Genistein effect on cognition in prodromal Alzheimer's disease patients. The GENIAL clinical trial

Background: Delaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet efective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defned polyphenol that acts by multimodal specifc mechanisms. Our group previously showed that genistein supplementation is efective to treat the double transgenic (APP/PS1) AD animal model. Methods: In this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the efect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer’s disease patients. The amyloidbeta deposition was analyzed using 18F-futemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test. Results: We report that genistein treatment results in a signifcant improvement in two of the tests used (dichotomized direct TAVEC, p=0.031; dichotomized delayed Centil REY copy p=0.002 and a tendency to improve in all the rest of them. The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p=0.878), while placebo-treated did increase it (p=0.036). We did not observe signifcant changes in other brain areas studied. Conclusions: This study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer’s dementia in patients with prodromal Alzheimer’s disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.This work was supported by the following grants: CB16/10/00435 (CIBERFES) from Instituto de Salud Carlos III, (PID2019-110906RB-I00/ AEI/10.13039/501100011033) and RED2018-102576-T from the Spanish Ministry of Innovation and Science, PROMETEO/2019/097 from “Consellería de Innovación, Universidades, Ciencia y Sociedad Digital de la Generalitat Valen ciana” and EU Funded H2020- DIABFRAIL-LATAM (Ref: 825546), European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) and of the ERA-NET Cofund ERA-HDHL (GA N° 696295 of the EU Horizon 2020 Research and Innovation Programme) and Fundación Ramón Areces y Fundación Soria Melguizo. to J.V. and Grant PID2020-113839RB-I00 funded by MCIN/ AEI/10.13039/501100011033, PCIN-2017-117 of the Ministry of Economy and Competitiveness, and the EU Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI HDHL INTIMIC-085) to CB. We also acknowledge funding from the Spanish Ministry of Science, Innovation, and Universities (RTI2018099200-B-I00), the Generalitat of Catalonia, Agency for management of University and Research Grants (2017SGR696) and the Department of Health (SLT002/16/00250) to RP. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-fnanced with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020). M.J. is a “Serra Hunter” Fellow

Real-Life Outcomes of a Multicomponent Exercise Intervention in Community-Dwelling Frail Older Adults and Its Association with Nutritional-Related Factors

Most of the studies on physical exercise in older adults have been conducted through randomized clinical trials performed under tight experimental conditions. Data regarding Real-Life physical exercise intervention programs in older adults with different conditions and in different settings, are lacking. This is an interventional, prospective and pragmatic Real-Life study in which fifty sedentary and frail individuals were enrolled. We aimed at determining if a Real-Life exercise intervention outweighs previously reported improvements in a Clinical Trial (NCT02331459). We found higher improvements in the Real-Life exercise intervention vs. the Clinical Trial in functional parameters, such as Fried’s frailty criteria, Tinetti, Barthel and Lawton & Brody scales. Similar results were found in the dietary habits, emotional and social networking outcomes determined through the Short-MNA, Yesavage, EuroQol and Duke scales. The Real-Life intervention led to a significant reduction in the number of falls, visits to the primary care centers and emergency visits when compared to the results of our previously published Clinical Trial. The implementation of a Real-Life exercise intervention is feasible and should be a major priority to improve health-span in the older population

Estimate of the Costs Caused by Adverse Effects in Hospitalised Patients Due to Hip Fracture: Design of the Study and Preliminary Results

Introduction: Hip fracture is a health problem that presents high morbidity and mortality, negatively influencing the patient’s quality of life and generating high costs. Structured analysis of quality indicators can facilitate decision-making, cost minimization, and improvement of the quality of care. Methods: We studied 1571 patients aged 70 years and over with the diagnosis of hip fracture at Hospital Universitario de la Ribera in the period between 1 January 2012 and 31 December 2016. Demographic, clinical, functional, and quality indicator variables were studied. An indirect analysis of the costs associated with adverse events arising during hospital admission was made. A tool based on the “Minimum Basic Data Set (CMBD)” was designed to monitor the influence of patient risk factors on the incidence of adverse effects (AE) and their associated costs. Results: The average age of the patients analysed was 84.15 years (SD 6.28), with a length of stay of 8.01 days (SD 3.32), a mean preoperative stay of 43.04 h (SD 30.81), and a mortality rate of 4.2%. Likewise, the percentage of patients with AE was 41.44%, and 11.01% of patients changed their cost as a consequence of these AEs suffered during hospital admission. The average cost of patients was €8752 (SD: 1,864) and the average cost increase in patients with adverse events was €2321 (SD: 3,164). Conclusions: Through the analysis of the main clinical characteristics and the indirect estimation of the complexity of the patients, a simple calculation of the average cost of the attention and its adverse events can be designed in patients who are admitted due to hip fracture. Additionally, this tool can fit the welfare quality indicators by severity and cost

Respiratory Complications Are the Main Predictors of 1-Year Mortality in Patients with Hip Fractures: The Results from the Alzira Retrospective Cohort Study

