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a The John Hopkins Medical Institutions, Baltimore, Maryland
b The University of Washington, Seattle
c The University of Pittsburgh, Pennsylvania
d The University of California at Davis, Sacramento
e St. Francis Hospital, Roslyn, New York
f The University of California at Los Angeles
g The University of Vermont, Burlington
h Uniformed Services University of the Health Sciences, Bethesda, Maryland
i Wake Forest University School of Medicine, Winston-Salem, North Carolina
Linda P. Fried, Director, Center on Aging and Health, The Johns Hopkins Medical Institutions, 2024 East Monument Street, Suite 2-700, Baltimore, MD 21205 E-mail: lfried{at}welch.jhu.edu.
Decision Editor: John E. Morley, MB, BCh
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Abstract |
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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.
FRAILTY is considered to be highly prevalent with increasing age and to confer high risk for adverse health outcomes, including mortality, institutionalization, falls, and hospitalization (1)(2)(3). Numerous geriatric interventions have been developed to improve clinical outcomes for frail older adults (3)(4)(5)(6)(7). A major obstacle to the success of such interventions has been the absence of a standardized and valid method for screening of those who are truly frail so as to effectively target care (1)(3).
Potential definitions of frailty abound, defining frailty as synonymous with disability (1)(8)(9), comorbidity (8), or advanced old age (3). Increasingly, geriatricians define frailty as a biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems, and causing vulnerability to adverse outcomes (9)(10)(11)(12)(13). This concept distinguishes frailty from disability (9)(10)(14)(15). There is a growing consensus that markers of frailty include age-associated declines in lean body mass, strength, endurance, balance, walking performance, and low activity (9)(10)(14)(15)(16)(17), and that multiple components must be present clinically to constitute frailty (9)(14). Many of these factors are related (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) and can be unified, theoretically, into a cycle of frailty associated with declining energetics and reserve (Fig. 1). The core elements of this cycle are those commonly identified as clinical signs and symptoms of frailty (9)(10)(14)(15)(16). Frailty likely also involves declines in physiologic complexity or reserve in other systems, leading to loss of homeostatic capability to withstand stressors and resulting vulnerabilities (2)(9)(11)(12).
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Methods |
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Baseline Evaluation
Standardized interviews ascertained self-assessed health, demographics, health habits, weight loss, medications used, and self-reported physician diagnosis of cardiovascular events, emphysema, asthma, diabetes, arthritis, renal disease, cancer, and hearing and visual impairment. A version of the Minnesota Leisure Time Activities Questionnaire (34) ascertained physical activities in the prior 2 weeks, plus frequency and duration. Physical function was ascertained by asking about difficulty with 15 tasks of daily life, including mobility, upper extremity, instrumental activities of daily living (IADL) and activities of daily living (ADL) tasks (35). Frequency of falls in the prior 6 months was assessed by self-report. The modified 10-item Center for Epidemiological Studies–Depression scale [CES–D; (36)] ascertained depressive symptoms.
Cardiovascular diseases [myocardial infarction (MI), congestive heart failure (CHF), angina, peripheral vascular disease, and stroke] were validated by ascertaining medications used and through standardized examinations: electrocardiogram, echocardiogram, and posterior tibial–brachial artery systolic (ankle–arm) blood pressure ratio (32)(37)(38). These data and medical records were then reviewed by clinicians for consensus-based adjudication of the presence of these diseases, based on standardized algorithms (37).
Additional examinations ascertained weight; blood pressure; carotid ultrasound measuring maximal stenosis of the internal and common carotid arteries (39); phlebotomy, under fasting conditions, with blood analyzed by the Laboratory for Clinical Biochemistry Research (University of Vermont) for fasting glucose, serum albumin, creatinine, and fibrinogen (32). Fasting plasma lipid analyses were performed, and low-density lipoprotein cholesterol was calculated (32). Cognitive function was assessed with the Mini-Mental State Examination (40) and the Digit Symbol Substitution test (41). Standardized performance-based measures of physical function included time (seconds) to walk 15 feet at usual pace and maximal grip strength (kilograms) in the dominant hand (3 measures averaged), using a Jamar hand-held dynamometer (32).
Mortality
Deaths were identified at semi-annual contacts and confirmed through intensive surveillance (37)(42). Mortality ascertainment was 100% complete through the eighth year.
