Frailty - UpToDate
Frailty - UpToDate
Frailty - UpToDate
Frailty
������: Jeremy D Walston, MD
������� ������: Kenneth E Schmader, MD
������ ������: Jane Givens, MD, MSCE
All topics are updated as new evidence becomes available and our peer review process is complete.
INTRODUCTION
Although there is no gold standard for detecting frailty, multiple frailty screening tools have
been developed and utilized for risk assessment and epidemiologic study.
This topic will review the definitions, pathophysiology, prevalence, and diagnosis of frailty and
clinical approaches that may attenuate vulnerability and relieve symptoms.
PREVALENCE
Many population-based studies of frailty have been performed using a variety of frailty
measures. Although the prevalence of frailty varies with the tool used and with the population
studied, prevalence in several studies in the United States ranges from 4 to 16 percent in
community-dwelling men and women aged 65 and older [1-5] and up to 43 percent of older
patients with cancer [6]. Pre-frailty (patients at risk for frailty who fulfill some, not but all,
criteria for frailty) has a prevalence ranging from 28 to 44 percent in those over 65 years old
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[1,4,5].
A 2012 systematic review found that when frailty was defined on the basis of physical findings
alone, overall prevalence in 15 studies (44,894 participants) was 9.9 percent; when
psychosocial aspects were included in the definition, prevalence was 13.6 percent among
eight studies (24,072 participants) [7]. In a European study (the Survey of Health, Ageing, and
Retirement in Europe [SHARE]) comparing eight frailty scales, frailty prevalence ranged from 6
to 44 percent when applied to a database of individuals aged 50 to 104 years [8]. In a US study
of people aged 90 and older, the prevalence of frailty was 24 percent for those aged 90 to 94
and 39.5 percent for those 95 and older [9].
In a study in the United States of nearly 6000 community-dwelling men aged 65 and older, at
an average follow-up of 4.6 years, 54.4 percent of men who were robust at baseline remained
robust, 25.3 percent became pre-frail, 1.6 percent became frail, 5.7 percent died, and the
remainder could not be assessed [5].
Frail older adults are less able to tolerate and adapt to stressors such as acute illness, surgical
or medical interventions, or trauma than younger or non-frail older adults. This increased
vulnerability contributes to increased risk for procedural complications, falls,
institutionalization, disability, and death [10]. After adjustment for comorbidities, frailty
predicts hip fractures, disability, and hospitalization [4]. Frailty also predicts adverse outcomes
related to renal transplantation, general surgery (elective and emergency), and cardiac
surgery interventions [11-15]. As such, frailty in older patients is considered to be the hallmark
geriatric syndrome that is a forerunner to other geriatric syndromes, including frequent falls,
fractures, delirium, cognitive impairment, and incontinence.
● In a study in men, mortality was twice as high for frail, compared with robust men (HR
2.05; 95% CI 1.55-2.72) [5].
● In a European study, mortality was best predicted by the Frailty Index and Edmonton
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scales, with death rates three to five times higher in cases classified as frail compared
with those not classified as frail [8].
● In analysis of data from the Longitudinal Aging Study Amsterdam, in which 2874 adults
aged 64 to 84 years were followed for 21 years, frailty (defined as ≥0.25 on the 32-item
frailty index) was associated with greater four-year mortality (odds ratio [OR] 2.79, 95%
CI 2.39-3.26) [16].
● In a cohort study of over two million United States veterans aged 65 years or older, the
risk of suicide attempt was higher in patients with all levels of frailty (prefrailty and mild,
moderate, and severe frailty) compared with those without frailty, as measured by the
frailty index assessing morbidity, function, sensory loss, cognition and mood, and other
functions [17].
Overview — It is generally recognized that the term “frailty” captures the essence of age-
related vulnerability and decline, and that it can be useful in clinical practice [18,19]. At
present, there are two major conceptual frameworks for the term “frailty” that have influenced
the development of multiple frailty measurement tools.
● Physical frailty, often termed phenotypic or syndromic frailty, was developed in part to
capture representative signs and symptoms (fatigue, low activity, weakness, weight loss,
and slow gait) of community-dwelling older adults that were most vulnerable to adverse
health outcomes.
In both physical frailty and deficit accumulation frailty, advanced frailty is consistent with
advanced vulnerability. Indeed, comparability studies have found that those who are most
vulnerable can be found by either tool. However, substantial discordance at individual level
classifications exists between the conceptual frameworks in the more intermediate levels of
frailty [20].
