Frailty syndrome

Frailty is a common geriatric syndrome that embodies an elevated risk of catastrophic declines in health and function among older adults. Frailty is a condition associated with ageing, and it has been recognized for centuries. As described by Shakespeare in As You Like It, "the sixth age shifts into the lean and slipper’d pantaloon, with spectacles on nose and pouch on side, his youthful hose well sav’d, a world too wide, for his shrunk shank…". The shrunk shank is a result of loss of muscle with aging. 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.

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.[1]

Epidemiology

Frailty is a common geriatric syndrome. Estimates of frailty's 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),[1] prevalence estimates of 7-16% have been reported in non-institutionalized, community-dwelling older adults.

The occurrence of frailty increases incrementally with advancing age, and 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;[2] (b) physiologic impairments, such as activation of inflammation and coagulation systems,[3] anemia,[4][5] atherosclerosis,[6] autonomic dysfunction,[4][7] hormonal abnormalities,[8] obesity,[9] hypovitaminosis D in men,[10] and environment-related factors such as life space and neighborhood characteristics.[11] 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.

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.[12] 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 [13] and eventually results in frailty typically manifesting as a syndrome of a constellation of weakness, slowness, reduced activity, low energy and unintended weight loss.[14] When most severe, i.e. when 3 or more of these manifestations are present, the individual is at a high risk of death.

Assessment of geriatric frailty

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).[15]

Two key approaches are discussed below:

Linda Fried / Johns Hopkins Frailty Criteria

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:

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),[14] 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)[1] 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.

Rockwood Frailty Index

Another notable approach to the assessment of geriatric frailty (if not also to some degree its conceptualization) is that of Rockwood and Mitnitski (2007)[16] 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)[17] 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.[18] This conceptualisation could be viewed as blending the phenotypic and index models. Researchers tested this model for signal in routinely collected hospital data,[19] and then used this signal in the development of a frailty model, finding even predictive capability across 3 outcomes of care.[20]

Biological underpinnings

It has been suggested that the biological underpinnings of frailty are multifactorial, involving dysregulation across many physiological systems.[13] A proinflammatory state,[3] sarcopenia,[21] anemia,[4][5] relative deficiencies in anabolic hormones (androgens and growth hormone)[8] and excess exposure to catabolic hormones (cortisol),[22] insulin resistance,[23] compromised altered immune function,[24][25] micronutrient deficiencies and oxidative stress[26] are each individually associated with a higher likelihood of frailty. Additional findings show that the risk of frailty increases with the number of dysregulated physiological systems in a nonlinear pattern, independent of chronic diseases and chronologic age, suggesting synergistic effects of individual abnormalities that on their own may be relatively mild.[13] The clinical implication of this finding is that interventions that affect multiple systems may yield greater, synergistic benefits in prevention and treatment of frailty than interventions that affect only one system.

Associations between specific disease states are also associated with and frailty have also been observed, including cardiovascular disease, diabetes mellitus, renal insufficiency and other diseases in which inflammation is prominent. To the extent that dysregulation across several physiologic systems underlie the pathogenesis of the frailty, specific disease states are likely concurrent manifestations of the underlying impaired physiologic function and regulation. 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.

Components

Sarcopenia

Sarcopenia (from the Greek meaning "poverty of flesh") refers to loss of muscle mass that occurs as a result of old age. It is characterized first by a decrease in muscle mass, which causes weakness and frailty. However, this loss of muscle mass may be caused by different cellular mechanisms than those that cause muscle atrophy. For example, during sarcopenia, there is a replacement of muscle fibres with fat and an increase in fibrosis.

Osteoporosis

Osteoporosis causes a hunched-over appearance in some people.

Osteoporosis is an age-related disease of bone that leads to an increased risk of fracture. In osteoporosis the bone mineral density (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 (WHO) in women as a bone mineral density 2.5 standard deviations 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.[27]

Osteoporosis is most common in women after menopause, 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 glucocorticoids, when the disease is called steroid- or glucocorticoid-induced osteoporosis (SIOP or GIOP). Given its influence in the risk of fragility fracture, osteoporosis may significantly affect life expectancy and quality of life.

Muscle weakness

Muscle weakness, also known as muscle fatigue, (or "lack of strength") refers to the inability to exert force with one's skeletal muscles. Weakness often follows muscle atrophy 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.