Operationalization of the frailty phenotype in CHS..-- Based on the scientific rationale above, a phenotype of frailty was proposed to include the elements summarized in Table 1 , column A. It was operationalized utilizing data collected in CHS at baseline for Cohort 1 and years 3 (baseline for Cohort 2) and 7 for both cohorts (Fig. 2 and Table 1 , column B). We specified that a phenotype of frailty was identified by the presence of three or more of the following components (see Appendix) of the hypothesized cycle of frailty (Fig. 1):
10 pounds in prior year or, at follow-up, of 5% of body weight in prior year (by direct measurement of weight). 
O2 max (43), and is predictive of cardiovascular disease (44).
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Data Analysis
Using CHS data, we identified the number of frailty characteristics present, as per definitions above. Those considered evaluable for frailty had three or more nonmissing frailty components among the five criteria (Table 1 ). We excluded those with a history of Parkinson's disease (n = 47), stroke (n = 245), or Mini-Mental scores <18 (n = 84), and those who were taking Sinemet, Aricept, or antidepressants (n = 235), as these conditions could potentially present with frailty characteristics as a consequence of a single disease. There were 4,735 in the original and 582 in the African American cohort who were eligible; the total baseline sample size after applying the exclusion criteria was 5,317. For the first cohort, frailty components were ascertained at baseline, and then 3 years and 7 years into the study. The second cohort, recruited 3 years after the initial cohort, had frailty components ascertained 4 years later (corresponding to year 7 for the first cohort; Fig. 2).
For associations of frailty with other factors, the trend p value based on the Cochran-Mantel-Haenszel (CMH) test was used. Comorbidity was defined as the presence of two or more of nine conditions: self-reported claudication, arthritis, cancer, hypertension, chronic obstructive pulmonary disease (COPD), and validated diabetes (ADA definition), CHF, angina, or MI. A Venn diagram illustrates the overlap of disability and comorbidity with frailty at baseline; percentages are based on all frail subjects.
Kaplan-Meier estimates were used to determine the percentage of subjects free of an event (e.g., hospitalization, fall, death) at 3 years after study entry and 7 years after study entry. Cohort 1 had a longer follow-up period (median 79 months, range 73–84) than Cohort 2 (median 38 months, range 37–43), so estimates at 7 years were based only on Cohort 1. The p values reported for the difference in survival curves between frailty phenotype groups were based on the logrank test.
Predictive Validity
Cox proportional hazard models were used to assess the independent contribution of baseline frailty status to incidence of major geriatric outcomes over 3 and 7 years, including: (a) incident falls (evaluated every 6 months); (b) worsening mobility or ADL function (evaluated annually); (c) incident hospitalization: from time of study entry to discharge date for the first confirmed overnight hospitalization; (d) death. Indicators for frail (3 or more frailty components) and at-risk (1 or 2 frailty components) were created, with the nonfrail group (0 frailty components) serving as the reference group. Unadjusted instantaneous hazard ratios (referred to as relative risk [RR] estimates) were estimated for each outcome. Covariate-adjusted Cox models were also fit, utilizing baseline covariates shown to be predictive of mortality in this cohort (42): age, gender, income, smoking status, diuretic use without a history of hypertension or congestive heart failure, fasting glucose, albumin, creatinine; objective measures of subclinical disease, including: brachial and tibial systolic blood pressure, abnormal left ventricular ejection fraction (LVEF; by echocardiography), major ECG abnormality, forced vital capacity (FVC), and maximal stenosis of the internal carotid artery (by ultrasound), congestive heart failure (validated history), digit symbol substitution score, depressive symptoms (CES–D score excluding the two questions utilized in the frailty definition), and difficulty in 1 IADL. Weight and physical activity were also found to be independent predictors of survival, but they were not included in the covariate-adjusted models, as they are components of the overall frailty score. Covariates selected were based on analyses performed on the first cohort; external validation using the second cohort showed good agreement. However, FVC and LVEF abnormality were not available at study entry for the second cohort, so they were not included in the covariate-adjusted frailty models. Adding these two covariates to models based only on the first cohort did not alter the frailty results.
Finally, a logistic model was used to evaluate whether the intermediate frailty group (1,2 criteria) was at higher risk of incident frailty than those who were not frail (0 criteria) at study entry. Only subjects who were alive, eligible (satisfied exclusion criteria), and evaluable (at least 3 nonmissing frailty components) at the subsequent visit were included in the analysis. The covariate-adjusted logistic model includes the same covariates described for the proportional hazards models (above).
