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PubMed2006

Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults.

Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty. Although social and psychological aspects of frailty are critically important and merit future research, these topics were largely beyond the scope of this meeting. Included in this article are sections on the evolving conceptualization and definitions of frailty; physiological underpinnings of frailty, including the potential contributions of inflammatory, endocrine, skeletal muscle, and neurologic system changes; potential molecular and genetic contributors; proposed animal models; and integrative, system biology approaches that may help to facilitate future frailty research. In addition, several specific recommendations as to future directions were developed from suggestions put forth by participants, including recommendations on definition and phenotype development, methodological development to perform clinical studies of individual-system and multiple-system vulnerability to stressors, development of animal and cellular models, application of population-based studies to frailty research, and the development of large collaborative networks in which populations and resources can be shared. This meeting and subsequent article were not meant to be a comprehensive review of frailty research; instead, they were and are meant to provide a more-targeted research agenda-setting process.

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PubMed2026

Prognostic Value of Frailty in Aortic Surgery: A Systematic Review and Meta-Analysis Comparing Frailty Assessment Tools.

BACKGROUND: Frailty is increasingly recognized as an important determinant of outcomes after aortic vascular surgery, but assessment methods vary substantially and the optimal tool for risk stratification remains uncertain. This systematic review and meta-analysis evaluated the prognostic value of preoperative frailty and compared the predictive performance of different frailty instruments in aortic surgery. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to April 27, 2026. Eligible studies included patients undergoing open, endovascular, or hybrid aortic procedures involving abdominal, thoracic, thoracoabdominal, arch, and proximal aortic diseases, including aneurysms and dissections, assessed frailty preoperatively, and reported postoperative outcomes. RESULTS: Thirty studies comprising 419,459 patients were included. Frailty was associated with higher early mortality (odds ratio [OR] 2.20; 95% confidence interval [CI] 1.54-3.14) and late mortality (hazard ratio 2.18; 95% CI 1.64-2.90). Frail patients also had increased risks of major complications (OR 2.52; 95% CI 1.22-5.19), acute kidney injury (OR 1.64; 95% CI 1.34-2.02), and nonhome discharge (OR 5.50; 95% CI 3.05-9.92). Associations were consistent across surgical approaches and aortic segments. Judgment-based or phenotype-like tools yielded higher effect estimates than deficit-accumulation indices, although differences were not statistically significant; among index-based tools, Modified Frailty Index (mFI)-11 outperformed mFI-5. CONCLUSION: Preoperative frailty strongly predicts mortality, morbidity, and loss of functional independence after open, endovascular, and hybrid aortic surgery across different aortic segments and pathologies, including aneurysmal and dissecting aortic disease. Routine frailty assessment may improve risk stratification and perioperative decision-making.

Humans↗

PubMed1996

Reducing frailty and falls in older persons: an investigation of Tai Chi and computerized balance training. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention Techniques.

OBJECTIVE: To evaluate the effects of two exercise approaches, Tai Chi (TC) and computerized balance training (BT), on specified primary outcomes (biomedical, functional, and psychosocial indicators of frailty) and secondary outcomes (occurrence of falls). DESIGN: The Atlanta FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques), a prospective, randomized, controlled clinical trial with three arms (TC, BT, and education [ED]. Intervention length was 15 weeks, with primary outcomes measured before and after intervention and at 4-month follow-up. Falls were monitored continuously throughout the study. SETTING: Persons aged 70 and older living in the community. PARTICIPANTS: A total of 200 participants, 162 women and 38 men; mean age was 76.2. MEASUREMENTS: Biomedical (strength, flexibility, cardiovascular endurance, body composition), functional (IADL), and psychosocial well-being (CES-D scale, fear of falling questionnaire, self-perception of present and future health, mastery index, perceived quality of sleep, and intrusiveness) variables. RESULTS: Grip strength declined in all groups, and lower extremity range of motion showed limited but statistically significant changes. Lowered blood pressure before and after a 12-minute walk was seen following TC participation. Fear of falling responses and intrusiveness responses were reduced after the TC intervention compared with the ED group (P = .046 and P = .058, respectively). After adjusting for fall risk factors, TC was found to reduce the risk of multiple falls by 47.5%. CONCLUSIONS: A moderate TC intervention can impact favorably on defined biomedical and psychosocial indices of frailty. This intervention can also have favorable effects upon the occurrence of falls. Tai Chi warrants further study as an exercise treatment to improve the health of older people.

