Frailty measurement in research and clinical practice: A review

  • Elsa Dent
    Correspondence
    Corresponding author at: Centre for Research in Geriatric Medicine, School of Medicine, The University of Queensland, Brisbane, Australia.
    Affiliations
    Centre for Research in Geriatric Medicine, School of Medicine, The University of Queensland, Brisbane, Australia

    School of Public Health, The University of Adelaide, Adelaide, Australia
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  • Paul Kowal
    Affiliations
    WHO SAGE, Department of Health Statistics and Information Systems, World Health Organization, Geneva, Switzerland

    University of Newcastle Research Centre for Generational Health and Ageing, Newcastle, Australia
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  • Emiel O. Hoogendijk
    Affiliations
    Department of General Practice & Elderly Care Medicine, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands

    Department of Epidemiology & Biostatistics, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
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Published:March 30, 2016DOI:https://doi.org/10.1016/j.ejim.2016.03.007

      Highlights

      • There is no international standard measurement for frailty.
      • Multiple frailty measurements exist, with varying levels of quality.
      • Frailty measurements can be used for population screening or clinical screening/assessment.
      • The two most common measurements are Fried's phenotype and Rockwood and Mitnitski's Frailty Index.
      • Frailty should be measured in clinical practice as part of routine care for older patients.

      Abstract

      One of the leading causes of morbidity and premature mortality in older people is frailty. Frailty occurs when multiple physiological systems decline, to the extent that an individual's cellular repair mechanisms cannot maintain system homeostasis. This review gives an overview of the definitions and measurement of frailty in research and clinical practice, including: Fried's frailty phenotype; Rockwood and Mitnitski's Frailty Index (FI); the Study of Osteoporotic Fractures (SOF) Index; Edmonton Frailty Scale (EFS); the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) Index; Clinical Frailty Scale (CFS); the Multidimensional Prognostic Index (MPI); Tilburg Frailty Indicator (TFI); PRISMA-7; Groningen Frailty Indicator (GFI), Sherbrooke Postal Questionnaire (SPQ); the Gérontopôle Frailty Screening Tool (GFST) and the Kihon Checklist (KCL), among others. We summarise the main strengths and limitations of existing frailty measurements, and examine how well these measurements operationalise frailty according to Clegg's guidelines for frailty classification — that is: their accuracy in identifying frailty; their basis on biological causative theory; and their ability to reliably predict patient outcomes and response to potential therapies.

      Keywords

      1. Introduction

      There is accumulating evidence that frailty may become one of the world's most serious health issues. A global epidemiological transition is currently occurring, in which mortality is becoming more likely to result from age-related degenerative diseases than from infectious diseases [
      • Vaupel J.W.
      Biodemography of human ageing.
      ]. These age-related diseases often manifest in frailty, which can result in serious functional limitations and susceptibility to adverse outcomes. Frailty exists in around a quarter of people aged over 85 years, and places a heavy burden on health and aged care systems [
      • Rochat S.
      • Cumming R.G.
      • Blyth F.
      • Creasey H.
      • Handelsman D.
      • Le Couteur D.G.
      • et al.
      Frailty and use of health and community services by community-dwelling older men: the Concord health and ageing in men project.
      ,
      • Song X.
      • Mitnitski A.
      • Rockwood K.
      Prevalence and 10-year outcomes of frailty in older adults in relation to deficit accumulation.
      ,
      • Sanchez-Garcia S.
      • Sanchez-Arenas R.
      • Garcia-Pena C.
      • Rosas-Carrasco O.
      • Avila-Funes J.A.
      • Ruiz-Arregui L.
      • et al.
      Frailty among community-dwelling elderly Mexican people: prevalence and association with sociodemographic characteristics, health state and the use of health services.
      ]. With the number of older people dramatically expanding in almost all countries, frailty prevalence is expected to soar [
      • Morley J.E.
      • Vellas B.
      • van Kan G.A.
      • Anker S.D.
      • Bauer J.M.
      • Bernabei R.
      • et al.
      Frailty consensus: a call to action.
      ].

      1.1 What is frailty?

      Frailty is a geriatric condition characterised by an increased vulnerability to external stressors [
      • Morley J.E.
      • Vellas B.
      • van Kan G.A.
      • Anker S.D.
      • Bauer J.M.
      • Bernabei R.
      • et al.
      Frailty consensus: a call to action.
      ,
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Newman A.B.
      • Hirsch C.
      • Gottdiener J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      ]. It is strongly linked to adverse outcomes, including mortality, nursing home admission, and falls [
      • Topinkova E.
      Aging, disability and frailty.
      ,
      • Kane R.L.
      • Shamliyan T.
      • Talley K.
      • Pacala J.
      The association between geriatric syndromes and survival.
      ,
      • Fang X.
      • Shi J.
      • Song X.
      • Mitnitski A.
      • Tang Z.
      • Wang C.
      • et al.
      Frailty in relation to the risk of falls, fractures, and mortality in older Chinese adults: results from the Beijing longitudinal study of aging.
      ,
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ,
      • Cawthon P.M.
      • Marshall L.M.
      • Michael Y.
      • Dam T.T.
      • Ensrud K.E.
      • Barrett-Connor E.
      • et al.
      Frailty in older men: prevalence, progression, and relationship with mortality.
      ]. Frailty is different conceptually from ageing, disability, and co-morbidity although it is distinctly related to these factors [
      • Rockwood K.
      • Mitnitski A.
      Frailty in relation to the accumulation of deficits.
      ,
      • Gobbens R.J.
      • van Assen M.A.
      • Luijkx K.G.
      • Wijnen-Sponselee M.T.
      • Schols J.M.
      Determinants of frailty.
      ,
      • De Saint-Hubert M.
      • Schoevaerdts D.
      • Cornette P.
      • D'Hoore W.
      • Boland B.
      • Swine C.
      Predicting functional adverse outcomes in hospitalized older patients: a systematic review of screening tools.
      ,
      • Kulminski A.
      • Yashin A.
      • Ukraintseva S.
      • Akushevich I.
      • Arbeev K.
      • Land K.
      • et al.
      Accumulation of health disorders as a systemic measure of aging: findings from the NLTCS data.
      ,
      • Armstrong J.J.
      • Stolee P.
      • Hirdes J.P.
      • Poss J.W.
      Examining three frailty conceptualizations in their ability to predict negative outcomes for home-care clients.
      ,
      • Martin F.C.
      • Brighton P.
      Frailty: different tools for different purposes?.
      ,
      • Kuzuya M.
      Process of physical disability among older adults—contribution of frailty in the super-aged society.
      ]. For example, although frailty prevalence increases with age, it occurs independently from chronological age [
      • Topinkova E.
      Aging, disability and frailty.
      ,
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ].
      Frailty does not yet have an internationally recognised standard definition, although the general premise is that frailty may be considered to be a geriatric syndrome [
      • Kuzuya M.
      Process of physical disability among older adults—contribution of frailty in the super-aged society.
      ,
      • Xue Q.L.
      The frailty syndrome: definition and natural history.
      ,
      • Rolland Y.
      • Benetos A.
      • Gentric A.
      • Ankri J.
      • Blanchard F.
      • Bonnefoy M.
      • et al.
      Frailty in older population: a brief position paper from the French society of geriatrics and gerontology.
      ,
      • Conroy S.
      Defining frailty—the Holy Grail of geriatric medicine.
      ,
      • Ruiz M.
      • Cefalu C.
      • Reske T.
      Frailty syndrome in geriatric medicine.
      ,
      • Gielen E.
      • Verschueren S.
      • O'Neill T.W.
      • Pye S.R.
      • O'Connell M.D.
      • Lee D.M.
      • et al.
      Musculoskeletal frailty: a geriatric syndrome at the core of fracture occurrence in older age.
      ,
      • Fulop T.
      • Larbi A.
      • Witkowski J.M.
      • McElhaney J.
      • Loeb M.
      • Mitnitski A.
      • et al.
      Aging, frailty and age-related diseases.
      ,
      • Chen X.
      • Mao G.
      • Leng S.X.
      Frailty syndrome: an overview.
      ] reflecting multi-system dysfunction [
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Newman A.B.
      • Hirsch C.
      • Gottdiener J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      ,
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ,
      • Gielen E.
      • Verschueren S.
      • O'Neill T.W.
      • Pye S.R.
      • O'Connell M.D.
      • Lee D.M.
      • et al.
      Musculoskeletal frailty: a geriatric syndrome at the core of fracture occurrence in older age.
      ,
      • Chen X.
      • Mao G.
      • Leng S.X.
      Frailty syndrome: an overview.
      ,
      • Rockwood K.
      • Mitnitski A.
      Frailty defined by deficit accumulation and geriatric medicine defined by frailty.
      ,
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ] and in which individuals are able to dynamically transition between severity states [
      • Rockwood K.
      • Mitnitski A.
      Frailty in relation to the accumulation of deficits.
      ,
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ,
      • Gill T.M.
      • Gahbauer E.A.
      • Allore H.G.
      • Han L.
      Transitions between frailty states among community-living older persons.
      ,
      • Campbell A.J.
      • Buchner D.M.
      Unstable disability and the fluctuations of frailty.
      ]. Multiple reasons exist as to why it is so difficult to define frailty, including: its complex aetiology [
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ,
      • Heuberger R.A.
      The frailty syndrome: a comprehensive review.
      ]; the often independent work of frailty researchers [
      • Karunananthan S.
      • Wolfson C.
      • Bergman H.
      • Beland F.
      • Hogan D.B.
      A multidisciplinary systematic literature review on frailty: overview of the methodology used by the Canadian initiative on frailty and aging.
      ,
      • Hogan D.B.
      • MacKnight C.
      • Bergman H.
      Models, definitions, and criteria of frailty.
      ]; and the inherent difficulty in distinguishing frailty from both ageing and disability [
      • Kuzuya M.
      Process of physical disability among older adults—contribution of frailty in the super-aged society.
      ,
      • Ruiz M.
      • Cefalu C.
      • Reske T.
      Frailty syndrome in geriatric medicine.
      ,
      • Fedarko N.S.
      The biology of aging and frailty.
      ]. Regardless of these issues, and perhaps because of them, international groups such as the World Health Organization (WHO) and the International Association of Geriatrics and Gerontology (IAGG) are working on an internationally accepted frailty definition [
      • Ruiz M.
      • Cefalu C.
      • Reske T.
      Frailty syndrome in geriatric medicine.
      ,
      • Berrut G.
      • Andrieu S.
      • Araujo de Carvalho I.
      • Baeyens J.P.
      • Bergman H.
      • Cassim B.
      • et al.
      Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Societe Francaise de Geriatrie et de Gerontologie) workshop—Athens January 20–21, 2012.
      ].

