Wikipedia

Frailty syndrome

(Redirected from Decrepitude)

Frailty is a common and clinically significant grouping of symptoms that occurs in aging and older adults. These symptoms can include decreased physical abilities such as walking, excessive fatigue, and weight and muscle loss leading to declined physical status. In addition, frailty encompasses a decline in both overall physical function and physiologic reserve of organ systems resulting in worse health outcomes for this population.[1][2] This syndrome is associated with increased risk of heart disease, falls, hospitalization, and death.[3][4] In addition, it has been shown that adults living with frailty face more anxiety and depression symptoms than those who do not.[5] The presence of frailty varies based on the assessment technique, however it is estimated that 4-16% of the population over 65 years old is living with frailty.[6]

Frailty syndrome
A woman supporting herself with a walking frame.
SpecialtyGeriatrics

Frailty can have impacts on public health due to the factors that comprise the syndrome affecting physical and mental health outcomes. There are several ways to identify, prevent, and mitigate the prevalence of frailty and the evaluation of frailty can be done through clinical assessments created to combine recognized signs and symptoms of frailty.

Definitions

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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.[7]

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.[8] 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 staus, weight fluctuations, or subjective symptoms.[9] 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.[10]

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.[11] 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.[11][12]

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Major contributors to frailty

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Decreases in skeletal muscle mass (sarcopenia) and bone density 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.[13] The development of sarcopenia or osteoporosis alone does not establish frailty, as there are many factors that are taken into account. Studies suggest that frailty is a result of multiple body systems experiencing dysregulation, and the more body systems that are affected, the higher the risk is for developing frailty. [1]

Sarcopenia

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Sarcopenia is the degenerative loss of skeletal muscle mass, quality, and strength associated with aging.[14] 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 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, in which muscle is degraded through cytokine-mediated degradation although both conditions may co-exist.[15]

Osteoporosis

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Osteoporosis is a disease of bone mineral density loss (usually age related) that leads to an increased risk of bone fractures, especially with falls.[16] Frailty is associated with an increased risk of osteoporosis related bone fractures.[17]

Muscle weakness

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Muscle weakness and associated muscle atrophy (muscle wasting, also known as sarcopenia) are more common in those with frailty. The prevalence of muscle weakness was more common in those with frailty in a population based study of older adults.[18] Aging, lower levels of DHEA, testosterone, IGF-1 and increased levels of cortisol are thought to contribute to muscle wasting in those with frailty.[11]

 
Muscle weakness makes it difficult to perform everyday activities, like getting into a bathtub.

Heart failure

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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. [19]

Depression, bipolar disorder, and anxiety disorders

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People who had mental disorders were found to be at increased risk of frailty.[20]

Biological and physiological mechanisms

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The causes of frailty are multifactorial involving dysregulation across many physiological systems.[21][11] Frailty may be related to a proinflammatory state. A common interleukin elevated in this state is IL-6. A pro-inflammatory cytokine, IL-6 was found to be common in older adults with frailty.[22] 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.[23]

Sarcopenia,[24] anemia,[25][26] anabolic hormone deficiencies,[27] and excess exposure to catabolic hormones such as cortisol[28] have been associated with an increased likelihood of frailty. Other mechanisms associated with frailty include insulin resistance,[29] increased glucose levels,[30] compromised immune function,[31][32] micronutrient deficiencies, and oxidative stress.[33]

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.[11]

Researchers found that individual abnormal body functions may not be the best predictor of risk of frailty. However, they did conclude that once the number of conditions reaches a certain threshold, the risk of frailty increases.[21] This finding suggests that treatment of frailty syndrome should not be focused on a single condition, but a multitude in order to increase the likelihood of better treatment results.

Theoretical understanding

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Declines in physiologic reserves and resilience contribute to frailty.[34] 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.[21][35]

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.[36]

Frailty assessment

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Further information: Frailty index and Physiological functional capacity

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).[37]

Two most widely used approaches, different in their nature and scopes,[38] are discussed below. Other approaches follow.

Physical frailty phenotype

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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.[39][11] These five dimensions are:

  • unintentional weight loss
  • exhaustion
  • muscle weakness
  • slowness while walking
  • low levels of activity

These five dimensions form 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".

