The effect of a multicomponent exercise protocol (VIVIFRAIL©) on inflammatory profile and physical performance of older adults with different frailty status: study protocol for a randomized controlled trial.

BACKGROUND: To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status. METHODS/DESIGN: This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change in physical performance using the Short Physical Performance Battery, handgrip strength, fatigue, gait speed, dual-task gait speed, depressive symptoms, FRAIL-BR and SARC-F scores, and quality of life at the 12-week period of intervention and after 3 months of follow-up. DISCUSSION: We expect a reduction in inflammatory interleukins or an increase in anti-inflammatory mediators in those who performed the VIVIFRAIL© protocol. The results of the study will imply in a better knowledge about the effect of a low-cost intervention that could be easily replicated in outpatient care for the prevention and treatment of frailty, especially regarding the inflammatory and anti-inflammatory pathways involved in its pathophysiology. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (RBR-9n5jbw; 01/24/2020). Registred January 2020. http://www.ensaiosclinicos.gov.br/rg/RBR-9n5jbw/ .

Design and protocol of the multimorbidity and mental health cohort study in frailty and aging (MiMiCS-FRAIL): unraveling the clinical and molecular associations between frailty, somatic disease burden and late life depression.

BACKGROUND: To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression and their interconnectedness. METHODS: MiMiCS-FRAIL is an ongoing observational cohort study of geriatric outpatients in Brazil, with an extensive baseline assessment and yearly follow-up assessments. Each assessment includes a comprehensive geriatric assessment to identify multimorbidity and geriatric syndromes, a structured psychiatric diagnostic interview and administration of the PHQ-9 to measure depression, and several frailty measures (FRAIL, Physical Phenotype criteria, 36-item Frailty Index). Fasten blood samples are collected at baseline to assess circulating inflammatory and anti-inflammatory cytokines, leukocytes' subpopulations, and to perform immune-metabolic-paired miRome analyses. The primary outcome is death and secondary outcomes are the number of falls, hospital admissions, functional ability, well-being, and dementia. Assuming a 5-year mortality rate between 25 and 40% and a hazard rate varying between 1.6 and 2.3 for the primary determinants require a sample size between 136 and 711 patients to detect a statistically significant effect with a power of 80% (beta = 0.2), an alpha of 5% (0.05), and an R2 between the predictor (death) and all covariates of 0.20. Local ethical board approved this study. DISCUSSION: Frailty might be hypothesized as a final common pathway by which many clinical conditions like depression and chronic diseases (multimorbidity) culminate in many adverse effects. The MiMiCS-FRAIL cohort will help us to understand the interrelationship between these variables, from a clinical perspective as well as their underlying molecular signature.

The association between cardiovascular risk factors and major cardiovascular diseases decreases with increasing frailty levels in geriatric outpatients.

BACKGROUND: Frailty marks a process of increasing dysregulation of physiological systems which increases the risk of adverse health outcomes. This study examines the hypothesis that the association between multiple cardiovascular risk factors (CVRF) and cardiovascular diseases (CVD) becomes stronger with increasing frailty severity. METHODS: Cross-sectional analysis of 339 older adults (55.2% women; aged 75.2 ±â€¯9.1 years) from an outpatient geriatric clinic from a middle-income country. The frailty index (FI) was calculated as the proportion of 30 possible health deficits. We assessed hypertension, diabetes, obesity, dyslipidemia, sedentarism and smoking as CVRF (determinants) and myocardial infarction, stroke, heart failure as CVD. Poisson regression models adjusted for age, sex, and education was applied to estimate the association between frailty as well as CVRF (independent variables) with CVD (dependent variable). RESULTS: Of the 339 patients, 18,3% were frail (FI ≥ 0.25) and 32.7% had at least one CVD. Both frailty and CVRF were significantly associated with CVD (PR = 1.03, 95% CI 1.01 to 1.05; p = 0.001, and PR = 1.46, 95% 1.24 to 1.71; p < 0.001, respectively) adjusted for covariates. The strength of the association between CVRF and CVD decreased with increasing frailty levels, as indicated by a significant interaction term of frailty and CVRF (p < 0.001). CONCLUSION: Frailty and CVRF are both associated with CVD, but the impact of CVRF decreases in the presence of frailty. When confirmed in longitudinal studies, randomized controlled trials or causal inference methods like Mendelian randomization should be applied to assess whether a shift from traditional CVRF to frailty would improve cardiovascular outcome in the oldest old.