to acute care for elderly units were randomized to multicomponent exercise emphasizing progressive resistance training or usual care. Functional assessments included Short Physical Performance Battery (SPPB), grip strength, Mini-Mental State Examination (MMSE), and health-related quality of life (EQ-VAS). Results. Exercising females showed more significant SPPB improvements than males (between-group difference 1.48 points, p = 0.027), exceeding the minimal clinically significant difference. While female participants significantly increased handgrip strength and male patients improved cognition after in-hospital exercise compared to the control group (all p < 0.001), no sex differences occurred. Conclusions. Females demonstrate more excellent physical function improvements compared to male older patients. Findings highlight the importance of tailored exercise incorporating patient factors like biological sex in geriatric medicine. Trial registration. NCT04600453
Open Access
Safety and effectiveness of long-term exercise interventions in older adults: a systematic review and meta-analysis of randomized controlled trials
(Springer, 2020-02-04) García Hermoso, Antonio; Ramírez Vélez, Robinson; López Sáez de Asteasu, Mikel; Martínez Velilla, Nicolás; Zambom Ferraresi, Fabrício; Valenzuela, Pedro L.; Lucía, Alejandro; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Background Physical exercise is benefcial to reduce the risk of several conditions associated with advanced age, but to our knowledge, no previous study has examined the association of long-term exercise interventions (≥1 year) with the occurrence of dropouts due to health issues and mortality, or the efectiveness of physical exercise versus usual primary care interventions on health-related outcomes in older adults (≥ 65 years old). Objective To analyze the safety and efectiveness of long-term exercise interventions in older adults. Methods We conducted a systematic review with meta-analysis examining the association of long-term exercise interventions (≥1 year) with dropouts from the corresponding study due to health issues and mortality (primary endpoint), and the efects of these interventions on health-related outcomes (falls and fall-associated injuries, fractures, physical function, quality of life, and cognition) (secondary endpoints). Results Ninety-three RCTs and six secondary studies met the inclusion criteria and were included in the analyses (n=28,523 participants, mean age 74.2 years). No diferences were found between the exercise and control groups for the risk of dropouts due to health issues (RR=1.05, 95% CI 0.95–1.17) or mortality (RR=0.93, 95% CI 0.83–1.04), although a lower mortality risk was observed in the former group when separately analyzing clinical populations (RR=0.67, 95% CI 0.48–0.95). Exercise signifcantly reduced the number of falls and fall-associated injuries, and improved physical function and cognition. These results seemed independent of participants’ baseline characteristics (age, physical function, and cognitive status) and exercise frequency. Conclusions Long-term exercise training does not overall infuence the risk of dropouts due to health issues or mortality in older adults, and results in a reduced mortality risk in clinical populations. Moreover, exercise reduces the number of falls and fall-associated injuries, and improves physical function and cognition in this population.
Open Access
Dose-response relationship between exercise duration and enhanced function and cognition in acutely hospitalized older adults: a secondary analysis of a randomized clinical Trial
(Oxford University Press, 2024-06-01) López Sáez de Asteasu, Mikel; Martínez Velilla, Nicolás; Zambom Ferraresi, Fabrício; Galbete Jiménez, Arkaitz; Ramírez Vélez, Robinson; Lusa Cadore, Eduardo; Abizanda, Pedro; Gómez-Pavón, Javier; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Institute of Smart Cities - ISC; Gobierno de Navarra / Nafarroako Gobernua
Background and objectives: exercise may reverse functional decline in hospitalized older adults, but the optimal duration is unclear. This study examined the potential relationship between in-hospital multicomponent exercise program duration and changes in physical function, cognition, and muscle function to maximize exercise-related health benefits in acutely hospitalized older patients. Research design and methods: this secondary analysis of a multicenter randomized controlled trial examined the relationship between the duration of an in-hospital multicomponent exercise program and changes in physical function, cognition, and muscle strength in 570 acutely hospitalized older adults. Participants completed 3, 4, or 5-7 consecutive days of exercise based on the progression of their acute medical illness. The acute clinical condition of the older patients was similar across the study groups (i.e., 3/4/5-7 days) at admission. Outcomes included the Short Physical Performance Battery (SPPB) for functional capacity, Gait Velocity Test for gait speed, handgrip for muscle strength, and cognitive tests. Results: of the 570 patients included in the analysis, 298 were women (52.3%), and the mean (SD) age was 87.3 (4.8) years. Exercise groups increased SPPB scores compared with controls, with gains of 1.09 points after three days, 1.97 points after four days, and 2.02 points after 5-7 days (p < .001). The 4-day program showed the most significant benefit for functional capacity. Gait velocity increased by 0.11 m/s after 4 and 5-7 days (p = .032). Similar dose-response relationships were seen for handgrip strength and cognition, with 5-7 days showing more significant gains than three days (p < .05). Discussion and implications: multicomponent exercise programs enhance physical and cognitive function in hospitalized older adults, regardless of exercise dosage. A 4-day program significantly boosts functional capacity, although 5-7 days improves handgrip strength and cognition, highlighting the importance of exercise dosage in countering functional decline. Implementing evidence-based inpatient exercise prescriptions can help reverse muscle weakness and improve cognitive and physical function.
