Frailty phenotypes, pathophysiology,

1. Frailty in Older Persons
Dr Doha Rasheedy Ali
Assistant Professor of Geriatrics and Gerontology
Faculty of Medicine- Ain Shams University

2. Definition
• Multiple operational definitions are available for capturing the risk
profile of frail elders, but a gold standard is currently missing.
• Frailty is “one of those complex terms … with multiple and slippery
meanings”
• Frailty can be defined a clinical state in which there is an increase in an
individual’s vulnerability to developing negative health-related events
(including disability, hospitalizations, institutionalizations, and death)
when exposed to endogenous or exogenous stressors.
• It can be considered as a progressive age-related decline in
physiological systems that results in decreased reserves of intrinsic
capacity, which confers extreme vulnerability to stressors and increases
the risk of a range of adverse health outcomes
• Age-associated declines in physiologic reserve and function across
multiorgan systems, leading to increased vulnerability for adverse
health outcomes.

3. • Physical frailty
• Psychological frailty
• More than 60% of cases with physical frailty had some
cognitive impairment.

4. When the frailty concept evolved??
• The concept of frailty can be found in the
geriatric medicine literature in articles that first
appeared in the 1950s and 1960s
• although the birth of frailty is usually dated to
2001 (when the frailty phenotype was
proposed by Fried and colleagues)
• However, this condition had been object of
study by geriatricians and gerontologists for
several decades prior Fried and colleagues
phenotype definition

5. • Two of the most commonly used approaches to
conceptualize and define frailty are the phenotypic
approach and the deficit accumulation approach.
• The phenotypic definition operationalizes frailty as
a biological syndrome, whereas the deficit
accumulation approach sees frailty as a
multidimensional risk state.
• currently, none of the proposed operational
definitions of frailty provide a definitive diagnosis.
• Most operational definitions of frailty specify
impairments in mobility, balance, muscle strength,
motor processing, physical function, disability,
cognition, nutrition, endurance, and physical
activity.

6. Epidemiology
• Although exact definitions and screening methods vary,
approximately 15 % of the US population over age 65 and
living in the community are considered frail.
• in 15 studies that included 44,894 participants identified a
prevalence of frailty of 9.9 %; when psychosocial aspects
were included in the definition, prevalence was 13.6 %
among eight studies that included 24,072 participants.
• Prefrail individuals, generally identified with a physical frailty
type tool , are more common in these population studies,
with prevalence ranging from 28 to 44 %.
• Of those individuals who were prefrail, over 10 %
went on to become frail over the next 3 years.

7. Demographic associations with frailty include
1. older age
2. lower educational level
3. Smoking
4. Unmarried status
5. Depression
6. African American or Hispanic ethnicity
7. A number of chronic disease states, including most
especially:
• congestive heart failure
• diabetes mellitus
• Hypertension
• peripheral artery disease

8. Considerations
• Frailty is not a disease but only the first step for the eventual
initiation of a specific care process (ie, the CGA and design of a
person tailored geriatric intervention)
• It is a warning sign for high risk of adverse health outcomes.
• The explanation for downward spiral in many elderly patients after
acute illness.
• Frailty has been widely utilized as a mortality risk assessment
tool. Reflects biological age that predicts mortality better than
chronological age.
• Frailty is often described as a transitional phase between successful
ageing and disability.
• Frail elderly need specific management: Regardless of age, a frail
person may be unable to withstand aggressive medical
treatment that could benefit a nonfrail person.

9. Continuum of resilience/frailty in older
adults

10. RELATED CONCEPTS

11. Resilience
• In parallel with the concept of frailty, the term, resilience, has
started being used more frequently during the last few years.
• It is described as “the human ability to adapt in the face of tragedy,
trauma, adversity, hardship, and ongoing significant life stressors.”
• Resilience explains why 2 apparently similar frail persons may
react differently to the same negative stimulus. The one able to
better cope with the stressor is considered characterized by higher
resilience, which is the external resources that an organism has
available for counteracting the negative forces challenging its
homeostasis (eg, more robust social network and higher economic
status).