Acceptance of a standardized definition for frailty in clinical practice has been slowed in part
by a proliferation of frailty measurement tools with differing conceptual bases and that often
fail to differentiate between disability, comorbidity, and frailty. A summary of conceptual
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● Age, chronic comorbidities, and disability, while associated with frailty, do not establish
the diagnosis of frailty [1,22-24].
● Frailty exists on a spectrum. The end stage of the continuum of frailty is often considered
to be failure to thrive. (See "Failure to thrive in older adults: Evaluation" and "Failure to
thrive in older adults: Management".)
Old age itself does not define frailty. Many older adults remain vigorous, despite advanced
age, while others have gradual yet unrelenting functional decline in the absence of apparent
disease states, or failure to rebound following illness or hospitalization.
A 2016 comprehensive review of the most frequently cited frailty measurement tools identified
67 different frailty instruments, capturing varying domains and criteria depending upon the
intended use of the instrument [27]. A subsequent study found a wide range of agreement (no
agreement to almost complete agreement) among these instruments when tested in the
same population [28].
The majority of screening tools used to determine frailty status have been developed based
upon one of two concepts: "physical" or "phenotypic" frailty versus "deficit accumulation" or
"index" frailty [25,29,30] (see 'Overview' above). Physical or phenotypic frailty is thought to
result from multisystem biological decline leading to specific symptoms such as weight loss,
weakness, and walking speed. Deficit accumulation or index frailty is measured by tabulating
the combination of comorbidities, social situations, and disabilities (rather than a specific
biology per se) to assess risk.
The physical frailty screening tool most often cited is often called the Fried Frailty Tool or
Frailty Phenotype [27]. This tool was developed to identify physical frailty in community-
dwelling older adults and was validated in the Cardiovascular Health Study (CHS), which
involved over 5000 men and women aged ≥65 years [1], and multiple other studies
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[11,12,31,32]. This tool requires patient participation and specialized equipment for grip
strength and walking speed measurements and defines the frailty phenotype as meeting
three or more of the following five criteria [1]. Pre-frailty is defined as one or two of these
characteristics, and not frail as having none:
The deficit accumulation or index approach to measuring frailty is based on the accumulation
of illnesses, functional and cognitive declines, and social situations that are added together to
calculate frailty [33]. It requires answering 20 or more medical and functional-related
questions. The higher the number of deficits, the higher the frailty score. The tool can be
adapted to information available in the medical record and does not require a patient
interview or exam for tabulation.
Rapid screening tools — Although the frailty phenotype assessment and the frailty index
approach are the most commonly cited and most validated approaches to frailty
measurement, clinicians and patients may benefit from using a quicker frailty screening
assessment tool. Such tools allow clinicians to more quickly flag vulnerable older adults and
work to alter care plans based on this vulnerability. Several studies have compared the most
commonly utilized screening tools and found that these indices were comparable in predicting
risk of adverse health outcomes and mortality [2,37,38].
In addition, several of the rapid screening tools described below can be utilized to identify
those who might need a more formal comprehensive geriatric assessment (CGA) [39].
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A tool that takes only minutes to perform, and can be incorporated into the history-taking
part, is the FRAIL scale, which is presented in a slightly modified version below [40,41]. The
mnemonic "FRAIL" is helpful in remembering the component questions:
● Fatigue ("Have you felt fatigued? Most or all of the time over the past month?") Yes = 1,
No = 0
● Resistance ("Do you have difficulty climbing a flight of stairs?") Yes = 1, No = 0
● Ambulation ("Do you have difficulty walking one block?") Yes = 1, No = 0
● Illnesses (“Do you have any of these illnesses: hypertension, diabetes, cancer (other than
a minor skin cancer), chronic lung disease, heart attack, congestive heart failure, angina,
asthma, arthritis, stroke, and kidney disease?”) Five or greater = 1, fewer than 5 = 0
● Loss of weight (“Have you lost more than 5 percent of your weight in the past year?”)
Yes= 1, No = 0
Frail scale scores range from 0 to 5 (0 = best, 5 = worst) and represent frail (3 to 5), pre-frail (1
to 2), and robust (0) health status.
Another assessment tool known for its ease in administering in most clinical settings is The
Study of Osteoporotic Fractures (SOF) frailty tool [37]. Frailty is defined as the presence of at
least two of three components:
The Edmonton Frail Scale has 14 questions that cover a variety of important domains,
including cognition, general health, function, social support, and nutrition. This validated tool,
while not diagnosing physical frailty or deficit accumulation frailty per se, is useful to identify a
number of measurement domains that are important to the health care of older adults [42].