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Results |
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3 frailty criteria, and 46% had none. Six percent of the initial cohort and 12% of the African American cohort were frail. Prevalence of frailty increased with each 5-year age group, and was up to twofold higher for women than men by age group (Table 4 ). The exception was those 90 years and older, where prevalence was lower in both subgroups of women and men in the minority cohort.
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Those who were frail were older, more likely to be female and African American, and had less education, lower income, poorer health, and higher rates of comorbid chronic diseases and of disability than those who were not frail or were in the intermediate group (p <.05 for each comparison; Table 2 ). They also had significantly higher rates of cardiovascular and pulmonary diseases, arthritis, and diabetes. There was no significant difference in cancer, possibly a result of recruitment criteria that excluded those under active treatment for cancer. The intermediate frailty group was intermediate between those who were frail and those not frail in all of these measures (p for trend <.05 in each case except cancer). Notably, 7% of those who were frail had none of these chronic diseases, and 25% had just one; they were: 56% arthritis, 25% hypertension, 8% diabetes, and less than 5% each of angina, congestive heart failure, cancer, and pulmonary disease. Both lower cognition and greater depressive symptomatology were associated with frailty (despite exclusion of those being treated with antidepressants or with MMSE <18).
Further analyses explored the association between the frailty phenotype and self-reported physical disability. In Table 2 , 72% and 60% of those who were frail reported difficulty in mobility tasks or IADLs, respectively, while only 27% of those who were frail had difficulty in ADLs. There was a step-wise increase in disability with increasing frailty status (p for trend <.001). Separately, among those with disability in ADLs, often considered synonymous with frailty, only 28% were in the frail group (Table 5 ). Fig. 3 displays the overlap between these characteristics, as well as with the presence of two or more comorbid diseases. There was only modest concordance between frailty and disability. Of those who were frail, 46% had comorbid disease, 6% had ADL disability, 22% had both comorbid disease and ADL disability, and 27% had neither ADL disability nor comorbidity.
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To assess the independent predictive validity of this frailty phenotype, we evaluated its association, prospectively, with five important adverse health outcomes ascertained in prospective follow-up, using Cox proportional hazards models. As seen in Table 7 , the RR ratio estimate, or hazard ratio, for the outcomes of interest over 3 and 7 years of follow-up is displayed for those who were in the intermediate and frail groups at baseline, each relative to those who were nonfrail. Bivariate (unadjusted) associations were significant (p < .05) for the predictive association of frailty and intermediate frailty status with incident falls, worsened mobility or ADL disability, incident hospitalization, and death over 3 or 7 years, with hazard ratios ranging from 1.82–4.46 and 1.28–2.10 for the frail and intermediate groups, respectively. After adjustment for covariates (42), the frailty phenotype remained an independent predictor of all adverse outcomes at both 3 and 7 years, with 7-year hazard ratios ranging from 1.23–1.79 (p < .05 for all, except falls, where p = .06). The intermediate group also significantly (p < .05) predicted all outcomes after adjustment, but with lower strengths of association. Results for both 3 and 7 years follow-up were consistent. The proportional hazards assumption was found reasonable for each model.
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Discussion |
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TopAbstractMethodsResultsDiscussionAppendix ENDIXReferences |
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This study provides insight into frailty and its outcomes in a population-based sample of older adults who were neither institutionalized nor end-stage, characterizing both early presentation, correlates, and long-term outcomes. A standardized phenotype provides a basis for future comparison with other populations. The exact frequencies identified are a function of the definitions of each criterion selected, and would (obviously) change if definition shifted. However, the approach selected indicates that frailty is not rare in a community-dwelling population, and is a meaningful predictor when people are relatively functional.
Prior to this, frailty has primarily been evaluated in hospitalized or nursing home populations (3)(4)(7)(8)(24)(46)(47). Such studies, due to the selection process by which their participants arrive in these settings, are likely to characterize persons with late-stage frailty, after the occurrence of related adverse outcomes, and having highly selected correlates. One recent study in a community-dwelling population in The Netherlands used a subset of the phenotype studied here, inactivity and weight loss over 5 years of >4 kg (48). They found a similar prevalence of 6% (26/440), and similar unadjusted associations with mortality and disability, providing evidence for consistency of findings across population. The phenotype proposed here offers greater predictive validity, compared with using only two criteria.
