Frailty A Multidimensional Biopsychosocial Syndrome

Frailty
A Multidimensional Biopsychosocial Syndrome
Carl I. Cohen, MD*, Rivka Benyaminov, BA,

Manumar Rahman, MD, Dilys Ngu, MD, Michael Reinhardt, MD
KEYWORDS
Frailty Cognitive frailty Social frailty Psychological frailty
KEY POINTS
The original conceptual landscape of frailty has evolved into a complex, multidimensional
biopsychosocial syndrome including physical, cognitive, social, and psychological
domains.
Many new tools are available to assess the frailty domains.
Frailty is a dynamic, potentially reversible state, and numerous biological, lifestyle, envi-
ronmental, and clinical risk and protective factors have been identified.
Research and care of persons with frailty have been hampered by a lack of consensus in
defining the frailty domains and a limited understanding of the mechanisms of how the do-
mains affect each other.
INTRODUCTION
Frailty is thought to be one of the most serious public health challenges of the twenty-
first century.1 All older adults are at risk for developing frailty, and it is associated with
many adverse outcomes including diminished quality of life and increased rates of
mortality, hospitalizations, falls, depression, and dementia.2 Recognition of frailty
and its risk factors can inform treatment decisions and prognosis. In recent years,
several features of frailty have become well-established: (1) Although the physical
dimension has been privileged, it is increasingly recognized that frailty is multidimen-
sional and complex, and includes physical, cognitive, psychological, and social do-
mains; that is, it is a “biopsychosocial” syndrome; (2) Frailty is a dynamic process
Partial support was provided by funding from HRSA Award No. U1QHP33077 and the SUNY
Health Network of Excellence.
SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
* Corresponding author. SUNY Downstate Health Sciences University, MSC 1203, 450 Clarkson
Avenue, Brooklyn, NY 11203.
E-mail address: carl.cohen@downstate.edu
Med Clin N Am 107 (2023) 183–197