      1.2 What causes frailty?

      Frailty has a strong biological component, and it is thought to result from cumulative cellular damage over the life-course [
      • Rockwood K.
      • Mitnitski A.
      Frailty in relation to the accumulation of deficits.
      ,
      • Wensink M.
      • Westendorp R.G.
      • Baudisch A.
      The causal pie model: an epidemiological method applied to evolutionary biology and ecology.
      ,
      • Cesari M.
      • Vellas B.
      • Gambassi G.
      The stress of aging.
      ]. The specific pathophysiological pathways underpinning frailty are not yet clearly known [
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ,
      • Ho Y.Y.
      • Matteini A.M.
      • Beamer B.
      • Fried L.
      • Xue Q.L.
      • Arking D.E.
      • et al.
      Exploring biologically relevant pathways in frailty.
      ], although there is evidence that both malnutrition and sarcopenia (muscle wastage) may have similar causal pathways [
      • Jeejeebhoy K.N.
      Malnutrition, fatigue, frailty, vulnerability, sarcopenia and cachexia: overlap of clinical features.
      ,
      • Calvani R.
      • Marini F.
      • Cesari M.
      • Tosato M.
      • Anker S.D.
      • von Haehling S.
      • et al.
      Biomarkers for physical frailty and sarcopenia: state of the science and future developments.
      ,
      • Cesari M.
      • Landi F.
      • Vellas B.
      • Bernabei R.
      • Marzetti E.
      Sarcopenia and physical frailty: two sides of the same coin.
      ]. Inflammation is one such pathway, and is well established as a causal factor for frailty [
      • Gielen E.
      • Verschueren S.
      • O'Neill T.W.
      • Pye S.R.
      • O'Connell M.D.
      • Lee D.M.
      • et al.
      Musculoskeletal frailty: a geriatric syndrome at the core of fracture occurrence in older age.
      ,
      • Fulop T.
      • Larbi A.
      • Witkowski J.M.
      • McElhaney J.
      • Loeb M.
      • Mitnitski A.
      • et al.
      Aging, frailty and age-related diseases.
      ,
      • Chen X.
      • Mao G.
      • Leng S.X.
      Frailty syndrome: an overview.
      ,
      • Heuberger R.A.
      The frailty syndrome: a comprehensive review.
      ,
      • Li H.
      • Manwani B.
      • Leng S.X.
      Frailty, inflammation, and immunity.
      ]. Pro-inflammatory cytokines can influence frailty either directly, for instance by promoting protein degradation [
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ], or indirectly by altering metabolic processes [
      • Heuberger R.A.
      The frailty syndrome: a comprehensive review.
      ].
      The biological causative mechanisms of frailty are different from those processes causing the ageing process [
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ]. Frailty occurs when not one, but multiple physiological systems decline [
      • Morley J.E.
      • Vellas B.
      • van Kan G.A.
      • Anker S.D.
      • Bauer J.M.
      • Bernabei R.
      • et al.
      Frailty consensus: a call to action.
      ,
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ,
      • Gielen E.
      • Verschueren S.
      • O'Neill T.W.
      • Pye S.R.
      • O'Connell M.D.
      • Lee D.M.
      • et al.
      Musculoskeletal frailty: a geriatric syndrome at the core of fracture occurrence in older age.
      ,
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ,
      • Cesari M.
      • Vellas B.
      • Gambassi G.
      The stress of aging.
      ]: the more physiological systems that are in a diminished state, the greater the likelihood of frailty [
      • Fried L.P.
      • Xue Q.L.
      • Cappola A.R.
      • Ferrucci L.
      • Chaves P.
      • Varadhan R.
      • et al.
      Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment.
      ]. While physiological systems do lose some of their homeostatic reserve at advanced ages, there is an inherent reserve buffer, suggested to be around 30%, which an individual can lose and still function well [
      • Bortz W.
      Human aging: normal and abnormal.
      ]. Frailty is thought to result when this threshold is surpassed in multiple physiological systems — so much so that repair mechanisms cannot maintain system homeostasis [
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ]. Pre-frailty (latent frailty) is thought to be the silent precursor to frailty, manifesting as frailty when external stressors, such as acute illness, injury or psychological stress, occur [
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ].
      Other factors linked with frailty development include (i) sociodemographic influences, such as poverty, living alone, area deprivation and low education level [
      • Xue Q.L.
      The frailty syndrome: definition and natural history.
      ,
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ,
      • Heuberger R.A.
      The frailty syndrome: a comprehensive review.
      ,
      • Hoogendijk E.O.
      • van Hout H.P.
      • Heymans M.W.
      • van der Horst H.E.
      • Frijters D.H.
      • Broese van Groenou M.I.
      • et al.
      Explaining the association between educational level and frailty in older adults: results from a 13-year longitudinal study in the Netherlands.
      ]; (ii) psychological factors, including depression [
      • Vaughan L.
      • Corbin A.L.
      • Goveas J.S.
      Depression and frailty in later life: a systematic review.
      ]; (iii) nutritional issues such as malnutrition and poor oral health, [
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ,
      • Lang P.O.
      • Michel J.P.
      • Zekry D.
      Frailty syndrome: a transitional state in a dynamic process.
      ,
      • Castrejón-Pérez R.
      • Borges-Yáñez S.
      Frailty from an oral health point of view.
      ]; (iv) polypharmacy [
      • Heuberger R.A.
      The frailty syndrome: a comprehensive review.
      ]; (v) diseases (cancer, endocrine disorders, dementia) and their associated complications [
      • Heuberger R.A.
      The frailty syndrome: a comprehensive review.
      ]; and (v) low physical activity [
      • Heuberger R.A.
      The frailty syndrome: a comprehensive review.
      ].