The characterization of frailty offered here also provides new insights into potential etiologies. Frailty in this study was strongly associated with a number of major chronic diseases, including cardiovascular and pulmonary diseases and diabetes, suggestive of etiologic associations with these single diseases. However, there was a greater likelihood of frailty when two or more diseases were present than with any one. Conversely, the observation that a subset of those who were frail reported none of the diseases assessed supports the hypothesis that there may be two different pathways by which individuals become frail: one, a result of physiologic changes of aging that are not disease-based (e.g., aging-related sarcopenia [16] or anorexia of aging [(30),(31),(49),(50)]), and the other a final common pathway of severe disease or comorbidity, as suggested by the higher rates of poor health status and greater extent of subclinical physiologic changes in the frail group. Individual or comorbid diseases could potentially initiate frailty via any point on the hypothesized cycle (Fig. 1). These hypotheses remain to be confirmed.
The likelihood of frailty was also higher among women and/or those with lower socioeconomic status. Female gender could confer intrinsic risk of frailty due to women starting with lower lean mass and strength than age-matched men; thereafter, women losing lean body mass with aging might be more likely to cross a threshold necessary for frailty. Women could also have greater vulnerability to frailty via extrinsic effects on sarcopenia (e.g., because older women have a greater likelihood of inadequate nutritional intake, compared to men, due to living alone more often [19]).
This study offers support for geriatricians' contention that frailty is a physiologic syndrome (9)(10)(11)(12)(13)(14)(15)(16), and it delineates frailty from comorbidity and disability—characteristics that are often treated as synonymous with frailty. Our findings support the hypothesis that frailty causes disability, independent of clinical and subclinical diseases (Table 7 ). The syndrome of frailty may be a physiologic precursor and etiologic factor in disability, due to its central features of weakness, decreased endurance, and slowed performance. The aspects of function likely affected by frailty are those dependent on energetics and speed of performance (e.g., mobility). It is notable that only 27% of those who were disabled in ADL tasks were also frail (Table 2 ), suggesting that frailty begins by affecting mobility tasks before causing difficulty in endstage function such as ADLs, or that there are additional pathways by which older adults can become disabled. For example, disability due to arthritis of the hands might very specifically affect ability to grasp or eat, without having any relationship to frailty. Thus, frailty does not appear to be synonymous with either disability or comorbidity. Given the findings here, the terms appear to apply to distinct, but related, entities and should not be used interchangeably.
The definition of frailty offered and validated here provides a standardized, physiologically based definition applicable to the spectrum of frailty presentations seen in community-dwelling older adults. The clear criteria (see Appendix) are relatively easy and inexpensive to apply, and offer a basis for standardized screening for frailty and risk of frailty in older adults. They can, potentially, be used to establish clinical risk of adverse outcomes. They also provide a phenotype applicable to future research on etiology and interventions to prevent or retard the progression of frailty.
The major limitation of this study is that the measures utilized to operationalize the phenotype of frailty were limited to those that were fortuitously collected 10 years ago for other purposes in this longitudinal study. In addition, weight loss prior to baseline was necessarily drawn from baseline self-report. On the other hand, few studies can offer the length of follow-up or the breadth of health and demographic characteristics available in this cohort for use in understanding frailty. A number of questions remain to be evaluated, including the role of frailty in health outcomes for different subgroups (e.g, African Americans and Caucasians). In this same issue, we separately examine the association of frailty with cardiovascular diseases (51).
Overall, these findings provide support for the hypotheses of a physiologic cycle of frailty (14) that serves as the basis for the phenotype considered here (Fig. 1). This incorporates prior research demonstrating pairwise associations between each two components in the cycle (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). This hypothesized cycle of frailty, representing an adverse, potentially downward spiral of energetics, is consistent with the clinical markers of frailty identified by geriatricians and gerontologists (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and our findings and others' proposals (46)(52)(53) of an intermediate and later stage of frailty in community-dwelling older adults. A more advanced stage may be observed in more debilitated populations, such as in nursing homes. This phenotype may not, however, fully explain the more subtle biologic underpinnings of decreased reserves and ability to maintain homeostasis (11)(12)(13), which may be latent prior to an insult, but be a basis for vulnerability to stressors (10)(11)(14). Further understanding of the basis for risk associated with frailty may ultimately be found in the alterations in multisystem function, complexity, and reserve with aging (12). It is possible that early frailty, or progression from the intermediate stage to frailty, might have one set of etiologic factors, whereas progression of the frailty observed here to a more end-stage point might be associated with others, such as declines in weight, albumin, or cholesterol as consequences of malnutrition or catabolism. This end stage has been reported to be irreversible and presage death (19)(24)(52)(53).