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184 Cohen et al
that can fluctuate between various states of frailty; and (3) Frailty is potentially prevent-
able, reversible, or can be slowed, until a point of “no return.”1,3 The conceptual
change of frailty as a biopsychosocial syndrome has broadened the field to include so-
cial and behavioral scientists and clinicians from a wide range of specialties.
Among the issues that have dominated discussions of frailty have been efforts to
more precisely define these domains and attain consensus regarding these defini-
tions; whether these conceptual domains can be best viewed as a single phenotype,
separate phenotypes, or overlapping of physical, cognitive, and social conditions; and
whether prevention and treatment strategies will have to target each type of frailty or
are there strategies that might act across these conditions? In this article, we will
address these issues by reviewing the concepts and definitions of each domain, their
epidemiology, the measures used for assessment, their risk factors, pathogenesis,
and suggestions for treatment and prevention. We conclude with a discussion of con-
troversies in the frailty literature and future directions for research.
DEFINITIONS
Physical Frailty
When first classified in 1986, frailty was associated with older individuals having mul-
tiple comorbidities that restricted their activities of daily living and were dependent on
assistance from others.4 Later definitions became more inclusive toward persons that
would be considered in a precursor state of disability. This perspective shifted the
focus toward early intervention in high-risk individuals. frailty can be dichotomized
into 2 broad conceptual systems that should be considered complementary but not
substitutable4,5: (1) Risk accumulation model.6 As people grow older, they will accu-
mulate diseases and impairments that will cause them to obtain a predisposition for
adverse outcomes. This model proposes that interventions be aimed at modifying
these risk factors. (2) Frailty as a syndrome.3 Frailty is seen as a set of signs and symp-
toms that define a health condition.
Although the accumulation model considers frailty solely as a “preclinical” entity (ie,
a risk), the syndrome model regards it primarily as a health condition or phenotype that
can be viewed as a progressive process to be staged across a range of severity states,
with lower and higher risk for adverse outcomes considered “prefrail” and “frail,”
respectively. Fried’s7 conceptualization operationalized frailty on the presence of
weak muscle strength, slow gait speed, unintentional weight loss, exhaustion, and
low physical activity. It did not include disabilities in its operationalization. However,
the deficit accumulation model includes health deficits such as signs, symptoms, dis-
abilities, and abnormal medical tests. Both models have been found to predict
adverse outcomes such as a higher risk for mortality and hospitalizations.
Many popular conceptualizations of physical frailty are hybrids of these 2 models
that focus on the risks for future adverse events. However, hybridization risks
conflating a syndrome (ie, phenotype) that should have specific symptoms and signs
with an accretion of deficits across multiple systems. For example, Panza and col-
leagues8 proposed a hybrid framework in which frailty would be considered “primary”
or “preclinical” when the state is not associated directly with a specific disease or has
no substantial disability. This definition is more akin to the physical phenotype of
frailty. Frailty is considered “secondary” or “clinical” when associated with known
comorbidities such as dementia or overt cardiovascular disease or disability. Second-
ary frailty is more congruent with the accumulation of deficits model. Kelaiditi and col-
leagues9 ruefully observed that despite several decades of research, there is a lack of
consensus about a unique operational definition of frailty.
reservados.
Frailty: A Biopsychosocial Syndrome 185
Cognitive Frailty
Cognitive frailty results from preexisting physical frailty and cognitive impairment,
generally considered mild or subjective. In 2013, the International Academy on Nutri-
tion and Aging and the International Association of Gerontology and Geriatrics (IANA-
IAGG)9 defined cognitive frailty as the presence of both physical frailty and mild cogni-
tive impairment (MCI), operationalized as a Clinical Dementia Rating score of 0.5, and
the exclusion of concurrent dementias such as Alzheimer disease (AD). The definition
suggests reduced cognitive reserve which is differentiated from normal aging. More-
over, there is a potential for reversibility in the cognitive and physical components. The
authors allow for the possibility that various neurocognitive disorders may ultimately
arise, although they should not be present when diagnosing cognitive frailty.
Recently, several investigators have proposed a modification of the framework for
the definition of cognitive frailty by identifying 2 subtypes: “potentially reversible”
cognitive frailty and “reversible” cognitive frailty; the aim being to make the potential
reversibility of physical frailty consistent with the potential reversibility of cognitive def-
icits.10 Thus, the physical frailty components for both cognitive frailty subtypes include
physical “prefrailty” and “frailty.” The cognitive impairment components of “potentially
reversible cognitive frailty” should be MCI (ie, mild objective cognitive deficits without
declines in daily functioning), whereas “reversible cognitive frailty” is defined as pre-
MCI “subjective” cognitive deficits. Subjective cognitive disorders are characterized
by self-reported memory complaints but no objective cognitive deficits or deficits in
daily living. Subjects with reversible cognitive frailty and no biomarker evidence of
AD pathologic condition may include individuals with normal cognitive aging or unde-
tectable preclinical AD.
Social Frailty
This syndrome has not received the attention given to physical and cognitive frailty.
There has been no consensus in the literature regarding the concept and methods
for assessment. Bunt and colleagues’11 review found that social frailty is most typically
defined on a continuum of being at risk of losing, or having lost, resources that are
important for fulfilling one or more basic social needs during the life span. They also
found that social frailty includes the threat or absence of self-management abilities
necessary to fulfill these social needs. Other items sometimes included within social
frailty are low income and housing insecurity. For the most part, social frailty has
not been operationalized to require the co-occurrence of physical frailty.
Psychological Frailty
This syndrome has been largely neglected or incorporated into other frailty dimen-
sions. A review by McKelvie and coauthors12 found that only 8% of articles on social
or psychological frailty were specifically devoted to psychological frailty. Psychologi-
cal frailty has been operationalized to include the co-occurrence of physical frailty with
low mood, apathy, depression, loneliness, and cognitive deficits.8,12 The latter 2 vari-
ables may sometimes be classified under social frailty and cognitive frailty, respec-
tively. Most studies have focused on depression, and Brown and colleagues13
proposed a “depressed frail” phenotype.
Table 1 describes the frailty domains.
EPIDEMIOLOGY
Siriwardhana and colleagues’31 meta-analysis of persons aged 50 years and older in

