Validation of a deficit-accumulation Frailty Index in the ASPREE study and its predictive capacity for disability-free survival

Author(s):  
Joanne Ryan ◽  
Sara Espinoza ◽  
Michael E Ernst ◽  
A R M Saifuddin Ekram ◽  
Rory Wolfe ◽  
...  

Abstract Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterise a 67-item deficit-accumulation frailty index (FI) in 19,110 community-dwelling individuals in the ASPREE clinical trial. Participants aged 65 to 98 years were recruited from the U.S. and Australia, and were without diagnosed dementia and cardiovascular disease, and without major physical disability. The median FI score was 0.10 (IQR: 0.07; 0.14) at baseline, and the prevalence of frailty (FI> 0.21) increased from 8.1% to 17.4% after six years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r =-0.31) and grip strength (r = -0.46), and strongly associated with a modified Fried frailty phenotype (p<0.0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (HR:21.3, 95% CI:15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals, and provides important information about an individual’s vulnerability to and risk of disease.

2021 ◽  
pp. 1-7
Author(s):  
A.R.M.S. Ekram ◽  
R.L. Woods ◽  
C. Britt ◽  
S. Espinoza ◽  
M.E. Ernst ◽  
...  

Frailty is associated with multiple adverse health outcomes, including mortality. Several methods have been used to characterize frailty, each based on different frailty scales. These include scales based on phenotype, multidomain, and deficit accumulations. Several systematic reviews have examined the association between frailty and mortality; however, it is unclear whether these different frailty scales similarly predict mortality. This umbrella review aims to examine the association between frailty assessed by different frailty scales and all-cause mortality among community-dwelling older adults. A protocol was registered at PROSPERO, and it was conducted following the PRISMA statement. MEDLINE, Embase, PubMed, Cochrane Database of Systematic Reviews, Joanna Briggs Institute (JBI) EBP database, and Web of Science database was searched. Methodological quality was assessed using the JBI critical appraisal checklist and online AMSTAR-2 critical appraisal checklist. For eligible studies, essential information was extracted and synthesized qualitatively. Five systematic reviews were included, with a total of 434,115 participants. Three systematic reviews focused on single frailty scales; one evaluated Fried’s physical frailty phenotype and its modifications; another focused on the deficit accumulation frailty index. The third evaluated the FRAIL (Fatigue, Resistance, Ambulation, Illness, and Loss of weight) scale. The two other systematic reviews determined the association between frailty and mortality using different frailty scales. All of the systematic reviews found that frailty was significantly associated with all-cause mortality. This umbrella review demonstrates that frailty is a significant predictor of all-cause mortality, irrespective of the specific frailty scale.


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
A R M Saifuddin Ekram ◽  
Joanne Ryan ◽  
Carlene Britt ◽  
Sara Espinoza ◽  
Robyn Woods

Abstract Background Frailty is increasingly recognised for its association with adverse health outcomes, including mortality. However, various measures are used to assess frailty, and the strength of association could vary depending on the specific definition used. This umbrella review aims to map which frailty scale can best predict the relationship between frailty and all-cause mortality among community-dwelling older people. Methods A protocol was registered at PROSPERO, and it was conducted following the PRISMA statement. MEDLINE, Embase, PubMed, Cochrane Database of Systematic Reviews, Joanna Briggs Institute (JBI) EBP database, and Web of Science database was searched. Methodological quality was assessed using the JBI critical appraisal checklist and online AMSTAR-2 critical appraisal checklist. For eligible studies, essential information was extracted and synthesized qualitatively. Results Five systematic reviews were included, with a total of 434,115 participants. Three systematic reviews focused on single frailty scales; one evaluated Fried's physical frailty phenotype and its modifications; another focused on the deficit accumulation frailty index. The third evaluated the FRAIL (Fatigue, Resistance, Ambulation, Illness, and Loss of weight) scale. The two other systematic reviews determined the association between frailty and mortality using different frailty scales. All of the systematic reviews found that frailty was significantly associated with all-cause mortality. Conclusion This umbrella review demonstrates that frailty is a significant predictor of all-cause mortality, irrespective of the specific frailty scale. Key messages Frailty is associated with an increased risk of all-cause mortality in community-dwelling individuals signifying the importance of assessment in the primary healthcare setting.


2020 ◽  
Vol 75 (6) ◽  
pp. 1143-1147 ◽  
Author(s):  
Il-Young Jang ◽  
Hee-Won Jung ◽  
Hea Yon Lee ◽  
Hyungchul Park ◽  
Eunju Lee ◽  
...  