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Acknowledgments |
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The authors thank Ray Burchfield for manuscript preparation and Carol Han for her assistance in development of figures. The opinions and assertions expressed herein are those of the authors and should not be construed as reflecting those of the Uniformed Services University of the Health Sciences or of the U.S. Department of Defense.
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Footnotes |
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Received June 30, 2000
Accepted September 19, 2000
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Appendix ENDIX |
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TopAbstractMethodsResultsDiscussionAppendix ENDIXReferences |
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References |
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G. Ravaglia, P. Forti, A. Lucicesare, N. Pisacane, E. Rietti, and C. Patterson Development of an easy prognostic score for frailty outcomes in the aged Age Ageing, March 1, 2008; 37(2): 161 - 166. [Abstract] [Full Text] [PDF]
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F. C. Martin and P. Brighton Frailty: different tools for different purposes? Age Ageing, March 1, 2008; 37(2): 129 - 131. [Full Text] [PDF]
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 K. E. Ensrud, S. K. Ewing, B. C. Taylor, H. A. Fink, P. M. Cawthon, K. L. Stone, T. A. Hillier, J. A. Cauley, M. C. Hochberg, N. Rodondi, et al. Comparison of 2 Frailty Indexes for Prediction of Falls, Disability, Fractures, and Death in Older Women Arch Intern Med, February 25, 2008; 168(4): 382 - 389. [Abstract] [Full Text] [PDF]
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 J.-P. Michel, J. L. Newton, and T. B. L. Kirkwood Medical Challenges of Improving the Quality of a Longer Life JAMA, February 13, 2008; 299(6): 688 - 690. [Full Text] [PDF]
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Functional Outcomes for Clinical Trials in Frail Older Persons: Time To Be Moving: Working Group on Functional Outcome Measures for Clinical Trials J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2008; 63(2): 160 - 164. [Full Text] [PDF]
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R. Varadhan, J. Walston, A. R. Cappola, M. C. Carlson, G. S. Wand, and L. P. Fried Higher Levels and Blunted Diurnal Variation of Cortisol in Frail Older Women J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2008; 63(2): 190 - 195. [Abstract] [Full Text] [PDF]
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Q.-L. Xue, L. P. Fried, T. A. Glass, A. Laffan, and P. H. M. Chaves Life-Space Constriction, Development of Frailty, and the Competing Risk of Mortality: The Women's Health and Aging Study I Am. J. Epidemiol., January 15, 2008; 167(2): 240 - 248. [Abstract] [Full Text] [PDF]
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 J. Afilalo, G. Duque, R. Steele, J. W. Jukema, A. J.M. de Craen, and M. J. Eisenberg Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis. J. Am. Coll. Cardiol., January 1, 2008; 51(1): 37 - 45. [Abstract] [Full Text] [PDF]
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 M. J. Peterson, R. Sloane, H. J. Cohen, G. M. Crowley, C. F. Pieper, and M. C. Morey Effect of Telephone Exercise Counseling on Frailty in Older Veterans: Project LIFE American Journal of Men's Health, December 1, 2007; 1(4): 326 - 334. [Abstract] [PDF]
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R. R. Miller, G. E. Hicks, M. D. Shardell, A. R. Cappola, W. G. Hawkes, J. A. Yu-Yahiro, A. Keegan, and J. Magaziner Association of Serum Vitamin D Levels With Inflammatory Response Following Hip Fracture: The Baltimore Hip Studies J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2007; 62(12): 1402 - 1406. [Abstract] [Full Text] [PDF]
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 B. Frye, S. Scheinthal, T. Kemarskaya, and R. Pruchno Tai Chi and Low Impact Exercise: Effects on the Physical Functioning and Psychological Well-Being of Older People Journal of Applied Gerontology, November 1, 2007; 26(5): 433 - 453. [Abstract] [PDF]
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L. Desquilbet, L. P. Jacobson, L. P. Fried, J. P. Phair, B. D. Jamieson, M. Holloway, J. B. Margolick, and for the Multicenter AIDS Cohort Study HIV-1 Infection Is Associated With an Earlier Occurrence of a Phenotype Related to Frailty J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2007; 62(11): 1279 - 1286. [Abstract] [Full Text] [PDF]