15 countries found that the pooled prevalence of physical frailty was 17.4% (range
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Cohen et al
Table 1
Frailty domains: Description and assessment scales
Frailty Domain Physical Frailty Cognitive Frailty Psychological Frailty Social Frailty
Description Two popular models: The co-occurrence of physical Often operationalized to Typically defined on a
Model 1: Risk accumulation frailty and cognitive include low mood, apathy, continuum of being at risk of
model—with increased age, impairment, usually defined and depression with the co- losing, or having lost,
a person will accumulate as mild. A modified occurrence of physical frailty resources that are important
diseases and impairments framework for the definition for fulfilling one or more
that will cause them to of cognitive frailty was basic social needs.
obtain a predisposition for developed based on Sometimes includes
adverse outcomes and identifying 2 subtypes: (1) sociodemographical risk
hospitalization. This model Potentially reversible— factors. Co-occurrence of
proposes that interventions simultaneous presence of physical frailty not usually
be aimed at modifying these physical prefrailty or physical required.
reservados.
risk factors frailty and mild cognitive

Model 2: Frailty as a impairment (MCI) (2)
syndrome—frailty is seen as a Reversible—the
set of signs and symptoms simultaneous presence of
that define a health physical prefrailty or physical
condition usually divided frailty and pre-MCI
into risk levels of “prefrail” subjective cognitive deficits
and frail
Selected Assessment Tools Fried Frailty Scale,7 FRAIL Brief screens: Mini-Cog,18 the Geriatric Depression Scale27; SOCIAL29; Social Frailty Scale30
questionnaire,14 Deficit MMSE,19 3-MS,20 SLUMs,38 CES-D28
Accumulation Index (Frailty and the MoCA21
Index),15 Clinical Frailty Comprehensive cognitive tests:
Scale,36 Edmonton Frailty Mattis DRS,22 Alzheimer’s
Scale,16 Tilburg Frailty Disease Assessment Scale,23
Scale17 and the CERAD
neuropsychological
battery24
Subjective Cognitive Decline
Questionnaire25
ADL assessment scales26
3.9% to 51.4%) and prefrailty was 49.3% (range: 13.4% to 71.6%). The study found
that the prevalence of frailty seems higher among community-dwelling older adults
in upper-middle-income countries than in high-income countries; there were insuffi-
cient data on low-income countries.
Since the 2013 IANA-IAGG consensus on cognitive frailty,9 various studies have
emerged studying the epidemiology of cognitive frailty using its newly proposed defi-
nition. There has been a wide variability in prevalence rates that has been attributed to
differences in models of cognitive frailty, age, gender, and setting.8 Once stratified, it
was found that studies of participants in a clinical setting had a higher prevalence
(10.7%–22.0%) of cognitive frailty when compared with population-based studies
(1.0%–4.4%).32 A recent meta-analysis by Qui and colleagues33 of 24 studies
involving 73,643 participants aged 60 years or older living in the community found
an estimated pooled prevalence of cognitive frailty of 9%. Because of the diverse def-
initions of cognitive frailty, the prevalence varied from 1% to 50% across the studies.
Of note, there have been changes in prevalence over time, with rates of 6% from 2012
to 2017 and 11% from 2018 to 2020. The estimated pooled prevalence of cognitive
frailty was 11% in men and 15% in women.
There have been no meta-analyses or systematic reviews of the prevalence of social
frailty. Studies by Tsutsumimoto and colleagues30 and Yamada and Arai34 in Japan
found a prevalence rate of 26.8% and 18%, respectively. The latter study found rates
of social prefrailty of 32%. Rates of social frailty increased from 16% in the 65 to 69
age group to 41% in those aged 90 years and older.
Vaughan and coauthors’35 literature review found that the prevalence rates of the
co-occurrence of depressive symptomatology and physical frailty in older adults
aged 55 years and older varied widely (range: 16.4%–53.8%). A large study in Japan
found that among older adults with any form of frailty status, the incidence of depres-
sive symptoms increased significantly in the presence of physical, cognitive, or social
frailty.30
DIAGNOSIS AND ASSESSMENT
Ruan and colleagues10 pointed out that many well-validated physical frailty models
have operationalized screening measures incorporating the various conceptual
models. The Fried phenotype of the Cardiovascular Health Study7 is the most com-
mon frailty-screening tool used worldwide. It is fast and easy to administer. Patients
are rated based on the presence of the following 5 signs/symptoms: unintentional
weight loss, self-reported exhaustion, poor grip strength, slow walking speed, or
low physical activity (scoring: 0 5 robust, 1–2 5 prefrail, 3–5 5 frail). The validated sim-
ple FRAIL questionnaire14 screening tool is a good alternative physical frailty
screening instrument without objective measures, and it can rapidly identify individ-
uals with physical frailty or physical prefrailty in large clinical cohort studies. It contains
5 items—fatigue, resistance, aerobic, illness accumulation, and loss of weight
(0 5 robust, 1–2 5 prefrail, 3–5 5 frail). A variety of more comprehensive batteries
exist. The deficit accumulation index (or frailty index) includes scales that assess dis-
eases, signs, symptoms, laboratory abnormalities, cognitive impairments, mood, and
disabilities in activities of daily living; most scales contain between 30 and 70 items. 15
Scores are calculated by summing the number of positive items divided by the total
number of items; scores range from 0 to 1.0. The use of cutoffs is controversial,
although 0.25 or greater has been proposed to indicate frailty. Rockwood also devel-
oped the Clinical Frailty Scale36 which appraises medical disease burden and func-
tionality based on 7 components ranging from 1 (robust health) to 7 (complete
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188 Cohen et al
functional dependence on others). An intermediate-length instrument within this