12. Intrinsic capacity
• the concepts of intrinsic capacity (ie, the
composite of all the physical and mental
capacities of an individual)

13. functional ability
• (ie, the health-related attributes that enable
people to be and to do what they have reason
to value),

14. Disability
• Disability suggests chronic limitations or
dependence in mobility and/or ADL or IADL.
• While many (but not all) frail individuals are
disabled, not all disabled persons are frail.
• For example, older patients who suffer severe
disability secondary to a major accident or stroke
may maintain relatively intact function in other
physiological systems, and thus are not frail.
• frailty is usually considered as a state preceding
disability which, in contrast to disability, is still
amenable to treatment interventions and reversible

15. Comorbidity
• Comorbidity indicates the presence of multiple chronic
diseases.
• Not surprisingly, comorbidity is associated with increased
risk of adverse clinical outcomes, as evidenced by higher
short-term and long-term mortality and significantly
increased physical disability compared with those without
diseases.
• However, the mere presence of two or more clinical
diagnoses in itself may not identify the vulnerable group of
older patients or those who are frail.
• When comorbid conditions worsen, are not adequately
treated, and/or more diseases are accumulated, these
patients may develop frailty.
• chronic disease accelerates the rate of functional loss, acting
as the precipitating factor of frailty and disability

16. Venn diagram of the frailty syndrome, activities of daily living (ADL) disability, and comorbidity (two or
more diseases) in the Cardiovascular Health Study dataset, demonstrating frailty as a distinct geriatric
syndrome with some overlap with disability and comorbidity. Fried LP, Tangen C, Walston J, et al.
Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56A:M1–M11

17. The relationship between frailty and
disability is controversial
• Analyses conducted on the rich databases of
studies have identified a wide range of risk
factors for disability which are potential targets
for preventive interventions, including health
behaviors, environmental exposures, diseases
and life-events.
• An accumulating body of literature prefers
framing frailty as a predisability condition:
– Thus, frailty becomes of special interest as a target
condition for preventive interventions against
disability

18. Longevity and Functional Reserve
• one of the most important changes accompanying the
aging process is a progressive loss of functional reserve.
• This process starts at the end of the maturational phase
and lasts until death.
• Only after losing around 70% of our functional capacity,
we are at risk of experiencing frailty or disability.
• When the loss exceeds 80%, the risk of death occurs.
• During lifetime, function declines at a rate of 0.5% per year
in all systems, with most data being available for those
aged 30–70 years. But this rates can be accelerated under
different extrinsic circumstances

19. Model for the relationship between aging and disease to produce frailty and
functional decline.

20. THE BIOLOGY OF FRAILTY

21. Again
• The 2 models approach
– Phenotypic frailty
– Deficit-driven frailty

22. Phenotypic frailty
• A cycle of physiological decline was hypothesized that
included interrelated and reinforcing declines in
metabolism, nutrition utilization, and skeletal muscle
that in sum drove worsening vulnerability.
• Triggers of this cycle of decline included acute
illnesses, some medications, and aging related
biological changes.
• this cycle is often related to disability and disease, but
can develop independently from disease states and
disability because of its hypothesized biological origin.
Triggers
MSK,
neuroendocrinal
inflammation
Vulnerability Adverse outcome

23. • Fried et al. have proposed that the signs and
symptoms of frailty result from dysregulated
energetics involving multiple molecular and
physiological pathways, which lead to sarcopenia,
inflammation, decreased heart rate variability,
altered clotting processes, altered insulin resistance,
anemia, altered hormone levels and micronutrient
deficiencies.
• These physiological impairments result in the five
clinical characteristics of frailty: weakness, low
energy, slow walking speed, low physical activity
and weight loss.
• The presence of any three of these phenotypes
indicates that a person is ‘frail’; one or two
phenotypes indicate that the person is ‘prefrail’ and
absence of these characteristics indicates the person
is ‘robust’.

