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Файл:Frailty syndrome clinic, diagnosis, treatment. Study aid
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11
2. ETIOLOGY AND PATHOGENESIS
OF THE FRAILTY SYNDROME
The concept of frailty was proposed in the early 2000s to characterize
the state of depletion of the body's internal reserves, which makes it possible
to predict a high risk of death and other adverse outcomes in elderly and
senile people. The concept is based on understanding the heterogeneity of
the population of elderly and senile people and the fact that not only age
and/or the presence of chronic diseases determine the prognosis for the life
and health of an elderly patient and the choice of optimal management
tactics. The development of frailty is accompanied by a decrease in physical
and functional activity, adaptive and regenerative reserve of the body,
increases the risk of adverse outcomes — hospitalization by 1.2–1.8 times,
development of functional deficits by 1.6–2.0 times, death by 1.8–2.3 times,
physical limitations by 1.5–2.6 times, falls and fractures by 1.2–2.8 times.
Risk factors for developing frailty in addition to age include: low
physical activity, poor nutrition, depression, polypharmacy, social factors
(low income, living alone, low education).
It has been proven that there is no single reason for frailty. Perhaps the
concept of fragility reflects the accumulated damage in multiple body
systems. Suggested mechanisms for aging and frailty include inflammation,
loss of stem cell regeneration, DNA damage, decreased metabolism,
hormonal dysregulation, epigenetic factors, and loss of proteostasis. Many
of these proposed mechanisms for the development of frailty may be caused
or exacerbated by environmental factors. These mechanisms are also
considered to be interrelated.
Numerous studies are currently underway on frailty. SUNFRAIL
project coordinated by the Emilia- Romagna region with scientific support
from Parma Health Trust aims to develop cutting-edge methods and tools to
improve the diagnosis, prevention, and treatment of frailty, as well as the
treatment of polymorbidity. SPRINTT project (the Sarcopenia and Physical
frailty in older people: multi-component treatment strategies) is a test of the
effectiveness of multi-component treatment of fragility and sarcopenia.
12
A number of authors consider the similarity of the pathogenetic
mechanisms of malnutrition, cachexia, sarcopenia and frailty. There are
many studies that study the relationship of fragility with various disorders
at the cellular, tissue, organ, systemic levels and the body as a whole. Recent
work reveals a link between the gut microbiota, sarcopenia and frailty. Thus,
the human gut microbiota regulates many processes, including nutrient
absorption, inflammation, oxidative stress, immune function, and anabolic
balance, and these phenomena may be of great importance for skeletal
muscle mass and function. There is a suggestion that there is a gut-muscle
axis that regulates the onset and progression of age-related physical
weakness and sarcopenia.
As the human body ages, hormonal changes occur, leading to a
functional deterioration in the functioning of organs and systems. Thus, ageassociated decline in sex hormones is a vital factor in the development of
frailty.
In an increasingly sedentary population, vitamin D deficiency is
becoming widespread and attracting considerable attention from clinicians
and researchers. Low levels of vitamin D have been shown to correlate with
increased levels of fragility.
A number of authors consider it necessary to study metabolic markers
to predict the onset of frailty in the elderly, as well as to identify new
prevention opportunities. The most promising of these is glycated
hemoglobin (HbA1c). HbA1c has been shown to be indicative of risk for
frailty, with elevated levels correlated with a higher incidence of frailty
syndrome.
There is a hypothesis about the pathogenesis of frailty, suggesting a
systemic dysregulation of protein synthesis and metabolism as part of the
pathological process leading to the appearance of frailty syndrome.
Although a wide range of serum markers have been investigated,
hemoglobin, glomerular filtration rate, and plasma albumin levels deserve
special attention as potential indicators of the risk of frailty. It has been
shown that a decrease in the level of circulating hemoglobin, albumin and a
low glomerular filtration rate correlate with the frequency of senile asthenia.
13
These markers are also associated with some of the key symptoms of frailty,
such as wasting and muscle weakness, and are likely to contribute to poor
outcomes in patients with this disease. Although these biomarkers have been
correlated with the incidence of frailty in some studies, their association
with a number of comorbidities common in the elderly makes them difficult
to use as a stand-alone indicator of frailty.
Senescent cells develop what has been termed a senescence —
associated secretory phenotype. secretory phenotype (SASP). In other
words, they secrete cytokines, chemokines, matrix remodeling proteases
and growth factors — all elements that are involved in the mechanism of
aging and systemic inflammation, the development of chronic diseases,
frailty.
A new advance in the field of aging and fragility research is the
development of so-called senolytic drugs. These biological or low molecular
weight compounds specifically induce the death of senescent cells and
thereby eliminate SASP.