framework is the Edmonton Frail Scale,16 which consists of 10 items examining cogni-
tion, functional performance, general health, functional independence, social support,
medication use, nutrition, mood, and continence. The Tilburg Frailty Index17 concep-
tualizes frailty as a multidimensional concept (physical, psychological, social) and in-
cludes 10 determinants and 15 components of frailty that classify patients into frail or
not. Other instruments include the Program of Research on Integration of Services for
the Maintenance of Autonomy (PRISMA-7) questionnaire, Timed Get-Up and Go Test,
and the Gerontopole Frailty Screening Tool (see Sukkriang37).
Diagnosing cognitive frailty requires the clinician to diagnose physical prefrailty
and frailty, MCI, subjective cognitive impairment (SCI), and to rule out dementia.
Cognitive deficits can be assessed with a variety of instruments. Brief measures
that can be administered quickly in an office setting include the Mini-Cog,18 the
Mini-Mental State Examination (MMSE),19 the Modified Mini-Mental State Examina-
tion (3-MS),2 the St. Louis Mental Status Examination (SLUMs),38 and the Montreal
Cognitive Assessment (MoCA).21 More comprehensive cognitive tests that include
a detailed assessment of cognitive dimensions include the Dementia Rating Scale
(DRS),22 Alzheimer’s Disease Assessment Scale,23 and the Consortium to Establish
a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery.24
Many researchers classify SCI based on a positive response to a single question
about perceived difficulty, change, or worry/concern about one’s memory or cogni-
tion, whereas others use cut scores/median split approaches on a questionnaire or
other methods.39 There are several batteries to test SCI; one of the most cited is
the Subjective Cognitive Decline Questionnaire.25 Rabin and colleagues39 argue
that it is critical to distinguish between those people whose concerns about cognition
reach a threshold for significance that may be attributed to underlying neurodegener-
ative changes consistent with prodromal AD (or other dementia subtypes) from those
whose concerns are generally mild and attributed to benign conditions associated
with normal aging. This is problematic because both the distinction between SCI
and cognitively normal aging are made based on subjective cognitive reports. Both
groups are considered unimpaired on standardized neurocognitive tests. Methods
to discriminate more benign conditions from those that may progress to AD have
incorporated the use of biomarkers, for example, cerebrospinal fluid ab42, tau, and
phosphorylated tau concentrations; amyloid deposition and glucose metabolism in
positron emission tomography; and hippocampal atrophy on magnetic resonance im-
aging. Finally, to distinguish between dementia and MCI/SCI, an assessment of daily
functioning must be done. There are a variety of simple measures to assess Instru-
mental Activities of Daily Living (ADL) and Basic Activities of Daily Living.26
There are several questionnaires to assess social frailty. These instruments assay a
broader spectrum of psychosocial risk factors for creating frailty, some focus on psy-
chological as well as social factors. Most are brief questionnaires such as the SOCIAL
(sadness, outside activities, cognition, income adequacy, attachment to neighbor-
hood, lethargy) with scores of 4 to 6 indicating social frailty and 2 to 3 indicating pre-
social frailty.29 A questionnaire developed by Tsutsumimoto and coauthors30 focuses
only on social network factors (going out less frequently, visiting friends, living alone,
feeling helpful, talking with someone daily) with scores of 2 to 5 indicating social frailty
and a score of 1 indicating presocial frailty.
There are no specific scales for psychological frailty. The 15-item Geriatric Depres-
sion Scale27 and the Center for Epidemiologic Studies-Depression (CES-D) question-
naire28 have been used in several studies.35,40
The scales are listed in Table 1.
reservados.
PREDICTORS, PATHOGENESIS, AND COURSE
Frailty is a dynamic potentially reversible state, and identifying the risk factors of frailty
will facilitate prevention and management.41 Recent studies have identified many risks
and protective factors including biological, lifestyle, environmental, and clinical ele-
ments (Table 2).
In addition to the risk factors and biomarkers summarized in Table 2, there are
important interactions between the various frailty domains. Physical frailty is associ-
ated with late-life cognitive impairment and decline, incident AD and MCI, vascular de-
mentia, other dementias, and AD pathologic conditions in older persons with and
without dementia; frail women are at higher risk of incident AD than frail men.8,46,47
The reciprocal relationship, that cognitive impairment predicts future physical frailty,
has also been reported in samples of community-dwelling older adults.48 While frailty
and cognitive impairment have been viewed as 2 independent concepts in which both
predict adverse outcomes,49 when they coexist, cumulative negative effects are often
detected.50 In support of a cognitive frailty phenotype, Bu and colleagues’51 meta-
analysis found that among older adults living in communities, cognitive frailty was a
significant predictor of all-cause mortality and dementia, and that cognitive frailty
was a better predictor of all-cause mortality and dementia than frailty alone. However,
several studies found no relationship between physical frailty and cognition.48 Thus,
some investigators suggest that frailty syndrome and neurocognitive disorders should
be treated as distinct conditions that may interact bidirectionally.42
Xie and coauthors52 found that advanced age, depression, and insomnia were
significantly associated with higher rates of cognitive frailty. Indeed, several investiga-
tors postulated that physical frailty, cognitive impairment, and depression are interre-
lated constructs.52 Vaughan and colleagues35 and Brown and colleagues13 concluded
that there is a bidirectional relationship between depression and physical frailty, and
together they increase the risk of dementia, suicidality, and mortality.
A systematic review of social frailty by McKelvie and colleagues12 showed that it led
to various health problems late in life. Compared with those who do not exhibit social
frailty, older adults with this condition have been found to have significantly lower
physical and cognitive functioning and a significantly higher risk of future incident
disability.40 For example, Teo and colleagues40 found that social frailty independently
predicted adverse health outcomes such as functional and severe disability, nursing
home referral, and mortality; combining social frailty with physical frailty increased
the prediction of adverse outcomes. Social frailty predicted physical and cognitive
decline in Japanese community-dwelling older adults, and social frailty had more
impact on depression than physical or cognitive frailty.30
Several studies have supported the conceptual framework that the frailty domains
are related but largely independent of each other and that each domain incrementally
increased risk estimates of various adverse health outcomes. Vermeiren and col-
leagues53 showed that combining various frailty dimensions increased mortality haz-
ard ratios (HRs); HRs associated with 1, 2, and 3 frailty dimensions were 1.9, 3.9, and
10.4, respectively.
Despite evidence of the close relationship between the various frailty domains, the
mechanisms involved in this association have not yet been determined.42 All the do-
mains are complex and have multifactorial influences. Fabricio and colleagues42 pro-
posed that the pathophysiologic mechanisms for these domains overlap considerably
and may develop positive feedback loops. Mechanisms involved in the onset of the
physical frailty syndrome are also found to promote neurodegeneration (eg, chronic
inflammation and oxidative stress), and many of these risk factors are also found in