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 K. L. Johansen, G. M. Chertow, C. Jin, and N. G. Kutner Significance of Frailty among Dialysis Patients J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2960 - 2967. [Full Text] [PDF]
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G. V. Ostir, Y.-F. Kuo, I. M. Berges, K. S. Markides, and K. J. Ottenbacher Measures of Lower Body Function and Risk of Mortality over 7 Years of Follow-up Am. J. Epidemiol., September 1, 2007; 166(5): 599 - 605. [Abstract] [Full Text] [PDF]
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 W. B. Ershler A gripping reality: oxidative stress, inflammation, and the pathway to frailty J Appl Physiol, July 1, 2007; 103(1): 3 - 5. [Full Text] [PDF]
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K. Rockwood and A. Mitnitski Frailty in Relation to the Accumulation of Deficits J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 722 - 727. [Abstract] [Full Text] [PDF]
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H. E. Whitson, J. L. Purser, and H. J. Cohen Frailty Thy Name Is ... Phrailty? J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 728 - 730. [Full Text] [PDF]
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H. Bergman, L. Ferrucci, J. Guralnik, D. B. Hogan, S. Hummel, S. Karunananthan, and C. Wolfson Frailty: An Emerging Research and Clinical Paradigm Issues and Controversies J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 731 - 737. [Abstract] [Full Text] [PDF]
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K. Rockwood, M. Andrew, and A. Mitnitski A Comparison of Two Approaches to Measuring Frailty in Elderly People J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 738 - 743. [Abstract] [Full Text] [PDF]
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K. E. Ensrud, S. K. Ewing, B. C. Taylor, H. A. Fink, K. L. Stone, J. A. Cauley, J. K. Tracy, M. C. Hochberg, N. Rodondi, P. M. Cawthon, et al. Frailty and Risk of Falls, Fracture, and Mortality in Older Women: The Study of Osteoporotic Fractures J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 744 - 751. [Abstract] [Full Text] [PDF]
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M. I. Frisard, J. M. Fabre, R. D. Russell, C. M. King, J. P. DeLany, R. H. Wood, E. Ravussin, and for the Louisiana Healthy Aging Study Physical Activity Level and Physical Functionality in Nonagenarians Compared to Individuals Aged 60 74 Years J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 783 - 788. [Abstract] [Full Text] [PDF]
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 A. S. Buchman, P. A. Boyle, R. S. Wilson, Y. Tang, and D. A. Bennett Frailty is Associated With Incident Alzheimer's Disease and Cognitive Decline in the Elderly Psychosom Med, June 1, 2007; 69(5): 483 - 489. [Abstract] [Full Text] [PDF]
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 M. Extermann and A. Hurria Comprehensive Geriatric Assessment for Older Patients With Cancer J. Clin. Oncol., May 10, 2007; 25(14): 1824 - 1831. [Abstract] [Full Text] [PDF]
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H. K. Sanoff, H. Bleiberg, and R. M. Goldberg Managing Older Patients With Colorectal Cancer J. Clin. Oncol., May 10, 2007; 25(14): 1891 - 1897. [Abstract] [Full Text] [PDF]
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I. Y. Leong, M. J. Farrell, R. D. Helme, and S. J. Gibson The Relationship Between Medical Comorbidity and Self-Rated Pain, Mood Disturbance, and Function in Older People With Chronic Pain J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2007; 62(5): 550 - 555. [Abstract] [Full Text] [PDF]
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 A. I Greenspan, S. L Wolf, M. E Kelley, and M. O'Grady Tai Chi and Perceived Health Status in Older Adults Who Are Transitionally Frail: A Randomized Controlled Trial Physical Therapy, May 1, 2007; 87(5): 525 - 535. [Abstract] [Full Text] [PDF]
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J. I. Barzilay, C. Blaum, T. Moore, Q. Li Xue, C. H. Hirsch, J. D. Walston, and L. P. Fried Insulin Resistance and Inflammation as Precursors of Frailty: The Cardiovascular Health Study Arch Intern Med, April 9, 2007; 167(7): 635 - 641. [Abstract] [Full Text] [PDF]
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K. Rockwood, D. Jones, Y. Wang, D. Carver, and A. Mitnitski Failure to complete performance-based measures is associated with poor health status and an increased risk of death Age Ageing, March 1, 2007; 36(2): 225 - 228. [Full Text] [PDF]
