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Frailty is a common
geriatric Geriatrics, or geriatric medicine, is a medical specialty focused on providing care for the unique health needs of older adults. The term ''geriatrics'' originates from the Greek γέρων ''geron'' meaning "old man", and ιατρός ''iatros' ...
syndrome that embodies an elevated risk of catastrophic declines in health and function among older adults. Frailty is a condition associated with
ageing Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
, and it has been recognized for centuries. It is also a marker of a more widespread syndrome of frailty, with associated weakness, slowing, decreased energy, lower activity, and, when severe, unintended weight loss. Frailty has been identified as a
risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often ...
for the development of
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. As a population ages, a central focus of geriatricians and public health practitioners is to understand, and then beneficially intervene on, the factors and processes that put elders at such risk, especially the increased vulnerability to stressors (e.g. extremes of heat and cold, infection, injury, or even changes in medication) that characterizes many older adults.


Geriatric syndromes related to frailty


Sarcopenia

Sarcopenia Sarcopenia is a type of muscle loss (muscle atrophy) that occurs with aging and/or immobility. It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength. The rate of muscle loss is dependent on exercise level, ...
is the degenerative loss of
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of mus ...
mass, quality, and strength associated with aging. The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. Sarcopenia can lead to reduction in functional status and cause significant
disability Disability is the experience of any condition that makes it more difficult for a person to do certain activities or have equitable access within a given society. Disabilities may be cognitive, developmental, intellectual, mental, physical, ...
from increased weakness. The muscle loss is related to changes in muscle synthesis signalling pathways although is incompletely understood. The cellular mechanisms are distinct from other types of muscle atrophy such as
cachexia Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart ...
, in which muscle is degraded through
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autoc ...
-mediated degradation although both conditions may co-exist.


Osteoporosis

Osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone am ...
is an age-related disease of
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, an ...
that leads to an increased risk of
fracture Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displ ...
. In osteoporosis the
bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optic ...
(BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of proteins in bone is altered. Osteoporosis is defined by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
(WHO) in women as a bone mineral density 2.5
standard deviation In statistics, the standard deviation is a measure of the amount of variation or dispersion of a set of values. A low standard deviation indicates that the values tend to be close to the mean (also called the expected value) of the set, whil ...
s below peak bone mass (20-year-old healthy female average) as measured by DXA; the term "established osteoporosis" includes the presence of a
fragility fracture A pathologic fracture is a bone fracture caused by weakness of the bone structure that leads to decrease mechanical resistance to normal mechanical loads. This process is most commonly due to osteoporosis, but may also be due to other pathologies ...
. Osteoporosis is most common in women after
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
, when it is called ''postmenopausal osteoporosis'', but may also develop in men, and may occur in anyone in the presence of particular hormonal disorders and other chronic diseases or as a result of medications, specifically
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s, when the disease is called steroid- or
glucocorticoid-induced osteoporosis Steroid-induced osteoporosis is osteoporosis arising from the use of glucocorticoids (a class of steroid hormones) analogous to Cushing's syndrome but involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug prednisone i ...
(SIOP or GIOP). Given its influence in the risk of fragility fracture, osteoporosis may significantly affect
life expectancy Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
and
quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
.


Muscle weakness

Muscle weakness Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includi ...
, also known as muscle fatigue, (or "lack of strength") refers to the inability to exert force with one's skeletal
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...
s. Weakness often follows
muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness ...
and a decrease in activity, such as after a long bout of bedrest as a result of an illness. There is also a gradual onset of muscle weakness as a result of sarcopenia – the age-related loss of skeletal muscle. A test of strength is often used during a
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems enginee ...
of a muscular disorder before the
etiology Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
can be identified. Such etiology depends on the type of muscle weakness, which can be true or perceived as well as variable topically. True weakness is substantial, while perceived rather is a sensation of having to put more effort to do the same task. On the other hand, various topic locations for muscle weakness are central, neural and peripheral. Central muscle weakness is an overall exhaustion of the whole body, while peripheral weakness is an exhaustion of individual muscles. Neural weakness is somewhere between.