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

A test of strength is often used during a diagnosis of a muscular disorder before the etiology 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.[28] 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.

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.[29] Assessment of older patients before elective surgeries can accurately predict the patients' recovery trajectories.[30] The most widely used frailty scale consists of five items:[1]

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.[30] 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.

References

  1. 1 2 3 4 5 Fried, LP; Tangen, CM; Walston, J; Newman, AB, Hirsch, C, Gottdiener, J, Seeman, T, Tracy, R, Kop, WJ, Burke, G, McBurnie, MA (Mar 2001). "Frailty in older adults: evidence for a phenotype". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 56 (3): M146–56. doi:10.1093/gerona/56.3.m146. PMID 11253156.
  2. ↑ 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.". J Gerontol A Biol Sci Med Sci. 59 (3): 255–63. PMID 15031310.
  3. 1 2 Walston, J; McBurnie, MA; Newman, A; Tracy, RP; Kop, WJ; Hirsch, CH; Gottdiener, J; Fried, LP; Cardiovascular Health Study (Nov 2002). "Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study". Arch Intern Med 162 (20): 2333–2341. doi:10.1001/archinte.162.20.2333. PMID 12418947.
  4. 1 2 3 Chaves, PH; Semba, RD; Leng, SX; Woodman, RC; Ferrucci, L; Guralnik, JM; Fried, LP (Jun 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". J Gerontol A Biol Sci Med Sci 60 (6): 729–35. doi:10.1093/gerona/60.6.729. PMID 1598317.
  5. 1 2 Roy, CN (Feb 2011). "Anemia in frailty.". Clin Geriatr Med. 27 (1): 67–78. doi:10.1016/j.cger.2010.08.005. PMC 2998908. PMID 21093723.
  6. ↑ Chaves, PH; Varadhan, R; Lipsitz, LA; Stein, PK; Windham, BG; Tian, J; Fleisher, LA; Guralnik, JM; Fried, LP (Sep 2008). "Physiological complexity underlying heart rate dynamics and frailty status in community-dwelling older women.". J Am Geriatr Soc. 56 (9): 1698–703. doi:10.1111/j.1532-5415.2008.01858.x. PMC 2848445. PMID 19166446.
  7. ↑ Varadhan, R; Chaves PH; Lipsitz LA; Stein PK; Tian J; Windham BG; Berger RD; Fried LP. (Jun 2009). "Frailty and impaired cardiac autonomic control: new insights from principal components aggregation of traditional heart rate variability indices.". J Gerontol A Biol Sci Med Sci. 64 (6): 682–7. doi:10.1093/gerona/glp013. PMC 2679422. PMID 19223607.
  8. 1 2 Cappola, AR; Xue QL; Fried LP. (Feb 2009). "Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women's Health and Aging studies.". J Gerontol A Biol Sci Med Sci. 64 (2): 243–8. doi:10.1093/gerona/gln026. PMC 2655016. PMID 19182229.
  9. ↑ Blaum, CS; Xue QL; Michelon E; Semba RD; Fried LP (Jun 2005). "The association between obesity and the frailty syndrome in older women: the Women's Health and Aging Studies". J Am Geriatr Soc. 53 (6): 927–34. doi:10.1111/j.1532-5415.2005.53300.x. PMID 15935013.
  10. ↑ Shardell, M; Hicks GE; Miller RR; Kritchevsky S; Andersen D; Bandinelli S; Cherubini A; Ferrucci L (Jan 2009). "Association of low vitamin D levels with the frailty syndrome in men and women". J Gerontol A Biol Sci Med Sci 64 (1): 69–75. doi:10.1093/gerona/gln007. PMC 2691187. PMID 19164273.
  11. ↑ Xue, QL; Fried LP; Glass TA; Laffan A; Chaves PH (Jan 2008). "Life-space constriction, development of frailty, and the competing risk of mortality: the Women's Health And Aging Study I". Am J Epidemiol. 167 (2): 240–8. doi:10.1093/aje/kwm270. PMID 17906296.
