Aug 2026· Aging Clinical and Experimental Research· 0 citations
TL;DR
Frailty components, especially weakness and slowness, are significantly associated with mortality and related outcomes, highlighting the urgency of early frailty detection to improve patient prognosis and urging early identification and intervention to enhance patient care and reduce clinical burden.
Abstract
Frailty, a prevalent geriatric syndrome, increases susceptibility to adverse outcomes like mortality, cardiovascular disease, and hospitalization. This study evaluated the Fried frailty phenotype and its components’ association with clinical outcomes, focusing on mortality.
We conducted a systematic review and meta-analysis of studies on individuals aged 50 or more from databases searched up to October 2024. Included studies assessed at least one frailty criterion (weakness, slowness, exhaustion, physical inactivity, weight loss) and reported hazard ratios (HRs) for mortality or other outcomes. Random-effects models and subgroup analyses (e.g., heart failure, chronic kidney disease) were employed.
From 3445 articles, 36 studies were included. All frailty components are significantly associated with all-cause mortality: weakness (HR: 1.44, 95%CI: 1.30–1.59, p < 0.01), slowness (HR: 1.75, 95%CI: 1.56–1.95, p < 0.01), exhaustion (HR: 1.47, 95%CI: 1.29–1.68, p < 0.01), physical inactivity (HR: 1.72, 95%CI: 1.55–1.92, p < 0.01), and weight loss (HR: 1.56, 95%CI: 1.31–1.84, p < 0.01). Slowness, weakness, and physical inactivity were linked to cardiovascular mortality (HRs: 1.97, 1.45, 1.26, respectively, p < 0.01), while slowness and exhaustion were also linked to an increased risk of hospitalization (HRs: 1.46, 1.25, p < 0.01). Slowness was associated with a two-fold higher mortality risk (I2 = 57%, HR: 1.99, 95%CI: 1.73–2.30, p < 0.01). Subgroup analyses confirmed these links in heart failure and chronic kidney disease patients.
Frailty components, especially weakness and slowness, are significantly associated with mortality and related outcomes, highlighting the urgency of early frailty detection to improve patient prognosis.
This systematic review and meta-analysis of 36 studies demonstrates that the components of frailty, when considered individually, are significantly associated with an increased mortality risk; weakness (HR: 1.44), slowness (HR: 1.75), exhaustion (HR: 1.47), physical inactivity (HR: 1.72), and unintentional weight loss (HR: 1.56). Slowness and weakness are also associated with cardiovascular mortality and hospitalization, with slowness associated with a two-fold higher mortality risk in community-dwelling older adults (HR: 1.99). These robust associations, confirmed in heart failure and chronic kidney disease subgroups, highlight frailty's critical role in adverse outcomes, urging early identification and intervention to enhance patient care and reduce clinical burden.
BACKGROUND
Risk stratification in elderly patients with heart failure (HF) remains challenging. Conventional risk models often fail to capture physiologic vulnerability, limiting personalized care. The Clinical Frailty Scale (CFS), a simple bedside measure of frailty, has not been systematically evaluated for its prognostic value in elderly HF populations.
METHODS
We performed a systematic review of MEDLINE, Scopus, ScienceDirect, and Cochrane databases through June 2026, including studies evaluating the prognostic value of the CFS in patients with HF. Multivariable-adjusted hazard ratios (HRs) for allcause mortality, HF hospitalization, and the composite outcome of all-cause mortality/HF hospitalization were pooled using a random-effects inverse-variance model in RevMan 5.4.
RESULTS
Five studies including 2,682 elderly HF patients were included in the quantitative synthesis (mean age 81.2 years; 45.4% male; mean LVEF 53.7%). Among studies reporting phenotype, approximately 75% had preserved or mildly reduced EF. Higher CFS scores were associated with statistically significant increases in the risk of all-cause mortality (HR 2.39; 95% CI 1.72-3.32; p<0.001; I²=45%), HF hospitalization (HR 1.52; 95% CI 1.18-1.95; p=0.001; I²=0%), and composite outcome (HR 1.75; 95% CI 1.41-2.16; <;0.001; I²=0%). Leave-one-out sensitivity analysis confirmed robust allcause mortality associations; exclusion of one study reduced heterogeneity to 0% (HR 2.02; 95% CI 1.56-2.63; p<0.001; I²=0%). These associations were derived from multivariable-adjusted models accounting for age, sex, LVEF, and comorbidities.
CONCLUSIONS
Frailty assessed by the Clinical Frailty Scale is associated with increased mortality and HF rehospitalization, with more than a two-fold increase in all-cause mortality independent of conventional risk factors.