Indeed, this tool functions like a short version of a CGA, which in turn may be helpful in the
identification of more areas that may benefit from further diagnostic efforts or care
management plans.
Finally, the Clinical Frailty Scale is a rapid frailty screening tool that is scored between 1 (very
fit) and 9 (terminally ill) based on self-report of comorbidities and the need for help with
activities of daily living (ADLs) ( figure 1) [43].
PATHOPHYSIOLOGY
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There is increasing evidence that dysregulated stress response systems, including immune,
endocrine, and energy response systems are important to the development of physical or
syndromic frailty. The basis of this dysregulation and ultimately frailty is hypothesized to be
driven by aging-related molecular changes, genetics, chronic environmental exposures, and
specific disease states ( figure 2) [44]. Sarcopenia, or age-related loss of skeletal muscle and
muscle strength, is a key physiologic component of frailty. Decline in skeletal muscle function
and mass are often consequences of age-related hormonal changes [45-48] and changes in
inflammatory pathways, including increase in inflammatory cytokines [49].
Endocrine — Multiple age-related hormone changes have been associated with frailty (see
"Growth hormone deficiency in adults"):
● Decreased growth hormone and insulin-like growth factor (IGF)-1 [45,50,51] – Associated
with lower strength and decreased mobility in a cohort of community-dwelling older
women [52].
● Increased cortisol levels [54] – May impact skeletal muscle and immune system
components.
● Decreased sex steroids – Evidence is mixed that lower levels of reproductive hormones
contribute to frailty [55-58].
● Serum levels of the proinflammatory cytokine interleukin (IL) 6 and C-reactive protein
(CRP), as well as white blood cell and monocyte counts, are elevated in community-
dwelling frail older adults [45,59-62]. In addition, elevated levels of these biomarkers in
female long-term care residents may predict worsening physical performance and gait
speed 12 months later [62]. IL-6 acts as a transcription factor and signal transducer that
adversely impacts skeletal muscle, appetite, adaptive immune system function, and
cognition [63] and contributes to anemia [64,65].
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● Immune system activation may trigger the clotting cascade, with a demonstrated
association between frailty and clotting markers (factor VIII, fibrinogen and D-dimer)
[60].
● Frail older adults are less likely to mount an adequate immune response to influenza
vaccination [31].
PATIENT EVALUATION
A consensus group of delegates from international and US societies has recommended that all
persons over age 70 and adults with chronic disease or weight loss exceeding 5 percent over a
year be screened for frailty using available screening tools [19]. However, there are no
available data from trials investigating whether screening an unselected geriatric population
for frailty, based on age alone, will improve outcomes.
For patients in whom frailty is a potential concern, based on the clinician's observations and
reports from the patient and patient's family related to activity levels, diet, cognition, and
weight, the following should be ascertained:
● The patient history should focus on energy levels and excessive fatigue, ability to
perform or maintain physical activities like stair climbing, and the ability to get out of the
home and walk at least one block.
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differential diagnosis list and rule out underlying medical or psychological issues that may be
driving signs and symptoms of frailty.
The most common conditions to be considered in older patients presenting with weight loss,
weakness, and impaired functional abilities include:
● Depression
● Malignancy – Lymphoma, multiple myeloma, occult solid tumors
● Rheumatologic disease – Polymyalgia rheumatica, vasculitis
● Endocrinologic disease – Hyper- or hypothyroidism, diabetes mellitus
● Cardiovascular disease – Hypertension, heart failure, coronary artery disease, peripheral
vascular disease
● Renal disease – Renal insufficiency
● Hematologic disease – Myelodysplasia, iron deficiency, and pernicious anemia
● Nutritional deficits – Vitamin deficiencies
● Neurologic disease – Parkinson disease, vascular dementia, serial lacunar infarcts
Laboratory testing — When evaluating a frail patient for the first time, laboratory testing
should be undertaken in order to rule out treatable conditions. A suggested initial screen
includes:
MANAGEMENT
Specific care plans for frailty have not yet been extensively developed or tested. Despite this,
there are emerging strategies that can be utilized to help mitigate the daily impact of frailty on
quality of life and overall health status.
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For robust older patients, the medical practitioner should appropriately treat known chronic
diseases, manage intermittent acute illness and events, and assure age-appropriate screening
measures and preventive care [69].
In the moderately to severely frail patient, often "less is more." Aggressive screening or
intervention for non-life-threatening conditions may be rife with complications. Procedures or
hospitalizations may bring about unnecessary burden and decreased quality of life to a
patient who is already at great risk of morbidity and mortality [70]. In some cases, referral to
palliative care may be the most appropriate intervention. (See 'Palliative care' below.)
