Effects of an educational intervention on frailty status, physical function, physical activity, sleep patterns, and nutritional status of older adults with frailty or pre-frailty: the FRAGSALUD study

Introduction: The prevalence of frailty is increasing worldwide, emphasizing the importance of prioritizing healthy ageing. To address this, cost-effective and minimally supervised interventions are being sought. This study aimed to assess the impact of an educational program on frailty status, physical function, physical activity, sleep patterns, and nutritional status in community-dwelling older adults with at least 1 Fried's frailty criteria. Methods: A 6-month multicentre randomized controlled trial was conducted from March 2022 to February 2023 in 14 health centres located in Cadiz and Malaga, Spain. The educational intervention consisted of 4 group sessions and 6 follow-up phone calls spread over 6 months. The program focused on educating participants about frailty and its impact on health, providing guidelines for physical activity, healthy dietary habits, cognitive training, psychological well-being and social activities. A total of 163 participants, divided into control (n = 80) and educational groups (n = 83) were assessed before and after the intervention. Results: The results showed a significant group-time interaction in the physical function evaluated with a large effect on Short Physical Performance Battery score (η2p = 0.179, -0.1 [-1.2-1.0] points for control group vs. 1.0 [0.0-3.0] points for educational group, p < 0.001), and an effect on the 4-meter gait test ((η2p = 0.122, 0.5 [0.1-0.0] s for control group vs. -0.4 [-0.5- -0.3] s for educational group, p < 0.001), and the 5-repetition sit-to-stand test (η2p = 0.136, 1.0 [0.0-1.2] s for control group vs. -4.3 [-7.0- -2.3] for educational group, p < 0.001). Additionally, the use of accelerometers to assess physical activity, inactivity, and sleep patterns revealed a significant small effect in the number of awakenings at night ((η2p = 0.040, 1.1 [-0.5-3.4] awakenings for control group vs. 0.0 [-2.2-0.0] awakenings for educational group, p = 0.009). The findings also highlighted a significant medium effect regarding malnutrition risk, which was assessed using the Mini-Nutritional Assessment score (η2p = 0.088, -0.7 [-2.3-1.5] points for control group vs. 1.5 [-0.5-3.0] points for educational group, p < 0.001). Discussion: Thus, the 6-month educational program effectively improved physical function, sleep patterns, and nutritional status compared to usual healthcare attendance in community-dwelling older adults with frailty or pre-frailty. These findings underscore the potential of minimally supervised interventions in promoting a healthy lifestyle in this vulnerable population

Health factors associated with cognitive frailty in older adults living in the community

IntroductionThis study aims to investigate the health factors associated with cognitive frailty in frail and pre-frail older adults living in the community.MethodsA total of 233 older adults meeting Fried’s criteria for pre-frailty or frailty were included. Cognitive status was evaluated using the Short Portable Mental Status Questionnaire. Health factors encompassed nutritional status (evaluated using the Mini Nutritional Assessment tool, body mass index, and waist, arm, and leg circumferences), physical function (assessed with the Short Physical Performance Battery), quality of life (measured with the total index of the EuroQoL 5-Dimension 5-Level questionnaire - EQoL-Index -, and the Visual-Analogue Scale - QoL-VAS - for today’s health state), as well as sleep, physical activity, and inactivity estimated through wrist-worn accelerometers. Multivariable logistic regression analyses were conducted to identify potential predictors of cognitive frailty, considering age as a confounding factor.ResultsCognitive frail participants exhibited advanced age, heightened self-reported exhaustion, diminished overall physical performance, reduced leg perimeter, decreased engagement in moderate-to-vigorous physical activity, and higher levels of inactivity (all p&lt;0.05). However, after adjusting for age, only QoL-VAS emerged as a cognitive frailty risk factor (Odds ratio: 1.024), while the EQoL-Index, calf perimeter, and levels of moderate-to-vigorous physical activity were identified as protective factors (Odds ratios: 0.025, 0.929, and 0.973, respectively).DiscussionThis study highlights the complex relationship between non-modifiable factors such as age, and modifiable factors including quality of life, nutritional status, and physical activity in the development of cognitive frailty among older adults with a frailty phenotype living in the community

