Investigating the prognostic meaning of frailty and sarcopenia definitions

Frailty and sarcopenia are common, but not yet recognized geriatric syndromes that have an impact on the health status of older adults. They are closely related, given that sarcopenia is considered the biological substrate of physical frailty. The approach to detect frail persons is still lacking a standardization, since a great variety of operational definitions have been developed over the last years. Furthermore, the algorithm for diagnosis of sarcopenia has been revised in 2019 by the European Working Group on Sarcopenia in Elderly People (EWGSOP2) but the effect of applying this new approach with regards to sarcopenia prevalence and predictive capacity towards adverse events is unknown. My PhD project is composed of three sequential studies, with the aim of analyzing the predictive ability of frailty towards incident adverse events and the changes in sarcopenia diagnosis in the light of the EWGSOP2 criteria. I analyzed data from the InCHIANTI Study, a population-based study of older persons living in the Chianti geographic area (Tuscany, Italy), including 1150 subjects of 65 years and older. In the first study I verified the predictive value of frailty defined using a multidimensional approach: despite including physical, psychological and social indicators, this approach resulted in a low sensitivity and positive predictive value towards incident disability [Costanzo L, et al. Geriatr Gerontol Int. 2018]. In a second work I studied the prognostic ability of Frailty Phenoype, that is one of the most commonly used definitions of frailty: when considering as an outcome the pattern of disability in an extended list of tasks, instead of loss of one or more Katz's activities of daily living, the ability of the Frailty Phenotype to identify people at risk of functional decline modestly improved, suggesting that the prognostic capacity of frailty assessment instruments may depend also on the definition of the outcome [Costanzo L, et al. JAMDA 2019]. Finally, in the third study, I focused on sarcopenia, defined according to EWGSOP2. Its estimated prevalence resulted to be lower compared to the 2010 definition, consequently a number of subjects at risk of adverse outcomes could be classified as non-sarcopenic according to EWGSOP2 [Costanzo L, et al. J Gerontol A Biol Sci Med Sci. 2020]. Similar to frailty, the presence of sarcopenia showed low sensitivity and positive predictive value towards mortality, therefore the current definition of sarcopenia seems to well discriminate people who would not die rather than identifying the individuals that are at increased risk. The results of this thesis made substantial contribution to current knowledge on frailty and sarcopenia diagnosis, that remains a challenge despite the growing interest on these topics. The thesis emphasizes that the definitions of these geriatric conditions should have good discriminative properties to be useful in clinical settings: in other words, they should correctly identify people at risk of adverse outcomes and not only show an association with the outcomes. Future research should continue with the aim to refine current diagnostic instruments for frailty and sarcopenia, in order to reach a universally accepted and easy-to-use definition and, ultimately, to promptly recognize people at risk of adverse outcomes in the need of preventive actions.