24. Deficit-driven frailty
• frailty as an aggregate of illnesses, disability
measures, cognitive and functional declines that
has been termed deficit-driven frailty
• According to this model, the more deficits or
conditions that an individual has, the more frail
the individual is.
• In this diagnostic approach , almost any conditions
or deficits are interchangeable in index tools.
• This conceptual basis has also been widely utilized
to develop risk assessment tools that tally a broad
range of comorbid illnesses , mobility and cognitive
measures, and environmental factors to capture
frailty.

26. Potential biological etiologies that drive physical frailty
and the vulnerability to adverse health outcomes
Chronic inflammation is likely a key pathophysiologic process that contributes to
the frailty syndrome directly and indirectly through other intermediate physiologic
systems, such as the musculoskeletal, endocrine, and hematologic systems

30. Initiators of frailty
• Aging
• Genetics
• Environmental factors
• specific disease states

31. pathophysiologic process of physical
frailty
• inflammation
• Sarcopenia
• Neurohormonal dysregulation
Chronic inflammation is likely a key pathophysiologic process that contributes to the
frailty syndrome directly and indirectly through other intermediate physiologic
systems, such as the musculoskeletal, endocrine, and hematologic systems

32. Phenotype of physical frailty
1. Weakness
2. Weight loss
3. Exhaustion
4. Slow speed
5. low physical activity

33. Outcomes of physical frailty
• Mortality
• Falls
• Disability
• Prolonged recovery from stressors
• Worsening chronic illnesses

34. Chronic inflammatory pathway activation
1. Serum levels of the proinflammatory cytokine IL-6 and C-reactive protein (CRP),
as well as white blood cell and monocyte counts, are elevated in community-
dwelling frail older adults.
2. IL-6 acts as a transcription factor and signal transducer that adversely impacts
skeletal muscle, appetite, adaptive immune system function, and cognition
and contributes to anemia.
3. chemokine ligand 10 (CXCCL-10) is produced by monocytes, and is a potent
proinflammatory mediator. In addition to higher circulating levels with age,
CXCCL10 has been shown to be significantly upregulated in frail compared to
non-frail individuals
4. Immune system activation may trigger the clotting cascade, with a
demonstrated association between frailty and clotting markers (factor VIII,
fibrinogen, and D-dimer).
5. there is evidence linking a senescent immune system to chronic CMV infection
and frailty.
6. Frail older adults are less likely to mount an adequate immune response to
influenza vaccination
7. dysregulation of the autonomic nervous system and age-related changes in the
renin angiotensin system and in mitochondria likely impact sarcopenia and
inflammation, important components of frailty

35. Sarcopenia
• age-related loss of skeletal muscle and muscle
strength , is a key component of physical frailty.
• Decline in skeletal muscle function and mass is
driven in part by age related hormonal changes and
increases in inflammatory pathway activation.
• Causes of sarcopenia:
• chronic inflammation
• age-related changes in α-motor neurons, type I muscle fibers, muscular
atrophy,
• poor nutrition
• ↓growth hormone (GH) production, sex-steroid levels, and physical activity.
• Age-related insulin resistance causes an increase of fat infiltration into
muscle and a decline in muscle strength .
• Mitochondrial dysfunction in aging skeletal muscle causes oxidative damage
and the decline of energy generation to maintain function properly

36. Hormonal changes with ageing
1. Decreased growth hormone and insulin-like growth factor-1 levels
in later life (IGF-1)
2. Decreased levels of the adrenal androgen dehydroepiandrosterone
sulfate (DHEA-S)(DHEA-S plays an important role in maintaining
muscle mass and indirectly prevents the activation of
inflammatory pathways that also are a component of frailty.
3. Chronically increased cortisol levels, blunted diurnal variation of
cortisol.
4. Evidence is mixed that lower levels of the reproductive hormones
estrogen and testosterone contribute to frailty.
5. there is stronger evidence that links decreased 25(OH) vitamin D
levels to frailty

37. A vicious cycle of frailty, resulting from dysregulated
energetics as well as altered physiologic functioning,
intra- and intersystem.