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Risk and Protective Factors for Frailty in Pre-Frail and Frail Older Adults

This study aims to evaluate the differences in body composition, physical function, and physical activity between pre-frail/frail older adults and to detect risk and protective factors against frailty and physical frailty. Fried’s criteria for frailty and physical frailty using the short-performance physical battery (SPPB) were measured in 179 older participants (75.3 ± 6.4 years old). Body weight, height, and waist, arm, and leg circumferences were obtained as body composition variables. Daily accelerometer outcomes (physical activity and inactivity) were obtained. Pre-frail participants showed overall better physical function and spent more time in physical activity and less time in long inactivity periods than frail participants (p < 0.05). Risk frailty factors were higher waist perimeter (Odds Ratio [OR]: 1.032, 95%CI: 1.003–1.062), low leg performance (OR: 1.025, 95%CI: 1.008–1.043), and inactivity periods longer than 30 min (OR:1.002, 95%CI: 1.000–1.005). Protective factors were standing balance (OR:0.908, 95%CI: 0.831–0.992) and SPPB score (OR: 0.908, 95%CI: 0.831–0.992) for frailty, handgrip strength (OR: 0.902, 95%CI: 0.844–0.964) for physical frailty, and light (OR: 0.986, 95%CI: 0.976–0.996) and moderate-to-vigorous (OR: 0.983, 95%CI: 0.972–0.996) physical activity for both. Our findings suggest that handgrip strength, balance, and physical activity are protective frailty factors and can be monitored in pre-frail older adults. Moreover, poor lower body performance and long inactivity periods are frailty risk factors, which highlights their importance in frailty assessment

Associations Between Physical Activity and Inactivity Levels on Physical Function and Sleep Parameters of Older Adults With Frailty Phenotype

This study investigated the relationship between physical activity, inactivity, physical function, and sleep in older adults with a frailty phenotype. A total of 184 pre-frail/frail older adults were included. Physical activity, inactive behavior, and sleep parameters were assessed using a wrist-worn accelerometer. Participants were categorized into four groups based on their levels of inactivity and physical activity. The results showed that individuals with lower levels of inactivity had better lower body mean velocity and sleep regularity than those with higher levels of inactivity. Physically active older adults exhibited faster gait speed and performed better in lower body strength tests than physically inactive participants. Further analysis revealed that specific combinations of inactivity and physical activity were associated with varying levels of physical function. The findings highlight the importance of physical activity and the negative impact of inactivity on physical function and sleep in older adults with a frailty phenotype

Optimization of adsorptive removal of α-toluic acid by CaO2 nanoparticles using response surface methodology

The present work addresses the optimization of process parameters for adsorptive removal of α-toluic acid by calcium peroxide (CaO2) nanoparticles using response surface methodology (RSM). CaO2 nanoparticles were synthesized by chemical precipitation method and confirmed by Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analysis which shows the CaO2 nanoparticles size range of 5–15 nm. A series of batch adsorption experiments were performed using CaO2 nanoparticles to remove α-toluic acid from the aqueous solution. Further, an experimental based central composite design (CCD) was developed to study the interactive effect of CaO2 adsorbent dosage, initial concentration of α-toluic acid, and contact time on α-toluic acid removal efficiency (response) and optimization of the process. Analysis of variance (ANOVA) was performed to determine the significance of the individual and the interactive effects of variables on the response. The model predicted response showed a good agreement with the experimental response, and the coefficient of determination, (R2) was 0.92. Among the variables, the interactive effect of adsorbent dosage and the initial α-toluic acid concentration was found to have more influence on the response than the contact time. Numerical optimization of process by RSM showed the optimal adsorbent dosage, initial concentration of α-toluic acid, and contact time as 0.03 g, 7.06 g/L, and 34 min respectively. The predicted removal efficiency was 99.50%. The experiments performed under these conditions showed α-toluic acid removal efficiency up to 98.05%, which confirmed the adequacy of the model prediction

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589