Open Access
Effects of short-term multicomponent exercise intervention on muscle power in hospitalized older patients: a secondary analysis of a randomized clinical trial
(Wiley, 2023) Lusa Cadore, Eduardo; Izquierdo Redín, Mikel; Teodoro, Juliana Lopes; Martínez Velilla, Nicolás; Zambom Ferraresi, Fabrício; Moriguchi, Emilio Hideyuki; López Sáez de Asteasu, Mikel; Ciencias de la Salud; Osasun Zientziak
Background: bed rest during hospitalization can negatively impact functional independence and clinical status of older individuals. Strategies focused on maintaining and improving muscle function may help reverse these losses. This study investigated the effects of a short-term multicomponent exercise intervention on maximal strength and muscle power in hospitalized older patients. Methods: this secondary analysis of a randomized clinical trial was conducted in an acute care unit in a tertiary public hospital. Ninety (39 women) older patients (mean age 87.7 ± 4.8 years) undergoing acute-care hospitalization [median (IQR) duration 8 (1.75) and 8 (3) days for intervention and control groups, respectively]) were randomly assigned to an exercise intervention group (n = 44) or a control group (n = 46). The control group received standard care hospital including physical rehabilitation as needed. The multicomponent exercise intervention was performed for 3 consecutive days during the hospitalization, consisting of individualized power training, balance, and walking exercises. Outcomes assessed at baseline and discharge were maximal strength through 1 repetition maximum test (1RM) in the leg press and bench press exercises, and muscle power output at different loads (≤ 30% of 1RM and between 45% and 55% of 1RM) in the leg press exercise. Mean peak power during 10 repetitions was assessed at loads between 45% and 55% of 1RM. Results: at discharge, intervention group increased 19.2 kg (Mean ∆% = 40.4%) in leg press 1RM [95% confidence interval (CI): 12.1, 26.2 kg; P < 0.001] and 2.9 kg (Mean ∆% = 19.7%) in bench press 1RM (95% CI: 0.6, 5.2 kg; P < 0.001). The intervention group also increased peak power by 18.8 W (Mean ∆% = 69.2%) (95% CI: 8.4, 29.1 W; P < 0.001) and mean propulsive power by 9.3 (Mean ∆% = 26.8%) W (95% CI: 2.5, 16.1 W; P = 0.002) at loads ≤30% of 1RM. The intervention group also increased peak power by 39.1 W (Mean ∆% = 60.0%) (95% CI: 19.2, 59.0 W; P < 0.001) and mean propulsive power by 22.9 W (Mean ∆% = 64.1%) (95% CI: 11.7, 34.1 W; P < 0.001) at loads between 45% and 55% of 1RM. Mean peak power during the 10 repetitions improved by 20.8 W (Mean ∆% = 36.4%) (95% CI: 3.0, 38.6 W; P = 0.011). No significant changes were observed in the control group for any endpoint. Conclusions An individualized multicomponent exercise program including progressive power training performed over 3 days markedly improved muscle strength and power in acutely hospitalized older patients.
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 Vivifrail multicomponent intervention on functional capacity: a multicentre, randomized controlled trial
(Wiley Open Access, 2022) Casas Herrero, Álvaro; Sáez de Asteasu, Mikel L.; 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.
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
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
Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults
(BMC, 2023) Cedeño Veloz, Bernardo Abel; Lozano Vicario, Lucía; Zambom Ferraresi, Fabrício; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Rodríguez-García, Alba; Romero Ortuno, Román; Mondragón Rubio, Jaime; Ruiz-Ruiz, Javier; Ramírez Vélez, Robinson; Izquierdo Redín, Mikel; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Osteoporosis is a skeletal disease that can increase the risk of fractures, leading to adverse health and socioeconomic consequences. However, current clinical methods have limitations in accurately estimating fracture risk, particularly in older adults. Thus, new technologies are necessary to improve the accuracy of fracture risk estimation. In this observational study, we aimed to explore the association between serum cytokines and hip fracture status in older adults, and their associations with fracture risk using the FRAX reference tool. We investigated the use of a proximity extension assay (PEA) with Olink. We compared the characteristics of the population, functional status and detailed body composition (determined using densitometry) between groups. We enrolled 40 participants, including 20 with hip fracture and 20 without fracture, and studied 46 cytokines in their serum. After conducting a score plot and two unpaired t-tests using the Benjamini-Hochberg method, we found that Interleukin 6 (IL-6), Lymphotoxin-alpha (LT-α), Fms-related tyrosine kinase 3 ligand (FLT3LG), Colony stimulating factor 1 (CSF1), and Chemokine (C-C motif) ligand 7 (CCL7) were significantly different between fracture and non-fracture patients (p < 0.05). IL-6 had a moderate correlation with FRAX (R2 = 0.409, p < 0.001), while CSF1 and CCL7 had weak correlations with FRAX. LT-α and FLT3LG exhibited a negative correlation with the risk of fracture. Our results suggest that targeted proteomic tools have the capability to identify differentially regulated proteins and may serve as potential markers for estimating fracture risk. However, longitudinal studies will be necessary to validate these results and determine the temporal patterns of changes in cytokine profiles.
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.