Accidental Falls↗

PubMed2027

Effectiveness of high-dose versus standard-dose influenza vaccines against hospitalisation according to frailty risk: a prespecified analysis of the randomised trial DANFLU-2.

BACKGROUND: Frailty is a major risk factor for influenza-related complications and can influence vaccine effectiveness. We aimed to assess the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) in older adults aged 65 years or older according to frailty risk. METHODS: This study was a prespecified analysis of DANFLU-2, an open-label, individually randomised trial, conducted in Denmark during three consecutive influenza seasons (2022-23, 2023-24, and 2024-25). Adults aged 65 years or older were randomised (1:1) to the HD-IIV or SD-IIV group. The primary endpoint was hospitalisation for influenza or pneumonia. Frailty was defined according to the validated Hospital Frailty Risk Score (HFRS) based on ICD-10 codes within 10 years before randomisation. Participants were stratified into three HFRS categories, namely low (<5 points), intermediate (5-15 points), and high (>15 points) frailty risk. The rVE of HD-IIV versus SD-IIV against the primary endpoint was assessed across prespecified HFRS categories and treating HFRS as a continuous variable. Pearson's chi-square test was used to compare safety events across frailty risk groups and randomisation groups. FINDINGS: Among 332 438 randomised participants (mean age 73·7 years [SD 5·8]; 161 538 [48·6%] were female), 276 173 (83·1%) had low frailty risk, 52 395 (15·8%) had intermediate frailty risk, and 3861 (1·2%) had high frailty risk. The primary endpoint of hospitalisation for influenza or pneumonia occurred in 1424 (0·5%) of 276 173 participants with low frailty risk, 761 (1·5%) of 52 395 with intermediate frailty risk, and 163 (4·2%) of 3861 with high frailty risk (relative risk [RR] for intermediate vs low frailty risk 2·8 [95% CI 2·6-3·1]; RR for high vs low frailty risk 8·2 [7·0-9·6]). HFRS as a continuous variable significantly modified the effect of HD-IIV versus SD-IIV against the primary endpoint with higher rVE estimates with increasing HFRS (pinteraction=0·020). The rVE was 0·2% (95% CI -10·8 to 10·2) among those with low frailty risk, 13·1% (-0·4 to 24·8) among those with intermediate frailty risk, and 19·9% (-10·3 to 42·1) among those with high frailty risk. No significant interaction was observed when HFRS was assessed according to the prespecified categorical frailty groups (pinteraction=0·17). The proportion of participants with at least one serious adverse event increased across frailty risk groups (13 366 [4·8%] of 275 795 for low frailty risk, 5475 [10·5%] of 52 315 for intermediate frailty risk, and 777 [20·2%] of 3850 for high frailty risk; p<0·0001), with similar proportions of serious adverse events in the HD-IIV and SD-IIV groups for each frailty risk group. INTERPRETATION: Among adults aged 65 years or older in Denmark, frailty risk might modify the effects of HD-IIV versus SD-IIV against hospitalisation for influenza or pneumonia, with higher rVE estimates with increasing frailty risk. These findings might support considering high-dose influenza vaccines for frail older adults. However, effect modification was not evident when frailty was assessed using prespecified categorical subgroups, and subgroup-specific estimates were imprecise, with 95% CIs crossing the null. These results should be considered exploratory, warranting further investigation. FUNDING: The DANFLU-2 trial was funded by Sanofi.

Journal Article↗

PubMed2026

Identifying potential drug targets for physical and cognitive frailty: an integrative analysis of CHARLS cohort, mendelian randomization, and gene colocalization.