Nonetheless, frail older adults may benefit from interventions targeting specific components
of their frailty exam, and from CGA [71,72].
Interventions
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activity was associated with severity and incidence of frailty measured by a comorbidity
or deficit accumulation index [74]. Compared with usual care, the intervention group had
a decreased risk of both developing increased numbers of comorbidities (hazard ratio
[HR] 0.72; 95% CI 0.55-0.93) and of persistent comorbidities/deficits (HR 0.53; 95% CI
0.33-0.85).
In treatment of weight loss, oral nutritional supplements between meals (low-volume, high
caloric drinks or puddings) may be helpful in adding protein and calories. A meta-analysis of
studies of nutritional supplements showed that providing nutritional supplements to older
undernourished adults yielded small gains in weight (2.2 percent) [83].
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serum levels of 25-hydroxyvitamin D (<20.0 ng/mL) were associated with a higher prevalence
of frailty at baseline in a group of 1600 men over age 65 but did not predict greater risk for
developing frailty at 4.6 years [90]. Given that vitamin D appears to play an important role in
both muscle and nervous tissue maintenance with aging, further studies to evaluate the
association between vitamin D and frailty are indicated. The daily intake of vitamin D in older
adults should be at least 800 to 1000 international units. (See "Falls: Prevention in community-
dwelling older persons" and "Geriatric health maintenance", section on 'Vitamin D'.)
Several hormonal and nutritional interventions have been evaluated in related geriatric
conditions.
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Further intervention studies in frailer, older individuals will be needed to determine the
effectiveness and potential harm of treatments that target endocrine or inflammatory biology
in frail older adults.
Palliative care — Diagnosing frailty helps identify those older adults at highest risk of adverse
health outcomes. Palliative care approaches may be helpful to alleviate symptoms of related
medical conditions and to help in consideration of the appropriateness of potential medical
and surgical interventions (such as chemotherapy or major surgery) and their impact on
mortality and quality of life for the frail older adult [98].
For those with advanced frailty and multiple comorbidities or those with failure to thrive, the
engagement of a palliative care team may help to identify methods to preserve or improve
quality of life and to clarify goals of care. (See "Benefits, services, and models of subspecialty
palliative care", section on 'Palliative care services'.)
Notably, in the United States, the Centers for Medicare and Medicaid Services (CMS) no longer
accept either debility or adult failure to thrive as a principal diagnosis for hospice services, and
these diagnoses should not be listed as the primary hospice diagnosis. However, progressive
inanition is one criterion which may be used to identify a likely life expectancy of six months or
less. (See "Hospice: Philosophy of care and appropriate utilization in the United States".)
Care for frail older adults is frequently challenging, related to their increased disability and
multiple chronic diseases. This is further heightened in frail individuals who lack social
supports. An interdisciplinary team-based approach to care is often important in meeting the
needs of frail adults, who may represent the population most likely to benefit from specialized
and targeted comprehensive interventions [99].
Outcomes of interdisciplinary interventions are mixed, however. In one small randomized trial,
an interdisciplinary intervention involving screening, home visits, and occupational and
physical therapy tailored to the patient's support needs, compared with usual care, resulted in
no difference in disability outcome at six-month, one-year, and two-year assessments [100].
However, in another randomized clinical trial, multidisciplinary approaches that focused on
improvement of specific diagnostic criteria for physical frailty resulted in improvement in
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frailty status and the potential for reduced health care costs [71,101].
A conceptual model of care has been outlined by one gerontology group, that proposes
several adjuncts and enhancements to the traditional one clinician/one patient visit [102].
Proposed practice changes include:
Comprehensive geriatric assessment — Frail older adults are at highest risk in the general
population of older adults, and may be expected to derive maximum benefit from
comprehensive geriatric assessment (CGA). The overall goals of CGA are:
CGA involves an interdisciplinary care team that coordinates evaluation of an older patient and
develops a plan for integrated care [103]. The team usually consists of a geriatrician or other
medical practitioner knowledgeable in the care of older adults, nurse, social worker,
pharmacist, and an occupational or physical therapist. (See "Comprehensive geriatric
assessment" and "Comprehensive geriatric assessment for patients with cancer".)
Outpatient PACE — The frailest older adults in the United States may benefit from the
Medicare Program of All-inclusive Care for the Elderly (PACE). The goals of this model are to
improve function, overcome environmental challenges, and keep older adults living in their
communities by preventing institutionalization.
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PACE was designated as a permanent Medicare program in 1997 because it was successful in
maintaining function and community-dwelling status and in providing lower-cost care
compared with traditional fee-for-service care [105].