Frailty index/deficit accumulation

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Another notable approach to the assessment of geriatric frailty 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.[40][41] 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.[40][11]

Four domains of frailty

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A model consisting of four domains of frailty was proposed in response to an article in the BMJ.[42] This conceptualisation could be viewed as blending the phenotypic and index models. Researchers tested this model for signal in routinely collected hospital data,[43] and then used this signal in the development of a frailty model, finding even predictive capability across 3 outcomes of care.[44] 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.[45]

SHARE Frailty Index

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The SHARE-Frailty Index (SHARE-FI) assesses frailty based on five domains of the frailty phenotype:[46]

  • Fatigue
  • Loss of appetite
  • Grip strength
  • Functional difficulties
  • Physical activity

Clinical Frailty Scale

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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 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.[9]

Edmonton Frail Scale

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The Edmonton Frail Scale (EFS) is another method used to screen frailty. This scale is given scores of up to 17 points.[47] 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. [48]

Electronic Frail Scale (eFI)

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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. [49]

Prevention

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As frailty arises as a result of reduced reserve capacity in a biological system and causes an individual to have 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.[50] Some signs of frailty include: unwanted weight loss, muscle weakness, low energy, and low grip strength.[51] Currently, preventative interventions focus on minimizing muscle loss and improvement of overall well-being in older adults or individuals with chronic illnesses.

Identification of risk factors

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When considering prevention of frailty, it is important to understand the risk factors that contribute to frailty and identify them early on. Early identification of risk factors allows for preventative interventions, reducing risks of future complications.

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.[52]

Exercise

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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.[53] The lower levels of physical activity and are associated with and a key component of frailty syndrome. Therefore, exercise regimens consisting of walking, strength training, and self-directed physical activity, have been examined in a number of studies as an intervention to prevent frailty.[54][55][56] 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.[54] 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

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Nutrition has also been a major target in the prevention of 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 postpone frailty. A 2019 review paper examined a variety of studies and found evidence of nutritional intervention as an effective way of preventing frailty.[57] Specifically, multiple studies showed adherence to the Mediterranean diet is associated with a decreased risk of incident frailty in the US.[58]

Non-surgical management

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Frailty management largely depends on an individual's classification (i.e. non-frail, pre-fail, and frail) and treatment needs.[3] Currently, there is a lack of strong evidence-based treatment and management plans for frailty. Physicians must work closely with patients to develop a realistic management plan to ensure patient compliance, leading to better health outcomes. In clinical practice, guidelines developed by International Conference on Frailty and Sarcopenia Research (ICFSR) can be used to identify and manage frailty based on classification.[3]

There are currently no pharmacological interventions available for frailty.[59]

Exercise

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Exercise is one of the major targets to prevent and manage frailty in older adults to improve and maintain mobility. 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 older.[60]

Individualized physical therapy programs developed by physicians can help improve frail status. For example, progressive resistance strength training for older adults can be used in clinical practice or at-home as a way to regain mobility. A systematic review conducted in 2022 across multiple countries using data from twelve randomized clinical trials found evidence that mobility training can increase mobility level and functioning in older adults living in community-dwellings, such as a nursing home.[61] However, the review also concluded little to no difference in the risk of falls.

Occupational therapy

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Activities of daily living (ADLs) include activities that are necessary to sustain life. Examples are brushing teeth, getting out of bed, dressing oneself, bathing, etc. Occupational therapy provided modest improvements in elderly adults mobility to do ADLs.[62]

Nutritional supplementation

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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.[63]

Vitamin D, omega-3 fatty acid, sex hormone (such as testosterone) or growth hormone supplementation have not shown benefits in physical functioning, activities of daily living or frailty.[11]

Palliative care

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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 other treatments that may be unnecessary and unhelpful.[64]

Surgical outcomes

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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.[65] Assessment of older patients before elective surgeries can accurately predict the patients' recovery trajectories.[66] One frailty scale consists of five items:[39]

  • unintentional weight loss >4.5 kg in the past year
  • self-reported exhaustion
  • <20th population percentile 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.[66] 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.

Another tool that has been used to predict frailty outcome post-surgery is the Modifies Frailty Index, or mFI-5. This scale consists of 5 key co-morbidities:[67]

  • 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.[67]

Frailty scales can be used to predict the risk of complications in patients before and after surgery. There is an association between frailty and delayed transplant function after a kidney transplant.[68] Other studies note that frailty scales alone may be innacurate in predicting outcomes for people undergoing surgical procedures, and other factors such as co-morbid medical conditions need to be considered.[69]

Epidemiology and public health

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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,[39] prevalence estimates of 7–16% have been reported in non-institutionalized, community-dwelling older adults. In a systemic review exploring the prevalence of frailty based on geographical location it was found that Africa and North and South America had the largest prevalence at 22% and 17% respectively. Europe had the lowest prevalence at 8%.[70]

The development of frailty occurs most often in individuals with low socio-economic status, those living with obesity, female sex, a history of smoking, limited activity levels, and older age.[71]

Epidemiologic research has also indicated that presence of multiple chronic diseases (such as cardiovascular disease, diabetes, or chronic kidney disease, anemia, atherosclerosis) depression, and cognitive impairment to be risk factors for frailty.[72][73][74][25][26][75] Autonomic dysfunction, hormonal abnormalities, and obesity have also been implicated in the development of frailty.[25][76][27] obesity,[77] Vitamin D deficiency in men may be associated with increased risk of frailty.[78] Environmental factors such as living space and neighborhood characteristics may also be related to frailty.[79]

