With increase in aging population, many clinical challenges
arise. Frailty is a geriatric medical syndrome that needs
utmost consideration. It is the inability to cope with
stressors of life and illness. We need clear objective
criteria to find out who is considered as frail or not frail.
Many frailty assessment tools and scales have been developed.
But a universally acceptable definition is yet to be formed.
Many genetic, environmental, lifestyle and disease factors are
associated with development of frailty. We need correct
clinical evaluation and adequate management interventions like
exercise, nutrition and medications to improve the quality of
life of frail older adults.
Keywords: Frail, exercise, sarcopenia
The world population is aging at a fast rate. According to
WHO, between 2015 and 2050 world population above 60 years is
going to almost double from 12 % to 22 %. By 2050, 80%
of world’s elderly population will be living in low-middle
income or developing countries [1]. This will create new
challenges in medical and social sectors. Aging puts an
individual in a state of increased risk of adverse health
conditions and death when exposed to stressful situations.
“Frailty” means “weakness” or “lack of strength or health”. It
refers to an important geriatric syndrome in which an aging
person exhibits diminished ability to perform essential social
and personal activities of daily living under minor stressful
situations. It is characterized by physiological decline in
late life and marked vulnerability to adverse health outcomes
[2].
Frail elder individuals are less able to adapt to stressors
like acute illness or trauma than younger or non-frail elder
individuals. Increased vulnerability contributes to increased
risk of multiple adverse outcomes like procedural
complications, falls, fractures, disability,
institutionalization, delirium, incontinence and death.
Frailty can be considered as a forerunner of many geriatric
syndromes. Old age alone cannot define frailty. Many older
individuals stay active and happy, but many others have
relentless functional decline even in the absence of a disease
[2].
Epidemiology and prognosis
The prevalence of frailty varies with the tool used to define
and assess. In U.S, several studies showed a prevalence of 4
to 16 % in men and women aged 65 years or older, and 43% among
older patients with cancer. A systematic review found that
when frailty was defined on basis of physical findings alone,
the overall prevalence according to 15 studies, was 9.9%. When
psychosocial aspects were also included it was 13.6 %. In a
European study (SHARE – Survey of Health, Aging &
Retirement) comparing 8 frailty scores, prevalence ranges from
6 to 44 % when applied to a database of individuals aged 50 to
104 years [2-5].
Mortality was increased in patients with baseline frailty in a
longitudinal Women’s health study. Studies in men showed
mortality is twice as high for frail, compared to robust men
[6,7].
As per available Indian literature, among older individuals
admitted to hospital, prevalence of frailty was about 33%
& they have poor outcome and prolonged stay. In community
setting about 27.9 % of older adults die of frailty [8].
Definition, concepts and domains
Frailty is a medical syndrome with many causes &
contributors, characterized by diminished strength and
endurance and reduced physiological function, leading to
vulnerability for adverse health outcomes such as functional
decline & early mortality [9].
1. Musculoskeletal function
2. Cardiorespiratory function
3. Cognitive function
4. Neurological function
5. Nutritional status
Frail persons exhibit impaired function in various domains.
Each domain should be examined in comprehensive assessment
prior to applying the term “frail” to an individual.
Till recently the assessment of frailty was subjective &
now many objective methods are formulated. An acceptable
standard definition was not formed yet due to differing
conceptual bases and difficulty in differentiating between
disability, comorbidity and frailty. The common concepts
include [2,9]:
1. Medical, environmental, educational and
psychological factors impact frailty, functional status and
physiologic reserve of older adults
2. Age, chronic disorders and disability are associated with
frailty, but do not establish diagnosis
3. Frailty exist on a spectrum and the end stage of the
spectrum is the failure to thrive
Majority of screening tools to determine frailty status are
developed on the basis of two concepts. Physical or
phenotypic frailty versus deficit accumulation frailty.
