Review ArticleFrailty measurement in research and clinical practice: A review
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 [1]. 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 [2], [3], [4]. With the number of older people dramatically expanding in almost all countries, frailty prevalence is expected to soar [5].
Frailty is a geriatric condition characterised by an increased vulnerability to external stressors [5], [6]. It is strongly linked to adverse outcomes, including mortality, nursing home admission, and falls [7], [8], [9], [10], [11]. Frailty is different conceptually from ageing, disability, and co-morbidity although it is distinctly related to these factors [12], [13], [14], [15], [16], [17], [18]. For example, although frailty prevalence increases with age, it occurs independently from chronological age [7], [10].
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 [18], [19], [20], [21], [22], [23], [24], [25] reflecting multi-system dysfunction [6], [10], [23], [25], [26], [27] and in which individuals are able to dynamically transition between severity states [12], [27], [28], [29]. Multiple reasons exist as to why it is so difficult to define frailty, including: its complex aetiology [10], [30]; the often independent work of frailty researchers [31], [32]; and the inherent difficulty in distinguishing frailty from both ageing and disability [18], [22], [33]. 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 [22], [34].
Frailty has a strong biological component, and it is thought to result from cumulative cellular damage over the life-course [12], [35], [36]. The specific pathophysiological pathways underpinning frailty are not yet clearly known [10], [37], although there is evidence that both malnutrition and sarcopenia (muscle wastage) may have similar causal pathways [38], [39], [40]. Inflammation is one such pathway, and is well established as a causal factor for frailty [23], [24], [25], [30], [41]. Pro-inflammatory cytokines can influence frailty either directly, for instance by promoting protein degradation [27], or indirectly by altering metabolic processes [30].
The biological causative mechanisms of frailty are different from those processes causing the ageing process [27]. Frailty occurs when not one, but multiple physiological systems decline [5], [10], [23], [27], [36]: the more physiological systems that are in a diminished state, the greater the likelihood of frailty [42]. 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 [43]. Frailty is thought to result when this threshold is surpassed in multiple physiological systems — so much so that repair mechanisms cannot maintain system homeostasis [27]. 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 [27].
Other factors linked with frailty development include (i) sociodemographic influences, such as poverty, living alone, area deprivation and low education level [19], [27], [30], [44]; (ii) psychological factors, including depression [45]; (iii) nutritional issues such as malnutrition and poor oral health, [10], [27], [46]; (iv) polypharmacy [30]; (v) diseases (cancer, endocrine disorders, dementia) and their associated complications [30]; and (v) low physical activity [30].
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 [47], [48]. 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 [6]. 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 [49]. 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 [12], [17], [19], [23], [31], [34], [50], [51], [52]. 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. [10] using Bell's disease classification guidelines [53] 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 [10]. 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.
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.
Section snippets
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
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
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,
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
Learning points
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Frailty measurement should be incorporated into clinical practice as part of routine care for older patients.
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There is no international standard measurement for frailty.
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A large number of frailty measurements exist, making it difficult to choose which frailty measurement to use.
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Frailty measurements range from short, fast and crude frailty screening instruments to sophisticated, time-consuming measurements.
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The quality of frailty measurements varies widely, with many measurements needing
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
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