      1.3 Frailty measurement

      Regardless of what definition of frailty is used, to be applied practically, frailty first needs to be operationally defined. A breakthrough in frailty measurement came in the mid-1990s, when it was verified that when frailty manifestations, such as slow walking speed and weight loss, were grouped together to form combination scores, prediction of adverse clinical outcomes was better than when components were considered alone [
      • Sager M.A.
      • Rudberg M.A.
      • Jalaluddin M.
      • Franke T.
      • Inouye S.K.
      • Landefeld C.S.
      • et al.
      Hospital admission risk profile (HARP): identifying older patients at risk for functional decline following acute medical illness and hospitalization.
      ,
      • Corti M.C.
      • Guralnik J.M.
      • Salive M.E.
      • Sorkin J.D.
      Serum albumin level and physical disability as predictors of mortality in older persons.
      ]. Frailty combination scores have been used to operationally define frailty ever since. In 2001, Fried and colleagues proposed their landmark frailty phenotype measurement, which assessed frailty by measuring five of its physical components [
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Newman A.B.
      • Hirsch C.
      • Gottdiener J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      ]. Following this, and also in 2001, Rockwood and Mitnitski released their accumulated deficits model of frailty, which considered not only the physical components of frailty, but also the psychosocial aspects of frailty [
      • Mitnitski A.B.
      • Mogilner A.J.
      • Rockwood K.
      Accumulation of deficits as a proxy measure of aging.
      ]. Both of these frailty models are highly regarded and in common use today.
      Nowadays, a plethora of frailty measurements are in existence. Identifying which frailty measurement is most suitable for clinical and/or research application is currently a topic of heated debate. Moreover, multiple reviews have highlighted the need for a standard measurement of frailty in research and/or clinical practice [
      • Rockwood K.
      • Mitnitski A.
      Frailty in relation to the accumulation of deficits.
      ,
      • Martin F.C.
      • Brighton P.
      Frailty: different tools for different purposes?.
      ,
      • Xue Q.L.
      The frailty syndrome: definition and natural history.
      ,
      • Gielen E.
      • Verschueren S.
      • O'Neill T.W.
      • Pye S.R.
      • O'Connell M.D.
      • Lee D.M.
      • et al.
      Musculoskeletal frailty: a geriatric syndrome at the core of fracture occurrence in older age.
      ,
      • Karunananthan S.
      • Wolfson C.
      • Bergman H.
      • Beland F.
      • Hogan D.B.
      A multidisciplinary systematic literature review on frailty: overview of the methodology used by the Canadian initiative on frailty and aging.
      ,
      • Berrut G.
      • Andrieu S.
      • Araujo de Carvalho I.
      • Baeyens J.P.
      • Bergman H.
      • Cassim B.
      • et al.
      Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Societe Francaise de Geriatrie et de Gerontologie) workshop—Athens January 20–21, 2012.
      ,
      • Rodriguez-Manas L.
      • Feart C.
      • Mann G.
      • Vina J.
      • Chatterji S.
      • Chodzko-Zajko W.
      • et al.
      Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project.
      ,
      • de Vries N.M.
      • Staal J.B.
      • van Ravensberg C.D.
      • Hobbelen J.S.
      • Olde Rikkert M.G.
      • Nijhuis van der Sanden M.W.
      Outcome instruments to measure frailty: a systematic review.
      ,
      • Rockwood K.
      What would make a definition of frailty successful?.
      ]. A standard measurement would allow for consistent recognition of frailty worldwide.
      Critically, a frailty measurement should fulfil a number of criteria. First and foremost, it should be able to accurately identify frailty. Additional qualities it should possess as identified by Clegg et al. [
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ] using Bell's disease classification guidelines [
      • Bell J.
      Redefining disease.
      ] include: (i) an ability to reliably predict adverse clinical outcomes; (ii) an ability to reliably predict patient response to potential therapies; and, (iii) be supported by a biological causative theory. Frailty measurements should also be simple to apply [
      • Clegg A.
      • Young J.
      • Iliffe S.
      • Rikkert M.O.
      • Rockwood K.
      Frailty in elderly people.
      ]. Of further importance is their level of application. For instance, some frailty measurements may be more applicable for use in population health studies as screening tools, whereas others may work best in the clinical setting either for the screening or diagnosis of frailty.

      1.4 Research question

      To date, no reviews have yet independently placed a wide range of frailty measurements under scrutiny using Clegg's criteria for frailty measurement. The aim of this review was to determine which operationalisations of frailty were best at measuring frailty according to Clegg's guidelines of frailty classification: that is, which measurements could accurately identify frailty; which could reliably predict patient outcomes and response to potential therapies; and which were based on biological theory.

      2. Methods

      To identify studies reporting frailty measurements, EMBASE and PubMed databases were searched. Search terms were broadly set as: ‘frail elderly’ and ‘Geriatric Assessment/methods’. The initial search was performed in July 2015 and was restricted to studies published between January 2009 and July 2015. Studies prior to 2009 were not included, because it was considered that if a frailty measurement had not been discussed in the literature in the past five years, then it was unlikely to have been recently used. The search was limited to English language articles.
      Titles and abstracts were screened against the inclusion criteria. Only full research papers and review articles were considered. A “lateral search” was also performed, in which the citations of relevant articles were searched. The following Population Implementation Comparator Outcome (PICO) was used:
      • Population: aged ≥65 years.
      • Implementation/indicator: frailty objectively measured in either observational, cross-sectional or randomised control trials.
      • Comparator: n/a.
      • Outcome: frailty classification or frailty prognosis.

      2.1 Critiquing of frailty measurements

      Frailty measurements were critiqued using the following standards:
      • 1.
        Time taken to perform the measurement.
      • 2.
        Data used to derive the frailty measurement is available from routinely collected CGA data.
      • 3.
        Specialised equipment is required to measure frailty (for instance, a grip strength dynamometer).
      • 4.
        Requirement for assessor training.
      • 5.
        Validity and reliability. Reviews were initially consulted to determine the reliability and validity of frailty measurements. If no discussion of validity/reliability was included in these reviews, then relevant individual articles were searched.
      • 6.
        The measurement is based on an underlying biological theory.
      • 7.
        The measurement takes into account the continuum of frailty.
      • 8.
        The measurement is able to predict surgical/medical outcomes and/or mortality.

      3. Results

      422 studies were identified. From these studies, 29 different frailty measurements were identified. Overall, frailty measurements were used for frailty classification and prognosis across a broad range of medical patients, including: geriatric, oncology, surgical, orthopaedic, cardiovascular and renal patients. The majority of these medical studies used frailty measurement as a prognostic tool, with Fried's frailty phenotype and the FI being the most common frailty measurements applied to these studies. Table 1 outlines the frailty measurements identified in the present study, and ranks them against quality criteria. The various frailty measurements identified and their details are outlined in 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 3.10, 3.11, 3.12, 3.13, 3.14, 3.15, 3.16.
      Table 1Comparisons of selected frailty operational definitions.
      Frailty measurements are evaluated by clinical or research staff, unless otherwise indicated (for example, by patient self-report). All frailty measurements were based on a biological theory, with the exception of the CFS.
      IndexCountry of originTime (min)# itemsComponentsFrailtyRequirements of frailty measurementsMeasurement used in the clinical or population setting?
      Data CGA
      ‘Data CGA’ implies that the data for the frailty measurement is obtainable readily from a Comprehensive Geriatric Assessment (CGA).
      Special equipmentAssessor trainingValid & reliableOutcome prediction
      CHSUSA<105Weight loss, low physical activity, exhaustion, slowness, weaknessFrailty ≥3items; pre-frail 1–2 items; Robust = nonexBoth
      FI-CDCanada20–3030+Accumulated health deficits: score of 0 (no deficits) to 1.0 (all deficits)A continuous score. Frailty cut-off suggested >0.25xBoth
      FI-CGACanada<1530+10 domains, 52 items (originally 14): including ADL, IADL, Co-morbidities, Mood & CognitionA continuous score. Frailty cut-off suggested >0.25xClinical
      SOFUSA<53Weight Loss, Exhaustion, Unable to Rise from Chair 5 timesFrailty ≥2 items; pre-frail = 1 item; robust = 0 itemsxxxBoth
      EFSCanada<59Cognition, health (2×), hospitalisation, social support, nutrition, mood, function, continenceFrailty = scores ≥7xxClinical
      FRAILUSA<105Fatigue, Resistance, Ambulation, Illness, Loss of WeightFrailty ≥3 items; Pre-frail 1–2 items; robust = 0 itemsxxMore studies neededBoth
      CFSCanada<51Visual and written chart for frailty with 9 graded pictures. 1 = very fit; 9 = terminally illA continuous score. Frailty cut-off point ≥5xxClinical
      MPIItaly<158Co-morbidity, Nutrition, Cognition, Polypharmacy, Pressure Sore Risk, Living Status, ADL, IADLFrailty >0.66; Pre-frailty = 0.34–0.66; robust <0.34xMore studies neededBoth
      TFIThe Netherlands<1515Self-reported in 3 domains: physical, psychological and socialFrailty = scores ≥5xxxMore studies neededPopulation-level screening
      PRISMA-7Canada<107Self-reported: age (>85 years), male, social support and ADLsFrailty = scores ≥3xxxMore studies neededPopulation-level screening
      GFIThe Netherlands<1515Self-reported in 4 domains: physical, cognitive, social and psychologicalFrailty = scores ≥4xxxxMore studies neededPopulation-level screening
      SPQCanada<56Self-reported: living alone, polypharmacy, mobility, eyesight, hearing, memoryFrailty = scores ≥2xxxxMore studies neededPopulation-level screening
      GFSTFrance<562 parts: (i) self-report (lives alone, weight loss, fatigue, mobile, memory, gait (ii) clinical judgementIdentified by clinical judgement, after screeningxxxMore studies neededPopulation-level screening
      KCLJapan<102525 items from CGA, scoring as per FI-CGAA continuous score. Frailty cut-off suggested >0.25xMore studies neededPopulation-level screening
      Abbreviations: CHS = Cardiovascular Health Study Index (Fried's Frailty Phenotype); FI-CD = Frailty Index of Accumulated Deficits; FI-CGA = Frailty Index derived from Comprehensive Geriatric Assessment; SOF = Study of Osteoporotic Fracture (SOF) Index; EFS = Edmonton Frailty Scale; FRAIL = Fatigue, Resistance, Ambulation, Illness and Loss of Weight Index; CFS = Clinical Frailty Scale; MPI = Multidimensional Prognostic Index; TFI = Tilburg Frailty Index; GFI = Groningen Frailty Indicator; SPQ = Sherbrooke Postal Questionnaire; GFST = Gérontopôle Frailty Screening Tool (GFST); KCL = Kihon Check-list.
      a Frailty measurements are evaluated by clinical or research staff, unless otherwise indicated (for example, by patient self-report). All frailty measurements were based on a biological theory, with the exception of the CFS.
      b ‘Data CGA’ implies that the data for the frailty measurement is obtainable readily from a Comprehensive Geriatric Assessment (CGA).