Sneha Annie Sebastian, A. Yehya· Current problems in cardiolo...· 0 citations
AIM
To determine whether frailty is associated with activities of daily living (ADL) and other clinical outcomes in hospitalized older adults.
METHODS
MEDLINE, Embase and CENTRAL were searched for English-language cohort studies published from 1 January 2001 to 23 October 2025. Eligible studies included hospitalized adults aged ≥ 65 years (or samples with ≥ 80% aged ≥ 65 years), used a defined frailty measure and compared frail with non-frail participants. Two reviewers independently selected studies, extracted data and assessed risk of bias using the Quality In Prognosis Studies tool. Random-effects meta-analyses generated standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
Fifty-seven cohort studies were included. Frailty was associated with worse ADL status (SMD -1.04, 95% CI -1.89 to -0.20), higher mortality (RR 2.26, 95% CI 1.86-2.76), lower likelihood of discharge home (RR 0.79, 95% CI 0.73-0.86), and higher 30-day (RR 1.47, 95% CI 1.13-1.90) and 90-day readmission risks (RR 1.75, 95% CI 1.07-2.86). Pneumonia risk was not statistically significant. Heterogeneity was substantial to considerable for all pooled outcomes.
CONCLUSIONS
Frailty identifies hospitalized older adults at increased risk of functional dependence, mortality, non-home discharge, and readmission. Substantial heterogeneity and residual confounding warrant cautious interpretation and support standardized frailty and functional-outcome assessment.
T. Kamo, R. Asahi, Y. Inaba et al.· Geriatrics & Gerontology Int...· 0 citations
Summary Background In parallel with diagnostic advances and awareness of cardiac amyloidosis (CA) in aging populations, frailty is increasingly observed in CA. However, the relationship between the frailty and CA remains poorly characterized owing to limited studies that have defined frailty a priori. We performed a meta-analysis to characterize the impact of frailty on clinical and functional patient outcomes in CA. Methods Systematic review of four electronic databases was performed for all studies reporting frailty prevalence, functional and clinical endpoints in patients with CA from January 2015 to April 2026 (CRD420251152212). Frailty was classified based on individual study scoring systems. The primary outcome of interest was all-cause mortality, expressed as pooled hazard (HR) or risk ratios (RR) with 95% confidence intervals (CI) using inverse-variance random-effects models. Other outcomes included hospitalizations, quality of life, functional status (6-min walk distance [6MWD]), and prescription of disease modifying treatment. Heterogeneity was summarized using the I2 statistic; study quality was rated with the Newcastle–Ottawa Scale; and certainty of evidence was graded using the GRADE framework. Leave-one-out sensitivity analyses and visual funnel plots were performed where applicable. Findings Fifteen studies with a total of 5048 patients, predominantly (>95%) with transthyretin amyloid cardiomyopathy (ATTR-CM), were included. The prevalence of frailty ranged between 6.7% and 75% across studies with a pooled mean of 33.9% (826/2435 frail). Pooling 2141 patients with outcomes available, both pre-frailty (RR 2.22, 95% CI 1.37–3.60, p < 0.01) and frailty (RR 3.93, 95% CI 2.09–7.40, p < 0.01) significantly associated with increased risks of all-cause mortality after adjustment for age and frailty assessment tool. 6MWD, a functional surrogate of frailty, predicted poorer outcomes both using baseline 6MWD (<350/300 m: HR 2.22, 95% CI 1.15–4.31, p = 0.02) and 1-year interval change in 6MWD (>35 reduction: HR 1.80, 95% CI 1.52–2.14; >5% reduction: HR 1.89, 95% CI 1.60–2.23; both p < 0.01). Beyond mortality, frailty also predicted increased risk of functional decline, poorer quality of life, and reduced prescription of disease-modifying treatment. Interpretation Patients with ATTR-CM and frailty have higher mortality risk, poorer functional outcomes and reduced prescription of disease-modifying treatment compared to those without frailty. Findings were consistent across frailty instruments and sensitivity analyses, supporting the incorporation of routine frailty assessment and 6MWD into clinical management of ATTR amyloidosis. Funding None.