With the aging of the population, frailty has become a common syndrome that severely affects the quality of life of older adults. This study aims to analyze the correlation between cognition and frailty, physical activity and frailty, and elucidate the potential pharmacological targets of cognitive frailty and physical frailty.We conducted logistic regression analyses using data from the China Health and Retirement Longitudinal Study (CHARLS) to examine the associations between total cognition and frailty, physical activity and frailty. Furthermore, summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (TSMR) were employed to explore potential pharmacological targets for frailty. Genes associated with physical frailty and cognitive frailty were identified, followed by analysis via colocalization analysis, phenome-wide association studies (PheWAS), and DsigDB drug prediction. Cross-sectional analysis of CHARLs revealed that total cognition(OR 0.93, 95% CI 0.92-0.95) and middle physical activity(OR 0.95, 95% CI 0.92-0.97) were negatively correlated with frailty. SMR identified 41 drug genes associated with frailty, and subsequent TSMR validation and co-localization analysis showed that 11 candidate genes exhibited strong colocalization (PP.H4 > 0.8). GRPEL 1, PABPC 4, and WBP 2NL were ultimately identified as potential drug targets associated with physical frailty, while LANCL1, LRPPRC, FADS1, and WBP2NL were identified as potential drug targets associated with cognitive frailty. Phenome-wide association analysis(PheWAS) did not reveal any significant associations between these genes and other phenotypes at the genome-wide significance threshold. Laudanosine, 25-hydroxycholesterol, and hexadecanal emerged as the top three candidate compounds for therapeutic intervention. We identified potential drug targets for physical frailty and cognitive frailty through comprehensive analysis and elucidated drugs associated with potentially relevant genetic markers, thereby laying the foundation for a deeper understanding of the mechanisms of frailty.

Humans↗

PubMed2001

Frailty in older adults: evidence for a phenotype.

BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

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PubMed2025

Finerenone According to Frailty in Heart Failure: A Prespecified Analysis of the FINEARTS-HF Randomized Clinical Trial.

IMPORTANCE: Patients with frailty are often perceived to have a less favorable benefit-risk profile for novel therapies and therefore may be less likely to receive these. OBJECTIVE: To examine the efficacy and safety of finerenone, compared with placebo, according to frailty status in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or with HF and preserved ejection fraction (HFpEF). DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of a phase 3 randomized clinical trial, the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), conducted across 653 sites in 37 countries. Patients with HF with New York Heart Association functional class II through IV, a left ventricular ejection fraction of 40% or higher, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized between September 2020 and January 2023. Data analysis was conducted from October 1 to November 30, 2024. INTERVENTION: Addition of once-daily finerenone or placebo to usual therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death and total worsening HF events. Frailty was measured using the Rockwood cumulative deficit approach. RESULTS: Of the 6001 patients randomized in FINEARTS-HF, a frailty index (FI) was calculable in 5952 patients (mean [SD] age, 72.0 [9.6] years; 3241 [54.4%] male). In total, 1588 patients (26.7%) had class I frailty (FI ≤0.210 [not frail]), 2141 (36.0%) had class II frailty (FI 0.211-0.310 [more frail]), and 2223 (37.3%) had class III frailty (FI ≥0.311 [most frail]). Compared with patients with class I frailty, those with class II and III frailty had a higher risk of the primary outcome (unadjusted rate ratio [RR], 1.88 [95% CI, 1.54-2.28] for class II and 3.86 [95% CI, 3.22-4.64] for class III). The effect of finerenone on the primary outcome did not vary significantly by frailty class (class I: RR, 1.07 [95% CI, 0.77-1.49]; class II: RR, 0.66 [95% CI, 0.52-0.83]; class III: RR, 0.91 [95% CI, 0.76-1.07]; P for interaction = .77). Frailty class did not modify the effects of finerenone on the components of the primary outcome, all-cause death, or improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score. The effects of finerenone, compared with placebo, on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty class. CONCLUSIONS AND RELEVANCE: In FINEARTS-HF, finerenone reduced the risk of total worsening HF events and cardiovascular death, and it improved symptoms; these effects were not modified by frailty status. In addition, the effects of finerenone on experiencing hypotension, elevated creatinine level, hyperkalemia, or hypokalemia did not differ by frailty status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435626.

Humans↗

PubMed2006

Transitions between frailty states among community-living older persons.