      3.1 Fried's Frailty Phenotype — the Cardiovascular Health Study (CHS) index

      Fried's Frailty Phenotype is a popular measurement of frailty, often known as the Cardiovascular Health Study (CHS) Index from the study it was originally applied to [
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Newman A.B.
      • Hirsch C.
      • Gottdiener J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      ]. The CHS index considers frailty by its physical characteristics, or ‘phenotype’, defining the condition as the presence of three or more of: shrinking (unintentional weight loss of 4.5 kg or more in the last year), weakness (low grip strength), exhaustion (self-reported), slowness (slow walking speed) and low physical activity [
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Newman A.B.
      • Hirsch C.
      • Gottdiener J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      ]. It has a solid foundation of biological causative theory [
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Newman A.B.
      • Hirsch C.
      • Gottdiener J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      ,
      • Xue Q.L.
      • Bandeen-Roche K.
      • Varadhan R.
      • Zhou J.
      • Fried L.P.
      Initial manifestations of frailty criteria and the development of frailty phenotype in the women's health and aging study II.
      ] and has been applied to multiple epidemiological studies where it is predictive of adverse clinical outcomes, including mortality [
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Newman A.B.
      • Hirsch C.
      • Gottdiener J.
      • et al.
      Frailty in older adults: evidence for a phenotype.
      ,
      • Bandeen-Roche K.
      • Xue Q.L.
      • Ferrucci L.
      • Walston J.
      • Guralnik J.M.
      • Chaves P.
      • et al.
      Phenotype of frailty: characterization in the women's health and aging studies.
      ,
      • Gill T.M.
      • Gahbauer E.A.
      • Han L.
      • Allore H.G.
      Trajectories of disability in the last year of life.
      ,
      • Lee L.
      • Heckman G.
      • Molnar F.J.
      Frailty: identifying elderly patients at high risk of poor outcomes.
      ]. Despite its widespread use, a major factor inhibiting clinical application of the CHS index is its inclusion of measurements not routinely used for patient assessment — grip strength, for example. Also of note, the CHS index does not include psychosocial components of frailty.

      3.2 Frailty Index of Accumulative Deficits (FI-CD)

      The Frailty Index (FI) of Accumulative Deficits (FI-CD) was first proposed by Rockwood and Mitnitski as a way to incorporate the multidimensional nature of frailty into an operational definition [
      • Mitnitski A.B.
      • Mogilner A.J.
      • Rockwood K.
      Accumulation of deficits as a proxy measure of aging.
      ]. The FI-CD is underpinned by biological causative theory [
      • Rockwood K.
      • Mitnitski A.
      Frailty in relation to the accumulation of deficits.
      ,
      • Rockwood K.
      • Rockwood M.R.
      • Mitnitski A.
      Physiological redundancy in older adults in relation to the change with age in the slope of a frailty index.
      ] and involves the accumulation of 30 or more co-morbidities, symptoms, diseases, disabilities or any deficiency in health with the idea that a greater number of health deficits indicates higher frailty [
      • Searle S.D.
      • Mitnitski A.
      • Gahbauer E.A.
      • Gill T.M.
      • Rockwood K.
      A standard procedure for creating a frailty index.
      ]. The FI-CD is expressed as a ratio. For instance, if a list of possible health deficits obtainable from a study cohort is 50, a person with five of these deficits has a frailty index of 0.1. The exact list of health deficits for inclusion in the FI-CD does not specifically matter, other than they should: increase in incidence but not have a ceiling effect with age; be reflective of a range of physiological systems; and be associated with health and not age per se [
      • Searle S.D.
      • Mitnitski A.
      • Gahbauer E.A.
      • Gill T.M.
      • Rockwood K.
      A standard procedure for creating a frailty index.
      ]. Comprehensive guidelines for creating a FI-CD have been provided by Searle et al. 2008 [
      • Searle S.D.
      • Mitnitski A.
      • Gahbauer E.A.
      • Gill T.M.
      • Rockwood K.
      A standard procedure for creating a frailty index.
      ].
      The FI-CD is well validated, and has been applied to multiple datasets, including the Survey of Health, Ageing and Retirement (SHARE) study in Europe, where it is termed the SHARE-FI [
      • Romero-Ortuno R.
      The frailty instrument for primary care of the survey of health, ageing and retirement in Europe predicts mortality similarly to a frailty index based on comprehensive geriatric assessment.
      ,
      • Romero-Ortuno R.
      • Soraghan C.
      A frailty instrument for primary care for those aged 75 years or more: findings from the survey of health, ageing and retirement in Europe, a longitudinal population-based cohort study (SHARE-FI75+).
      ]. Ideally, the FI-CD should be used as a continuous variable, however for comparison studies, various cut-off points have been considered to identify frailty [
      • Dent E.
      • Perez-Zepeda M.
      Comparison of five indices for prediction of adverse outcomes in hospitalised Mexican older adults: a cohort study.
      ,
      • Blodgett J.
      • Theou O.
      • Kirkland S.
      • Andreou P.
      • Rockwood K.
      Frailty in NHANES: comparing the frailty index and phenotype.
      ]. Importantly, the FI-CD has been recently adapted to a clinical model for mice, which has huge implications for frailty intervention studies [
      • Kane A.E.
      • Hilmer S.N.
      • Boyer D.
      • Gavin K.
      • Nines D.
      • Howlett S.E.
      • et al.
      Impact of longevity interventions on a validated mouse clinical frailty index.
      ,
      • Parks R.J.
      • Fares E.
      • Macdonald J.K.
      • Ernst M.C.
      • Sinal C.J.
      • Rockwood K.
      • et al.
      A procedure for creating a frailty index based on deficit accumulation in aging mice.
      ].
      Several studies have found that the FI-CD has a higher predictive ability of adverse clinical events than other frailty measurements in both hospital and community settings [
      • Dent E.
      • Perez-Zepeda M.
      Comparison of five indices for prediction of adverse outcomes in hospitalised Mexican older adults: a cohort study.
      ,
      • Theou O.
      • Brothers T.D.
      • Mitnitski A.
      • Rockwood K.
      Operationalization of frailty using eight commonly used scales and comparison of their ability to predict all-cause mortality.
      ,
      • Dent E.
      • Chapman I.
      • Howell S.
      • Piantadosi C.
      • Visvanathan R.
      Frailty and functional decline indices predict poor outcomes in hospitalised older people.
      ]. Additionally, it has been reported that it is the total FI-CD score, rather than type of health deficits included in the FI-CD, that is most predictive of adverse outcomes [
      • Rockwood K.
      • Mitnitski A.
      Frailty in relation to the accumulation of deficits.
      ]. An upper limit the FI-CD is believed to exist at around 0.67, beyond which survival is unlikely [
      • Rockwood K.
      • Mitnitski A.
      Limits to deficit accumulation in elderly people.
      ].
      Despite its many positive attributes, the FI-CD does have its limitations: it can be time consuming to calculate and its mathematical nature, although simple, renders it unpopular clinically [
      • Hubbard R.E.
      • O'Mahony M.S.
      • Woodhouse K.W.
      Characterising frailty in the clinical setting—a comparison of different approaches.
      ]. However, when derived from data already collected in a Comprehensive Geriatric Assessment (CGA), construction of a FI can be time-efficient, as detailed in Section 3.3.