Frailty is more common in those with diabetes plus peripheral arterial disease and in those with heart failure.[80][81]

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[82]

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.[83]

Sex and ethnicity differences in frailty

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Meta-analyses have shown that the prevalence of frailty is higher in female older adults compared to male older adults.[84][85] This sex difference was consistently found in pre-clinical research models as well.[86] Studies have found that the incidence of frailty was higher in females with more medical comorbidities.[87] In recent research where muscle-biopsies were taken from fit and weak older adults of both sexes, it was shown that there were sex-specific alterations in muscle content in association with frailty-related physical weakness.[88]

In a population based study, Non-Hispanic Black-Americans and Hispanic-Americans had a higher incidence of frailty compared to non-Hispanic White-Americans.[89]

Ongoing clinical trials

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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[90]
  • the use of "pre-habilitation," an exercise regimen used before transplant surgery, to prevent the frailty effects of kidney transplant in recipients[91]
  • defining the acute changes in frailty following sepsis in the abdomen[92]
  • the efficacy of the anti-inflammatory drug, Fisetin, in reducing frailty markers in elderly adults[93]
  • Physical Performance Testing and Frailty in Prediction of Early Postoperative Course After Cardiac Surgery (Cardiostep)[94]

See also

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References

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  1. ^ a b "Guidelines on Integrated Care for Older People (ICOPE): Guidance for Person-Centred Assessment and Pathways in Primary Care". WHO Clinical Consortium on Healthy Ageing: Topic focus: frailty and intrinsic capacity: Report of consortium meeting 1–2 December 2016 in Geneva, Switzerland (PDF) (Report). World Health Organization. 2017. hdl:10665/272437/WHO-FWC-ALC-17.2-eng. WHO/FWC/ALC/17.2.
  2. ^ Whitson HE, Cohen HJ, Schmader KE, Morey MC, Kuchel G, Colon-Emeric CS (August 2018). "Physical Resilience: Not Simply the Opposite of Frailty". Journal of the American Geriatrics Society. 66 (8): 1459–61. doi:10.1111/jgs.15233. PMC 6157007. PMID 29577234.
  3. ^ a b c Allison R, Assadzandi S, Adelman M (February 2021). "Frailty: Evaluation and Management". American Family Physician. 103 (4): 219–226. PMID 33587574.
  4. ^ "How to avoid frailty and stay strong as you age". www.heart.org. Retrieved 2024-07-25.
  5. ^ Ní Mhaoláin AM, Fan CW, Romero-Ortuno R, Cogan L, Cunningham C, Kenny RA, et al. (August 2012). "Frailty, depression, and anxiety in later life". International Psychogeriatrics. 24 (8): 1265–74. doi:10.1017/S1041610211002110. hdl:2262/67243. PMID 22333477.
  6. ^ Waltson JD (June 12, 2023). "Frailty". UpToDate. Retrieved July 26, 2024.
  7. ^ Xue QL, Tian J, Walston JD, Chaves PH, Newman AB, Bandeen-Roche K (January 2020). "Discrepancy in Frailty Identification: Move Beyond Predictive Validity". J Gerontol A Biol Sci Med Sci. 75 (2): 387–393. doi:10.1093/gerona/glz052. PMC 7176056. PMID 30789645.
  8. ^ "Age". National Institutes of Health (NIH). 2022-08-11. Retrieved 2024-07-26.
  9. ^ a b Mendiratta P, Schoo C, Latif R (2024). "Clinical Frailty Scale". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 32644435. NBK559009.
  10. ^ Ward DD, Ranson JM, Wallace LM, Llewellyn DJ, Rockwood K (April 2022). "Frailty, lifestyle, genetics and dementia risk". Journal of Neurology, Neurosurgery, and Psychiatry. 93 (4): 343–350. doi:10.1136/jnnp-2021-327396. PMC 8921595. PMID 34933996.
  11. ^ a b c d e f g h Kim DH, Rockwood K (8 August 2024). "Frailty in Older Adults". New England Journal of Medicine. 391 (6): 538–548. doi:10.1056/NEJMra2301292. PMID 39115063.
  12. ^ Ryan J, Espinoza S, Ernst ME, Ekram AR, Wolfe R, Murray AM, et al. (7 January 2022). "Validation of a Deficit-Accumulation Frailty Index in the ASPirin in Reducing Events in the Elderly Study and Its Predictive Capacity for Disability-Free Survival". The Journals of Gerontology: Series A. 77 (1): 19–26. doi:10.1093/gerona/glab225. PMC 8751791. PMID 34338761.
