Trajectories of frailty with aging:Coordinated analysis of five longitudinal studies

BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions

Contributions of the MyD88-Dependent Receptors IL-18R, IL-1R, and TLR9 to Host Defenses following Pulmonary Challenge with Cryptococcus neoformans

Signaling via the adapter protein, MyD88, is important in the host defense against Cryptococcus neoformans infection. While certain Toll-like receptors (TLRs) can enhance the clearance of Cryptococcus, the contributions of MyD88-dependent, TLR-independent pathways have not been fully investigated. We examined the roles of IL-1R and IL-18R in vivo by challenging C57BL/6 mice with a lethal strain of Cryptococcus. We found that the absence of IL-18R, but not IL-1R, causes a shift in the survival curve following pulmonary delivery of a virulent strain of C. neoformans (H99). Specifically, IL-18R-deficient mice have significantly shorter median survival times compared to wild-type mice following infection. Cytokine analysis of lung homogenates revealed that deficiency of IL-IR, IL-18R, or MyD88 is associated with diminished lung levels of IL-1β. In order to compare these findings with those related to TLR-deficiency, we studied the effects of TLR9-deficiency and found that deficiency of TLR9 also affects the survival curve of mice following challenge with C. neoformans. Yet the lungs from infected TLR9-deficient mice have robust levels of IL-1β. In summary, we found that multiple signaling components can contribute the MyD88-dependent host responses to cryptococcal infection in vivo and each drives distinct pulmonary responses

Foundations and strategic vision of the Canadian Translational Geroscience Network

Geroscience is an emerging interdisciplinary field that explores the biological connections between aging and the development of chronic diseases, with the ultimate goal of identifying interventions to extend healthspan and delay age-related conditions. Recognizing the growing importance of this field, the Canadian Translational Geroscience Network (geroscience.ca) was officially launched during a conference held in Montreal on September 5-6, 2024. Building on the momentum of successful Geroscience meetings in Toronto and Montreal in 2023, this milestone event marked a transformative step forward for geroscience in Canada. This event brought together key stakeholders, including the Canadian Frailty Network (CFN), the Canadian Institutes of Health Research Institute of Aging (CIHR-IA), the Réseau Québécois de Recherche sur le Vieillissement (RQRV), the Simone & Edouard Schouela RUISSS McGill Centre of Excellence for Sustainable Health of Seniors (Schouela CEDurable), the Division of Geriatric Medicine at McGill University, and the Department of Biochemistry at the University of Toronto. Additionally, a broad coalition of geriatricians, healthcare professionals, and researchers convened to discuss and advance the field of geroscience in Canada. The 2-day conference focused on creating a multidisciplinary community to address the challenges of an aging population, emphasizing the importance of funding, national and international collaboration, and training the next generation of researchers and clinicians. Workshops and presentations showcased a range of innovative research, from cellular studies to clinical trials, aimed at understanding and treating age-related diseases. Key discussions highlighted the critical role of partnerships among research institutions, healthcare systems, and biotech companies in translating research findings into practical interventions. The Canadian Translational Geroscience Network\u27s strategic objectives focus on expanding funding opportunities for geroscience, developing specialized training programs, and increasing membership to cultivate a diverse, multidisciplinary, and collaborative network. This network aims to include students, basic and clinical researchers, citizens, government entities, and organizations or professionals interested in advancing the geroscience field. With a clear roadmap for future growth, the Canadian Translational Geroscience Network aims to position Canada at the forefront of geroscience, fostering evidence-based innovation that improves the health and quality of life for aging populations

The Life-Space Assessment Measure of Functional Mobility has Utility in Community-Based Physical Therapist Practice in the United Kingdom