BACKGROUND: Little is known about the natural course of frailty. We performed a prospective study to determine the transition rates between frailty states and to evaluate the effect of the preceding frailty state on subsequent frailty transitions. METHODS: We studied 754 community-living persons, aged 70 years or older, who were nondisabled in 4 essential activities of daily living. Frailty, assessed every 18 months for 54 months, was defined on the basis of weight loss, exhaustion, low physical activity, muscle weakness, and slow walking speed. Participants were classified as frail if they met 3 or more of these criteria, as prefrail if they met 1 or 2 of the criteria, and as nonfrail if they met none of the criteria. RESULTS: Of the 754 participants, 434 (57.6%) had at least 1 transition between any 2 of the 3 frailty states during 54 months. The rates were 36.8%, 21.5%, and 9.2% for 1, 2, and 3 transitions, respectively. During the 18-month intervals, transitions to states of greater frailty were more common (rates up to 43.3%) than transitions to states of lesser frailty (rates up to 23.0%), and the probability of transitioning from being frail to nonfrail was very low (rates, 0%-0.9%), even during an extended period. The likelihood of transitioning between frailty states was highly dependent on one's preceding frailty state. CONCLUSIONS: Frailty among older persons is a dynamic process, characterized by frequent transitions between frailty states over time. Our findings suggest ample opportunity for the prevention and remediation of frailty.

Aged↗

PubMed2005

Frailty predicts long-term mortality in elderly subjects with chronic heart failure.

BACKGROUND: The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study aimed to examine the predictive role of frailty on long-term mortality in elderly subjects with CHF. MATERIALS AND METHODS: The study assessed long-term mortality after 12-year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a 'Frailty Staging System'. RESULTS: Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75.9 +/- 6.7); subjects without CHF were prevalently female (56.4%) and younger than 75 years (mean 74.0 +/- 6.3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70.0% to 94.4%, P < 0.03) than in those without (43.8.% to 88.3%, P < 0.0001) CHF. The Kaplan-Meier analysis shows that at 9 years the probability of survival progressively decreased as frailty increased (45.5% to 0%) in subjects with CHF and from 62.8% to 25.9% in subjects without CHF. The Cox regression analysis indicated that frailty is predictive of mortality in the multivariate model adjusted for several variables including sex and age in subjects with and without CHF. Moreover, the analysis showed that frailty is more predictive of mortality in elderly subjects with CHF when it was analyzed either as continuous (1.48 vs. 1.36) or as a dummy (3 vs. 1 = 1.62 vs. 1.24) variable. CONCLUSIONS: Thus mortality among elderly subjects with or without CHF increases with frailty. Moreover, frailty is more predictive of long-term mortality in elderly subjects with than in those without CHF. Hence, frailty represents a new independent variable for predicting long-term mortality in elderly subjects with CHF.

Aged↗

PubMed2025

Multi-Polygenic prediction of Frailty and its Trajectories highlights Chronic Pain, Rheumatoid Arthritis, and Educational Attainment pathways.

Frailty is a complex ageing-related trait with a growing evidence base for genetic influence. While a single polygenic score (PGS) for frailty has shown predictive value, few studies have examined the joint effect of multiple genetic risks. This study used a multi-polygenic score (MPS) approach to evaluate the combined and relative contributions of 26 PGSs to frailty, measured via the Frailty Index (FI), in two UK cohorts aged 65 and older: the English Longitudinal Study of Ageing (ELSA) and the Lothian Birth Cohort 1936 (LBC1936). Using elastic net regression with repeated cross-validation, we identified chronic pain and depressive symptoms PGSs as the strongest risk predictors of cross-sectional frailty status, while educational attainment, parental longevity, and rheumatoid arthritis PGSs were protective. Compared to single PGS models, MPS models provided improved prediction of frailty levels, explaining up to 4.7% of variance in frailty status - an improvement over the best single PGS (2.5%). To assess whether PGSs also predicted longitudinal frailty progression, we applied generalized additive mixed models (GAMMs) to model age-related trajectories. In ELSA, five PGSs (chronic pain, depressive symptoms, rheumatoid arthritis, educational attainment, and parental death) significantly interacted with age, influencing the rate of frailty change. In LBC1936, consistent though weaker effects were observed for chronic pain and education PGSs. These findings show that polygenic liability shapes both frailty levels and trajectories in later life. Our results support the use of multi-trait genomic models to improve risk prediction and understanding of frailty's complex aetiology.

Journal Article↗

PubMed2005

Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study.

OBJECTIVES: To define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability. DESIGN: Prospective study, the Women's Health Initiative Observational Study. SETTING: Forty U.S. clinical centers. PARTICIPANTS: Forty thousand six hundred fifty-seven women aged 65 to 79 at baseline. MEASUREMENTS: Components of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up. RESULTS: Baseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions. CONCLUSION: These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.