  13. ^ Greco EA, Pietschmann P, Migliaccio S (2019-04-24). "Osteoporosis and Sarcopenia Increase Frailty Syndrome in the Elderly". Frontiers in Endocrinology. 10: 255. doi:10.3389/fendo.2019.00255. PMC 6491670. PMID 31068903.
  14. ^ Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. (July 2010). "Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People". Age and Ageing. 39 (4): 412–423. doi:10.1093/ageing/afq034. PMC 2886201. PMID 20392703.
  15. ^ Peterson SJ, Mozer M (February 2017). "Differentiating Sarcopenia and Cachexia Among Patients With Cancer". Nutrition in Clinical Practice. 32 (1): 30–39. doi:10.1177/0884533616680354. PMID 28124947. S2CID 206555460.
  16. ^ "Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group". World Health Organization Technical Report Series. 843: 1–129. 1994. PMID 7941614.
  17. ^ Li G, Thabane L, Papaioannou A, Ioannidis G, Levine MA, Adachi JD (December 2017). "An overview of osteoporosis and frailty in the elderly". BMC Musculoskeletal Disorders. 18 (1): 46. doi:10.1186/s12891-017-1403-x. PMC 5270357. PMID 28125982.
  18. ^ Makizako H, Kubozono T, Kiyama R, Takenaka T, Kuwahata S, Tabira T, et al. (January 2019). "Associations of social frailty with loss of muscle mass and muscle weakness among community-dwelling older adults". Geriatrics & Gerontology International. 19 (1): 76–80. doi:10.1111/ggi.13571. PMID 30575241.
  19. ^ Pandey A, Kitzman D, Reeves G (December 2019). "Frailty Is Intertwined With Heart Failure: Mechanisms, Prevalence, Prognosis, Assessment, and Management". JACC. Heart Failure. 7 (12): 1001–1011. doi:10.1016/j.jchf.2019.10.005. PMC 7098068. PMID 31779921.
  20. ^ Mutz J, Choudhury U, Zhao J, Dregan A (August 2022). "Frailty in individuals with depression, bipolar disorder and anxiety disorders: longitudinal analyses of all-cause mortality". BMC Medicine. 20 (1): 274. doi:10.1186/s12916-022-02474-2. PMC 9425946. PMID 36038880.
  21. ^ a b c Fried LP, Xue QL, Cappola AR, Ferrucci L, Chaves P, Varadhan R, et al. (October 2009). "Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (10): 1049–57. doi:10.1093/gerona/glp076. PMC 2737590. PMID 19567825.
  22. ^ Chen X, Mao G, Leng SX (2014-03-19). "Frailty syndrome: an overview". Clinical Interventions in Aging. 9: 433–441. doi:10.2147/CIA.S45300. PMC 3964027. PMID 24672230.
  23. ^ Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, et al. (November 2002). "Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study". Archives of Internal Medicine. 162 (20): 2333–41. doi:10.1001/archinte.162.20.2333. PMID 12418947.
  24. ^ Ferrucci L, Penninx BW, Volpato S, Harris TB, Bandeen-Roche K, Balfour J, et al. (December 2002). "Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels". Journal of the American Geriatrics Society. 50 (12): 1947–54. doi:10.1046/j.1532-5415.2002.50605.x. PMID 12473005. S2CID 30586299.
  25. ^ a b c Chaves PH, Semba RD, Leng SX, Woodman RC, Ferrucci L, Guralnik JM, et al. (June 2005). "Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: the Women's Health and Aging Studies I and II". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 60 (6): 729–735. doi:10.1093/gerona/60.6.729. PMID 15983175.
  26. ^ a b Roy CN (February 2011). "Anemia in frailty". Clinics in Geriatric Medicine. 27 (1): 67–78. doi:10.1016/j.cger.2010.08.005. PMC 2998908. PMID 21093723.
  27. ^ a b Cappola AR, Xue QL, Fried LP (February 2009). "Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women's Health and Aging studies". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (2): 243–8. doi:10.1093/gerona/gln026. PMC 2655016. PMID 19182229.
  28. ^ Varadhan R, Walston J, Cappola AR, Carlson MC, Wand GS, Fried LP (February 2008). "Higher levels and blunted diurnal variation of cortisol in frail older women". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 63 (2): 190–5. doi:10.1093/gerona/63.2.190. PMID 18314456.
  29. ^ Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD, et al. (April 2007). "Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study". Archives of Internal Medicine. 167 (7): 635–641. doi:10.1001/archinte.167.7.635. PMID 17420420.
  30. ^ Zaslavsky O, Walker RL, Crane PK, Gray SL, Larson EB (September 2016). "Glucose Levels and Risk of Frailty". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 71 (9): 1223–9. doi:10.1093/gerona/glw024. PMC 4978362. PMID 26933160.
