Frailty syndrome

Frailty refers to an age-related functional decline and heightened state of vulnerability. It is a worsening of functional status compared to the normal physiological process of aging. It can refer to the combination of a decline of physical and physiological aspects of a human body. The reduced reserve capacity of organ systems, muscle, and bone create a state where the body is not capable of coping with stressors such as illness or falls. Frailty can lead to increased risk of adverse side effects, complications, and mortality. Older age by itself is not what defines frailty, it is however a syndrome found in older adults. Many adults over 65 are not living with frailty. Frailty is not one specific disease, however is a combination of many factors. Frailty does not have a specific universal criteria on which it is diagnosed; there are a combination of signs and symptoms that can lead to a diagnosis of frailty. Evaluations can be done on physical status, weight fluctuations, or subjective symptoms. Frailty most commonly refers to physical status and is not a syndrome of mental capacity such as dementia, which is a decline in cognitive function. Although, frailty can be a risk factor for the development of dementia. Although no universal diagnostic criteria exist, some clinical screening tools are commonly used to identify frailty. These include the Fried Frailty Phenotype and a deficit accumulation frailty index. The Fried Frailty Phenotype assesses five domains commonly affected by frailty: exhaustion, weakness, slowness, physical inactivity, and weight loss. The presence of 1-2 findings is classified as "pre-frailty", 3 or more as frailty and the presence of all 5 indicates "end-stage frailty" and is associated with poor prognosis. The deficit accumulation characterization of frailty tallies deficits present in a variety of clinical areas (including nutritional deficiency, laboratory abnormalities, disability index, cognitive and physical impairment) to create a frailty index. A higher number of deficits is associated with a worse prognosis. ==Signs and symptoms==

Frailty is a complex condition that is a result of multiple body systems experiencing decline in function, and the more body systems that are affected, the higher the risk is for developing frailty. There is a variety of risk factors and signs that can suggest an older person having frailty. However, the development of any of these risk factors or signs alone does not establish frailty as they can be symptoms of numerous other health conditions. For establishing that a person has frailty multiple factors or signs need to be present at the same time. Health-related Decreases in skeletal muscle mass (sarcopenia) and bone density (osteopenia and osteoporosis) are two major contributors to developing frailty in older adults. In early to middle age, bone density and muscle mass are closely related. As adults age, skeletal muscle mass or bone density may begin to decline. This decline can lead to frailty and both have been identified as contributors to disability. Sarcopenia is the degenerative loss of skeletal muscle mass, quality, and strength associated with aging. The rate of muscle loss is dependent on exercise level, co-existing health conditions, nutrition and other factors. Sarcopenia can lead to reduction in functional status and cause significant disability from increased muscle weakness. Aging, lower levels of DHEA, testosterone, IGF-1 and increased levels of cortisol are thought to contribute to muscle wasting in those with frailty. Frailty is associated with an increased risk of osteoporosis related bone fractures. Frailty is also common in those with heart failure. Both frailty and heart failure share similar methods of progressive health decline and often lead to worsened health conditions when combined. There are many other health-related factors that can be present in frailty including incontinence, lung disease, having multiple long-term health conditions, taking multiple medications regularly, malnutrition, cognitive impairment, diabetes, and obesity. Poor oral health, difficulties with chewing and swallowing, dry mouth and pain in the mouth are also signs of frailty in some people. Conditions and symptoms related to mental health that can increase the likelihood of frailty include depression and loneliness. Lifestyle Lifestyle factors and behaviors that increase the likelihood of having or developing frailty include smoking, sedentary lifestyle, low level of physical exercise. Dietary factors include low intake of certain vitamins (D, E, C, folate, carotenoids, α-tocopherol) and having a higher score on the Dietary Inflammatory Index. Demographic characteristics People in certain demographic groups have a higher risk of frailty than others either due to direct or indirect reasons. Demographic factors include older age, being female, having lower level of education, and having low income. Social Certain factors in social background and situation, interpersonal relationships can also be risk factors for frailty. Such factors include living alone, being single or widowed, having lower family income or having suffered abuse. Living in poor neighborhood conditions, in a rural area, and having low social support are also potential risk factors for frailty. ==Mechanism==