A number of studies have examined cytokine changes with aging,
frailty, and polymorbidity. The balance between pro-inflammatory and antiinflammatory cytokines is disrupted during aging in such a way that the
balance shifts from anti-inflammatory to pro-inflammatory. It is possible
that age-associated and frailty-related dysfunction reflects a complex
imbalance between pro- and anti-inflammatory cytokines rather than
changes in any one particular cytokine.
Not all, but most patients with frailty syndrome have multiple chronic
conditions. Associations of frailty with cardiovascular diseases — arterial
hypertension, coronary heart disease, chronic heart failure, as well as
diabetes mellitus, chronic kidney disease, diseases of the joints and lower
respiratory tract, and oncological diseases have been identified.
The development of frailty occurs gradually, however, the decrease in
the level of functional activity in a patient with frailty syndrome can occur
quite quickly. In a stressful situation (infectious process, hospitalization,
change of drug therapy, etc.), such patients are highly likely to develop or
increase dependence on outside help, recovery and recovery is slower than
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in patients without frailty, and often functional activity does not return to its
original level.
Development of the frailty syndrome is preceded by pre-frail older
adults, characterized by the presence of its individual signs, quantitatively
not sufficient to establish the diagnosis of frailty.
Senile asthenia is considered a potentially reversible condition, but
progresses rather than regresses more often. The frailty syndrome is not an
integral part of the frailty aging process, but is considered as its unfavorable
variant. With the development of frailty, the vulnerability of older people to
the action of adverse factors increases significantly, which can be, for
example, an acute illness or injury, a change in treatment or surgery.
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3. CLASSIFICATION OF THE FRAILTY SYNDROME
Depending on the severity of the decrease in functional activity, frailty is distinguished as mild, moderate and
severe (Table 1).
Table 1
Clinical classification of frailty and its severity
Category
Description
Functional category
Geriatric syndromes
Dementia
Excellent
health
condition
Patients are active, energetic, high
level of motivation, no restrictions
on physical activity.
Independent of outside help
Not
Not
Good health
There are diseases in the inactive
phase. The level of physical
activity is slightly lower than that
of patients from the category.
Often perform physical exercises,
high seasonal activity (for
example, in summer).
Independent of outside help
Not
Not
Satisfactory
state of
health
There are chronic diseases that are
well controlled by treatment.
Irregular activity other than routine
walking.
Independent of outside help
No or single mild geriatric
syndromes. For example,
urinary incontinence or
decreased vision/hearing.
Mobility preserved
Not
16
Category
Description
Functional category
Geriatric syndromes
Dementia
Pre-frail
older adults
Despite independence from outside
assistance, physical activity is
limited. Typical complaints of
slowness, increased fatigue
Basically independent of outside
help. Assistance may be required if
necessary to reach places that are out
of the usual distance. basic functional
activity is preserved (Bartel index
100/100 points). basic functional
activity is preserved or slightly
reduced (Lawton index 7–8/8 points)
A slight decrease in
mobility + the appearance
or increase in the severity
of geriatric syndromes ,
but geriatric syndromes
are still single
Not
Mild frailty
They are much slower, they need
help in carrying out activities from
the category of instrumental
functional activity (financial
issues, transport, housework,
taking medications). Trouble
shopping and walking, cooking
and housework on their own
Dependent on outside help. basic
functional activity is preserved
(Bartel index 100/100 points). basic
functional activity is moderately
reduced (Lawton index 3–6/8 points)
Multiple geriatric
syndromes
Not
May have
mild to
moderate
dementia
Moderate
frailty
They need help in almost all types
of instrumental functional
activities and housekeeping.
Trouble climbing stairs, need help
with hygiene measures. Minimum
need for assistance with dressing
Dependent on outside help. Basic
functional activity is moderately
reduced (Bartel index > 60 points),
basic functional activity is
significantly reduced (Lawton index
1–2/8 points)
Multiple geriatric
syndromes
Not
May have
mild to
severe
dementia
17
Category
Description
Functional category
Geriatric syndromes
Dementia
Severe
frailty
From outside help — physically or
cognitively. In general, the state is
relatively stable. Not a high risk of
death within the next 6 months.
Dependent on outside help. basic
functional activity is significantly
reduced (Bartel index < 60 points),
basic functional activity is completely
reduced (Loughton index 0–1/8
points)
Multiple geriatric
syndromes
Not
May have
mild to
severe
dementia
Very severe
frailty
Completely dependent on outside
help, approaching the end of life.
Usually unable to recover even
after mild illness
Completely dependent on outside
help (Bartel index < 20 points,
Lawton index — 1/8 points).