  31. ^ Wang GC, Talor MV, Rose NR, Cappola AR, Chiou RB, Weiss C, et al. (March 2010). "Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling older women". The Journal of Clinical Endocrinology and Metabolism. 95 (3): 1161–8. doi:10.1210/jc.2009-1991. PMC 2841533. PMID 20061418.
  32. ^ Yao X, Li H, Leng SX (February 2011). "Inflammation and immune system alterations in frailty". Clinics in Geriatric Medicine. 27 (1): 79–87. doi:10.1016/j.cger.2010.08.002. PMC 3011971. PMID 21093724.
  33. ^ Semba RD, Ferrucci L, Sun K, Walston J, Varadhan R, Guralnik JM, et al. (December 2007). "Oxidative stress and severe walking disability among older women". The American Journal of Medicine. 120 (12): 1084–9. doi:10.1016/j.amjmed.2007.07.028. PMC 2423489. PMID 18060930.
  34. ^ Varadhan R, Seplaki CL, Xue QL, Bandeen-Roche K, Fried LP (November 2008). "Stimulus-response paradigm for characterizing the loss of resilience in homeostatic regulation associated with frailty". Mechanisms of Ageing and Development. 129 (11): 666–670. doi:10.1016/j.mad.2008.09.013. PMC 2650618. PMID 18938195.
  35. ^ Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, et al. (March 2006). "Phenotype of frailty: characterization in the women's health and aging studies". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 61 (3): 262–6. doi:10.1093/gerona/61.3.262. PMID 16567375.
  36. ^ Kravvariti E, Ntouros PA, Vlachogiannis NI, Pappa M, Souliotis VL, Sfikakis PP (March 2023). "Geriatric Frailty Is Associated With Oxidative Stress, Accumulation, and Defective Repair of DNA Double-Strand Breaks Independently of Age and Comorbidities". J Gerontol A Biol Sci Med Sci. 78 (4): 603–610. doi:10.1093/gerona/glac214. PMID 36209410.
  37. ^ de Vries NM, Staal JB, van Ravensberg CD, Hobbelen JS, Olde Rikkert MG, Nijhuis-van der Sanden MW (January 2011). "Outcome instruments to measure frailty: a systematic review". Ageing Research Reviews. 10 (1): 104–114. doi:10.1016/j.arr.2010.09.001. PMID 20850567. S2CID 28785385.
  38. ^ Cesari M, Gambassi G, van Kan GA, Vellas B (January 2014). "The frailty phenotype and the frailty index: different instruments for different purposes". Age and Ageing. 43 (1): 10–12. doi:10.1093/ageing/aft160. PMID 24132852.
  39. ^ a b c Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. (March 2001). "Frailty in older adults: evidence for a phenotype". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 56 (3): M146–M156. doi:10.1093/gerona/56.3.m146. PMID 11253156.
  40. ^ a b Rockwood K, Mitnitski A (July 2007). "Frailty in relation to the accumulation of deficits". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 62 (7): 722–7. doi:10.1093/gerona/62.7.722. PMID 17634318.
  41. ^ Rockwood K, Andrew M, Mitnitski A (July 2007). "A comparison of two approaches to measuring frailty in elderly people". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 62 (7): 738–743. doi:10.1093/gerona/62.7.738. PMID 17634321.
  42. ^ Soong JT (2011). "Re: Functional assessment in older people". BMJ. 343: d4681. doi:10.1136/bmj.d4681. PMID 21859792. Retrieved 9 March 2024.
  43. ^ Soong J, Poots AJ, Scott S, Donald K, Woodcock T, Lovett D, et al. (October 2015). "Quantifying the prevalence of frailty in English hospitals". BMJ Open. 5 (10): e008456. doi:10.1136/bmjopen-2015-008456. PMC 4621378. PMID 26490097.
  44. ^ Soong J, Poots AJ, Scott S, Donald K, Bell D (October 2015). "Developing and validating a risk prediction model for acute care based on frailty syndromes". BMJ Open. 5 (10): e008457. doi:10.1136/bmjopen-2015-008457. PMC 4621379. PMID 26490098.
  45. ^ Sunkersing D, Martin FC, Reed J, Woringer M, Bell D (March 2019). "What do care home managers believe constitutes an 'assessment for frailty' of care home residents in North-West London? A survey". BMC Geriatrics. 19 (1): 62. doi:10.1186/s12877-019-1083-5. PMC 6397475. PMID 30823874.
  46. ^ Romero-Ortuno R, Walsh CD, Lawlor BA, Kenny RA (August 2010). "A frailty instrument for primary care: findings from the Survey of Health, Ageing and Retirement in Europe (SHARE)". BMC Geriatrics. 10 (1): 57. doi:10.1186/1471-2318-10-57. PMC 2939541. PMID 20731877.
  47. ^ "Tools for Clinical History-Taking". British Geriatrics Society. Retrieved 2024-07-31.