38. Many other altered molecular
processes play a role in frailty
• Impaired autophagy:
– Autophagy, an intracellular process responsible for the recycling of
damaged or redundant organelles or proteins, becomes less effective
with age. This results in an intracellular accumulation of dysfunctional
mitochondria and proteins, which in turn can trigger cellular
dysregulation via increased levels of free radicals, lower mitochondrial
energy production, and programmed cell death or apoptosis.
• Accelerated Apoptosis:
– Apoptosis is a normal cellular program that serves to kill and dissemble
damaged or redundant cells in all tissues. However, it appears to
accelerate and likely contributes to the vulnerability to chronic disease
states such as Parkinson’s disease and congestive heart failure, or to the
generalized loss of cells in many tissues.
• Increased TGF-β signaling:
– likely plays an important role in the fibrotic changes that are observed in heart and
lung tissue

39. • Genomic instability refers to the high frequency of
mutations and deletions within the genome (both
nuclear and mitochondrial DNA)
• caused by DNA damage and inefficient repair
Evidence for a role of increased reactive oxygen
species, altered intracellular calcium homeostasis,
and iron dysregulation in advancing age has been
proposed to induce age-related alterations in
nuclear and mitochondrial DNA and may play a
role in frailty

40. PSYCHOLOGICAL FRAILTY

41. • There is little written in the geriatric literature about
the concept of psychological frailty which encompasses
cognitive, mood, and motivational components
• The concept is intended to consider brain changes that
are beyond normal aging, but not necessarily
inclusive of disease, that result in decreased cognitive
or mood resilience in the presence of modest stressors,
and may eventually lead to negative health outcomes
in a manner parallel to physical frailty,
• the interface between cognition, mood, and physical
frailty is a bidirectional. Psychological symptoms or
deficits have been described as either worsening the
degree of physical frailty, or physical frailty has been
viewed as a risk to a worsening cognition or
depression.

42. 1- COGNITIVE FRAILTY

43. • To date, most research efforts on frailty have
focused on its ‘physical’ aspects, and little
work has been done, however, to clarify how
the process of frailty itself affects the brain
studies are limited

44. • Frailty is highly associated with an increased risk
of mild cognitive impairment and an increased
rate of cognitive decline with aging.
• Conversely, the presence of cognitive impairment
increases the likelihood of adverse health
outcomes in older adults who meet criteria for
physical frailty.
• Hence, it may be considered an additive risk
factor to frailty in those older adults with both
conditions.

45. • cognitive frailty’ has been proposed as a
heterogeneous clinical manifestation
characterized by the simultaneous presence of
both physical frailty and cognitive impairment. In
particular, the key factors defining such a
condition include:
1. the presence of physical frailty and cognitive
impairment (Clinical Dementia Rating = 0.5)
2. exclusion of concurrent Alzheimer’s disease or
other dementias
3. linked to a reduction in cognitive ‘reserve’.
4. A potential for reversibility

46. Cognitive Frailty as a Reduction in
Cognitive Reserve.
• reserve is defined in terms of the amount of
brain damage that can be sustained before
reaching a threshold of clinical expression.
• Significant variability exists in cognitive
reserve among individuals, and epidemiologic
studies have suggested that good proxies for
the amount of cognitive reserve include
measures of economic attainment, level of
education, IQ, and degree of literacy

47. • Primary cognitive frailty will be worsened by
the presence of brain and systemic disease,
preclinical or not, as cognitive reserve and
compensatory mechanisms would be
additionally challenged by disease-specific
neurodegenerative or vascular processes with
a predilection for particular brain circuitry and
areas beyond what is likely to be affected in
nondiseased aging

48. Is it cognitive frailty or preclinical
dementia
• As we become more able to image occult brain
diseases (e.g. amyloid imaging in asymptomatic
AD) and confirm the presence of preclinical
disease with biomarkers (e.g. amyloid β42 and
phosphorylated tau), we will be able to separate
those individuals who are developing intrinsic
primary cognitive frailty, as evidenced by
challenge test results, from those who harbor
occult disease and may also underperform during
a challenge paradigm.