Abstract Background To determine the clinically meaningful changes and responsiveness of widely used frailty measures. Methods We analyzed data from a prospective cohort study of 1,135 community-dwelling older adults who underwent assessments of frailty and health-related quality of life using the EuroQol-5D at baseline and 1 year later. Frailty measures included deficit-accumulation frailty index (FI); frailty phenotype; Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale; and the Study of Osteoporotic Fracture (SOF) index. We determined the clinically meaningful changes by the distribution-based method and the anchor-based method using the EuroQol-5D score and responsiveness indices. Results Frailty measures were available in 925 participants at 1 year (81.5%). Based on the distribution-based method, small and large clinically meaningful changes were 0.019 and 0.057 for FI, 0.249 and 0.623 for frailty phenotype, 0.235 and 0.587 for FRAIL scale, and 0.116 and 0.289 for SOF index, respectively. The anchor-based estimates of small and large changes were 0.028 and 0.076 for FI, 0.097 and 0.607 for frailty phenotype, 0.269 and 0.368 for FRAIL scale, and 0.023 and 0.287 for SOF index, respectively. Based on the responsiveness index, per-group sample sizes to achieve 80% power in clinical trials, ranged from 51 (FI) to 7,272 (SOF index) for a small change and 9 (FI) to 133 (FRAIL scale) for a large change. Conclusions The estimates of clinically meaningful change of frailty measures can inform the choice of frailty measures to track longitudinal changes of frailty in clinical trials and clinical care of community-dwelling older adults.


2020 ◽  
Author(s):  
A R M Saifuddin Ekram ◽  
Robyn Woods ◽  
Carlene Britt ◽  
Sara E Espinoza ◽  
Michael E Ernst ◽  
...  

Abstract Background Frailty is associated with multiple adverse health outcomes, including mortality. Several methods have been used to characterize frailty, each based on different frailty scales. These include scales based on a phenotype, multidomain, and deficit accumulations. Several systematic reviews have examined the association between frailty and mortality; however, it is unclear whether these different frailty scales similarly predict mortality. This umbrella review aims to examine the association between frailty assessed by different frailty scales and all-cause mortality among community-dwelling older adults. Methods The umbrella review protocol was registered at PROSPERO, and it was conducted following the PRISMA statement. MEDLINE, Embase, PubMed, Cochrane Database of Systematic Reviews, Joanna Briggs Institute (JBI) EBP database, and Web of Science database was searched to identify systematic reviews and meta-analyses examining the association between frailty and all-cause mortality. Methodological quality was assessed using the JBI. Critical Appraisal Checklist and online AMSTAR-2 critical appraisal checklist. For eligible studies, essential information was extracted and synthesized qualitatively. Results Five systematic reviews were included, with a total of 434,115 participants. Three systematic reviews focused on single frailty scales; one evaluated Fried physical frailty phenotype and its modifications; another focused on the deficit accumulation frailty index. The third evaluated the FRAIL (Fatigue, Resistance, Ambulation, Illness, and Loss of weight) scale. The two other systematic reviews determined the association between frailty and mortality using different frailty scales. All the systematic reviews performed meta-analyses and assessed between-study heterogeneity. All of the systematic reviews found that frailty was significantly associated with all-cause mortality.Conclusion This umbrella review demonstrates that frailty is a significant predictor of all-cause mortality, irrespective of the specific frailty scale.


2021 ◽  
Vol 12 ◽  
Author(s):  
Antonio Guaita ◽  
Laura Brunelli ◽  
Annalisa Davin ◽  
Tino Emanuele Poloni ◽  
Roberta Vaccaro ◽  
...  

Frailty is an important age-related syndrome associated with several adverse health outcomes. Its biological basis is undefined. Raised plasma homocysteine (HOcy) is an established risk factor for cardiovascular disease, dementia, cognitive impairment, and mortality, but little is known about the possible role of plasma HOcy, cyanocobalamin (B12), and folate (FO levels in the development of frailty. Our first aim was to explore the possible association between frailty and plasma concentrations of HOcy, FO, and B12 in a cohort of community-dwelling older people. The second was to assess the influence of these metabolic factors on six-year incidence of frailty in the 875 individuals eligible for inclusion in this study (those with a full follow-up dataset). This research is based on data from three waves – 2012 (herein taken as baseline), 2014, and 2018 – of a longitudinal study (InveCe.Ab) in which non-frail men and women born between 1935 and 1939 underwent multidimensional assessments. Frailty was estimated using a deficit accumulation-based frailty index (FI). HOcy concentration was significantly positively correlated with FI at all timepoints, while B12 and FO levels were not. Plasma concentration of HOcy emerged as a predictor of six-year cumulative incidence of frailty, independent of age, sex, and education, while B12 and FO levels showed no relationship with frailty incidence. Individuals with plasma HOcy in the top quintile showed five months less frailty-free survival (HR 1.487; 95% CI: 1.063–2.078), regardless of age, sex, and education. These results demonstrate that higher HOcy is a risk factor for frailty onset in older adults.