reservados.
190 Cohen et al
Table 2
Risk factors/markers for development and progression of various cognitive domains and
potential treatment approaches
Possible Treatment
Biological Factors Description Approach
Inflammation High levels of C-Reactive Exercise, healthy diet,
Protein, Interleukin-6, smoking cessation,
TumorNecrosis Factor treatment of medical
-alpha illnesses,
pharmacological agents
with anti-inflammatory
effects
Mitochondrial Diminished functioning Aerobic exercise
bioenergetics interventions have
resulted in improved
muscle oxidative capacity
and upregulated
mitochondrial genes,
improved skeletal muscle
mitochondrial content in
sedentary older adults,
and are effective for
improving physical
functioning in frail elders
Dopamine dysfunction Diminution Pharmacologic
augmentation of
dopaminergic
neurotransmission may
be beneficial to
ameliorating cognitive
and physical slowing and
depressive symptoms in
adults within the
depressed frail
phenotype.
Hypothalmic Pituitary Especially hypercortisol and Assessment and medical
Adrenal axis dysfunction hypocortisol dysfunction treatment
Epigenetic changes Frailty is associated with Exercise, psychosocial, and
epigenetically nutritional interventions
accelerated aging are potential therapeutic
measured by the targets. Additional study
difference between is needed.
predicted DNA
methylation age and
chronologic age
Undernutrition/ Protein-energy Nutrient supplementation
Micronutrient deficits undernutrition is
associated with poorer
cognitive performance.
Weight loss, reduced
caloric intake, and the
reduced intake or deficits
of specific micronutrients
(eg, carotenoids, Vitamin
(continued on next page)