      3.3 Frailty index derived from comprehensive geriatric assessment (FI-CGA)

      The frailty index derived from CGA (FI-CGA) is simply a FI-CD using data from a CGA. CGA is the global standard clinical assessment for older people, and includes medical, nutritional, functional and psychological assessments by a multidimensional team. The FI-CGA was initially developed as a ten-domain index, with 14 CGA components included [
      • Jones D.M.
      • Song X.
      • Rockwood K.
      Operationalizing a frailty index from a standardized comprehensive geriatric assessment.
      ,
      • Jones D.
      • Song X.
      • Mitnitski A.
      • Rockwood K.
      Evaluation of a frailty index based on a comprehensive geriatric assessment in a population based study of elderly Canadians.
      ]. It was later expanded out by Rockwood and colleagues to include 52 CGA components [
      • Rockwood K.
      • Rockwood M.R.
      • Mitnitski A.
      Physiological redundancy in older adults in relation to the change with age in the slope of a frailty index.
      ]. The CGA is used as a clinical standard for frailty assessment and has been found to be highly associated with the FI-CD [
      • Jones D.M.
      • Song X.
      • Rockwood K.
      Operationalizing a frailty index from a standardized comprehensive geriatric assessment.
      ]. Nowadays, many clinical studies have adopted a FI-CGA for frailty assessment. FI-CGA has been found to predict patient response in multiple fields, including: oncology, orthopaedics, immunology, urology, pulmonology, and cardiology [
      • Chen X.
      • Mao G.
      • Leng S.X.
      Frailty syndrome: an overview.
      ,
      • Hamaker M.E.
      • Jonker J.M.
      • de Rooij S.E.
      • Vos A.G.
      • Smorenburg C.H.
      • van Munster B.C.
      Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review.
      ,
      • Afilalo J.
      • Alexander K.P.
      • Mack M.J.
      • Maurer M.S.
      • Green P.
      • Allen L.A.
      • et al.
      Frailty assessment in the cardiovascular care of older adults.
      ].

      3.4 Study of Osteoporotic Fractures (SOF) Index

      The Study of Osteoporotic Fractures (SOF) frailty index, like the CHS index, considers frailty to be phenotypic in nature, with an underlying biological causative theory [
      • Ensrud K.E.
      • Ewing S.K.
      • Taylor B.C.
      • Fink H.A.
      • Stone K.L.
      • Cauley J.A.
      • et al.
      Frailty and risk of falls, fracture, and mortality in older women: the study of osteoporotic fractures.
      ]. The SOF is easy to apply, with frailty classified as the presence of ≥2 components out of list of three: weight loss (intentional/unintentional, >5% in the last year), exhaustion (an answer of ‘no’ to the question ‘do you feel full of energy?’) and low mobility (inability to perform a chair rise five times). The SOF is valid and reliable, and has been found to be an independent predictor of adverse outcomes in community-dwelling older people [
      • Bilotta C.
      • Nicolini P.
      • Case A.
      • Pina G.
      • Rossi S.
      • Vergani C.
      Frailty syndrome diagnosed according to the study of osteoporotic fractures (SOF) criteria and adverse health outcomes among community-dwelling older outpatients in Italy. A one-year prospective cohort study.
      ]. It generally compares well to the FI and the CHS regarding adverse outcome prediction [
      • Dent E.
      • Perez-Zepeda M.
      Comparison of five indices for prediction of adverse outcomes in hospitalised Mexican older adults: a cohort study.
      ,
      • Dent E.
      • Chapman I.
      • Howell S.
      • Piantadosi C.
      • Visvanathan R.
      Frailty and functional decline indices predict poor outcomes in hospitalised older people.
      ,
      • Ensrud K.E.
      • Ewing S.K.
      • Taylor B.C.
      • Fink H.A.
      • Stone K.L.
      • Cauley J.A.
      • et al.
      Frailty and risk of falls, fracture, and mortality in older women: the study of osteoporotic fractures.
      ,
      • Ensrud K.E.
      • Ewing S.K.
      • Cawthon P.M.
      • Fink H.A.
      • Taylor B.C.
      • Cauley J.A.
      • et al.
      A comparison of frailty indexes for the prediction of falls, disability, fractures, and mortality in older men.
      ]. The SOF is suited for both population screening and clinical assessment, although it does tend to over-screen frailty in the hospital setting because patients with an acute medical condition often cannot perform a five-times-chair-rise.

      3.5 Edmonton Frailty Scale (EFS)

      The Edmonton Frail Scale (EFS) is a valid and reliable measurement tool for the identification of frailty in the hospital setting [
      • Rolfson D.B.
      • Majumdar S.R.
      • Tsuyuki R.T.
      • Tahir A.
      • Rockwood K.
      Validity and reliability of the Edmonton frail scale.
      ]. The EFS is scored out of 17, and contains nine components: cognition; general health status: self-reported health: functional independence: social support; polypharmacy; mood; continence; and functional performance [
      • Rolfson D.B.
      • Majumdar S.R.
      • Tsuyuki R.T.
      • Tahir A.
      • Rockwood K.
      Validity and reliability of the Edmonton frail scale.
      ]. Component scores are summed, and the following cut-off scores used to classify frailty severity: not frail (0–5); apparently vulnerable (6–7); mildly frail (8–9); moderately frail (10–11) and severely frailty (12–17) [
      • Rolfson D.B.
      • Majumdar S.R.
      • Tsuyuki R.T.
      • Tahir A.
      • Rockwood K.
      Validity and reliability of the Edmonton frail scale.
      ]. With only nine components, the EFS is much simpler to extract from CGAs than the FI-CGA. The EFS is increasingly being used to identify frailty in specific clinical populations [
      • Partridge J.S.
      • Fuller M.
      • Harari D.
      • Taylor P.R.
      • Martin F.C.
      • Dhesi J.K.
      Frailty and poor functional status are common in arterial vascular surgical patients and affect postoperative outcomes.
      ,
      • Graham M.M.
      • Galbraith P.D.
      • O'Neill D.
      • Rolfson D.B.
      • Dando C.
      • Norris C.M.
      Frailty and outcome in elderly patients with acute coronary syndrome.
      ], and an adapted version, the Reported EFS has been developed for acute care [
      • Hilmer S.N.
      • Perera V.
      • Mitchell S.
      • Murnion B.P.
      • Dent J.
      • Bajorek B.
      • et al.
      The assessment of frailty in older people in acute care.
      ].

      3.6 Fatigue, Resistance, Ambulation, Illness, Loss of Weight (FRAIL) Index

      Recently proposed by the International Association of Nutrition and Ageing (IANA), FRAIL is comprised of five components: Fatigue (self-report), Resistance, Ambulation (slow walking speed), Illness and Loss of weight (5% or more in the past year) [
      • Morley J.E.
      • Malmstrom T.K.
      • Miller D.K.
      A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans.
      ]. When three or more of these components are present, an older person is classified as frail. FRAIL is judged to be clinically advantageous due to its simple nature and ability to be obtained from data already included in a patient CGA [
      • Morley J.E.
      • Malmstrom T.K.
      • Miller D.K.
      A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans.
      ]. It has been found to be predictive of mortality in specific populations [
      • Woo J.
      • Leung J.
      • Morley J.E.
      Comparison of frailty indicators based on clinical phenotype and the multiple deficit approach in predicting mortality and physical limitation.
      ,
      • Malmstrom T.K.
      • Miller D.K.
      • Morley J.E.
      A comparison of four frailty models.
      ]. Further validation studies of FRAIL are needed for both hospitalised and community dwelling older people.

      3.7 Clinical Frailty Scale (CFS)

      The Clinical Frailty Scale (CFS) is a well validated frailty measurement that originated from Dalhousie University in Canada [
      • Rockwood K.
      • Song X.
      • MacKnight C.
      • Bergman H.
      • Hogan D.B.
      • McDowell I.
      • et al.
      A global clinical measure of fitness and frailty in elderly people.
      ]. It is scored on a scale from 1 (very fit) to 9 (terminally ill) and is based on clinical judgement [
      • Rockwood K.
      • Song X.
      • MacKnight C.
      • Bergman H.
      • Hogan D.B.
      • McDowell I.
      • et al.
      A global clinical measure of fitness and frailty in elderly people.
      ]. Each point on its scale corresponds with a written description of frailty, complemented by a visual chart to assist with the classification of frailty. A score ≥5 is considered to be frail [
      • Rockwood K.
      • Song X.
      • MacKnight C.
      • Bergman H.
      • Hogan D.B.
      • McDowell I.
      • et al.
      A global clinical measure of fitness and frailty in elderly people.
      ]. The CFS can be extracted from data from medical charts, and therefore can also be derived from CGAs. The CFS has been validated as an adverse outcome predictor in hospitalised older people [
      • Basic D.
      • Shanley C.
      Frailty in an older inpatient population: using the clinical frailty scale to predict patient outcomes.
      ,
      • Wallis S.J.
      • Wall J.
      • Biram R.W.
      • Romero-Ortuno R.
      Association of the clinical frailty scale with hospital outcomes.
      ].