49. 2-MOOD AND MOTIVATIONAL
FRAILTY

50. 2-Mood and Motivational Frailty
• The term mood describes a relatively persistent state of
emotion such as depression, fear, anxiety, or anger.
• Motivation, the drive toward a goal, or lack thereof (apathy), is
linked to mood but can be largely independent of it.
• the elaboration of emotion and mood is dependent on particular
brain circuitry involving limbic and neocortical structures such as
the amygdala, hippocampus, hypothalamus, anterior cingulate,
ventral striatum, and orbital and medial prefrontal cortices.
• There is usually circuit overlap between emotions, but there are
also differences. This may explain why in the presence of a
disorder such as depression, other emotions such as anxiety and
irritability can also be present.
• The development of mood disorders appears dependent on the
interaction of genetic circuitry predispositions and a variety of
stressors.

51. • Much of the work examining the relationship of physical
frailty to mood has focused on depressive symptoms.
• Depression and physical frailty share several clinical
characteristics such as loss of energy, fatigability, poor
sleep, and reduced interest. A number of clinical studies
have strongly suggested a bidirectional association
between depression in later life and physical frailty.
• It has not been explored, the possibility of the existence of
a primary, intrinsic vulnerability to emotional stressors
with age that might signal mood frailty, a possible
precursor to depression and its negative health outcomes.
– A state of mood frailty could possibly be demonstrated by
monitoring a subject’s response to an emotional challenge test
such as visualizing or imagining a sad situation, then being able
to quickly revert to positive thoughts. Failure to make a rapid
switch could have the potential to invite an earlier preventive
intervention. As is the case with cognitive frailty, stressors,
either external or internal, such as the presence ofdisease, will
likely augment mood frailty.

52. FREQUENT CLINICAL
PRESENTATIONS OF FRAILTY
Non-specific
Falls
Fluctuating disability
Delirium

53. Non-specific
• Extreme fatigue
• Unexplained weight loss
• Frequent infections.

54. Falls
• Balance and gait impairment are major features of
frailty, and are important risk factors for falls.
• A so-called hot fall is related to a minor illness that
reduces postural balance below a crucial threshold
necessary to maintain gait integrity.
• Spontaneous falls occur in more severe frailty when
vital postural systems (vision, balance, and strength)
are no longer consistent with safe navigation through
undemanding environments.
• Spontaneous falls are typically repeated and are closely
associated with the psychological reaction of fear of
further falls that causes the patient to develop severely
impaired mobility

55. Delirium
• Delirium (sometimes called acute confusion) is
characterized by the rapid onset of fluctuating
confusion and impaired awareness.
• Delirium is related to reduced integrity of
brain function and is independently associated
with adverse outcomes.
• Roughly 30% of elderly people admitted to
hospital will develop delirium, and the point
prevalence estimate for delirium for patients
in long-term care is 15%.

56. Fluctuating disability
• Fluctuating disability is day-to-day instability,
resulting in patients with ”good”, independent
days, and ”bad” days on which (professional)
care is often needed.

57. Triggers, stressors

58. • Can be external or internal triggers:
– insult can be minor (new drug, surgery, infection)
will lead to disproportionate change in health
status
– Lack of activity
– Inadequate nutritional intake
– Stress
– Depression

59. • the same stressor may cause different
consequences when soliciting a frail
individual.
(ie, severe and prolonged functional loss and
higher likelihood of incomplete recovery)
compared with a robust person (ie, prompt and
complete recovery with minor— if any—
consequences)