  48. ^ Cappe M, Laterre PF, Dechamps M (February 2023). "Preoperative frailty screening, assessment and management". Current Opinion in Anesthesiology. 36 (1): 83–88. doi:10.1097/ACO.0000000000001221. PMC 9794163. PMID 36476726.
  49. ^ Walsh B, Fogg C, Harris S, Roderick P, de Lusignan S, England T, et al. (May 2023). "Frailty transitions and prevalence in an ageing population: longitudinal analysis of primary care data from an open cohort of adults aged 50 and over in England, 2006-2017". Age and Ageing. 52 (5): afad058. doi:10.1093/ageing/afad058. PMC 10158172. PMID 37140052.
  50. ^ Whitson HE, Cohen HJ, Schmader KE, Morey MC, Kuchel G, Colon-Emeric CS (August 2018). "Physical Resilience: Not Simply the Opposite of Frailty". Journal of the American Geriatrics Society. 66 (8): 1459–61. doi:10.1111/jgs.15233. PMC 6157007. PMID 29577234.
  51. ^ Xue QL (February 2011). "The frailty syndrome: definition and natural history". Clinics in Geriatric Medicine. 27 (1): 1–15. doi:10.1016/j.cger.2010.08.009. PMC 3028599. PMID 21093718.
  52. ^ Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL, et al. (August 2005). "Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study". Journal of the American Geriatrics Society. 53 (8): 1321–30. doi:10.1111/j.1532-5415.2005.53405.x. PMID 16078957. S2CID 2191077.
  53. ^ Sallis JF (September 2000). "Age-related decline in physical activity: a synthesis of human and animal studies". Medicine and Science in Sports and Exercise. 32 (9): 1598–1600. doi:10.1097/00005768-200009000-00012. PMID 10994911.
  54. ^ a b Nascimento CM, Ingles M, Salvador-Pascual A, Cominetti MR, Gomez-Cabrera MC, Viña J (February 2019). "Sarcopenia, frailty and their prevention by exercise". Free Radical Biology & Medicine. 132: 42–49. doi:10.1016/j.freeradbiomed.2018.08.035. PMID 30176345. S2CID 52147328.
  55. ^ Serra-Prat M, Sist X, Domenich R, Jurado L, Saiz A, Roces A, et al. (May 2017). "Effectiveness of an intervention to prevent frailty in pre-frail community-dwelling older people consulting in primary care: a randomised controlled trial". Age and Ageing. 46 (3): 401–7. doi:10.1093/ageing/afw242. PMID 28064172.
  56. ^ Cadore EL, Sáez de Asteasu ML, Izquierdo M (July 2019). "Multicomponent exercise and the hallmarks of frailty: Considerations on cognitive impairment and acute hospitalization". Experimental Gerontology. 122: 10–14. doi:10.1016/j.exger.2019.04.007. PMID 30995516.
  57. ^ Feart C (December 2019). "Nutrition and frailty: Current knowledge". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 95: 109703. doi:10.1016/j.pnpbp.2019.109703. PMID 31325470. S2CID 197464368.
  58. ^ Ni Lochlainn M, Cox NJ, Wilson T, Hayhoe RP, Ramsay SE, Granic A, et al. (July 2021). "Nutrition and Frailty: Opportunities for Prevention and Treatment". Nutrients. 13 (7): 2349. doi:10.3390/nu13072349. PMC 8308545. PMID 34371858.
  59. ^ Dent E, Morley JE, Cruz-Jentoft AJ, Woodhouse L, Rodríguez-Mañas L, Fried LP, et al. (2019-11-01). "Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management". The Journal of Nutrition, Health & Aging. 23 (9): 771–787. doi:10.1007/s12603-019-1273-z. PMC 6800406. PMID 31641726.
  60. ^ Apóstolo J, Cooke R, Bobrowicz-Campos E, Santana S, Marcucci M, Cano A, et al. (January 2018). "Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults: a systematic review". JBI Database of Systematic Reviews and Implementation Reports. 16 (1): 140–232. doi:10.11124/JBISRIR-2017-003382. PMC 5771690. PMID 29324562.
  61. ^ Treacy D, Hassett L, Schurr K, Fairhall NJ, Cameron ID, Sherrington C, et al. (Cochrane Musculoskeletal Group) (June 2022). "Mobility training for increasing mobility and functioning in older people with frailty". The Cochrane Database of Systematic Reviews. 2022 (6): CD010494. doi:10.1002/14651858.CD010494.pub2. PMC 9245897. PMID 35771806.
  62. ^ De Coninck L, Bekkering GE, Bouckaert L, Declercq A, Graff MJ, Aertgeerts B (August 2017). "Home- and Community-Based Occupational Therapy Improves Functioning in Frail Older People: A Systematic Review". Journal of the American Geriatrics Society. 65 (8): 1863–9. doi:10.1111/jgs.14889. PMID 28369719. S2CID 25247416.