Smurfness

Recent findings suggest that the end-of-life is molecularly and physiologically highly stereotyped, evolutionarily conserved and predictable. The Smurf phenotype "is a dramatic increase of intestinal permeability that can be observed ''in vivo'' using a non-invasive assay. The proportion of individuals showing that phenotype increases quasi linearly as a function of chronological age and every individual will undergo this change prior to death from non-pathological causes, in other words ‘occurring during normal aging’".


Biological and physiological mechanisms

It has been suggested that the causes of frailty are multifactorial, involving dysregulation across many physiological systems. A proinflammatory state, sarcopenia, anemia, relative deficiencies in anabolic hormones (androgens and growth hormone) and excess exposure to catabolic hormones (cortisol), insulin resistance, glucose levels, compromised altered immune function, micronutrient deficiencies and oxidative stress are each individually associated with a higher likelihood of frailty. Additional findings show that the risk of frailty increases with an increased number of abnormal bodily systems. This finding shows that interventions that target multiple systems may yield greater results in prevention and treatment of frailty than interventions that target only one system. Associations between specific disease states are also associated with and frailty have also been observed, including cardiovascular disease,
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
,
chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...
and other diseases in which inflammation is prominent. It is possible that clinically measurable disease states can manifest themselves or be captured prior to the onset of frailty. No single disease state is necessary and sufficient for the pathogenesis of frailty, since many individuals with chronic diseases are not frail. Therefore, rather than being dependent on the presence of measurable diseases, frailty is an expression of a critical mass of physiologic impairments. Frailty has been identified as a risk factor for the development of
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
.


Theoretical understanding

Recent work on frailty has sought to characterize both the underlying changes in the body and the manifestations that make frailty recognizable. It is well-agreed upon that declines in physiologic reserves and resilience is the essence of being frail. Similarly, scientists agree that the risk of frailty increases with age and with the incidence of diseases. Beyond that, there is now strong evidence to support the theory that the development of frailty involves declines in energy production, energy utilization and repair systems in the body, resulting in declines in the function of many different physiological systems. This decline in multiple systems affects the normal complex adaptive behavior that is essential to health and eventually results in frailty typically manifesting as a syndrome of a constellation of weakness, slowness, reduced activity, low energy and unintended weight loss. When most severe, i.e. when 3 or more of these manifestations are present, the individual is at a high risk of death.


Frailty assessment

The syndrome of geriatric frailty is hypothesized to reflect impairments in the regulation of multiple physiologic systems, embodying a lack of resilience to physiologic challenges and thus elevated risk for a range of deleterious endpoints. Generally speaking, the empirical assessment of geriatric frailty in individuals seeks ultimately to capture this or related features, though distinct approaches to such assessment have been developed in the literature (see de Vries et al., 2011 for a comprehensive review). Two most widely used approaches, different in their nature and scopes, are discussed below. Other approaches follow.


Physical frailty phenotype

A popular approach to the assessment of geriatric frailty encompasses the assessment of five dimensions that are hypothesized to reflect systems whose impaired regulation underlies the syndrome. These five dimensions are: * unintentional weight loss, * exhaustion, * muscle weakness, * slowness while walking, and * low levels of activity. Corresponding to these dimensions are five specific criteria indicating adverse functioning, which are implemented using a combination of self-reported and performance-based measures. Those who meet at least three of the criteria are defined as "frail", while those not matching any of the five criteria are defined as "robust". Additional work on the construct is done by Bandeen-Roche et al. (2006), though some of the exact criteria and measures differ (see Table 1 in the paper for this contrast). Other studies in the literature have also adopted the general approach of Linda P. Fried et al. (2001) though, again, the exact criteria and their particular measures may vary. This assessment approach was developed and refined by Fried and colleagues at the Johns Hopkins University's Center on Aging and Health. This center is home to Johns Hopkins Claude D. Pepper Older Americans Independence Center, which focuses on frailty research and has launched a website dedicated to frailty science: https://frailtyscience.org.