Hospital care and ACE — Hospitalization increases risk for institutionalization and decrease in
quality of life for a frail older adult. Change in environment, exposure to new medications, and
immobility, combined with acute illness, can lead to devastating outcomes for these
vulnerable patients. Often, the decline in level of function and ability to care for oneself that
occurs during hospitalization persists after discharge [106,107]. In one study, frail individuals
had a sevenfold increased risk of progressing from no disability to mild disability within one
month of hospitalization, compared with non-frail patients (35 versus 7 percent) [108].
Acute Care for Elders (ACE) is a model of care for the acutely ill hospitalized older adult
designed to prevent functional decline and improve functional independence if decline has
occurred. The model typically includes a specially designed environment that is a more home-
like environment, patient-centered medical care that focuses on the prevention of disability,
and comprehensive discharge planning and management. In a randomized controlled trial of
1531 community-dwelling adults aged 70 and older, this model decreased the likelihood of
decline in activities of daily living (ADLs) or nursing home placement both at hospital
discharge and at 12 months without an increase in hospital length of stay or hospital costs
[109].
SUMMARY
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● An international consensus group has recommended that all persons over age 70, and
adults with chronic disease or weight loss exceeding 5 percent over a year, be screened
for frailty, though evidence supporting this approach is not robust. The FRAIL scale is one
tool that can be readily incorporated into history-taking, but multiple other screening
tools are available and have been validated. Physical examination should include
assessment of the patient's ability to rise from a firm chair five times without use of arms
and their ability to walk across the room. (See 'Patient evaluation' above and
'Instruments developed to identify frailty' above.)
● Goal-setting with patients and their families is crucial in providing care for the frail
individual, establishing individual priorities, weighing risks and benefits of interventions,
and making decisions regarding aggressiveness of care. Interventions have focused on
components of frailty, such as strength. Activity interventions have been shown to have a
positive impact on even the frailest older adults. To date, no biological or pharmaceutical
interventions are recommended for frailty per se, although biologically targeted
interventions may play a role in the future. (See 'Establishing goals of care' above and
'Interventions' above.)
● Clinical geriatric evaluation teams and specialized programs can play an important role
in improving the quality of life for older adults. (See 'Model systems of care' above.)
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Topic 3010 Version 51.0
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GRAPHICS
Reproduced with permission from: Dalhousie University. Clinical Frailty Scale. Available at: https://www.dal.ca/sites/gmr/our-tools/clinical-
frailty-scale.html (Accessed on October 20, 2020). Copyright © 2020 Rockwood K, et al.
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CRP: C-reactive protein; IL: interleukin; IGF: insulin-like growth factor; DHEA-S:
dehydroepiandrosterone sulfate.
Reproduced with permission from: Walston J, Hadley EC, Ferrucci L, et al. Research Agenda for Frailty in Older
Adults: Towards a Better Understanding of Physiology and Etiology. J Am Geriatr Soc 2006; 54:991. Copyright ©
2006 Wiley-Blackwell.
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ACE unit: Acute Care for Elders unit; GEM: Geriatric Evaluation and Management;
PACE: Program for All-Inclusive Care of the Elderly.
Modified with permission from: Walston JD, Fried LP. Frailty and its Implications for Care. Chapter 9.
In: Geriatric Palliative Care, Morrison RS, Meire DE. Oxford University Press, New York 2003. p.93.
Copyright ©2003 Oxford University Press.
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MEALS ON WHEELS
M Medications
S Swallowing disorders
O Oral factors
N No money
H Hyperthyroidism, hyperparathyroidism
E Entry problems/malabsorption
Reproduced with permission from: Saint Louis University Geriatric Evaluation Mnemonics Screening Tools. Compiled by
faculty from Saint Louis University Geriatrics Division. Copyright ©2002 Saint Louis University.
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Approach
Review current drug therapy
Consider adverse drug events as a potential cause for any new symptom
Reproduced with permission from: Rochon PA, Gurwitz JH. Drug Therapy. The Lancet 1995; 346:32. Copyright © 1995
Elsevier.
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Contributor Disclosures
Jeremy D Walston, MD No relevant financial relationship(s) with ineligible companies to
disclose. Kenneth E Schmader, MD No relevant financial relationship(s) with ineligible companies to
disclose. Jane Givens, MD, MSCE No relevant financial relationship(s) with ineligible companies to
disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for references
to be provided to support the content. Appropriately referenced content is required of all authors and
must conform to UpToDate standards of evidence.
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