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E. P. Weiss, S. B. Racette, D. T. Villareal, L. Fontana, K. Steger-May, K. B. Schechtman, S. Klein, A. A. Ehsani, J. O. Holloszy, and Washington University School of Medicine CALERIE G Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss J Appl Physiol, February 1, 2007; 102(2): 634 - 640. [Abstract] [Full Text] [PDF]
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A. R. Folsom, L. L. Boland, M. Cushman, S. R. Heckbert, W. D. Rosamond, and J. D. Walston Frailty and Risk of Venous Thromboembolism in Older Adults J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2007; 62(1): 79 - 82. [Abstract] [Full Text] [PDF]
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 F. Lally and P. Crome Understanding frailty Postgrad. Med. J., January 1, 2007; 83(975): 16 - 20. [Abstract] [Full Text] [PDF]
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A. S. Buchman, J. A. Schneider, R. S. Wilson, J. L. Bienias, and D. A. Bennett Body mass index in older persons is associated with Alzheimer disease pathology Neurology, December 12, 2006; 67(11): 1949 - 1954. [Abstract] [Full Text] [PDF]
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K. S. Boockvar and D. E. Meier Palliative care for frail older adults: "there are things I can't do anymore that I wish I could . . . ". JAMA, November 8, 2006; 296(18): 2245 - 2253. [Abstract] [Full Text] [PDF]
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E. Orwoll, L. C. Lambert, L. M. Marshall, J. Blank, E. Barrett-Connor, J. Cauley, K. Ensrud, S. R. Cummings, and for the Osteoporotic Fractures in Men Study Group Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med, October 23, 2006; 166(19): 2124 - 2131. [Abstract] [Full Text] [PDF]
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D. B. Rolfson, S. R. Majumdar, R. T. Tsuyuki, A. Tahir, and K. Rockwood Validity and reliability of the Edmonton Frail Scale Age Ageing, September 1, 2006; 35(5): 526 - 529. [Full Text] [PDF]
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G. Onder, S. Volpato, R. Liperoti, C. D'Arco, C. Maraldi, R. Fellin, R. Bernabei, F. Landi, and on Behalf of the GIFA Investigators Total serum cholesterol and recovery from disability among hospitalized older adults. J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2006; 61(7): 736 - 742. [Abstract] [Full Text] [PDF]
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H. A. Bischoff, H. B. Staehelin, and W. C. Willett The effect of undernutrition in the development of frailty in older persons. J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2006; 61(6): 585 - 589. [Full Text] [PDF]
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K. M Palombaro, R. L Craik, K. K Mangione, and J. D Tomlinson Determining Meaningful Changes in Gait Speed After Hip Fracture Physical Therapy, June 1, 2006; 86(6): 809 - 816. [Abstract] [Full Text] [PDF]
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 M. Cesari, C. Leeuwenburgh, F. Lauretani, G. Onder, S. Bandinelli, C. Maraldi, J. M Guralnik, M. Pahor, and L. Ferrucci Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study Am. J. Clinical Nutrition, May 1, 2006; 83(5): 1142 - 1148. [Abstract] [Full Text] [PDF]
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S. M. Lichtman, D. Hollis, A. A. Miller, G. L. Rosner, C. A. Rhoades, E. P. Lester, F. Millard, J. Byrd, S. A. Cullinan, D. M. Rosen, et al. Prospective Evaluation of the Relationship of Patient Age and Paclitaxel Clinical Pharmacology: Cancer and Leukemia Group B (CALGB 9762) J. Clin. Oncol., April 20, 2006; 24(12): 1846 - 1851. [Abstract] [Full Text] [PDF]
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 K. M. Schaefer An operational definition of frailty predicted death and other adverse outcomes in older women Evid. Based Nurs., April 1, 2006; 9(2): 57 - 57. [Full Text] [PDF]
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K. Bandeen-Roche, Q.-L. Xue, L. Ferrucci, J. Walston, J. M. Guralnik, P. Chaves, S. L. Zeger, and L. P. Fried Phenotype of Frailty: Characterization in the Women's Health and Aging Studies. J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2006; 61(3): 262 - 266. [Abstract] [Full Text] [PDF]
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A. Ble, A. Cherubini, S. Volpato, B. Bartali, J. D. Walston, B. G. Windham, S. Bandinelli, F. Lauretani, J. M. Guralnik, and L. Ferrucci Lower Plasma Vitamin E Levels Are Associated With the Frailty Syndrome: The InCHIANTI Study. J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2006; 61(3): 278 - 283. [Abstract] [Full Text] [PDF]