Resumen: Introducción: Las fracturas de cadera representan un desafío importante para las personas mayores dada su Alta incidencia y tasa de mortalidad a un año. El objetivo de este estudio fue identificar las principales predictores de mortalidad a un año en adultos mayores hospitalizados por fracturas de cadera. Métodos: Realizamos un estudio de cohorte retrospectivo en el que participaron adultos de 70 años o más que ingresaron en el hospital para fracturas de cadera por fragilidad entre el 1 de enero de 2014 y el 31 de diciembre de 2021. Un total de 3229 pacientes fueron reclutados, y 846 (26,2%) experimentaron mortalidad al año. Resultados: complicaciones respiratorias (HR 2,42, IC 95% 1,42–4,14; p = 0,001) fueron los predictores más significativos de mortalidad a un año, seguido del reingreso hospitalario (HR 1,96, IC 95% 1,66-2,32; p < 0,001), el sexo masculino (HR 1,88, IC 95% 1,46–2,32; p < 0,001), complicaciones cardíacas (HR 1,88, IC 95% 1,46-2,32; p < 0,001) y un diagnóstico de demencia al ingreso (HR 1,37, IC95% 1,13-1,66; p = 0,001). El índice Charlson y el índice americano El sistema de clasificación del estado físico de la Sociedad de Anestesiólogos también aumentó significativamente el riesgo de mortalidad. Por el contrario, niveles más altos de hemoglobina al ingreso y albúmina elevada al alta. redujo significativamente el riesgo de mortalidad. Conclusiones: La tasa de mortalidad a un año es sustancial. en adultos mayores con fracturas de cadera que ingresan en una unidad de ortogeriatría. La Apropiada Manejo de la anemia, los trastornos nutricionales y la comorbilidad al ingreso y durante el seguimiento. podría potencialmente mitigar la mortalidad a largo plazo después de fracturas de cadera. Palabras clave: fractura de cadera; adultos mayores; Mortalidad a 1 año; factores de riesgo; atención ortogeriátrica; fragilidad fracturasQ2Q2Abstract: Introduction: Hip fractures pose a significant challenge for older individuals given their high incidence and one-year mortality rate. The objective of this study was to identify the primary predictors of one-year mortality in older adults hospitalized for hip fractures. Methods: We conducted a retrospective cohort study involving adults aged 70 years or older who were admitted to the hospital for fragility hip fractures between 1 January 2014 and 31 December 2021. A total of 3229 patients were recruited, with 846 (26.2%) experiencing one-year mortality. Results: Respiratory complications (HR 2.42, 95%CI 1.42–4.14; p = 0.001) were the most significant predictors of one-year mortality, followed by hospital readmission (HR 1.96, 95%CI 1.66–2.32; p < 0.001), the male sex (HR 1.88, 95%CI 1.46–2.32; p < 0.001), cardiac complications (HR 1.88, 95%CI 1.46–2.32; p < 0.001), and a diagnosis of dementia at admission (HR 1.37, 95%CI 1.13–1.66; p = 0.001). The Charlson Index and the American Society of Anesthesiologists physical status classification system also significantly increased the mortality risk. Conversely, higher hemoglobin levels at admission and elevated albumin at discharge significantly reduced the mortality risk. Conclusions: The one-year mortality rate is substantial in older adults with hip fractures who are admitted to an orthogeriatric unit. The appropriate management of anemia, nutritional disorders, and comorbidity at admission and during the followup could potentially mitigate long-term mortality after hip fractures. Keywords: hip fracture; older adults; 1-year mortality; risk factors; orthogeriatric care; fragility fractureshttps://orcid.org/0000-0001-5832-0603https://scholar.google.com/citations?user=MrICwaMAAAAJ&hl=enhttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001429659Revista Internacional - IndexadaS

Implementing Precision Medicine in Human Frailty through Epigenetic Biomarkers

The main epigenetic features in aging are: reduced bulk levels of core histones, altered pattern of histone post-translational modifications, changes in the pattern of DNA methylation, replacement of canonical histones with histone variants, and altered expression of non-coding RNA. The identification of epigenetic mechanisms may contribute to the early detection of age-associated subclinical changes or deficits at the molecular and/or cellular level, to predict the development of frailty, or even more interestingly, to improve health trajectories in older adults. Frailty reflects a state of increased vulnerability to stressors as a result of decreased physiologic reserves, and even dysregulation of multiple physiologic systems leading to adverse health outcomes for individuals of the same chronological age. A key approach to overcome the challenges of frailty is the development of biomarkers to improve early diagnostic accuracy and to predict trajectories in older individuals. The identification of epigenetic biomarkers of frailty could provide important support for the clinical diagnosis of frailty, or more specifically, to the evaluation of its associated risks. Interventional studies aimed at delaying the onset of frailty and the functional alterations associated with it, would also undoubtedly benefit from the identification of frailty biomarkers. Specific to the article yet reasonably common within the subject discipline

Frailty Assessment in a Stable COPD Cohort: Is There a COPD-Frail Phenotype?

The frailty syndrome increases the morbidity/mortality in older adults, and several studies have shown a higher prevalence of this syndrome in patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to identify the characteristics of frail patients with COPD to define a new phenotype called "COPD-frail." We conducted a cross-sectional study in a cohort of patients with stable COPD, classified as either frail, pre-frail, or non-frail. Sociodemographic, clinical, and biochemical variables were compared between the three groups of patients. The study included 127 patients, of which 31 were frail, 64 were pre-frail, and 32 non-frail. All subjects had FEV1/FVC below the lower limit of normal (range Z-score: −1.66 and −5.32). Patients in the frail group showed significantly higher scores in the mMRC (modified Medical Research Council) scale, the CAT (COPD Assessment Test), and the BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index. They also showed differences in symptoms according to GOLD (Global Initiative for Chronic Obstructive Lung Disease), as well as more COPD exacerbations, less physical activity, more anxiety and depression symptoms based on HADS (Hospital Anxiety and Depression Scale), and lower hemoglobin, hematocrit, and 25-hydroxycholecalciferol levels. Variables with independent association with frailty included the mMRC score, the HAD index for depression and age. In summary, differential characteristics of frail patients with COPD encourage the definition of a "COPD-frail" phenotype that−if identified early−would allow performing interventions to prevent a negative impact on the morbidity/mortality of these patients