The causes of frailty are multifactorial involving dysregulation across many physiological systems. IL-6 is typically up-regulated by inflammatory mediators, such as C-reactive protein, released in the presence of chronic disease. Increased levels of inflammatory mediators are often associated with chronic disease; however, they may also be elevated even in the absence of chronic disease. Sarcopenia, anemia, anabolic hormone deficiencies, and excess exposure to catabolic hormones such as cortisol have been associated with an increased likelihood of frailty. Other mechanisms associated with frailty include insulin resistance, increased glucose levels, compromised immune function, micronutrient deficiencies, and oxidative stress. Mitochondrial dysfunction, including mitochondrial DNA mutations, cellular respiration dysfunction, and changes in mitochondrial hemostasis is thought to contribute to reduced cellular energy, production of reactive oxygen species and inflammation. This mitochondrial dysfunction is thought to contribute to the signs of frailty. The risk of frailty increases with age and with the incidence of diseases. The development of frailty is also thought to involve 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. A comparison of peripheral blood mononuclear cells from frail older individuals to cells from healthy younger individuals showed evidence in the frail older individuals of increased oxidative stress, increased apurinic/pyrimidinic sites in DNA, increased accumulation of endogenous DNA damage and reduced ability to repair DNA double-strand breaks. ==Diagnosis==

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 frailty in individuals seeks ultimately to capture this or related features, though distinct approaches to such assessment have been developed in the literature. Two most widely used approaches, different in their nature and scopes, are the physical frailty phenotype and frailty index/deficit accumulation model. Physical frailty phenotype A popular approach to the assessment of frailty encompasses the assessment of five dimensions that are hypothesized to reflect systems whose impaired regulation underlies the syndrome. This score is based the presence of deficits in may areas related to frailty, including symptoms of cognitive or physical impairment, laboratory abnormalities, nutritional deficits, or disability. CGAs for older people with frailty who do not live in a long-term care institution could improve medication adherence, patient functioning, quality of care, and reduce the risk of unplanned hospital admissions. In the United Kingdom, best practice guidelines recommend a medical review based on CGA to establish the management plan for people with frailty. Four domains of frailty A model consisting of four domains of frailty uses a conceptualisation that could be viewed as blending the phenotypic and index models. The model was developed from routinely collected hospital data, and was found to have 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) assesses frailty based on five domains of the frailty phenotype: • Fatigue • Loss of appetite • Grip strength • Functional difficulties • Physical activity Clinical Frailty Scale The Clinical Frailty Scale (CFS) is a scale used to assess frailty which was evolved from the Canadian Study of Health and Aging. It is among the few assessment tools that have demonstrated adaptability for remote use. The CFS is a 9-point scale used to assess a persons frailty level, where a score of 1 point would mean a person is very fit and robust, to a score of 9 points meaning the person is severely frail and terminally ill. It has been assessed to screen all domains of frailty, and is said to be easy to perform by clinicians. Specific tests used in this scaling system are walking tests and clock drawing. Electronic Frail Scale (eFI) The electronic Frail Scale (eFI) is a scale weighted out of 36 deficit points where the higher the number in the score will represent the more frail, or more prone to frailty. Each frailty-related deficit the person has is given a point and the more deficits the person is experiencing the more likely they are frail or will experience frailty in the future. The total number of deficits is divided by 36. Then, a frailty category is assigned. A person with a score of 0.00–0.12 is in the "Fit" category. A person with a score of 0.13–0.24 is in the "Mild" category. A person with a score of 0.25–0.36 is in the "Moderate" category. Finally, a person with the score of 0.36 or above is considered to be in the "Severe" category. Hospital Frailty Risk Score (HFRS) The Hospital Frailty Risk Score (HFRS) uses diagnostic codes from the International Classification of Diseases, tenth revision (ICD10). It is calculated by combining a weighted set of 109 ICD10 diagnostic codes recorded in the person's medical record during the current hospital admission and the two previous emergency admissions occurring in the prior two years. Each of the 109 ICD10 codes has an associated weight, from 0.1 up to 7.1. These weights are summed to give the frailty risk score for each person. The resulting HFRS values ranging from 0 (zero frailty risk) for those with none of the 109 codes to 173.2 for someone with all 109 codes. People can be categorised into four groups: zero risk (HRFS=0), lower risk (0 15). Originally the HFRS was developed for people aged 75 years or older but it can be used to identify frailty risk for all adults admitted to hospital. Assessment for 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. One frailty scale consists of five items: • Congestive heart failure within 1 month of surgery • Diabetes mellitus • Chronic Obstruction Pulmonary Disease or pneumonia in the past • Individuals needing additional assistance to perform everyday activities of living • High blood pressure that is controlled with medication An individual without one of these conditions would be given a score of 0 for the condition absent. An individual who does have one of the conditions would be given a score of 1 for each of the conditions present. In an initial study using the mFI-5 scale, individuals with a sum mFI-5 score of 2 or greater were predicted to experience post-surgery complications due to frailty, which was supported by the results of the study. Other studies note that frailty scales alone may be inaccurate in predicting outcomes for people undergoing surgical procedures, and other factors such as co-morbid medical conditions need to be considered. For people with frailty undergoing abdominal surgery, prehabilitation programmes that include exercise, improved diet and psychological support can reduce the length of hospital stay and decrease the risk of serious complications. == Prevention ==