  12. ↑ Varadhan, R; Seplaki CL; Xue QL; Bandeen-Roche K; Fried LP (Nov 2008). "Stimulus-response paradigm for characterizing the loss of resilience in homeostatic regulation associated with frailty". Mech Ageing Dev. 129 (11): 666–70. doi:10.1016/j.mad.2008.09.013. PMC 2650618. PMID 18938195.
  13. 1 2 3 Fried, LP; Xue QL; Cappola AR; Ferrucci L; Chaves P; Varadhan R; Guralnik JM; Leng SX; Semba RD; Walston JD; Blaum CS; Bandeen-Roche K (Oct 2009). "Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment". J Gerontol A Biol Sci Med Sci 64 (10): 1049–57. doi:10.1093/gerona/glp076. PMC 2737590. PMID 19567825.
  14. 1 2 Bandeen-Roche, K; Xue QL; Ferrucci L; Walston J; Guralnik JM; Chaves P; Zeger SL; Fried LP (Mar 2006). "Phenotype of frailty: characterization in the women's health and aging studies". J Gerontol A Biol Sci Med Sci 61 (3): 262–6. PMID 16567375.
  15. ↑ de Vries, NM; Staal, JB; van Ravensberg, CD; Hobbelen, JS; Olde Rikkert, MG; Nijhuis-van der Sanden, MW (Jan 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.
  16. ↑ Rockwood, K; Mitnitski A (Jul 2007). "Frailty in relation to the accumulation of deficits". J Gerontol A Biol Sci Med Sci 62 (7): 722–7. PMID 17634318.
  17. ↑ Rockwood, K; Andrew M; Mitnitski A (Jul 2007). "A comparison of two approaches to measuring frailty in elderly people". J Gerontol A Biol Sci Med Sci 62 (7): 738–43. PMID 17634321.
  18. ↑ Soong, J. "Re: Functional assessment in older people". BMJ.
  19. ↑ Soong, J; Poots, AJ; Scott, S; Donald, K; Woodcock, T; Lovett, D; Bell, D (21 October 2015). "Quantifying the prevalence of frailty in English hospitals". BMJ Open 5 (10): e008456. doi:10.1136/bmjopen-2015-008456.
  20. ↑ Soong, J; Poots, A J; Scott, S; Donald, K; Bell, D (21 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.
  21. ↑ Ferrucci, Luigi; Penninx BW; Volpato S; et al. (2002). "Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels.". J Am Geriatr Soc 50: 1947–54. doi:10.1046/j.1532-5415.2002.50605.x.
  22. ↑ Varadhan, Ravi; Walston J; Cappola AR; Carlson MC; Wand GS; Fried LP (2008). "Higher Levels and Blunted Diurnal Variation of Cortisol in Frail Older Women.". J Gerontol A Biol Sci Med Sci 63: 190–195. doi:10.1093/gerona/63.2.190.
  23. ↑ Barzilay, JI; Blaum C; Moore T; et al. (2007). "Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study.". Arch Intern Med 167: 635–641. doi:10.1001/archinte.167.7.635.
  24. ↑ Wang, George C; Talor MV; Rose NR; et al. (2010). "Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling older women.". J Clin Endocrinol Metab 95: 1161–8. doi:10.1210/jc.2009-1991.
  25. ↑ Yao, X; Li H; Leng SX. (2011). "Inflammation and immune system alterations in frailty.". Clin Geriatr Med. 27 (1): 79–87. doi:10.1016/j.cger.2010.08.002. PMID 21093724.
  26. ↑ Semba, Richard D.; Ferrucci L; Sun K; Walston J; Varadhan R; Guralnik JM; Fried LP. (Dec 2007). "Oxidative stress and severe walking disability among older women.". Am J Med. 120 (12): 1084–9. doi:10.1016/j.amjmed.2007.07.028. PMID 18060930.
  27. ↑ WHO (1994). "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. PMID 7941614.
  28. ↑ Muscle Weakness Coding Checklist by Jun Mapili, PT, MAEd
  29. ↑ Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA5, Popma JJ, Ferrucci L, Forman DE (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. PMID 24291279.
  30. 1 2 Makary MA, Segev DL, Pronovost PJ, et al. (June 2010). "Frailty as a predictor of surgical outcomes in older patients". J. Am. Coll. Surg. 210 (6): 901–8. doi:10.1016/j.jamcollsurg.2010.01.028. PMID 20510798. Lay summary (28 December 2010).
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