Frailty index / Deficit accumulation

Another notable approach to the assessment of geriatric frailty (if not also to some degree its conceptualization) is that of Rockwood and Mitnitski (2007) in which frailty is viewed in terms of the number of health "deficits" that are manifest in the individual, leading to a continuous measure of frailty (see Rockwood, Andrew, and Mitnitski (2007) for a contrast of the two approaches). This approach was developed by Dr. Rockwood and colleagues at Dalhousie University.


Four domains of frailty

A four domains of frailty model was proposed in response to an article in the BMJ. This conceptualisation could be viewed as blending the phenotypic and index models. Researchers tested this model for signal in routinely collected hospital data, and then used this signal in the development of a frailty model, finding even predictive capability across 3 outcomes of care. In the care home setting, one study indicated that not all four domains of frailty were routinely assessed in residents, giving evidence to suggest that frailty may still primarily be viewed only in terms of physical health.


SHARE Frailty Index

The SHARE-Frailty Index (SHARE-FI) was originally developed by Romero-Ortuno (2010) and researchers as part of the Survey of Healthy Ageing and Retirement in Europe. It consists of five domains of the frailty phenotype: *Fatigue *Loss of appetite *Grip strength *Functional difficulties *Physical activity The SHARE-FI calculator is freely available to use online. The calculator classifies individuals as: # frail # pre-frail # non-frail / robust The SHARE-FI has good clinical utility as it provides relatively quick assessment of frailty in often time-poor healthcare settings.


Prevention


Identification of risk factors

When considering prevention of frailty, it is important to understand the risk factors that contribute to frailty and identify them early on. A 2005 observational study found associations between frailty and a number of risk factors such as: low income, advanced age, chronic medical conditions, lack of education, and smoking.


Exercise

A significant target in the prevention of frailty is physical activity. As people age, physical activity markedly drops, with the steepest declines seen in adolescence and continuing on throughout life. The lower levels of physical activity and are associated with and a key component of frailty syndrome. Therefore, exercise regimens have been examined in a number of studies as an intervention to prevent frailty. A randomized control trial published in 2017 found significantly lower rates of frailty in older adults who were assigned an exercise regimen vs those who were in the control group. In this study, 15.3% of the control group became frail in the time frame of the study, in comparison to 4.9% of the exercise group. The exercise group also received a nutritional assessment, which is another target in frailty prevention.


Nutrition

Nutrition has also been a major target in the prevention of frailty. A 2019 review paper examined a variety of studies and found evidence of nutritional intervention as an effective way of preventing frailty. With the
mediterranean diet The Mediterranean diet is a diet inspired by the eating habits of people who live near the Mediterranean Sea. When initially formulated in the 1960s, it drew on the cuisines of Greece, Italy, France and Spain. In decades since, it has also incor ...
in particular reducing risk of frailty up to 60%.


Non-surgical management


Exercise

Individuals partaking in exercise appear to have potential in preventing frailty. In 2018, a systemic review concluded that group exercise had the benefit of delaying frailty in older adults aged 65 and above. Elderly adults are also less likely to sustain fall injuries.


Occupational therapy

Activities of daily living Activity may refer to: * Action (philosophy), in general * Human activity: human behavior, in sociology behavior may refer to all basic human actions, economics may study human economic activities and along with cybernetics and psychology may stu ...
(ADLs) include activities that are necessary to sustain life. Examples are brushing teeth, getting out of bed, dressing oneself, bathing, etc.
Occupational therapy Occupational therapy (OT) is a global healthcare profession. It involves the use of assessment and intervention to develop, recover, or maintain the meaningful activities, or ''occupations'', of individuals, groups, or communities. The field of ...
provided modest improvements in elderly adults mobility to do ADLs.


Nutritional supplementation

Frailty can involve changes such as weight loss. Interventions should focus on any difficulties with supplementation and diet. For those who may be undernourished and not acquiring adequate calories, oral nutritional supplements in between meals may decrease nutritional deficits. With age comes decreased bone density. Therefore,
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 ...
supplementation may provide the benefits of improving stability and muscle strength retention.


Palliative care

Palliative care may be helpful for individuals who are experiencing an advanced state of frailty with possible other co-morbidities. Improving quality of life by reducing pain and other harmful symptoms is the goal with palliative care. One study showed the cost reduction by focusing on palliative care rather than expensive treatments that may be unnecessary and unhelpful.