  63. ^ Milne AC, Potter J, Vivanti A, Avenell A (April 2009). "Protein and energy supplementation in elderly people at risk from malnutrition". The Cochrane Database of Systematic Reviews. 2009 (2): CD003288. doi:10.1002/14651858.CD003288.pub3. PMC 7144819. PMID 19370584.
  64. ^ Manfredi PL, Morrison RS, Morris J, Goldhirsch SL, Carter JM, Meier DE (September 2000). "Palliative care consultations: how do they impact the care of hospitalized patients?". Journal of Pain and Symptom Management. 20 (3): 166–173. doi:10.1016/s0885-3924(00)00163-9. PMID 11018334.
  65. ^ Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA, et al. (March 2014). "Frailty assessment in the cardiovascular care of older adults". Journal of the American College of Cardiology. 63 (8): 747–762. doi:10.1016/j.jacc.2013.09.070. PMC 4571179. PMID 24291279.
  66. ^ a b Makary MA, Segev DL, Pronovost PJ, Syin D, Bandeen-Roche K, Patel P, et al. (June 2010). "Frailty as a predictor of surgical outcomes in older patients". Journal of the American College of Surgeons. 210 (6): 901–8. doi:10.1016/j.jamcollsurg.2010.01.028. PMID 20510798.
  67. ^ a b Weaver DJ, Malik AT, Jain N, Yu E, Kim J, Khan SN (April 2019). "The Modified 5-Item Frailty Index: A Concise and Useful Tool for Assessing the Impact of Frailty on Postoperative Morbidity Following Elective Posterior Lumbar Fusions". World Neurosurgery. 124: e626–e632. doi:10.1016/j.wneu.2018.12.168. PMID 30639495.
  68. ^ Garonzik-Wang JM, Govindan P, Grinnan JW, Liu M, Ali HM, Chakraborty A, et al. (February 2012). "Frailty and delayed graft function in kidney transplant recipients". Archives of Surgery. 147 (2): 190–3. doi:10.1001/archsurg.2011.1229. PMID 22351919.
  69. ^ Lee AC, Lee SM, Ferguson MK (November 2022). "Frailty Is Associated With Adverse Postoperative Outcomes After Lung Cancer Resection". JTO Clinical and Research Reports. 3 (11): 100414. doi:10.1016/j.jtocrr.2022.100414. PMC 9634029. PMID 36340797.
  70. ^ O'Caoimh R, Sezgin D, O'Donovan MR, Molloy DW, Clegg A, Rockwood K, et al. (January 2021). "Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies". Age and Ageing. 50 (1): 96–104. doi:10.1093/ageing/afaa219. hdl:10468/11159. PMID 33068107.
  71. ^ Niederstrasser NG, Rogers NT, Bandelow S (2019-10-30). "Determinants of frailty development and progression using a multidimensional frailty index: Evidence from the English Longitudinal Study of Ageing". PLOS ONE. 14 (10): e0223799. Bibcode:2019PLoSO..1423799N. doi:10.1371/journal.pone.0223799. PMC 6821067. PMID 31665163.
  72. ^ Garcia-Garcia FJ, Gutierrez Avila G, Alfaro-Acha A, Amor Andres MS, De Los Angeles De La Torre Lanza M, Escribano Aparicio MV, et al. (December 2011). "The prevalence of frailty syndrome in an older population from Spain. The Toledo Study for Healthy Aging". The Journal of Nutrition, Health & Aging. 15 (10): 852–6. doi:10.1007/s12603-011-0075-8. PMID 22159772.
  73. ^ Casas-Herrero A, Cadore EL, Zambom-Ferraresi F, Idoate F, Millor N, Martínez-Ramirez A, et al. (October 2013). "Functional capacity, muscle fat infiltration, power output, and cognitive impairment in institutionalized frail oldest old". Rejuvenation Research. 16 (5): 396–403. doi:10.1089/rej.2013.1438. PMC 3804230. PMID 23822577.
  74. ^ Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G (March 2004). "Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 59 (3): 255–263. doi:10.1093/gerona/59.3.m255. PMID 15031310.
  75. ^ Chaves PH, Varadhan R, Lipsitz LA, Stein PK, Windham BG, Tian J, et al. (September 2008). "Physiological complexity underlying heart rate dynamics and frailty status in community-dwelling older women". Journal of the American Geriatrics Society. 56 (9): 1698–1703. doi:10.1111/j.1532-5415.2008.01858.x. PMC 2848445. PMID 19166446.
  76. ^ Varadhan R, Chaves PH, Lipsitz LA, Stein PK, Tian J, Windham BG, et al. (June 2009). "Frailty and impaired cardiac autonomic control: new insights from principal components aggregation of traditional heart rate variability indices". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (6): 682–7. doi:10.1093/gerona/glp013. PMC 2679422. PMID 19223607.
  77. ^ Blaum CS, Xue QL, Michelon E, Semba RD, Fried LP (June 2005). "The association between obesity and the frailty syndrome in older women: the Women's Health and Aging Studies". Journal of the American Geriatrics Society. 53 (6): 927–934. doi:10.1111/j.1532-5415.2005.53300.x. hdl:2027.42/65446. PMID 15935013. S2CID 231645.