61. Inadequate nutritional intake
• Several observational studies have shown an association between
inadequate nutritional intake and frailty.
• Bartali et al. [1] found that daily energy intake ≤ 21 kcal/kg body weight
was significantly associated with frailty (OR: 1.24; 95% CI: 1.02–1.5). This
study also analyzed the association between frailty and nutrients; after
adjusting for energy intake, low intakes of protein (OR: 1.98; 95% CI: 1.18–
3.31); vitamin D (OR: 2.35; 95% CI: 1.48–3.73), vitamin E (OR: 2.06; 95% CI:
1.28–3.33), vitamin C (OR: 2.15; 95% CI: 1.34–3.45) and folate (OR: 1.84;
95% CI: 1.14–2.98) were significantly and independently related to frailty
• (2) Independent of the body mass index, daily energy intake was lowest in
people who were frail, followed by prefrail people, and highest in people
who were not frail.
• Energy-adjusted macronutrient intakes were similar in people with and
without frailty.
• Frail [adjusted odds ratio (AOR): 4.7; 95% confidence interval (CI): 1.7–
12.7] and prefrail (AOR: 2.1; 95% CI: 0.8–5.8) people were more likely to
report being food insufficient than nonfrail people; serum albumin,
carotenoids and selenium levels were lower in frail adults than nonfrail
adults
1. Bartali B, Frongillo EA, Bandinelli S, et al: Low nutrient intake is an essential component of frailty in older persons. J Gerontol A Biol Sci Med Sci 2006; 61:
589–593
2. Smit E, Winters-Stone KM, Loprinzi PD, et al: Lower nutritional status and higher food insufficiency in frail older US adults. Br J Nutr 2013; 110: 172–178.
.

62. Obesity and frailty
• In the Women’s Health and Aging Studies
including 599 women aged 70–79 years and a
body mass index greater than 18.5, Blaum et al.
showed that being overweight was significantly
associated with prefrailty, and obesity was
associated with prefrailty and frailty.
• In the English Longitudinal Study of Ageing,
Hubbard et al. showed in 3,055 patients aged 65
years and older that the association between
body mass index and frailty showed a U-shaped
curve.
• Blaum CS, Xue QL, Michelon E, et al: The association between obesity and the frailty syndrome in older women: the
Women’s Health and Aging Studies. J Am Geriatr Soc 2005; 53: 927–934.
• Hubbard RE, Lang IA, Llewellyn DJ, et al: Frailty, body mass index, and abdominal obesity in older people. J Gerontol
A Biol Sci Med Sci 2010; 65: 377–381.

63. ASSESSMENT
DIFFERENT MODELS
The phenotype model
The Deficit Accumulation model
The biopsychosocial model

64. • More than 40 operational definitions of frailty
have been proposed in the literature (and the
number is continuously increasing).
• Every instrument has been shown to possess
a certain capacity of predicting negative
outcomes in the elderly. Nevertheless, each
tool tends to identify a specific population at
risk of negative outcomes, and the agreement
of results across instruments remains modest.

65. Frailty
operational
models
The biopsychosocial
model
The phenotype modelThe Deficit Accumulation
model

66. 1- The frailty phenotype
• The frailty phenotype is probably the most popular model
for assessing the condition of interest.
• The frailty phenotype (Fried et al., 2001) is based on 5
predetermined criteria (ie, involuntary weight loss,
exhaustion, muscle weakness, slow gait speed, and
sedentary behavior).
– The number of positive criteria defines the individual as frail (3),
prefrail (1–2), and robust (none).
– Many modifications were developed.
• Unfortunately, these symptoms of frailty are commonly
attributed to normal ageing, without the recognition that
they are potentially reversible and preventable

68. Frail ibstrument
Morley JE. Frailty: a time for action. Eur Geriatr Med 2013;4:215–6.

69. 2- The Deficit Accumulation, or Frailty
Index, Approach
• An individual’s frailty index score is calculated based on the
number of deficits a person has in relation to the total
number of measures included in the index (e.g. someone
with 10 deficits out of 40 counted has a frailty index of
10/40 = 0.25). In this way, the frailty index score is
continuous (0–1); the higher the score, the more likely that
the individual is vulnerable to adverse health outcomes.
• The Frailty Index estimates the accumulation of deficits
occurring with the aging process. It is arithmetically
defined as the ratio between the deficits (ie, signs,
symptoms, diseases, and disabilities) presented by an
individual and the total number of deficits considered
in the evaluation