Physical or phenotypic frailty is a result of multisystem
biological decline leading to specific symptoms like weight
loss, weakness and reduced walking speed. Deficit
accumulation or index frailty is the combination of
comorbidities, social situations, and disabilities that are
added to assess the risk [2,10].
Most common frailty screening tool is Fried or Hopkins frailty
phenotype developed by Linda Fried and colleagues. It has been
validated in the Cardiovascular Health Study (CHS), involving
over 5000 men and women aged more than 65 years. It needs
patient participation and special special tool to measure grip
strength.
Frailty is defined if there are 3 or more attributes among the
following five. Pre-frailty is defined if patient has one or
two attributes [3]. The attributes for diagnosis are:
1. Unintentional weight loss of ≥ 5 % of
body weight in last year
2. Exhaustion (Physical exhaustion by self-report in
response to questions)
3. Weakness (muscle weakness measured by Grip strength)
4. Gait speed (decline in walking speed, > 6-7 seconds to
walk 15 feet)
5. Reduced physical activity (males spending <383
Kcals/week, and females < 270Kcal)
The deficit accumulation or index approach to measure frailty
can be based on information in medical records or by answering
20 or more medical and functional related questions. This
approach doesn’t require active patient participation. Higher
the number of deficits, higher the frailty score.
Although above mentioned approaches are the commonly cited and
validated methods, clinicians and patients may benefit from a
simple, fast to perform tool that can be incorporated to
history taking. It is the “FRAIL’ scale. It includes component
(Yes/No) questions regarding ‘Fatigue’ (do you feel fatigue?),
‘Resistance’ (Any difficulty in climbing a flight of stairs?),
‘Ambulation’ (Any difficulty in walking a block?), ‘Illnesses’
(list of illness or co-morbidities > 5) and ‘Loss of
weight’ (≥ 5% of body weight). Each yes =1, and No =0.
Frail scale score - 0 is best, 5 is worst, 3-5 is Frail, 1-2
is pre-frail [11].
Aetiology and pathophysiology
The development of frailty is related to genetic,
environmental and lifestyle factors. Aging is associated with
dysregulation in anatomical, physiological and molecular
aspects. Loss of skeletal muscle mass or strength (Sarcopenia)
is a key factor of frailty. Sarcopenia is a consequence of
hormonal changes and changes in inflammatory pathways.
Dysregulation in immune, endocrine, stress and energy response
systems leads to frailty. Correlation of biomarkers of immune
system and frailty is significant. There is an increased serum
level of IL-6, CRP and blood Monocyte counts in older adults.
Immune system activation may increase inflammation and trigger
clotting mechanisms [2].
Frail adults have inadequate immune response to vaccination.
Endocrine factors include reduced growth hormone and IGF-1,
decreased DHEAS, increased cortisol and decreased sex
steroids, all of them will lead to decline in muscle mass and
strength. There are reduced 25(OH) vitamin D levels also.
There is dysregulation of autonomic nervous system and age
related changes in renin-angiotensin system. Important changes
responsible for frailty are [12]:
1. Increased free radical production and DNA
damage
2. Shortening of telomeres
3. Gene expression changes
4. Cellular senescence
Clinical evaluation
Clinician have to elicit a detailed history which should have
information regarding the onset, duration and progress of
presenting complaint, on-going and past medications, details
of activities of daily living, and details of mental function.
Physical examination should include gait, balance and stamina,
muscle bulk and strength, vision, hearing and cognitive
function. Frailty may be defined based on the findings with
the help of Frailty assessment tools or FRAIL-Scale as
described above.
The important differential diagnosis should be considered in
an older individual coming with loss of weight. These include
various rheumatologic (polymyalgia, vasculitis), endocrine
(hyperthyroidism, diabetes), cardiovascular (heart failure,
coronary artery disease), renal (chronic kidney disease), and
hematologic disorders (myelodysplastic syndrome, iron
deficiency); depression, malignancies, nutritional
deficiencies, and neurologic disease (Parkinsonism, dementia).