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 S. Burdette-Radoux and H. B. Muss Adjuvant chemotherapy in the elderly: whom to treat, what regimen? Oncologist, March 1, 2006; 11(3): 234 - 242. [Abstract] [Full Text] [PDF]
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T. M. Gill, E. A. Gahbauer, H. G. Allore, and L. Han Transitions between frailty States among community-living older persons. Arch Intern Med, February 27, 2006; 166(4): 418 - 423. [Abstract] [Full Text] [PDF]
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S. L. Wolf, M. O'Grady, K. A. Easley, Y. Guo, R. W. Kressig, and M. Kutner The influence of intense tai chi training on physical performance and hemodynamic outcomes in transitionally frail, older adults. J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2006; 61(2): 184 - 189. [Abstract] [Full Text] [PDF]
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M. Cesari, S. B. Kritchevsky, B. J. Nicklas, B. W. H. J. Penninx, P. Holvoet, P. Koh-Banerjee, S. R. Cummings, T. B. Harris, A. B. Newman, and M. Pahor Lipoprotein Peroxidation and Mobility Limitation: Results From the Health, Aging, and Body Composition Study Arch Intern Med, October 10, 2005; 165(18): 2148 - 2154. [Abstract] [Full Text] [PDF]
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L. A. Wray, M. B. Ofstedal, K. M. Langa, and C. S. Blaum The Effect of Diabetes on Disability in Middle-Aged and Older Adults J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2005; 60(9): 1206 - 1211. [Abstract] [Full Text] [PDF]
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 L. P. Fried, E. C. Hadley, J. D. Walston, A. B. Newman, J. M. Guralnik, S. Studenski, T. B. Harris, W. B. Ershler, and L. Ferrucci From Bedside to Bench: Research Agenda for Frailty Sci. Aging Knowl. Environ., August 3, 2005; 2005(31): pe24 - pe24. [Abstract] [Full Text]
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 E. W Gregg and C. J Caspersen Review: Physical disability and the cumulative impact of diabetes in older adults The British Journal of Diabetes & Vascular Disease, January 1, 2005; 5(1): 13 - 17. [Abstract] [PDF]
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T. M. Gill, H. G. Allore, T. R. Holford, and Z. Guo Hospitalization, Restricted Activity, and the Development of Disability Among Older Persons JAMA, November 3, 2004; 292(17): 2115 - 2124. [Abstract] [Full Text] [PDF]
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A. M. Payne, S. L. Dodd, and C. Leeuwenburgh Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space J Appl Physiol, December 1, 2003; 95(6): 2554 - 2562. [Abstract] [Full Text]
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A. Mitnitski and K. Rockwood Help Available--Phenomenological Models for Research on Aging Sci. Aging Knowl. Environ., March 26, 2003; 2003(12): vp2 - 2. [Abstract] [Full Text]
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J. E. Morley and J. H. Flaherty Editorial It's Never Too Late: Health Promotion and Illness Prevention in Older Persons J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2002; 57(6): M338 - 342. [Full Text]
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W. M. Bortz II A Conceptual Framework of Frailty: A Review J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2002; 57(5): M283 - 288. [Abstract] [Full Text]
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A. M. Matsumoto Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M76 - 99. [Full Text]
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J. E. Morley Editorial: Drugs, Aging, and the Future J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2002; 57(1): M2 - 6. [Full Text] [PDF]
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J. E. Morley Editorial: Andropause: Is It Time for the Geriatrician to Treat It? J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2001; 56(5): 263M - 265. [Full Text]
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M. Gillick Guest Editorial: Pinning Down Frailty J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2001; 56(3): 134M - 135. [Full Text]
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A. B. Newman, J. S. Gottdiener, M. A. McBurnie, C. H. Hirsch, W. J. Kop, R. Tracy, J. D. Walston, and L. P. Fried Associations of Subclinical Cardiovascular Disease With Frailty J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2001; 56(3): 158M - 166. [Abstract] [Full Text]
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