Activities of Daily Living↗

PubMedDate not supplied

Bone mass cannot be predicted by estimations of frailty in elderly ambulatory women.

BACKGROUND/METHODS: High biological age, or frailty, a possible risk factor for fragility fracture, and its relation to known risk factors for fracture (low bone mineral density (BMD), low muscle strength, poor gait performance and poor balance, previous falls, previous fractures and future risk of falls) were investigated in 993 randomly selected 75-year-old women. Frailty, which has no accepted definition, was here defined as a subjective immediate impression of an individual's general health appearance and was transferred into an arbitrary scale. 993 individuals were scored by at least one of four observers. RESULTS: The frailty score and BMD were not correlated. A high frailty score was significantly correlated to poor gait (r = 0.53-0.59, p < 0.0001), poor balance (r = -0.49, p < 0.0001), low muscle strength (r = -0.25 to -0.41, p < 0.0001), low activity level (r = -0.43, p < 0.0001) and a high risk of falling (r = 0.24, p < 0.0001). The group of women who had experienced at least one fall the previous year had a higher frailty score (p < 0.0001) compared to those who had not. Women who had sustained a hip or femoral fracture after the age of 70 had a higher frailty score than women with no earlier fracture at all. CONCLUSIONS: Bone mass cannot be predicted by our subjective frailty score in elderly, ambulant women. Since a high frailty score correlates with factors that affect or are likely to affect fall propensity, this could indicate that a high frailty score is a risk factor for fracture, independent of bone mass. Frailty may be regarded as a complex risk factor, including several assessments that can be objectively measured. Whether estimation of frailty is a method to improve the assessment of the patient at risk for a fragility fracture is yet to be proven and can only be shown in a prospective study of fracture occurrence.

Aged↗

PubMed2004

Use of a questionnaire to screen for frailty in the elderly: an exploratory study.

BACKGROUND AND AIMS: In a pilot study of community-dwelling geriatric clinic patients (N=48, aged 63-90) we examined the use of a questionnaire to classify frailty status by comparing it with standardized markers of frailty. The questionnaire, developed by Strawbridge et al. in 1998, defines frailty as difficulty in more than one of four domains of functioning: physical, cognitive, sensory, and nutritive. METHODS: Subjects were classified as frail or not frail by questionnaire and assignment was compared with testing of physical and cognitive measures in cross-sectional analysis. Demographic variables, functional inventories, physical activity levels, clinician impression of frailty, and 3-year health outcomes were also examined. RESULTS: Thirty-three percent of subjects were classified as frail. Frailty classification by the Strawbridge questionnaire was correlated to Timed Up and Go and repetitive Sit-to-Stand tests, bimanual dexterity and cognitive tests. A discrepancy was found between assignment of cognitive difficulty, by questionnaire and cognitive performance. When overall Strawbridge frailty scores were modified to account for those with poor cognitive performance who did not report cognitive difficulty, the prevalence of frailty increased to 42%. At 3-year follow-up, the modified Strawbridge frailty classification (p<0.05) and clinician impression of frailty (p<0.01) were both significant predictors of death and institutionalization combined. CONCLUSIONS: This study serves as an initial inquiry into the potential validity and utility of the Strawbridge frailty questionnaire as a simple screening tool to identify patients who may warrant detailed functional testing.

Aged↗

PubMed2005

Frailty, morbidity and survival.

Frailty, as a reflection of decreased physical reserve rather than disability, is assessed by various functional tests rather than by specific disease burden. We investigated association of measures of frailty to disease outcomes and survival in a population-based study of Midwestern adults. The markers of frailty we evaluated were: time to walk a measured course (gait-time), handgrip strength, peak respiratory flow rate, ability to stand from a sitting position without using arms, and best corrected visual acuity. A history of cardiovascular disease, cancer, and hypertension were obtained. Data were collected at the third examination (1998--2000) of the Beaver Dam Eye Study cohort (n=2962). Follow-up for mortality occurred up to 412 years after the 1998--2000 examinations. Markers of frailty were significantly associated with age. Values in the highest quartile (slowest) of gait-time, lowest quartile of peak expiratory flow rate, lowest quartile of handgrip strength, inability to stand from sitting in one try (those not in a wheelchair), and visual impairment were combined in an index to denote a general description of frailty. The range of the index was 0 (no frailty) to 5 (maximum frailty). Greater frailty was significantly associated with cardiovascular disease and hypertension. Frailty was associated with poorer survival over an interval of 412 years after adjusting for age, sex, hypertension, diabetes, and cardiovascular disease. Greater frailty was associated with greater likelihood of concurrent medical conditions and with decreased survival.