Basic laboratory testing should be done to rule out treatable
conditions. These include complete blood count, basic
metabolic panel, liver function test including albumin,
vitamin B12, vitamin D and thyroid function test.
Management
There is no specific treatment for frailty. The treatment
should be patient centered and will be different according to
the needs and priorities of the individual and family. The
management involves treatment of acute or presenting illness
and the loss of function, early intervention to prevent
further loss of function; followed by a multipronged approach
to improve musculoskeletal function, nutrition and cognitive
function.
Establishing the management goal: Setting goals
of care is very important in the management. The provider
should establish the individual needs and priorities, weigh
the risks and benefits of interventions, and make decisions
regarding aggressiveness of care. If the frail adult develops
severe disease, the medical care should be tailored according
to the needs of the vulnerable patient while keeping his
personal values and goals in mind. Comprehensive geriatric
assessment (CGA) may help in development of management and
intervention plans and goals [2,13].
For robust adults, medical practitioner can manage chronic
diseases, acute illness and assure screening measures and
preventive care appropriate for their age. For moderate to
severe frail adults, aggressive screening or interventions may
lead to complications. Hospitalization and procedures may be a
burden to those who already has high risk of morbidity and
mortality. In some cases palliative care may be planned. All
these interventions should be guided by CGA and by targeting
specific components of their frailty examination.
Interventions: Many interventions, including
exercise, nutritional supplements, cognitive training and
review of medications were analysed and shown to be effective
for prevention and reduction of frailty. In randomized trials,
group exercise programs were shown to be more effective than
individual exercise programs in reducing or delaying physical
frailty as measured by validated frailty tools or scales.
Older adults undergoing lifestyle interventions like cognitive
training, nutritional supplementation and advice regarding
physical activities have decreased risk of development and
persistence of co-morbidities or deficits.
Exercise: Exercise is very much beneficial in
frail individuals even if they are very frail. It improves
muscle strength, balance and flexibility. It will increase
mobility, enhance ADL, improve bone mineral density, improve
general well being and decrease the falls. Physical inactivity
will result in skeletal muscle apoptosis and sarcopenia.
Exercise can help to stop frailty. Resistance exercise or
graded weight training will increase muscle cross sectional
area, and increase mixed protein synthesis in frail
individuals and is a counter measure to sarcopenia. Aerobic
exercise alone cannot increase muscle mass and strength.
Occupational training in some frail individual will increase
social participation [2,14].
Nutrition: Reduced food intake in elderly will
lead to weight loss and muscle mass. We have to look for any
difficulties in eating and swallowing; or anorexia due to some
disease or as a side effect of a drug, prior to addressing the
nutritional need. Elderly frail adults need increased dietary
protein and amino acid. Increased protein supplementation rich
in essential amino acid leucine may improve muscle protein
anabolism. Creatine and vitamin D supplementation may be
beneficial. Elderly patients may exhibit proximal muscle
weakness due to vitamin D deficiency. Calcium and vitamin D
supplementation also considered for osteoporosis [15-17].
Medications should be reviewed in regular intervals.
Underlying diseases like diabetes, CCF, Parkinsonism,
osteoarthritis and anemia should be properly treated. ACE
inhibitors may be associated with increase in lower extremity
lean body mass as compared to other antihypertensives.
Patients may need physiotherapy and analgesics for gait
disturbances. Also we have to pay attention to postural
hypotension. Hormone therapy (testosterone, growth hormone)
may not be beneficial. Visual and hearing problems also needs
to be addressed with care [2].
Palliative care: Frailty diagnostic scales can
detect adults with high risk of adverse outcomes. Those
persons may not be able to undergo above mentioned
interventions. Such individuals are planned for palliative
care to alleviate symptoms of underlying diseases (cancer)
medical or surgical interventions.