Multiple geriatric
syndromes
Not
May have
mild to
very
severe
dementia
and
Terminal
state
Approaching the end of life. Life
expectancy less than 6 months
The level of dependence on outside
help can be different.
May have multiple
geriatric syndromes
Not
May have
mild to
severe
dementia
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4. CLINICAL PICTURE OF THE FRAILTY SYNDROME
The basis of modern geriatrics is the concept of senile asthenia and
related geriatric syndromes. The syndrome of senile asthenia (eng. frailty)
in the literature, when literally translated from English, is interpreted in
different ways: as senile decrepitude, senile decrepitude, senile infirmity,
senile vulnerability or “fragility”.
In domestic geriatrics, the definition of “senile asthenia” is considered
the most successful. This is the most important syndrome that characterizes
the patient's condition after 65 years and reflects the degree of his
dependence on outside help in everyday life.
Senile asthenia is a specific condition that can develop in a person of
elderly and senile age and is characterized by symptoms such as:
• weight loss, when there is a decrease in body weight at a rate of no
more than 10 % per year;
• violation of gait;
• decrease in muscle strength;
• development of cognitive disorders and decrease in motivation, loss
of former vital interests;
• low level of physical activity.
Patients with frailty syndrome may complain of increased fatigue,
reduced activity, increasing difficulty walking, changes in gait, as well as
complaints due to the presence of chronic diseases and geriatric syndromes.
Often, the elderly themselves do not complain, considering weakness and
slowness as natural manifestations of aging. Patients with cognitive
impairment or depression may present no or minimal complaints. Relatives
of patients can seek help from a doctor in connection with changes that occur
with an elderly person. Elderly and senile patients may have a number of
non-specific signs and symptoms that indicate the possible presence of
frailty syndrome or an increased risk of its formation (table 2). The most
significant signs of frailty are unintentional weight loss of 4.5 kg or more in
the past year, falls, urinary incontinence, development of delirium,
dementia, dependence on outside help, significant limitation of mobility
19
Frailty is characterized by a gradual progression of symptoms. A rapid
(days, weeks) decrease in functional activity requires the exclusion of other
causes — chronic decompensation or the addition of acute
diseases/conditions, as well as the development of complications of drug
therapy. It is necessary to actively identify the symptoms and signs of senile
asthenia, evaluate their duration and development in dynamics, identify
direct and indirect signs of a decrease in autonomy, the ability to selfservice.
Symptoms inherent in frailty can be manifestations not only of
geriatric syndromes, but also of chronic diseases. Identification of frailty in
a patient should not lead to a rejection of a possible diagnostic search for
other, potentially correctable diseases and syndromes that may contribute to
the existing clinical picture and the functional state of the patient.
Senile asthenia is the final stage of the aging process of the human
body, leads to the loss of self-service, necessitates the provision of social
and medical assistance and geriatric care.
The development of the syndrome of senile asthenia is facilitated by:
• consequences of long-term chronic diseases (diabetes mellitus,
chronic heart and respiratory failure, neurological deficit as a consequence
of a stroke);
• age-related dysfunction of the nervous system;
• age-related hormonal deficiency — age-related androgen deficiency
in men, menopause in women, somatopause, which is accompanied by an
age-related decrease in insulin-like growth factor-1;
• anemic syndrome;
• chronic pain syndrome;
• a sedentary lifestyle with a significant limitation in the level of
physical activity;
• apathy and depression, chronic stress;
• side effects of medications that in old age can cause conditions such
as loss of appetite, sedation, falls.
It has now been established that more than 65 age-dependent geriatric
syndromes can lead to the development of senile asthenia.
20
The main geriatric syndromes are represented by three groups:
• 1st group — somatic:
malnutrition syndrome (malnutrition);
violation of walking and general motor activity;
fall syndrome;
bedsores;
urinary incontinence (incontinence);
stool disorders;
hearing and vision impairments;
decreased muscle mass and muscle strength (sarcopenia);
sleep disturbance (insomnia);
pain syndrome;
• 2nd group — mental:
cognitive decline and dementia;
anxiety-depressive syndrome;
delirium;
violations of behavior and adaptation;
• 3rd group — social:
loss of self-care;
dependence on outside help;
social isolation;
violence syndrome;
disruption of family ties.
The combination of three or more of these symptoms suggests the
development of senile asthenia, and one or two symptoms indicate the
presence of senile pre-frail older adults. With the progression of geriatric
syndromes and the aggravation of the phenomena of senile asthenia, a
complete loss of mobility develops (a person moves only within the bed),
there is constant urinary incontinence, frequent delirious states, marked
changes in nutritional status, and social contacts are reduced to a minimum
level.
The main risk of frailty is the loss of the ability to care for oneself,
which makes the elderly vulnerable.
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