Frailty is not an inevitable part of aging, and its development (or worsening) can be prevented or delayed. Lower levels of physical activity are a key component of developing frailty. Therefore, regular exercise such as walking, strength training, and self-directed physical activity is an important way to prevent frailty. Nutrition Having a healthy diet and balanced nutrition also plays a major role in preventing frailty. A healthy dietary pattern consisting of high consumption of healthy fats, fruits, vegetables, low-fat dairy products, and whole grains can contribute to maintaining a healthy weight and prevent or postpone frailty. Specifically, an adherence to the Mediterranean diet may help decreasing the risk of frailty. A higher protein intake and a higher intake of certain vitamins (B6, C, D, α-carotene, β-carotene, α-tocopherol, and folate) might also support prevention. == Management ==

Through management and interventions, it is possible to decrease frailty or slow down its progress. As frailty comes with a heightened vulnerability to stress, avoiding known stressors (ie. surgeries, infections, etc.) and understanding mechanisms to reduce frailty can help older adults prevent worsening their frail status. Currently, preventative interventions focus on minimizing muscle loss and improvement of overall well-being in older adults or individuals with chronic illnesses. Exercise Physical activity is the most effective way of decreasing frailty and increasing the quality of life. Nutritional supplementation Nutritional supplementation (including protein supplementation) is another effective way of managing frailty. Nutritional supplementation is even more effective when coupled with regular physical activity. Medication review It is common for people with frailty to regularly take 5 or more medications (polypharmacy). As a result this group is at a greater risk of adverse drug reactions that can contribute to falls and hospitalisation. People with frailty are also at risk of receiving potentially inappropriate prescribing. This can include being prescribed unnecessary medications (overprescribing), incorrect drug or dose (misprescribing), and not receiving beneficial medication (underprescribing). Long-term care Specific ways of frailty management largely depends on an individual's classification (i.e. pre-fail, frail) and treatment needs. Palliative care may be helpful for individuals who are experiencing an advanced state of frailty with possible other co-existing health conditions. The goal of palliative care in people with frailty is improving quality of life by reducing pain and other harmful symptoms. ==Epidemiology==

Frailty is a common geriatric syndrome. Due to the absence of international diagnostic criteria, the prevalence estimates may not be accurate. Estimates of frailty prevalence in older populations 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 definition used for frailty. Using the widely used frailty phenotype framework, Frailty is more common in those with mental health conditions including anxiety disorders, bipolar disorder and depression. The presence of frailty with these mental disorders was also associated with a poor prognosis and increased mortality Research comparing case management trials to standard care for people living with frailty in high-income countries found that there was no difference in reducing cost or improving patient outcomes between the two approaches. Sex and ethnicity differences in frailty Frailty is more common in female older adults compared to male older adults. This difference is influenced by various biological, social, and environmental factors influence. Studies have found that the incidence of frailty was higher in females with more medical comorbidities. Frailty-related physical changes in muscle also show sex-specific differences. In a population based study, Non-Hispanic Black-Americans and Hispanic-Americans had a higher incidence of frailty compared to non-Hispanic White-Americans. == Research directions ==

, 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 in the abdomen • the efficacy of the anti-inflammatory drug, Fisetin, in reducing frailty markers in elderly adults • Physical Performance Testing and Frailty in Prediction of Early Postoperative Course After Cardiac Surgery (Cardiostep) == See also ==