reservados.
Table 2
(continued )
Possible Treatment
B6, Vitamin D, Vitamin E)
are associated with
detectable changes in
body composition and
physical function
characterizing the
transition from
independence to
disability, with weight
loss also proposed as a
dementia risk factor
Low testosterone Testosterone may promote Exogenous testosterone
hippocampal synaptic increases physical
plasticity and regulate performance and
amyloid deposition, strength in older
whereas age-related testosterone-deficient
depletion may be men. Testosterone may
associated with frailty by decrease depressive
reducing muscle mass symptoms in men with
and strength late-life depression
Increased volumes of white Found in cognitively frail Cardiovascular risk
matter hyperintensities; and prefrail persons prevention, reduction,
loss of structure of the and treatment strategies;
thalamus and cognitive exercises
hippocampus on MRI
Clinical Factors
Diabetes and Elevated Hemoglobin A1C, Medication, dietary
hyperinsulinemia obesity changes, and exercise
Cardiovascular risk Atrial fibrillation Cardiovascular
factors congestive heart failure risk prevention,
cerebral vascular reduction, and treatment
accident, hypoxia, strategies including
peripheral vascular appropriate medication,
disease, hypertension, lifestyle changes, and
hypercholesterolemia, dietary modificatons
smoking, high-fat diets including the
Mediterranean diet,
smoking cessation, and
exercise
Sarcopenia Decline in skeletal mass and Physical exercise and
function strength training in
combination with
protein supplementation
Miscellaneous physical Anemia, low serum Determine cause and treat
markers and symptoms albumin, low glomerular
filtration rate, sensory
deficits, pain
(continued on next page)