Aged↗

PubMed2001

Associations of subclinical cardiovascular disease with frailty.

BACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology. METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing. RESULTS: Of 4,735 eligible participants, 2,289 (48%) were not frail, 299 (6%) were frail, and 2.147 (45%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05). CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.

Black or African American↗

PubMed2005

Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: the Women's Health and Aging Studies I and II.

BACKGROUND: The physiological basis of the geriatric syndrome of frailty, a clinical state of increased vulnerability to adverse outcomes such as disability and mortality, remains to be better characterized. We examined the cross-sectional relationship between hemoglobin (Hb) and a recently-validated measure of frailty in community-dwelling older women, and whether this relationship was modified by cardiovascular disease (CVD) status. METHODS: Data were pooled from women 70-80 years old participating in the Women's Health and Aging Studies I and II (Baltimore, MD, 1992-1996) with known frailty status and Hb > or = 10 g/dL (n = 670). Logistic regression was used to model the relationship between frailty and Hb, adjusting for demographics, major chronic diseases, and physiologic and functional impairments. RESULTS: Prevalence of frailty was 14%. Frailty risk was highest at the lowest Hb levels, and lowest at mid-normal Hb levels (e.g., 13-14 g/dL). Mildly low and low-normal Hb concentrations were independently associated with frailty. Compared to an Hb concentration equal to 13.5 g/dL, the adjusted odds of being frail were 1.9 (95% confidence interval: 1.1-3.4) and 1.5 (95% confidence interval: 1.0-2.1) times higher for Hb concentrations equal to 11.5 g/dL and 12 g/dL, respectively. A statistically significant (p <.05) multiplicative interaction between Hb level and CVD status with respect to frailty risk was observed. CONCLUSION: In community-dwelling older women, mildly low and low-normal Hb levels were independently associated with increased frailty risk. This risk was synergistically modified by the presence of CVD. These results suggest that mild anemia, and even low-normal Hb levels are independent, potentially modifiable risk factors for frailty in community-dwelling older adults.

Aged↗

PubMed2005

A global clinical measure of fitness and frailty in elderly people.

BACKGROUND: There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. METHODS: We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. RESULTS: The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%-30.6%) and entry into an institution (23.9%, 95% CI 8.8%-41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). INTERPRETATION: Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

Aged↗

PubMed2005

The hormonal pathway to frailty in older men.

Frailty, which is a state of high vulnerability that imparts a high risk of developing adverse health outcomes, affects many elderly subjects, especially men and women aged 80 yr and older (1). Although many different definitions of frailty have been proposed (2), a large portion of the recent literature has focused on the definition developed by L. Fried et al. (1) using the data from the Cardiovascular Health Study. Although this definition has not been officially recognized as the "gold standard" for the diagnosis of frailty, nonetheless most of the studies on frailty in the last 5 yr have used this definition. Several mechanisms have been hypothesized to have an important role in the development of frailty, including inflammation, coagulation and oxidative stress (3). Many authors implicate age-related hormonal changes to be directly or indirectly involved in the development of the frailty syndrome (4). Alterations in hypothalamic- pituitary-testicular, hypothalamic-pituitary-adrenal (HPA) and GH-IGF-I axes that accompany aging have been associated with single components of frailty, such as reduced muscle strength, bone strength or poor mobility (5, 6). However, most of these studies have focused on single hormonal changes rather than evaluating the parallel effect of aging on multiple hormonal axes. In addition, no interventional studies have specifically targeted frail older subjects (7). Since frailty by definition is a multi-system disorder, it is unlikely that changes in one axis (leading to a change in a single hormone) will explain the complexity of the dysregulation leading to frailty. Therefore, global measures of endocrine dysregulation that can discriminate between specific endocrine diseases and endocrine senescence should be developed. Observational and interventional studies will be needed to better define the role of "hormonal dysregulation", alone and in combination with other pathways, in the development of frailty in older men.

Aged, 80 and over↗