Overviews of Frailty: research and clinical applications

Integrating Frailty Research into the Medical Specialties-Report from a U13 Conference

Although the field of frailty research has expanded rapidly, it is still a nascent concept within the clinical specialties. Frailty, conceptualized as greater vulnerability to stressors because of significant depletion of physiological reserves, predicts poorer outcomes in several medical specialties, including cardiology, human immunodeficiency virus care, and nephrology, and in the behavioral and social sciences. Lack of a consensus definition, proliferation of measurement tools, inadequate understanding of the biology of frailty, and lack of validated clinical algorithms for frail individuals hinders incorporation of frailty assessment and frailty research into the specialties. In 2015, the American Geriatrics Society, the National Institute on Aging (NIA), and the Alliance for Academic Internal Medicine held a conference for awardees of the NIA-sponsored Grants for Early Medical/Surgical Specialists Transition into Aging Research program to review the current state of knowledge regarding frailty in the subspecialties and to highlight examples of integrating frailty research into the medical specialties. Research questions to advance frailty research into specialty medicine are proposed.

© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Frailty consensus: a call to action


Frailty is a clinical state in which there is an increase in an individual’s vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. 1. Physical frailty is an important medical syndrome. The group defined physical frailty as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.” 2. Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy. 3. Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons. 4. For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (>5%) due to chronic disease should be screened for frailty.

Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

Frailty in elderly people


Frailty is the most problematic expression of population ageing. It is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. In landmark studies, investigators have developed valid models of frailty and these models have allowed epidemiological investigations that show the association between frailty and adverse health outcomes. We need to develop more efficient methods to detect frailty and measure its severity in routine clinical practice, especially methods that are useful for primary care. Such progress would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Frailty: a review of the first decade of research


Frailty is an emerging geriatric syndrome that refers to a state of increased vulnerability to adverse events including mortality, morbidity, disability, hospitalization, and nursing home admission. Despite its long conceptual and operational history in research and publications, frailty and mechanisms of frailty development are still poorly understood. In this review, we describe a number of conceptual models-reliability, allostatic load, and complexity-that have been put forward to explain the dynamic nature of frailty. We illustrate a consolidated pathophysiological model of frailty, taking into consideration the large and exponentially growing body of studies regarding predictors, indicators, and outcomes of frailty. The model addresses cellular (e.g., oxidative damage and telomere length) and systemic mechanisms (e.g., endocrinal, inflammatory, coagulatory, and metabolic deficiencies) of frailty, moderating or risk factors (e.g., ethnicity, lifestyle, and comorbidities), and outcomes (morbidity, disability, and cognitive decline). Finally, we identify the weaknesses of traditional epidemiological approaches for studying complex phenomena related to frailty and propose areas for future methodological and physiological inquiry.

The frailty syndrome: definition and natural history


This article reviews the current state of knowledge regarding the epidemiology of frailty by focusing on 6 specific areas: (1) clinical definitions of frailty, (2) evidence of frailty as a medical syndrome, (3) prevalence and incidence of frailty by age, gender, race, and ethnicity, (4) transitions between discrete frailty states, (5) natural history of manifestations of frailty criteria, and (6) behavior modifications as precursors to the development of clinical frailty.

Copyright © 2011 Elsevier Inc. All rights reserved.

Frailty: an emerging research and clinical paradigm–issues and controversies

Clinicians and researchers have shown increasing interest in frailty. Yet, there is still considerable uncertainty regarding the concept and its definition. In this article, we present perspectives on key issues and controversies discussed by scientists from 13 different countries, representing a diverse range of disciplines, at the 2006 Second International Working Meeting on Frailty and Aging. The following fundamental questions are discussed: What is the distinction, if any, between frailty and aging? What is its relationship with chronic disease? Is frailty a syndrome or a series of age-related impairments that predict adverse outcomes? What are the critical domains in its operational definition? Is frailty a useful concept? The implications of different models and approaches are examined. Although consensus has yet to be attained, work accomplished to date has opened exciting new horizons. The article concludes with suggested directions for future research.

Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults.


Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty. Although social and psychological aspects of frailty are critically important and merit future research, these topics were largely beyond the scope of this meeting. Included in this article are sections on the evolving conceptualization and definitions of frailty; physiological underpinnings of frailty, including the potential contributions of inflammatory, endocrine, skeletal muscle, and neurologic system changes; potential molecular and genetic contributors; proposed animal models; and integrative, system biology approaches that may help to facilitate future frailty research. In addition, several specific recommendations as to future directions were developed from suggestions put forth by participants, including recommendations on definition and phenotype development, methodological development to perform clinical studies of individual‐system and multiple‐system vulnerability to stressors, development of animal and cellular models, application of population‐based studies to frailty research, and the development of large collaborative networks in which populations and resources can be shared. This meeting and subsequent article were not meant to be a comprehensive review of frailty research; instead, they were and are meant to provide a more‐targeted research agenda‐setting process.

From bedside to bench: research agenda for frailty.

The American Geriatrics Society sponsored a working conference in January 2004, funded by the National Institute on Aging, to establish the state of the art in frailty research and to set a research agenda for the future. The invited participants included senior basic biologists, epidemiologists, geneticists, and clinical investigators who study aging-related issues. This article summarizes the central theoretical observations on frailty and research needs and opportunities presented and discussed at this conference, and lays out an agenda for future research on frailty.

Models, definitions, and criteria of frailty

In this paper we will provide an overview of various models, definitions, and criteria proposed for furthering our understanding of frailty but we will not systematically evaluate and compare them. Models are descriptions or analogies that are used to help us visualize something that typically cannot be directly observed. They are at an abstract or conceptual level.

Definitions are statements expressing the essential nature of something. They should make our understanding of the topic both definite and clear. Criteria are operational definitions that outline the characterizing traits of an entity. There are overlaps and connections across the various models, definitions, and criteria proposed for frailty. Some investigators have suggested all three – a model, a definition derived from the model, and explicit criteria for recognizing frail older persons.

Moving Frailty Toward Clinical Practice: NIA Intramural Frailty Science Symposium Summary

Frailty has long been an important concept in the practice of geriatric medicine and in gerontological research, but integration and implementation of frailty concepts into clinical practice in the United States has been slow. The National Institute on Aging (NIA) Intramural Research Program and the Johns Hopkins Older Americans Independence Center sponsored a symposium to identify potential barriers that impede the movement of frailty into clinical practice and to highlight opportunities to facilitate the further integration of frailty into clinical practice.