Correct clinical evaluation, establishing treatment goals,
timely interventions and adequate nutritional therapy will
have a great impact on quality of life in frail older adults.
References
1. WHO | Ageing and Life Course - World Health
Organization . www.who.int › ageing.
2. UpToDate, the evidence-based clinical decision support
resource from Wolters Kluwer - Frailty by Jeremy D
walston, MD.
3. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C,
Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA,
Cardiovascular Health Study Collaborative Research Group.
4. Kiely DK, Cupples LA, Lipsitz LA. Validation and
comparison of two frailty indexes: The MOBILIZE Boston Study.
J Am Geriatr Soc. 2009;57(9):1532.
5. Theou O, Brothers TD, Mitnitski A, Rockwood K.
Operationalization of frailty using eight commonly used scales
and comparison of their ability to predict all-cause
mortality.J Am Geriatr Soc. 2013;61(9):1537.
6. Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB,
Brunner RL, Masaki K, Murray A, Newman AB. Frailty: emergence
and consequences in women aged 65 and older in the Women's
Health Initiative Observational Study. J Am Geriatr Soc.
2005;53(8):1321.
7. Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik
JM, Chaves P, Zeger SL, Fried LJ. Phenotype of frailty:
characterization in the women's health and aging studies.
Gerontol A Biol Sci Med Sci. 2006;61(3):262.
8. Khandelwal D1, Goel A, Kumar U, Gulati V, Narang R, Dey AB.
Frailty is associated with longer hospital stay and increased
mortality in hospitalized older patients. J Nutr Health Aging.
2012 Aug;16(8):732-5.
9. Rodríguez-Mañas L, Féart C, Mann G, Viña J, Chatterji S,
Chodzko-Zajko W, Gonzalez-Colaço Harmand M, Bergman H,
Carcaillon L, Nicholson C, Scuteri A, Sinclair A, Pelaez M,
Van der Cammen T, Beland F, Bickenbach J, Delamarche P,
Ferrucci L, Fried LP, Gutiérrez-Robledo LM, Rockwood K,
Rodríguez Artalejo F, Serviddio G, Vega E, FOD-CC group.
Searching for an operational definition of frailty: a Delphi
method based consensus statement: the frailty operative
definition-consensus conference project.
10. Song X, Mitnitski A, Rockwood K. Prevalence and 10-year
outcomes of frailty in older adults in relation to deficit
accumulation. J Am Geriatr Soc. 2010 Apr;58(4):681-7.
11. Morley JE, Malmstrom TK, Miller DK. A simple frailty
questionnaire (FRAIL) predicts outcomes in middle aged African
Americans. J Nutr Health Aging. 2012 Jul;16(7):601-8.
12. Leng S, Chaves P, Koenig K, Walston J. Serum interleukin-6
and hemoglobin as physiological correlates in the geriatric
syndrome of frailty: a pilot study. J Am Geriatr
Soc. 2002 Jul;50(7):1268-71.
13. Turner G, Clegg A. Best practice guidelines for the
management of frailty: a British Geriatrics Society, Age UK
and Royal College of General Practitioners report. British
Geriatrics Society, Age UK, Royal College of General
Practioners. Age Ageing. 2014 Nov;43(6):744-7.
14. Daley MJ, Spinks WL. Exercise, mobility and aging. Sports
Med. 2000;29(1):1.
15. Spirduso WW, Cronin DL. Exercise dose-response effects on
quality of life and independent living in older adults. Med
Sci Sports Exerc. 2001;33(6 Suppl):S598.
16. Jackson C, Gaugris S, Sen SS, Hosking D. The effect of
cholecalciferol (vitamin D3) on the risk of fall and fracture:
a meta-analysis. QJM. 2007;100(4):185.
17. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC,
Staehelin HB, Bazemore MG, Zee RY, Wong JB. Effect of Vitamin
D on falls: a meta-analysis. JAMA. 2004;291(16):1999.