Author(s):  
Eva Ntanasi ◽  
Maria Maraki ◽  
Mary Yannakoulia ◽  
Maria Stamelou ◽  
Georgia Xiromerisiou ◽  
...  

Abstract Background To investigate the association between frailty, Parkinson’s disease (PD), and the probability of prodromal Parkinson’s disease (prodromal PD) in Greek community-dwelling older individuals. Methods Parkinson’s disease diagnosis was reached through standard clinical research procedures. Probability of prodromal PD was calculated according to the International Parkinson and Movement Disorder Society’s research criteria for PD-free participants. Frailty was evaluated according to definitions of the phenotypic and multidomain approach. Logistic and linear regression models were performed to investigate associations between frailty (predictor) and the probability of prodromal PD, either continuous or dichotomous (≥30% probability score), or PD (outcome). Results Data from 1765 participants aged 65 and older were included in the present analysis. Parkinson’s disease and prodromal PD prevalence were 1.9% and 3.0%, respectively. Compared to nonfrail participants, those who were frail, as identified with either the Fried frailty phenotype or Frailty Index had approximately 4 (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.54–10.89) and 12 times (OR 12.16, 95% CI 5.46–27.09) higher odds of having a PD diagnosis, respectively. Moreover, compared to the nonfrail, frail participants as identified with either the Fried frailty phenotype or Frailty Index had 2.8 (OR 2.83, 95% CI 1.09–7.37) and 8.3 times (OR 8.39, 95% CI 4.56–15.42) higher odds of having possible/probable prodromal PD, respectively. Conclusions Frailty status was associated with prodromal PD and PD, suggesting common characteristics or underlying mechanisms of these conditions. Although prospective studies are warranted, acknowledging the possible association of frailty, PD, and prodromal PD may improve their clinical management.


2019 ◽  
Vol 75 (6) ◽  
pp. 1120-1125 ◽  
Author(s):  
Dae Hyun Kim ◽  
Elisabetta Patorno ◽  
Ajinkya Pawar ◽  
Hemin Lee ◽  
Sebastian Schneeweiss ◽  
...  

Abstract Background There has been increasing effort to measure frailty in the U.S. Medicare data. The performance of claims-based frailty measures has not been compared. Methods This cross-sectional study included 3,097 community-dwelling fee-for-service Medicare beneficiaries (mean age 75.6 years) who participated in the 2008 Health and Retirement Study examination. Four claims-based frailty measures developed by Davidoff, Faurot, Segal, and Kim were compared against frailty phenotype, a deficit-accumulation frailty index (FI), and activities of daily living (ADL) dependence using Spearman correlation coefficients and C-statistics. Results Claims-based frailty measures were positively associated with frailty phenotype (prevalence in ≤10th vs >90th percentile: 8.0% vs 41.3% for Davidoff; 5.9% vs 53.1% for Faurot; 3.3% vs 48.0% for Segal; 2.9% vs 51.0% for Kim) and FI (mean in ≤10th vs >90th percentile: 0.17 vs 0.33 for Davidoff; 0.13 vs 0.37 for Faurot; 0.12 vs 0.31 for Segal; 0.10 vs 0.37 for Kim). The age and sex-adjusted C-statistics for frailty phenotype for Davidoff, Faurot, Segal, and Kim indices were 0.73, 0.74, 0.73, and 0.78, respectively, and partial correlation coefficients with FI were 0.18, 0.32, 0.26, and 0.55, respectively. The results for ADL dependence were similar (prevalence in ≤10th vs >90th percentile: 3.7% vs 50.5% for Davidoff; 2.3% vs 55.0% for Faurot; 3.0% vs 38.3% for Segal; 2.3% vs 50.8% for Kim). The age and sex-adjusted C-statistics for the indices were 0.79, 0.80, 0.74, and 0.81, respectively. Conclusions The choice of a claims-based frailty measure can influence the identification of older adults with frailty and disability in Medicare data.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 573-573
Author(s):  
A R M Saifuddin Ekram ◽  
Joanne Ryan ◽  
Sara Espinoza ◽  
Michael Ernst ◽  
Anne Murray ◽  
...  