  78. ^ Shardell M, Hicks GE, Miller RR, Kritchevsky S, Andersen D, Bandinelli S, et al. (January 2009). "Association of low vitamin D levels with the frailty syndrome in men and women". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (1): 69–75. doi:10.1093/gerona/gln007. PMC 2691187. PMID 19164273.
  79. ^ Xue QL, Fried LP, Glass TA, Laffan A, Chaves PH (January 2008). "Life-space constriction, development of frailty, and the competing risk of mortality: the Women's Health And Aging Study I". American Journal of Epidemiology. 167 (2): 240–8. doi:10.1093/aje/kwm270. PMID 17906296.
  80. ^ Jakubiak GK, Pawlas N, Cieślar G, Stanek A (December 2020). "Chronic Lower Extremity Ischemia and Its Association with the Frailty Syndrome in Patients with Diabetes". International Journal of Environmental Research and Public Health. 17 (24): 9339. doi:10.3390/ijerph17249339. PMC 7764849. PMID 33327401.
  81. ^ Newman AB, Gottdiener JS, Mcburnie MA, Hirsch CH, Kop WJ, Tracy R, et al. (March 2001). "Associations of subclinical cardiovascular disease with frailty". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 56 (3): M158–M166. doi:10.1093/gerona/56.3.M158. PMID 11253157.
  82. ^ Mutz J, Choudhury U, Zhao J, Dregan A (August 2022). "Frailty in individuals with depression, bipolar disorder and anxiety disorders: longitudinal analyses of all-cause mortality". BMC Medicine. 20 (1): 274. doi:10.1186/s12916-022-02474-2. PMC 9425946. PMID 36038880.
  83. ^ Sadler E, Khadjesari Z, Ziemann A, Sheehan KJ, Whitney J, Wilson D, et al. (May 2023). "Case management for integrated care of older people with frailty in community settings". The Cochrane Database of Systematic Reviews. 2023 (5): CD013088. doi:10.1002/14651858.CD013088.pub2. PMC 10204122. PMID 37218645.
  84. ^ Gordon EH, Peel NM, Samanta M, Theou O, Howlett SE, Hubbard RE (March 2017). "Sex differences in frailty: A systematic review and meta-analysis". Experimental Gerontology. 89: 30–40. doi:10.1016/j.exger.2016.12.021. PMID 28043934. S2CID 4652963.
  85. ^ O'Caoimh R, Sezgin D, O'Donovan MR, Molloy DW, Clegg A, Rockwood K, et al. (January 2021). "Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies". Age and Ageing. 50 (1): 96–104. doi:10.1093/ageing/afaa219. hdl:10468/11159. PMID 33068107.
  86. ^ Kane AE, Howlett SE (September 2021). "Sex differences in frailty: Comparisons between humans and preclinical models". Mechanisms of Ageing and Development. 198: 111546. doi:10.1016/j.mad.2021.111546. PMID 34324923.
  87. ^ Zeidan RS, McElroy T, Rathor L, Martenson MS, Lin Y, Mankowski RT (December 2023). "Sex differences in frailty among older adults". Experimental Gerontology. 184: 112333. doi:10.1016/j.exger.2023.112333. PMID 37993077.
  88. ^ de Jong JC, Verschuren L, Caspers MP, van der Hoek MD, van der Leij FR, Kleemann R, et al. (July 2023). "Evidence for sex-specific intramuscular changes associated to physical weakness in adults older than 75 years". Biology of Sex Differences. 14 (1): 45. doi:10.1186/s13293-023-00531-w. PMC 10332038. PMID 37430322.
  89. ^ Usher T, Buta B, Thorpe RJ, Huang J, Samuel LJ, Kasper JD, et al. (January 2021). "Dissecting the Racial/Ethnic Disparity in Frailty in a Nationally Representative Cohort Study with Respect to Health, Income, and Measurement". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 76 (1): 69–76. doi:10.1093/gerona/glaa061. PMC 7756712. PMID 32147727.
  90. ^ Clinical trial number NCT04524247 for "Frailty and Physician Modified Fenestrated Endograft for Thoracoabdominal Aortic Pathologies" at ClinicalTrials.gov
  91. ^ Clinical trial number NCT04954690 for "Structured Program of Exercise for Recipients of Kidney Transplantation (SPaRKT)" at ClinicalTrials.gov
  92. ^ Clinical trial number NCT02711709 for "Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care and Induced Frailty" at ClinicalTrials.gov
  93. ^ Clinical trial number NCT03675724 for "Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults (AFFIRM-LITE)" at ClinicalTrials.gov
  94. ^ Clinical trial number NCT05166863 for "Physical Performance Testing and Frailty in Prediction of Early Postoperative Course After Cardiac Surgery (Cardiostep)" at ClinicalTrials.gov
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