Haowen Jiang, D. J. Lim, C. Khoo et al.· EClinicalMedicine· 1 citation
Objective To systematically investigate the prevalence and influencing factors of cognitive frailty in patients with chronic heart failure, and to provide evidence-based support for subsequent clinical intervention development. Methods We retrieved relevant studies focusing on the prevalence and influencing factors of cognitive frailty in patients with chronic heart failure from Embase, Cochrane Library, PubMed, Web of Science, CINAHL, SinoMed, CNKI, VIP, and Wanfang databases. The search period covered from the inception of each database to December 2025. Two researchers independently conducted study screening, data extraction, and methodological quality assessment. Meta-analysis was performed using Stata 15.0 software. Results Fourteen studies involving 5,127 patients with chronic heart failure were included, among which 1,875 cases of cognitive frailty were reported, and 30 risk factors were identified. Meta-analysis showed that the pooled prevalence of cognitive impairment in patients with chronic heart failure was 39.3% (95% CI: 31.0%–47.7%). Further analysis identified age, age ≥ 80 years, New York Heart Association (NYHA) classification, comorbidity burden, polypharmacy, malnutrition, and depression as significant risk factors for cognitive impairment in this population. Higher educational attainment, engaging in physical exercise ≥ 3 times per week, and regular participation in intellectual activities were confirmed as protective factors against cognitive impairment in patients with chronic heart failure. Conclusion Current evidence confirms that cognitive impairment is highly prevalent among patients with chronic heart failure, and its occurrence is influenced by multiple modifiable and non-modifiable risk factors. Therefore, clinical healthcare providers should strengthen routine cognitive function screening for this population, and implement targeted interventions based on the identified risk factors to delay the onset of cognitive impairment and improve overall patient prognosis. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251247352, PROSPERO CRD420251247352.
Meiwan Zhang, Chen Zhou, Min Hu et al.· Frontiers in Cardiovascular...· 0 citations
Objectives To explore the prevalence and associated factors of cognitive frailty in older adults with heart failure. Design A systematic review and meta-analysis. Methods We systematically searched China National Knowledge Infrastructure (CNKI), Wanfang Data, the VIP Database, SinoMed, PubMed, Web of Science, Embase, the Cochrane Library and Scopus from their inception to March 30, 2026. Results A total of 22 studies involving 8,892 older adults with heart failure were included. The meta-analysis showed that the pooled prevalence of cognitive frailty in older adults with heart failure was 32% (95% CI: 27%-37%). Descriptive stratified analyses yielded pooled prevalence estimates of 37% in women and 31% in men. According to New York Heart Association functional classification, the corresponding estimates were 44% among patients classified as class IV and 28% among those classified as classes II-III.The prevalence was also higher in patients with comorbid chronic obstructive pulmonary disease (46%) and coronary heart disease (31%). Older age was associated with higher odds of cognitive frailty (adjusted OR = 1.12, 95% CI 1.06–1.18). Depression was also associated with higher odds, whereas exercise and intellectual activity were associated with lower odds. Conclusions and Implications Cognitive frailty appears to be common among older adults with heart failure, although prevalence estimates vary across populations and assessment approaches. Older age and depression were associated with higher odds of cognitive frailty, whereas exercise and intellectual activity were associated with lower odds. These findings support early screening and comprehensive assessment, while the observed associations should not be interpreted as causal because the available evidence was predominantly observational and cross-sectional. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261360024, PROSPERO, identifier CRD420261360024.
Min Cheng, Jing Zhao, Juan Hu· Frontiers in Public Health· 0 citations
BACKGROUND
Cognitive frailty, defined as the co-occurrence of physical frailty/prefrailty and cognitive impairment in the absence of dementia, is a potentially reversible condition that may signal high risk for disability and dementia. This systematic review and meta-analysis estimated the global prevalence of cognitive frailty among community-dwelling older adults and examined methodological and contextual moderators of prevalence differences.
METHODS
We searched for relevant studies published up to October 22, 2025 in international (PubMed, Web of Science, Embase, PsycINFO) and Chinese (CNKI, Wanfang) databases. Pooled prevalence rates and 95% confidence intervals (CIs) were calculated with random-effects models. Subgroup and meta-regression analyses examined possible sociodemographic, methodological, and clinical moderators. Study quality was assessed with the Joanna Briggs Institute checklist.
RESULTS
Sixty-six studies of 127 556 participants were included. The pooled prevalence of cognitive frailty was 12.2% (95% CI: 9.4%-15.7%). Prevalence was higher in studies using the "Fatigue, Resistance, Ambulation, Illness, and Loss of weight" (FRAIL) scale or Fried phenotype and those using the Montreal Cognitive Assessment (MoCA) or composite cognitive criteria, in upper-middle-income countries, and in studies published after 2021. In meta-regression analyses, alcohol use status was significantly associated with cognitive frailty prevalence but most sociodemographic factors were not related to rates of cognitive frailty. Trim-and-fill analysis suggested that potential publication bias may have led to underestimation of prevalence.
CONCLUSION
Cognitive frailty is common among community-dwelling older adults worldwide. Given its potential reversibility and strong links to adverse outcomes, systematic identification and targeted multi-domain interventions should be prioritized in aging societies.
Yi-Ran Huang, Shu-Ying Rao, Hui Li et al.· Asia-Pacific Psychiatry· 0 citations