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192 Cohen et al
Table 2
(continued )
Possible Treatment
Depression Associated with physical Psychotherapy and/or
and cognitive frailty pharmacotherapy;
ameliorate
environmental stressors
Environmental Factors
Social and demographic Social isolation, loneliness, Promotion of emotional
risk factors low income, housing resilience, active and
insecurity, low education, socially integrated
advanced age, female lifestyles; enhance safety
gender, unmarried, rural net for at-risk older
residence, low-income adults
neighborhood, low
quality of life
Lifestyle Factors Low physical activity, Individual and group
smoking, high alcohol exercise, balance, and
consumption strength training;
counseling and
pharmacologic
interventions regarding
smoking and alcohol
intake
References: Kelaiditi et al;9 Panza et al;8 Brown et al;13 Fabricio et al ;42 Briej et al;2 Vatatabe et al;43
Feng et al;44 Elwood et al;33 Facal et al.45
late-life depression. Other clinical conditions can increase the risk of both frailty and
dementia, such as heart failure, peripheral vascular disease, diabetes, and hyperten-
sion. Therefore, it is likely that physical frailty, neurocognitive disorders, and depres-
sion share common risk factors and biological mechanisms.
Finally, frailty is a dynamic state with heterogeneous outcomes, although most per-
sons remain in their baseline state and a substantial percentage die (about one-third),
on 4 to 5-year mean follow-up, up to 37% experienced transitions in their status, either
improvement or decline.3 Notably, several investigators found improvement rates
among frail elders of between 15.5% and 27%53–56; 12% of pre-frail improved.54
TREATMENT AND PREVENTION
Dent and colleagues1 reviewed the treatment literature and found that the “certainty of
evidence” for any management strategy was low. The main strategies have included
physical activities (aerobic training, resistance-based, balance coordination) in indi-
vidual or group sessions, health behavior advice, protein and micronutrient supple-
mentation, social support strategies, hormonal therapy, cognitive training,
comprehensive geriatric assessments, and multicomponent packages. First-line man-
agement has focused primarily on physical activities and adequate protein intake.
These approaches are listed in Table 2.
Primary prevention of frailty has focused on changing unhealthy lifestyles and be-
haviors, identifying and modifying various risk factors for frailty, and conducting reg-
ular screenings for physical frailty, cognitive decline, mood changes, and social and
reservados.
functional decline.3 A patient-centered (personalized) clinical approach is essential,

and it is necessary to identify the relevant risk factors across domains for each patient.
These are summarized in Table 2. An especially challenging and understudied topic is
how to reorganize healthcare systems to focus on frailty assessment and manage-
ment. There is increasing evidence that many of the risk factors emerge in midlife,
so early interventions are desirable.3
UNRESOLVED ISSUES
1. Virtually every review article bemoans the lack of consensus regarding the defini-
tion of frailty within all domains. Physical frailty is dominated by 2 distinct
competing paradigms—the phenotype model and the deficit accumulation model.
Sometimes, hybrid approaches have been used or alternative frameworks based
on resiliency have been proposed. Researchers in cognitive frailty debate whether
to include subjective cognitive frailty as a “prefrail” measure but the definitions of
SCI are varied, and it is unclear if it is a valid clinical concept. Similarly, definitions
of psychological frailty usually include mood but may include cognition, anxiety,
and motivation; social frailty tends to focus on social supports and activities but
may encompass safety net issues such as income, housing insecurity, and the like.
2. Frailty was originally conceived as a physical condition. However, in recent years a
broader biopsychosocial approach has been proffered. Frailty has evolved from a
A
Physical
Frailty
+ /x B Physical
= = Cognitive
= = Psychological
= = Social
Frailty Frailty Frailty Frailty
Cognitive
Frailty D
Physical
+ /x C Frailty
Physical
Cognitive
Psychological frailty
frailty
Frailty
Cognitive
+/x Frailty
Psychological Social
frailty frailty
Social
Frailty
Psychological
.
Frailty
Social
Frailty
Fig. 1. Conceptual frameworks for biopsychosocial model of frailty. (A) Each frailty domain
is largely independent of the other domains but may have additive (1) or interactive (x) ef-
fects with the other domains on outcome measures. (B) Each domain is part of a singular
phenotype that has a common underlying mechanism. (C) Each domain may have some
overlapping features and some underlying mechanisms with the other domains. (D) Each
domain is largely separate but has unidirectional or bidimensional effects on other domains.
(Modified from Brown et al, 2016.13)
reservados.
194 Cohen et al
biological/physical entity to encompass cognitive brain functions and psychologi-

