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
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
The impact of loneliness and social isolation on the benefits of an exercise program with hospitalised older adults
(Elsevier, 2024-06-03) Martínez Velilla, Nicolás; López Sáez de Asteasu, Mikel; Zambom Ferraresi, Fabrício; Galbete Jiménez, Arkaitz; Marín Epelde, Itxaso; Ferrara, Maria Cristina; Yanguas-Lezáun, José Javier; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika
Objectives: this study aimed to assess the prevalence and impact of loneliness (De Jong Gierveld scale) and isolation (Lubben scale) on the effects of a hospital-based exercise programme. Design: secondary analysis of a randomised clinical trial. Setting: Acute Geriatric Unit of a tertiary hospital in Spain. Participants: 103 hospitalised older adults. Intervention: individualised multicomponent exercise program (20-minute sessions twice a day for 3 consecutive days). Results: among the 103 randomised patients included in the analysis (both arms included), 58.3% were male, and their mean age was 87.3 (4.5) years. According to the Lubben scale, 15.8% of patients were at risk of isolation, while 62.7% were in a situation of severe or moderate loneliness according to the De Jong Gierveld scale. In the non-isolated group, training showed a substantial positive impact on Geriatric Depression Scale (B = -1.25, 95% CI = -0.24 to -0.27). In the isolated group, all outcomes improved, but only the Quality of Life showed significant changes (B = 35, 95% CI = 4.96-35.8). The SPPB test (B = 1.62, 95% CI = 0.19-3.04) and Quality of Life, (B = 17.1, 95% CI = 1.84-32.3) showed a significant improvement in the non-loneliness exercise group while no differences were found in the loneliness group. Conclusion: despite the high prevalence of loneliness and social isolation, individualised exercise programs provide significant benefits to hospitalised patients, especially in quality of life.
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
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 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
Effectiveness of a multicomponent exercise training program for the management of delirium in hospitalized older adults using near-infrared spectroscopy as a biomarker of brain perfusion: study protocol for a randomized controlled trial
(Frontiers Media, 2022) Lozano Vicario, Lucía; Zambom Ferraresi, Fabíola; Zambom Ferraresi, Fabrício; Casa Marín, Antón de la; Ollo Martínez, Iranzu; López Sáez de Asteasu, Mikel; Cedeño Veloz, Bernardo Abel; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Romero Ortuno, Román; Izquierdo Redín, Mikel; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak
Delirium is an important cause of morbidity and mortality in older adults admitted to hospital. Multicomponent interventions targeting delirium risk factors, including physical exercise and mobilization, have been shown to reduce delirium incidence by 30–40% in acute care settings. However, little is known about its role in the evolution of delirium, once established. This study is a randomized clinical trial conducted in the Acute Geriatric Unit of Hospital Universitario de Navarra (Pamplona, Spain). Hospitalized patients with delirium who meet the inclusion criteria will be randomly assigned to the intervention or the control group. The intervention will consist of a multicomponent exercise training program, which will be composed of supervised progressive resistance and strength exercise over 3 consecutive days. Functional Near-Infrared Spectroscopy (NIRS) will be used for assessing cerebral and muscle tissue blood flow. The objective is to assess the effectiveness of this intervention in modifying the following primary outcomes: duration and severity of delirium and functional status. This study will contribute to determine the effectiveness of physical exercise in the management of delirium. It will be the first study to evaluate the impact of a multicomponent intervention based on physical exercise in the evolution of delirium.
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.