Surgical outcomes

Frail elderly people are at significant risk of post-surgical complications and the need for extended care. Frailty more than doubles the risk of morbidity and mortality from surgery and cardiovascular conditions. Assessment of older patients before elective surgeries can accurately predict the patients' recovery trajectories. * The most widely used frailty scale consists of five items: *unintentional weight loss >4.5 kg in the past year *self-reported exhaustion *<20th population
percentile In statistics, a ''k''-th percentile (percentile score or centile) is a score ''below which'' a given percentage ''k'' of scores in its frequency distribution falls (exclusive definition) or a score ''at or below which'' a given percentage fall ...
for grip strength *slowed walking speed, defined as lowest population quartile on 4-minute walking test *low physical activity such that persons would only rarely undertake a short walk A healthy person scores 0; a very frail person scores 5. Compared to non-frail elderly people, people with intermediate frailty scores (2 or 3) are twice as likely to have post-surgical complications, spend 50% more time in the hospital, and are three times as likely to be discharged to a skilled nursing facility instead of to their own homes. Frail elderly patients (score of 4 or 5) have even worse outcomes, with the risk of being discharged to a nursing home rising to twenty times the rate for non-frail elderly people.


Epidemiology and public health

Frailty is a common geriatric syndrome. Estimates of frailty prevalence in older populations may vary according to a number of factors, including the setting in which the prevalence is being estimated – e.g., nursing home (higher prevalence) vs. community (lower prevalence) – and the operational definition used for defining frailty. Using the widely used frailty phenotype framework proposed by Fried et al. (2001), prevalence estimates of 7–16% have been reported in non-institutionalized, community-dwelling older adults. The occurrence of frailty increases incrementally with advancing age, is more common in older women than men, and among those of lower socio-economic status. Frail older adults are at high risk for major adverse health outcomes, including disability, falls, institutionalization, hospitalization, and mortality. Epidemiologic research to date has led to the identification of a number of risk factors for frailty, including: (a) chronic diseases, such as cardiovascular disease, diabetes, chronic kidney disease, depression, and cognitive impairment; (b) physiologic impairments, such as activation of inflammation and coagulation systems, anemia, atherosclerosis, autonomic dysfunction, hormonal abnormalities, obesity, hypovitaminosis D in men, and environment-related factors such as life space and neighborhood characteristics. Advances about potentially modifiable risk factors for frailty now offer the basis for translational research effort aimed at prevention and treatment of frailty in older adults. A recent systematic review found that exercise interventions can increase muscle strength and improve physical function; however, results are inconsistent in frail older adults living in the community. A review looked at the relationship between the frailty syndrome and chronic lower extremity
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...
in those people with diabetes. On the one hand, chronic lower limb ischemia may predispose to the development of frailty, on the other hand, the presence of the frailty may affect the prognosis in patients with peripheral arterial disease.


Ongoing clinical trials

As of September 2021
ongoing clinical trials on frailty syndrome in the US
include: * the impact of frailty on clinical outcomes of patients treated for abdominal aortic aneurysms * the use of "pre-habilitation," an exercise regimen used before transplant surgery, to prevent the frailty effects of kidney transplant in recipients * defining the acute changes in frailty following
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
in the abdomen * the efficacy of the anti-inflammatory drug,
Fisetin Fisetin (7,3′,4′- flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It can be found in many plants, where it serves as a yellow/ochre colouring agent. It is also found in many fruits and vegetables, such as strawberries, ...
, in reducing frailty markers in elderly adults * Physical Performance Testing and Frailty in Prediction of Early Postoperative Course After Cardiac Surgery (Cardiostep)https://clinicaltrials.gov/ct2/show/NCT05166863?cond=rehabilitation+after+cardiac+surgery&draw=2&rank=10 Up-to-date information on ongoing clinical trials on frailty syndrome and other conditions can be found at clinicaltrials.gov.


References

{{DEFAULTSORT:Frailty Syndrome Geriatrics Gerontology