Abstract This study examined factors associated with frailty and studied the association between frailty status and mortality in healthy community-dwelling older persons. Participants included 19,114 individuals from the “ASPirin in Reducing Events in the Elderly” (ASPREE) trial. Frailty was defined using modified Fried phenotype comprising exhaustion, body mass index, grip strength, gait speed and physical activity. A deficit accumulation frailty index (FI) using 66 items was also developed. Correlates of frailty were examined using multinomial logistic regression. The association between frailty status at baseline and mortality was analyzed using Cox regression. At baseline, 39.0% (95% CI: 38.3, 39.7) of participants were prefrail, and 2.2% (95% CI: 2.0, 2.4) were frail according to Fried phenotype, while 40.6% (95% CI: 40.0, 41.3) of participants were pre-frail and 8.1% (95% CI: 7.7, 8.5) were frail according to FI. Older age, female sex, lower education, African-American and Hispanic ethno-racial status, smoking, alcohol use, comorbidities, and polypharmacy were associated with frailty status. Pre-frailty increased risk of all-cause mortality significantly (Fried HR: 1.48; 95% CI: 1.28, 1.71; FI HR: 1.54; 95% CI: 1.31, 1.81); and the risk was even higher for frailty (Fried HR: 2.24; 95% CI: 1.67, 3.00; FI HR: 2.34; 95% CI: 1.83, 2.99) after adjustment for covariates. Cardiovascular disease (CVD) and non-CVD-related mortality showed similar trends. These results highlight a considerable burden of pre-frailty among a large group of community-dwelling, initially healthy older adults. Both Fried phenotype and deficit accumulation FI similarly predicted all-cause, CVD and non-CVD-related mortality in relatively healthy older adults.


Author(s):  
Quoc Dinh Nguyen ◽  
Erica M Moodie ◽  
Mark R Keezer ◽  
Christina Wolfson

Abstract Background Deficit-accumulation frailty indices (FIs) are widely used to characterize frailty. FIs vary in number and composition of items; the impact of this variation on reliability and clinical applicability is unknown. Methods We simulated 12,000 studies using a set of 70 candidate deficits in 12,080 community-dwelling participants 65 years and older. For each study, we varied the number (5, 10, 15, 25, 35, 45) and composition (random selection) of items defining the FI and calculated descriptive and predictive estimates: frailty score, prevalence, frailty cut-off, mortality odds ratio, predicted probability of mortality for FI=0.28 (prevalence threshold), and FI cut-off predicting 10% mortality over the follow-up. We summarized the estimates’ medians and spreads (0.025-0.975 quantiles) by number of items and calculated intraclass correlation coefficients (ICC). Results Medians of frailty scores were 0.11-0.12 with decreasing spreads from 0.04-0.24 to 0.10-0.14 for 5-item and 45-item FIs. The median cut-offs identifying 15% as frail was 0.19-0.20 and stable; the spreads decreased with more items. However, medians and spreads for the prevalence of frailty (medians: 11% to 3%), mortality odds ratio (medians:1.24 to 2.19), predicted probability of mortality (medians: 8% to 17%), and FI cut-off predicting 10% mortality (medians: 0.38 to 0.20) varied markedly. ICC increased from 0.19 (5-item FIs) to 0.84 (45-item FIs). Conclusions Variability in the number and composition of items of individual FIs strongly influences their reliability. Estimates using FIs may not be sufficiently stable for generalizing results or direct application. We propose avenues to improve the development, reporting, and interpretation of FIs.


2017 ◽  
Vol 20 (2) ◽  
pp. 273-285 ◽  
Author(s):  
Alexandre Alves Pereira ◽  
Flávia Silva Arbex Borim ◽  
Anita Liberalesso Neri

Abstract Objective: to systematize studies evaluating the relationship between frailty and mortality in community-dwelling elderly persons. Method: Frailty was defined according to the frailty phenotype proposed by Fried et al. and the frailty index described by Rockwood et al. The study included epidemiologic population-based studies, cohort surveys, systematic reviews and meta-analyses published in English between 2006 and March 2016 based on the use of the terms: "frail elderly" and "mortality". Only study samples that exclusively comprised adults 65 years old or older who lived in the community were included. Studies investigating hospitalized and institutionalized elderly persons, and those examining the relationship between frailty and mortality through a disease-specific target were excluded. Results: a total of 244 studies were identified, of which 17 met the inclusion criteria. Thirteen studies used the frailty phenotype and four studies used the frailty index. Conclusion: both assessment measures found that frail elderly persons have a higher risk of death than robust elderly persons.


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