      3.8 Multidimensional Prognostic Instrument (MPI)

      The Multidimensional Prognostic Instrument (MPI) was developed as a prognostic tool for hospitalised older patients [
      • Pilotto A.
      • Ferrucci L.
      • Franceschi M.
      • D'Ambrosio L.P.
      • Scarcelli C.
      • Cascavilla L.
      • et al.
      Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients.
      ], and has been judged to be a multidimensional frailty instrument, albeit with a simpler nature than the FI-CD [
      • Pilotto A.
      • Rengo F.
      • Marchionni N.
      • Sancarlo D.
      • Fontana A.
      • Panza F.
      • et al.
      Comparing the prognostic accuracy for all-cause mortality of frailty instruments: a multicentre 1-year follow-up in hospitalized older patients.
      ]. The MPI is derived from eight CGA components: medication number, instrumental ADLs (IADLs), ADLs, cognitive status, nutritional status, risk of developing pressure sores, co-morbidity and living status [
      • Pilotto A.
      • Ferrucci L.
      • Franceschi M.
      • D'Ambrosio L.P.
      • Scarcelli C.
      • Cascavilla L.
      • et al.
      Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients.
      ]. Problems for each component are classified as either classed as major (1 point), minor (0.5 points) or none (0 points) [
      • Pilotto A.
      • Ferrucci L.
      • Franceschi M.
      • D'Ambrosio L.P.
      • Scarcelli C.
      • Cascavilla L.
      • et al.
      Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients.
      ,
      • Pilotto A.
      • Rengo F.
      • Marchionni N.
      • Sancarlo D.
      • Fontana A.
      • Panza F.
      • et al.
      Comparing the prognostic accuracy for all-cause mortality of frailty instruments: a multicentre 1-year follow-up in hospitalized older patients.
      ]. Scores are then summed and divided by eight, with scores >0.66 graded as frailty [
      • Pilotto A.
      • Ferrucci L.
      • Franceschi M.
      • D'Ambrosio L.P.
      • Scarcelli C.
      • Cascavilla L.
      • et al.
      Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients.
      ,
      • Pilotto A.
      • Rengo F.
      • Marchionni N.
      • Sancarlo D.
      • Fontana A.
      • Panza F.
      • et al.
      Comparing the prognostic accuracy for all-cause mortality of frailty instruments: a multicentre 1-year follow-up in hospitalized older patients.
      ]. Compared with other frailty measurements, the MPI shows a higher predictive ability of adverse outcomes [
      • Pilotto A.
      • Rengo F.
      • Marchionni N.
      • Sancarlo D.
      • Fontana A.
      • Panza F.
      • et al.
      Comparing the prognostic accuracy for all-cause mortality of frailty instruments: a multicentre 1-year follow-up in hospitalized older patients.
      ], although additional research is needed to confirm this finding.

      3.9 Tilburg Frailty Indicator (TFI)

      The Tilburg Frailty Indicator (TFI) is a self-administered questionnaire developed in the Netherlands during 2010 [
      • Gobbens R.J.
      • van Assen M.A.
      • Luijkx K.G.
      • Wijnen-Sponselee M.T.
      • Schols J.M.
      The Tilburg frailty indicator: psychometric properties.
      ,
      • Gobbens R.J.
      • van Assen M.A.
      • Luijkx K.G.
      • Schols J.M.
      Testing an integral conceptual model of frailty.
      ]. It contains 15 simple self-reported items, encompassing: physical components (health, weight loss, difficulty in walking, balance, hearing, vision, gripping and tiredness); psychological factors (memory, feeling down, anxiety and coping); and social elements (living alone, social isolation, social support). Scores ≥5 are indicative of frailty [
      • Gobbens R.J.
      • van Assen M.A.
      • Luijkx K.G.
      • Wijnen-Sponselee M.T.
      • Schols J.M.
      The Tilburg frailty indicator: psychometric properties.
      ]. The TFI shows good validity and reliability for community-dwelling older people [
      • Gobbens R.J.
      • van Assen M.A.
      • Luijkx K.G.
      • Wijnen-Sponselee M.T.
      • Schols J.M.
      The Tilburg frailty indicator: psychometric properties.
      ,
      • Gobbens R.J.
      • van Assen M.A.
      The prediction of quality of life by physical, psychological and social components of frailty in community-dwelling older people.
      ]. The physical components of the TFI have been found to show good predictive ability of adverse outcomes, as opposed to its social components [
      • Gobbens R.J.
      • van Assen M.A.
      • Luijkx K.G.
      • Schols J.M.
      Testing an integral conceptual model of frailty.
      ].

      3.10 PRISMA-7

      PRISMA-7 contains seven simple self-reported components to identify frailty: older than 85 years; male; health problems which limit activities; support of another person needed; health problems requiring staying at home; social support; and use of a cane/walker/wheelchair [
      • Raiche M.
      • Hebert R.
      • Dubois M.F.
      PRISMA-7: a case-finding tool to identify older adults with moderate to severe disabilities.
      ]. Each component is scored with a ‘yes/no’ answer, with a total score ≥3 deemed as frailty [
      • Raiche M.
      • Hebert R.
      • Dubois M.F.
      PRISMA-7: a case-finding tool to identify older adults with moderate to severe disabilities.
      ]. The PRISMA-7 shows good accuracy in identifying frailty in community-dwelling older people [
      • Hoogendijk E.O.
      • van der Horst H.E.
      • Deeg D.J.
      • Frijters D.H.
      • Prins B.A.
      • Jansen A.P.
      • et al.
      The identification of frail older adults in primary care: comparing the accuracy of five simple instruments.
      ], however it has a tendency to over-screen for frailty [
      • Clegg A.
      • Rogers L.
      • Young J.
      Diagnostic test accuracy of simple instruments for identifying frailty in community-dwelling older people: a systematic review.
      ], thereby limiting its ability as a screening tool.

      3.11 Groningen Frailty Indicator (GFI)

      The Groningen Frailty Indicator (GFI) is a widely used frailty measurement developed in the Netherlands, with moderate internal consistency and adequate discriminative ability [
      • Peters L.L.
      • Boter H.
      • Buskens E.
      • Slaets J.P.
      Measurement properties of the Groningen frailty indicator in home-dwelling and institutionalized elderly people.
      ,
      • Metzelthin S.F.
      • Daniels R.
      • van Rossum E.
      • de Witte L.
      • van den Heuvel W.J.
      • Kempen G.I.
      The psychometric properties of three self-report screening instruments for identifying frail older people in the community.
      ,
      • Bielderman A.
      • van der Schans C.P.
      • van Lieshout M.R.
      • de Greef M.H.
      • Boersma F.
      • Krijnen W.P.
      • et al.
      Multidimensional structure of the Groningen frailty indicator in community-dwelling older people.
      ,
      • Steverink N.
      • Slaets J.
      • Schuurmans H.
      • Van Lis M.
      Measuring frailty: developing and testing of the Groningen frailty indicator (GFI).
      ]. It contains 15 dichotomous self-reported items, comprising of: physical factors (independence in shopping, walking, dressing, toileting; physical fitness, vision, hearing; weight loss and polypharmacy); a cognitive component (memory issues); social factors (emptiness, missing others, feeling abandoned); and a psychological component (feeling downhearted or sad; feeling nervous or anxious) [
      • Bielderman A.
      • van der Schans C.P.
      • van Lieshout M.R.
      • de Greef M.H.
      • Boersma F.
      • Krijnen W.P.
      • et al.
      Multidimensional structure of the Groningen frailty indicator in community-dwelling older people.
      ,
      • Steverink N.
      • Slaets J.
      • Schuurmans H.
      • Van Lis M.
      Measuring frailty: developing and testing of the Groningen frailty indicator (GFI).
      ]. Frailty by GFI is classified on a spectrum ranging from a score of 0 (normal activity without restriction) to 15 (completely disabled), with scores ≥4 indicative of frailty [
      • Peters L.L.
      • Boter H.
      • Buskens E.
      • Slaets J.P.
      Measurement properties of the Groningen frailty indicator in home-dwelling and institutionalized elderly people.
      ]. The GFI shows good feasibility and reliability as a frailty measurement [
      • Peters L.L.
      • Boter H.
      • Buskens E.
      • Slaets J.P.
      Measurement properties of the Groningen frailty indicator in home-dwelling and institutionalized elderly people.
      ,
      • Bielderman A.
      • van der Schans C.P.
      • van Lieshout M.R.
      • de Greef M.H.
      • Boersma F.
      • Krijnen W.P.
      • et al.
      Multidimensional structure of the Groningen frailty indicator in community-dwelling older people.
      ], and has been proposed for co-use with the FI as part of a two-step frailty screening process: the FI extracted from healthcare data to be used initially, with referral to a GFI questionnaire for patients with a high FI score [
      • Drubbel I.
      • Bleijenberg N.
      • Kranenburg G.
      • Eijkemans R.J.
      • Schuurmans M.J.
      • de Wit N.J.
      • et al.
      Identifying frailty: do the frailty index and Groningen frailty indicator cover different clinical perspectives? A cross-sectional study.
      ]. Studies of the GFI have been predominantly been confined to the Netherlands, and cross-cultural validation studies are required.

