Frailty at a glance

Frailty is a multidimensional geriatric syndrome characterized by increased vulnerability to stressors as a result of reduced capacity of different physiological systems. It has been associated with an increased risk of adverse health-related outcomes in older persons, including falls, disability, hospitalizations and mortality, and has further been associated with biological abnormalities (e.g. biomarkers of inflammation) regardless of the definition used to assess frailty. This clearly suggests that frailty is influenced by a number of pathophysiological modifications involving the body’s diverse physiological systems.

Homeostatic Equilibrium
Frailty increases substantially with age and is particularly developed in subjects older than 80 years. The prevalence of frailty varies between different populations, ranging from 4.0 to 59.1%. It is higher in populations of southern Europe than in those living in the to northern part of European continent. This variation is largely explained by the use of different operational definitions for frailty and the use of different inclusion and exclusion criteria. Therefore, the use of different cut-offs for frailty might be needed for diverse populations.

Pathophysiology

This figure depicts an orderly alignment of eggs, representing various biologic systems, in a state of homeostatic equilibrium.

Fig. 1 – Homeostatic Equilibrium

A number of interrelated physiological changes underlie the frailty syndrome with a consequent decline of the organism’s homeostatic mechanisms. Genetic, epigenetic, and environmental factors (such as nutrition and physical activity) are strongly related to frailty. Yet, reduced physiological reserve of a number of systems (such as the brain, skeletal muscle, and immune, endocrine, respiratory, renal, cardiovascular and hematopoietic systems) have also been associated with frailty.

Diagnosis / Screening Tools
Several operational definitions of frailty are currently available. However, the most commonly used criteria are those proposed by Fried et al.—the so-called ‘frailty phenotype’. This is defined by the presence of at least three of five signs/symptoms, including poor muscle strength, slow gait speed, unintentional weight loss, exhaustion, and sedentary behavior.

Simple screening tests have been developed and validated in order to identify frail persons. Commonly used and validated frailty tools include the Cardiovascular Health Study frailty screening measure, the FRAIL questionnaire screening tool, the Clinical Frailty Scale, and the Gérontopôle Frailty Screening Tool. The Frailty Consensus Conference held in Orlando, Florida, USA in 2013 agreed that persons aged 70 years and older, as well as any person with significant weight loss (≥5% over the past year) due to chronic illnesses should be screened for frailty.

Evaluation
The integration of frailty into clinical practice is emerging. The most common evidence-based approach to evaluate frailty is the comprehensive geriatric assessment. However, the updating and validation of existing multidimensional questionnaires specific for frailty and clinically friendly are needed. Recently, the Gérontopôle of the Toulouse University Hospital (France), in collaboration with the University Department of General Medicine of Toulouse and the regional health authority, has developed an innovative Platform for the Evaluation of Frailty and the Prevention of Disability, thereby integrating frailty into clinical practice. This is the first example of a clinical evaluation and intervention on frailty setup at the general-population level.

Management / Interventions
Identification of the causes of frailty will enable the implementation of multidomain evidence-based, personalized interventions. This approach will greatly support the future design of preventive strategies against disability in older persons. Multidomain interventions might prove useful if focused on the physical, nutritional, and behavioral/social/psychological domains in order to improve well-being and quality of life in older persons.

It is obvious that nutritional interventions may improve the older person’s risk profile by directly acting on all of the five criteria of the ‘frailty phenotype’, addressing mainly impaired nutrition and weight loss. Similarly, exercise interventions may also directly reverse at least four of the five components of frailty (i.e., poor muscle strength, slow gait speed, unintentional weight loss, and sedentary behavior). Indeed, exercise interventions have been shown to improve outcomes of mobility and functional ability in frail populations. Both nutrition and exercise may be considered “multidomain” interventions per se, given their capacity to provide beneficial effects on multiple systems at a biological, clinical, and social level. However, it is likely that their combination may further enhance their beneficial effects through direct and indirect interactions.

Selected References
Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet 2013;381:752-62.
Ferrucci L, Gwen Windham B, Fried LP. Frailty in older persons. Genus 2005;LXI:39-53.
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-56.
Morley JE, Vellas B, Abellan van Kan G, et al. Frailty consensus: a call to action. J Am Med Dir Assoc 2013;14:392-7.
Santos-Eggimann B, Cuenoud P, Spagnoli J, Junod J. Prevalence of frailty in middle-aged and older community-dwelling Europeans living in 10 countries. J Gerontol A Biol Sci Med Sci 2009;64:675-81.
Subra J, Gillette-Guyonnet S, Cesari M, Oustric S, Vellas B. The integration of frailty into clinical practice: preliminary results from the Gérontopôle. J Nutr Health Aging 2012;16:714-20.