70. Rockwood and colleagues

71. • Rockwood et. al. described the Clinical Frailty Scale, a
measure of frailty based on clinical judgment in 2005.
• The scale ranges from 1 (robust health) to 7 (complete
functional dependence on others).
• In comparison with the Frailty Index, a count of 70 clinical
deficits from the Canadian Study of Health and Aging, the
Clinical Frailty Scale had comparable performance. Each 1-
category increment of the Clinical Frailty Scale significantly
increased the medium-term risks of death, and entry into
institutional care. The Clinical Frailty Scale is easy to use
and may readily be administered in a clinical setting, an
advantage over previously developed tools.
• Clinical judgments about frailty can yield useful predictive
information. The tool can aid communication with older
adult patients, and their substitute decision makers. It has
potential to standardize assessment and understanding
when communicating between colleagues in primary care,
emergency room and long-term care settings.

72. Mitnitski and colleagues

73. 3- The biopsychosocial model
• proposed by Gobbens and colleagues and
operationalized with the Tilburg Frailty Indicator.
• This step for a more global appreciation of
frailty might be considered necessary if the
role played by the socioeconomic context in
determining the vulnerability status of an
older person is taken into account.
• Can be categorized as deficit accumulation
model.

75. Tilburg Frailty Indicator

78. Groningen Frailty Index

79. The Edmonton Frail scale

80. A frailty index from common clinical
and laboratory tests
• Three FIs were constructed: a 36-item FI using
self-reported questionnaire data (FI-Self-
report); a 32-item FI using data from
laboratory test values plus pulse and blood
pressure measures (FI-Lab); and a 68-item FI
that combined all items from each index (FI-
Combined)
Blodgett JM, Theou O, Howlett SE, Rockwood K. A frailty index from common clinical and laboratory tests predicts
increased risk of death across the life course. GeroScience. 2017;39(4):447-455. doi:10.1007/s11357-017-9993-7.

81. Laboratory frailty index FI-Lab

82. self-reported questionnaire data (FI-Self-report

84. Physical performance measures
• Physical performance measures (eg, gait speed
and the Short Physical Performance Battery, TUG)
may also serve for capturing the increased
vulnerability of an individual to stressors.
• Pulmonary function VO2 max is associated with
sarcopenia and frailty
• These tests were originally designed for
assessing the physical domain of an older person,
but it is acknowledged that they are able to
robustly estimate an individual’s biological age

85. MANAGEMENT OF FRAIL
OLDER ADULTS

86. Management
• Once a frail or prefrail patient is identified there
are no succinct guidelines on how to best mange
them.
1. Diagnosis, differential diagnosis (rule out
underlying medical or psychological issues that may be driving
signs and symptoms of frailty)
2. CGA:Laboratory Testing (in order to rule out treatable
conditions, A suggested initial screen, based on the differential diagnosis,
might include: Complete blood count, basic metabolic panel, liver
biochemical tests, including albumin, vitamin B12, vitamin D, and TSH).
3. Establishing Goals of Care: goal setting with patients and
their families is crucial in providing care, establishing individual priorities,
weighing risks and benefits of interventions
• At late stages of frailty, the appropriate interventions, although useful,
might have limited benefit to reverse the frailty state.

87. Managing
frail,
pre frail
CGA
nutritional
supplement
Exercise
Pre-
rehabilitation
treat
known
chronic
diseases
manage
intermittent
acute
illness and
events
Modify
the
screening,
preventive
care plan

88. Exercise
1. Exercise is believed to be the most effective intervention in
older adults to improve quality of life and functionality.
However, data on specific exercise interventions designed to
improve outcomes in patients with frailty are limited.
2. The demonstrated benefits of exercise in older adults
include increased mobility, enhanced performance of
activities of daily living (ADL), improved gait, decreased falls,
improved bone mineral density, and increased general well-
being.
3. Even simple interventions can be helpful. For example,
walking as little as a mile in a 1-week period was associated
with a slower progression of functional limitations over a
follow-up period of 6 months (Miller et al.,2000)