      3.12 Sherbrooke Postal Questionnaire (SPQ)

      The Sherbrooke Postal Questionnaire (SPQ) comprises six questions with dichotomous answers: living alone; ≥3 medications; mobility; eyesight; hearing; and memory problems [
      • Hebert R.
      • Bravo G.
      • Korner-Bitensky N.
      • Voyer L.
      Predictive validity of a postal questionnaire for screening community-dwelling elderly individuals at risk of functional decline.
      ]. Component scores are summed, with a total score ≥2 considered to be frailty [
      • Daniels R.
      • van Rossum E.
      • Beurskens A.
      • van den Heuvel W.
      • de Witte L.
      The predictive validity of three self-report screening instruments for identifying frail older people in the community.
      ]. The SPQ shows inconsistent validity in frailty identification when compared to TFI and GFI [
      • Metzelthin S.F.
      • Daniels R.
      • van Rossum E.
      • de Witte L.
      • van den Heuvel W.J.
      • Kempen G.I.
      The psychometric properties of three self-report screening instruments for identifying frail older people in the community.
      ,
      • Daniels R.
      • van Rossum E.
      • Beurskens A.
      • van den Heuvel W.
      • de Witte L.
      The predictive validity of three self-report screening instruments for identifying frail older people in the community.
      ]. Further validation studies of SPQ are needed, as are studies determining its ability to predict adverse outcomes in older people.

      3.13 Gérontopôle Frailty Screening Tool (GFST)

      The Gérontopôle Frailty Screening Tool (GFST) is designed for early recognition of frailty in community-dwelling older people and shows good potential as a frailty screening tool [
      • Morley J.E.
      • Vellas B.
      • van Kan G.A.
      • Anker S.D.
      • Bauer J.M.
      • Bernabei R.
      • et al.
      Frailty consensus: a call to action.
      ,
      • Subra J.
      • Gillette-Guyonnet S.
      • Cesari M.
      • Oustric S.
      • Vellas B.
      The integration of frailty into clinical practice: preliminary results from the Gerontopole.
      ]. It comprises two steps: a questionnaire is performed first, followed by a clinician's judgement of frailty status [
      • Vellas B.
      • Balardy L.
      • Gillette-Guyonnet S.
      • Abellan Van Kan G.
      • Ghisolfi-Marque A.
      • Subra J.
      • et al.
      Looking for frailty in community-dwelling older persons: the Gerontopole frailty screening tool (GFST).
      ]. The questionnaire includes six components: living alone, involuntary weight loss, fatigability, mobility, memory complaints and slow gait speed (≥4 s for 4 m), with all questionnaire components having three potential answers: yes/no/unknown [
      • Vellas B.
      • Balardy L.
      • Gillette-Guyonnet S.
      • Abellan Van Kan G.
      • Ghisolfi-Marque A.
      • Subra J.
      • et al.
      Looking for frailty in community-dwelling older persons: the Gerontopole frailty screening tool (GFST).
      ].
      A downside of the GFST is that does not give any specific guidance for the clinician about how to identify frailty, and after the six initial screening questions, it contains one question for the clinician to answer: “do you think your patient is frail?” No reliability studies have yet been performed on the GFST and its predictive ability has not yet been established. Validation studies of the GFST also need to be performed cross-culturally.

      3.14 Kihon Check-list (KCL)

      The Kihon Check-list (KCL) is a recently validated frailty measurement tool containing 25 items widely used in Japan [
      • Fukutomi E.
      • Okumiya K.
      • Wada T.
      • Sakamoto R.
      • Ishimoto Y.
      • Kimura Y.
      • et al.
      Relationships between each category of 25-item frailty risk assessment (Kihon Checklist) and newly certified older adults under long-term care insurance: a 24-month follow-up study in a rural community in Japan.
      ,
      • Satake S.
      • Senda K.
      • Hong Y.J.
      • Miura H.
      • Endo H.
      • Sakurai T.
      • et al.
      Validity of the Kihon Checklist for assessing frailty status.
      ]. It is based on similar principles to the FI-CGA and shows predictive ability for functional decline in community-dwelling older people [
      • Fukutomi E.
      • Okumiya K.
      • Wada T.
      • Sakamoto R.
      • Ishimoto Y.
      • Kimura Y.
      • et al.
      Importance of cognitive assessment as part of the “Kihon Checklist” developed by the Japanese Ministry of Health, Labor and Welfare for prediction of frailty at a 2-year follow up.
      ]. Cross-cultural validation of the KCL is needed.

      3.15 Individual frailty measurements

      Individual factors underlying frailty can also be used to screen for frailty. Gait speed is one such example [
      • Clegg A.
      • Rogers L.
      • Young J.
      Diagnostic test accuracy of simple instruments for identifying frailty in community-dwelling older people: a systematic review.
      ,
      • Abellan van Kan G.
      • Rolland Y.
      • Andrieu S.
      • Bauer J.
      • Beauchet O.
      • Bonnefoy M.
      • et al.
      Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) task force..
      ,
      • Gill T.M.
      • Allore H.G.
      • Gahbauer E.A.
      • Murphy T.E.
      Change in disability after hospitalization or restricted activity in older persons.
      ], and in all likelihood, may be best indicator of frailty among all of Fried's frailty components [
      • Hoogendijk E.O.
      • van Kan G.A.
      • Guyonnet S.
      • Vellas B.
      • Cesari M.
      Components of the frailty phenotype in relation to the frailty index: results from the Toulouse frailty platform.
      ]. Importantly, gait speed also has a close association with adverse health outcomes in older people [
      • Toots A.
      • Rosendahl E.
      • Lundin-Olsson L.
      • Nordstrom P.
      • Gustafson Y.
      • Littbrand H.
      Usual gait speed independently predicts mortality in very old people: a population-based study.
      ,
      • Stanaway F.F.
      • Gnjidic D.
      • Blyth F.M.
      • Le Couteur D.G.
      • Naganathan V.
      • Waite L.
      • et al.
      How fast does the Grim Reaper walk? Receiver operating characteristics curve analysis in healthy men aged 70 and over.
      ]. Gait speed is applicable clinically, although it does over-screen for frailty [
      • Clegg A.
      • Rogers L.
      • Young J.
      Diagnostic test accuracy of simple instruments for identifying frailty in community-dwelling older people: a systematic review.
      ], and there are fundamental difficulties in measuring out a walking course in a clinical setting.
      Low grip strength can also be used as a single measure of frailty, and has been found to be predictive of both functional decline and long LOS in hospitalised older patients [
      • Garcia-Pena C.
      • Garcia-Fabela L.C.
      • Gutierrez-Robledo L.M.
      • Garcia-Gonzalez J.J.
      • Arango-Lopera V.E.
      • Perez-Zepeda M.U.
      Handgrip strength predicts functional decline at discharge in hospitalized male elderly: a hospital cohort study.
      ,
      • Roberts H.C.
      • Syddall H.E.
      • Cooper C.
      • Aihie Sayer A.
      Is grip strength associated with length of stay in hospitalised older patients admitted for rehabilitation? Findings from the Southampton grip strength study.
      ], and mortality in community-dwelling adults [
      • Leong D.P.
      • Teo K.K.
      • Rangarajan S.
      • Lopez-Jaramillo P.
      • Avezum Jr., A.
      • Orlandini A.
      • et al.
      Prognostic value of grip strength: findings from the prospective urban rural epidemiology (PURE) study.
      ]. It has also been found to be a good marker of poor mobility [
      • Stevens P.J.
      • Syddall H.E.
      • Patel H.P.
      • Martin H.J.
      • Cooper C.
      • Aihie Sayer A.
      Is grip strength a good marker of physical performance among community-dwelling older people?.
      ].