Background: The Life-Space Assessment (LSA) has demonstrable validity and reliability among people sampled from nonclinical settings. Its properties in clinical settings, especially physical therapy services, are less well established.Objective: The aim of this study was to test the construct/convergent validity, responsiveness, and floor/ceiling effects of the LSA among patients who had musculoskeletal, orthopedic, neurological, or general surgical presentations and were receiving individually tailored, community-based physical therapist interventions to address gait/balance impairments in an urban location in the United Kingdom.Design: A prospective, repeated-measures, comparative cohort design was used.Methods: Two hundred seventy-six community-dwelling, newly referred patients were recruited from 3 cohorts (outpatients; domiciliary, nonhospitalized; and domiciliary, recent hospital discharge). Data were collected from the LSA and the Performance-Oriented Mobility Assessment (POMA1) at initial assessment and discharge. Two hundred twenty-eight participants were retained at follow-up.Results: The median age was 80.5 years, 73.6% were women, and the median number of physical therapist contacts over 53 days was 5. LSA scores at assessment and changes over treatment distinguished between cohorts, even after adjustment for covariates. Weak correlations (0.14–0.41) were found between LSA and POMA1 scores. No LSA floor/ceiling effects were found. Significant improvements in the LSA score after the intervention were found for each cohort and for the sample overall. For the whole sample, the mean change in the LSA score was 10.5 points (95% CI = 8.3–12.8).Limitations: The environmental demands participants faced were not measured. Caregivers answered the LSA questions on behalf of participants when necessary. Assessors were not always masked with regard to the measurement point.Conclusions: The LSA has utility as an outcome measure in routine community-based physical therapist practice. It has satisfactory construct validity and is sensitive to change over a short time frame. The LSA is not a substitute for the POMA1; these measures complement each other, with the LSA bringing the added value of measuring real-life functional mobility

Extended Exercise Rehabilitation After Hip Fracture Improves Patients' Physical Function: A Systematic Review and Meta-Analysis

BackgroundAlthough the principal goal of hip fracture management is a return to the pre-event functional level, most survivors fail to regain their former levels of autonomy. One of the most effective strategies to mitigate the fracture's consequences is therapeutic exercise.PurposeThe purpose of this study was to review and quantify the reported effects of an extended exercise rehabilitation program offered beyond the regular rehabilitation period on improving physical functioning for patients with hip fractures.SourcesThe Cochrane libraries, PubMed, CINAHL, PEDro, and EMBASE were searched to April 2012.Study SelectionAll randomized controlled trials comparing extended exercise programs with usual care for community-dwelling people after hip fracture were included in the review.Data Extraction and SynthesisTwo reviewers conducted each step independently. The data from the included studies were summarized, and pooled estimates were calculated for 11 functional outcomes.ResultsThirteen trials were included in the review and 11 in the meta-analysis. The extended exercise program showed modest effect sizes (ESs), which reached significance, under random theory, for knee extension strength for the affected and nonaffected sides (ES=0.47, 95% confidence interval [CI]=0.27–0.66, and ES=0.45, 95% CI=0.16–0.74, respectively), balance (ES=0.32, 95% CI=0.15–0.49), physical performance-based tests (ES=0.53, 95% CI=0.27–0.78), Timed “Up &amp; Go” Test (ES=0.83, 95% CI=0.28–1.4), and fast gait speed (ES=0.42, 95% CI=0.11–0.73). Effects on normal gait speed, Six-Minute Walk Test, activities of daily living and instrumental activities of daily living, and physical function subscale of the 36-Item Short-Form Health Survey (SF-36-PF) did not reach significance. Community-based programs had larger ESs compared with home-based programs.ConclusionsTo the authors' knowledge, this is the first meta-analysis to provide evidence that an extended exercise rehabilitation program for patients with hip fractures has a significant impact on various functional abilities. The focus of future research should go beyond just effectiveness and study the cost-effectiveness of extended programs.</jats:sec

Supplementary Material for: A Regression Tree Analysis to Identify Factors Predicting Frailty: The International Mobility in Aging Study

Introduction: Frailty is a complex geriatric syndrome with a multifaceted etiology. We aimed to identify the best combinations of risk factors that predict the development of frailty using recursive partitioning models. Methods: We analyzed reports from 1,724 community-dwelling men and women aged 65–74 years participating in the International Mobility in Aging Study (IMIAS). Frailty was measured using frailty phenotype scale that included five physical components: unintentional weight loss, weakness, slow gait, exhaustion, and low physical activity. Frailty was defined as presenting three of the above five conditions, having one or two conditions indicated prefrailty and showing none as robust. Socio-demographic, physical, lifestyle, psycho-social, and life-course factors were included in the analysis as potential predictors. Results: 21% of pre-frail and robust participants showed a worse stage of frailty in 2014 compared to 2012. In addition to functioning variables, fear of falling (FOF), income, and research site (Canada vs. Latin America vs. Albania) were significant predictors of the development of frailty. Additional significant predictors after exclusion of functioning factors included education, self-rated health, and BMI. Conclusions: In addition to obvious risk factors for frailty (such as functioning), socio-economic factors and FOFs are also important predictors. Clinical assessment of frailty should include measurement of these factors to identify high-risk individuals