cal conditions that involve emotions and socially mediated elements such as lan-
guage and thoughts. Moreover, social frailty focuses on the social domain and
doesn’t typically require the co-occurrence of physical frailty. Conversely, the bio-
psychosocial model proposes that the external social domain affects the internal
domain, that is, it must be “embodied.” This broader biopsychosocial conceptual-
ization of frailty is not universally accepted or widely used and understanding the
complexities of how the 4 domains interact is daunting.
3. How the different domains relate to each other is another contested area. One pos-
sibility is that each domain is a separate clinical entity and that each has indepen-
dent additive or interactive (nonlinear) effects on outcome measures such as
disability and mortality (Fig. 1A). A second possibility is that several or all of them
have common underlying mechanisms and could therefore be considered a single
phenotype (Fig. 1B). A third possibility is that they are separate entities with some
common underlying pathogenesis (Fig. 1C). A fourth possibility is that they are
separate entities that can affect each other, either unidirectionally, or most likely,
bidirectionally, perhaps through some underlying common pathways (Fig. 1D).
Developing appropriate prevention measures and treatment will depend on
resolving these issues.
SUMMARY
It is now recognized that frailty is a common, dynamic, heterogeneous, multidimen-

sional syndrome in older adults that is germane to a broad range of clinicians and re-
searchers. Although studies on frailty have burgeoned—PubMed reports a 6-fold
increase in frailty articles over 10 years (2012–2021)—their utility has been hampered
by a lack of consensus regarding definitions of frailty within each domain as well as a
lack of understanding of the mechanisms by which these domains are related to each
other. A variety of treatment measures has been evaluated but most findings have a
low level of certainty. These issues need to be resolved, and future research must pro-
vide clinicians with the tools to identify and treat this complex syndrome more
precisely.
CLINICS CARE POINTS
Frailty is associated with many serious outcomes, but it can be potentially prevented,
reversed, or slowed.
Frailty is a multidimensional concept affecting physical, cognitive, psychological, and social
domains, and the more domains that are affected, the worse the prognosis.
The frailty domains are interrelated and addressing one domain may improve the status of
other domains; conversely, the worsening of one domain may adversely affect other
domains.
There are simple, time-efficient assessment tools to identify pre-frailty and frailty in the
physical, cognitive, psychological, and social domains.
DISCLOSURE
The authors have nothing to disclose.

reservados.
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Frailty A Multidimensional Biopsychosocial Syndrome

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Frailty

A Multidimensional Biopsychosocial Syndrome

Carl I. Cohen, MD*, Rivka Benyaminov, BA,

Med Clin N Am 107 (2023) 183–197

Siriwardhana and colleagues’31 meta-analysis of persons aged 50 years and older in

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risk factors frailty and mild cognitive

DIAGNOSIS AND ASSESSMENT

functional dependence on others). An intermediate-length instrument within this

PREDICTORS, PATHOGENESIS, AND COURSE

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(continued on next page)

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TREATMENT AND PREVENTION

functional decline.3 A patient-centered (personalized) clinical approach is essential,

biological/physical entity to encompass cognitive brain functions and psychologi-

It is now recognized that frailty is a common, dynamic, heterogeneous, multidimen-

CLINICS CARE POINTS

The authors have nothing to disclose.

1. Dent E, Martin FC, Bergman H, et al. Management of frailty: opportunities, chal-

Descargado para Anonymous User (n/a) en University Foundation of Health Sciences de

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