      3.16 Other frailty measurements

      Other frailty measurements beyond the scope of this review include: the self-rated Health Deficits Index (HDI) [
      • Lucicesare A.
      • Hubbard R.E.
      • Searle S.D.
      • Rockwood K.
      An index of self-rated health deficits in relation to frailty and adverse outcomes in older adults.
      ], the Frailty Risk Score (FRS) [
      • Pijpers E.
      • Ferreira I.
      • van de Laar R.J.
      • Stehouwer C.D.
      • Nieuwenhuijzen Kruseman A.C.
      Predicting mortality of psychogeriatric patients: a simple prognostic frailty risk score.
      ], the Vulnerable Elders Survey (VES) (vulnerability is considered to be frailty) [
      • Chapman M.D.
      • Le B.H.
      • Gorelik A.
      The vulnerable elders survey and its prognostic relationship to survival in an older community-based palliative population.
      ], the Frailty Trail Scale (FTS) [
      • Garcia-Garcia F.J.
      • Carcaillon L.
      • Fernandez-Tresguerres J.
      • Alfaro A.
      • Larrion J.L.
      • Castillo C.
      • et al.
      A new operational definition of frailty: the frailty trait scale.
      ], the Frail Non-Disabled (FiND) instrument for frailty screening [
      • Cesari M.
      • Demougeot L.
      • Boccalon H.
      • Guyonnet S.
      • Abellan van Kan G.
      • Vellas B.
      • et al.
      A self-reported screening tool for detecting community-dwelling older persons with frailty syndrome in the absence of mobility disability: the FiND questionnaire.
      ], the ‘G8’ (specifically for cancer patients) [
      • Baitar A.
      • Van Fraeyenhove F.
      • Vandebroek A.
      • De Droogh E.
      • Galdermans D.
      • Mebis J.
      • et al.
      Evaluation of the Groningen frailty indicator and the G8 questionnaire as screening tools for frailty in older patients with cancer.
      ], and multiple others. In addition, given that functional decline is an outcome of frailty, functional decline indices may also be considered to be frailty measurements [
      • De Saint-Hubert M.
      • Schoevaerdts D.
      • Cornette P.
      • D'Hoore W.
      • Boland B.
      • Swine C.
      Predicting functional adverse outcomes in hospitalized older patients: a systematic review of screening tools.
      ]. These indices include: the Identification of Seniors at Risk (ISAR) score [
      • McCusker J.
      • Bellavance F.
      • Cardin S.
      • Trepanier S.
      • Verdon J.
      • Ardman O.
      Detection of older people at increased risk of adverse health outcomes after an emergency visit: the ISAR screening tool.
      ] the Score Hospitalier d'Evaluation du Risque de Perte d'Autonomie (SHERPA) [
      • Cornette P.
      • Swine C.
      • Malhomme B.
      • Gillet J.B.
      • Meert P.
      • D'Hoore W.
      Early evaluation of the risk of functional decline following hospitalization of older patients: development of a predictive tool.
      ] and the Hospital Admission Risk Profile (HARP) [
      • Sager M.A.
      • Rudberg M.A.
      • Jalaluddin M.
      • Franke T.
      • Inouye S.K.
      • Landefeld C.S.
      • et al.
      Hospital admission risk profile (HARP): identifying older patients at risk for functional decline following acute medical illness and hospitalization.
      ]. Important to note is that a more objective assessment/measurement tool like the Short Physical Performance Battery (SPPB) [
      • Guralnik J.M.
      • Simonsick E.M.
      • Ferrucci L.
      • Glynn R.J.
      • Berkman L.F.
      • Blazer D.G.
      • Scherr P.A.
      • Wallace R.B.
      A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      ] may well be the unifying tool for frailty, and while not included in this review, has many of the same limitations as other measurements of frailty which are based on physical performance.

      4. Discussion

      This review showed that there are a multiple measurements used to identify frailty in older people. There was a wide range in the applicability of these frailty measurements: from short, fast and crude frailty screening instruments to the sophisticated, time-consuming measurements. Many frailty measurements had not been robustly validated in the literature, and their prognostic ability was rarely determined. Moreover, many frailty measurements were modified somewhat from their original, validated version, which in turn, can have a striking impact on frailty classification. This concern is echoed in a recent meta-analysis by Theou and colleagues, which found 262 different versions of Fried's Frailty Phenotype [
      • Theou O.
      • Cann L.
      • Blodgett J.
      • Wallace L.M.
      • Brothers T.D.
      • Rockwood K.
      Modifications to the frailty phenotype criteria: systematic review of the current literature and investigation of 262 frailty phenotypes in the survey of health, ageing, and retirement in Europe.
      ].
      Based on the findings of this review, there are three potential future options for frailty measurement. Firstly, as part of a consensus, we can decide on one frailty measurement from the multitude of already existing measurements. Having just one measurement would be advantageous given that it would allow comparison of frailty prevalence worldwide. However, having one frailty measurement may not be best route forward. Frailty measurements can be likened to ‘horses for courses’, wherein different frailty measurements are suited to different populations [
      • Martin F.C.
      • Brighton P.
      Frailty: different tools for different purposes?.
      ]. Some are better for population-level frailty screening, whereas others are best suited for clinical screening, or for clinical assessment. For instance, the visual-chart based CFS or the easy-to-apply SOF are both well suited for clinical screening, whereas the FI-CGA is designed for frailty assessment in the clinical setting, the latter of which can be applied to almost any dataset that records CGA patient-level data.
      Secondly, a new gold frailty standard measurement could be developed. However, countless research groups have done exactly this, which partially explains why there are so many frailty measurements in existence today. Thirdly, we could use one frailty measurement for screening and a second one for a full assessment, as suggested by recent research. For instance, frailty screening and assessment combinations could be performed by pairing the CHS index and the FI [
      • Cesari M.
      • Gambassi G.
      • van Kan G.A.
      • Vellas B.
      The frailty phenotype and the frailty index: different instruments for different purposes.
      ]. It remains to be seen which of these three future options for frailty measurement will be chosen.
      Nonetheless, no matter what frailty measurement/s become the international standard, it is important that frailty is recognised in the clinical setting. Frailty is often misconstrued to be part of the normal ageing process and older patients are treated on the basis of their medical condition/s alone, rather than accounting for their frailty status [
      • Lee L.
      • Heckman G.
      • Molnar F.J.
      Frailty: identifying elderly patients at high risk of poor outcomes.
      ]. Incorporating measurement of frailty into clinical practice may provide a means for clinicians to identify and manage the condition early into its progression. Advancements in health informatics and electronics will play a role in future frailty measurement [
      • Zaslavsky O.
      • Thompson H.
      • Demiris G.
      The role of emerging information technologies in frailty assessment.
      ].

      5. Conclusion

      As the world's population ages, frailty is moving to the forefront of health and medical research. Multiple factors contribute to frailty, including malnutrition, pathophysiology and psychological factors. Frailty does not yet have a gold standard definition, although it is generally considered to be geriatric condition characterised by an increased vulnerability to external stressors. There are a plethora of frailty measurements worldwide, with the quality of measurements varying widely. A quality frailty measurement should be able to identify frailty; be able to predict patient outcomes and response to potential treatments; and be based on biological theory. Based on these criteria, the two most common frailty measurements, Fried's Frailty Phenotype (the CHS index) and Rockwood and Mitnitski's FI, appear to be the most robust assessment tools for use by clinicians and researchers today. Future studies should focus on comparing frailty measurements worldwide. Frailty measurement should be incorporated into clinical practice as part of routine care for older patients.

      Learning points

      • Frailty measurement should be incorporated into clinical practice as part of routine care for older patients.
      • There is no international standard measurement for frailty.
      • A large number of frailty measurements exist, making it difficult to choose which frailty measurement to use.
      • Frailty measurements range from short, fast and crude frailty screening instruments to sophisticated, time-consuming measurements.
      • The quality of frailty measurements varies widely, with many measurements needing cross-cultural validation studies.
      • The two most commonly used frailty measurements (both with high validity and reliability) are Fried's frailty phenotype and Rockwood and Mitnitski's Frailty Index.
      • There is no “one” perfect frailty measurement in existence today. Some measurements are better for population-level frailty screening, whereas others are best suited for clinical screening, or assessment.

      Conflict of interest statement

      The authors state that they have no conflicts of interest.

      Acknowledgement

      The authors wish to thank Dr. Gareth Furber for his structural editing of the manuscript. ED is currently a National Health and Medical Research Council (NHMRC) Early Career Fellow (Grant ID: 1112672 ). The early workings of this review were developed during the doctoral candidature of ED, of which Prof Ian Chapman and Prof Renuka Visvanathan were supervisors of. Financial support for earlier work on this study was provided by PhD scholarship funds from the Centre of Research Excellence (CRE) in Translating Nutritional Science into Good Health, The University of Adelaide (NHMRC Grant ID: 1041687 ).

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