89. Nutritional, hormonal
Supplementation
1. 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.
2. Vitamin D supplementation for those with low serum vitamin D
levels (< 20 ng/ml)is effective for fall prevention, improving
balance, and preserving muscle strength.
3. those taking leucine-enriched whey protein plus vitamin D had
significant improvement in physical frailty related measurements
4. Whey protein, omega 3 fatty acids rich items, amino acid
glutamine, carnitine have been suggested for their useful role.
5. Even growth hormone, DHEA, testosterone when deficient, may
be considered

90. Multidisciplinary approach
• Optimize sensory inputs
• Assess cognition and mood
• Exercise
• Diet
• Ensure that chronic disease control is
optimised.

91. • In one trial conducted in community dwelling
frail and prefrail individuals, interventions
aimed at cognitive skills (weekly training for
12 weeks followed by fortnightly “booster”
sessions for 12 weeks), physical exercise
(supervised group exercises 2 days per week
for 12 weeks), and nutrition (supplemental
iron, calcium, vitamins, and calories),
individual or combination interventions
improved frailty scores at 3 and 6 months, but
did not impact patient-meaningful secondary
outcomes (hospitalizations, falls, or
performance of activities of daily living).
(Feng et al., 2015)

92. Pharmacological approach
• not adequately evaluated.
• Such hormonal therapy as testosterone, while it improves muscle
strength, has significant systemic side effects. Estrogen-replacement
therapy in postmenopausal women also has an unfavorable safety
profile.
• Friedlander et al reported that IGF-1 therapy had a beneficial impact
on bone density, muscle strength, or physical function in elderly
women with no clinical IGF-1 deficiency.
• Currently available anti-inflammatory agents, while not formally
evaluated in clinical trials in treating the frailty syndrome, also have
significant adverse effects, particularly in the elderly. Statin has no
effect in management of frailty.
• While vitamin D and angiotensin-converting enzyme inhibitors have
favorable pharmacological and safety profiles, their clinical utility in
the prevention and treatment of frailty has yet to be investigated.

93. Frailty sarcopenia overlap

94. • The term “sarcopenia” was coined by Rosenberg (1989) to
indicate the loss of muscle mass that accompanies aging.
• The European Working group on sarcopenia diagnosis is based
on loss of muscle mass combined with decreased strength
and or poor physical performance

95. • Loss of muscle mass (DXA, MRI, Bioimpedance analysis, CT)
• Decreased strength (grip strength, knee extension strength)
• Poor physical performance (gait velocity, TUG)
Osteosarcopenia
• Fracture risk increase dramatically with age much greater
than corresponding BMD decline
• Sarcopenia can explain the increase in fracture risk attributed
to age
• Staging
1. Presarcopenia – low muscle mass no impact on strength or
physical performance
2. Sarcopenia – low muscle mass +low strength or physical
performance
3. Severe sarcopenia – all three criteria

97. • It cannot be ignored that the Physical Frailty phenotype presents
substantial overlaps with sarcopenia, “a syndrome characterized by
progressive and generalized loss of skeletal muscle mass and
strength with a risk of adverse outcomes such as physical disability,
poor quality of life and death”.
• Many of the adverse outcomes of frailty are probably mediated by
sarcopenia.
• sarcopenia may be considered both as the biological substrate for
the development of PF and the pathway through which the
negative health outcomes of frailty ensue.
• Determining whether frailty is due to sarcopenia or sarcopenia is a
clinical manifestation of frailty is consuming considerable efforts,
but (from a very practical viewpoint) rather resembles the problem
of "the egg and the chicken".
• However, the interventions specifically targeting the skeletal muscle
may provide therapeutic and preventive advantages against frailty
and its clinical correlates

98. Pharmacological agents in development with
potential for treating sarcopenia

99. Pharmacological interventions to
reverse muscle loss
• Selective Androgen Receptor Modulators
(SARMs), Myostatin (powerful inhibitor of
muscle growth) antagonists

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101. THANK YOU