Frailty: Past, present, and future?

Dongmin Kwak, LaDora V Thompson, Dongmin Kwak, LaDora V Thompson

Abstract

The prevalence of frailty across the world in older adults is increasing dramatically and having frailty places a person at increased risk for many adverse health outcomes, including impaired mobility, falls, hospitalizations, and mortality. Globally, the concept of frailty is gaining attention and the scientific field has made great strides in identifying and conceptually defining frailty through consensus conferences, in advancing the overall science of frailty by drawing on basic science discoveries including concepts surrounding the hallmarks of aging, resilience, and intrinsic capacities, and in identifying the many challenges faced by professionals within diverse clinical settings. Currently, it is thought that frailty is preventable, thus the identification of a person's degree of frailty is vital. Identification of frailty is achievable through widely used frailty screening tools, which are valid, reliable, and easy to use. Following the identification of a person's degree of frailty, targeted intervention strategies, such as physical activity programs must be implemented. In this perspective, we provide a historical perspective of the frailty field since the last quarter of the 20th century to present. We identify the proposed underlying pathophysiology of multiple physiological systems, including compromised homeostasis and resilience. Next, we outline the available screening tools for frailty with a physical performance assessment and highlight specific benefits of physical activity. Lastly, we discuss current scientific evidence supporting the physical activity recommendations for the aging population and for older adults with frailty. The goal is to emphasize early detection of frailty and stress the value of physical activity.

Keywords: 2018 PAGAC Scientific Report; Frailty phenotype; Intrinsic capacity; Multicomponent physical activity programs; Physical activity guidelines.

Conflict of interest statement

The authors have no conflict of interest to report.

© 2020 The Authors.

Figures

Fig. 1
Fig. 1
The hallmarks of aging and the seven pillars of aging outlined a basic set of interconnecting biological mechanisms to understand the processes of aging. These hallmarks and the pillars provide a roadmap to understand the underpinnings of frailty development and progression. Understanding the molecular biology of aging and frailty could lead to increasing physiological potential, physical resilience and intrinsic capacity.

References

    1. Mattson M.P., Arumugam T.V. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metabol. 2018;27(6):1176–1199. doi: 10.1016/j.cmet.2018.05.011.
    1. Ward B.W., Schiller J.S. Prevalence of multiple chronic conditions among US adults: estimates from the National Health Interview Survey, 2010. Prev Chronic Dis. 2013;10:E65. doi: 10.5888/pcd10.120203.
    1. Bandeen-Roche K., Seplaki C.L., Huang J., et al. Frailty in older adults: a nationally representative profile in the United States. J Gerontol A Biol Sci Med Sci. 2015;70(11):1427–1434. doi: 10.1093/gerona/glv133.
    1. Hale M., Shah S., Clegg A. Frailty, inequality and resilience. Clin Med. 2019;19(3):219–223. doi: 10.7861/clinmedicine.19-3-219.
    1. Garatachea N., Pareja-Galeano H., Sanchis-Gomar F., et al. Exercise attenuates the major hallmarks of aging. Rejuvenation Res. 2015;18(1):57–89. doi: 10.1089/rej.2014.1623.
    1. Stamford B.A. Physiological effects of training upon institutionalized geriatric men. J Gerontol. 1972;27(4):451–455. doi: 10.1093/geronj/27.4.451.
    1. Braun J.V., Wykle M.H., Cowling W.R., 3rd Failure to thrive in older persons: a concept derived. Gerontol. 1988;28(6):809–812. doi: 10.1093/geront/28.6.809.
    1. Fried L.P., Ferrucci L., Darer J., Williamson J.D., Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255–263. doi: 10.1093/gerona/59.3.m255.
    1. Winograd C.H., Gerety M.B., Chung M., Goldstein M.K., Dominguez F., Jr., Vallone R. Screening for frailty: criteria and predictors of outcomes. J Am Geriatr Soc. 1991;39(8):778–784. doi: 10.1111/j.1532-5415.1991.tb02700.x.
    1. Winograd C.H. Targeting strategies: an overview of criteria and outcomes. J Am Geriatr Soc. 1991;39(9 Pt 2):25S–35S. doi: 10.1111/j.1532-5415.1991.tb05930.x.
    1. Buchner D.M., Wagner E.H. Preventing frail health. Clin Geriatr Med. 1992;8(1):1–17.
    1. Bortz W.M., 2nd The physics of frailty. J Am Geriatr Soc. 1993;41(9):1004–1008.
    1. Rockwood K., Stadnyk K., MacKnight C., McDowell I., Hebert R., Hogan D.B. A brief clinical instrument to classify frailty in elderly people. Lancet. 1999;353(9148):205–206. doi: 10.1016/S0140-6736(98)04402-X.
    1. Campbell A.J., Buchner D.M. Unstable disability and the fluctuations of frailty. Age Ageing. 1997;26(4):315–318. doi: 10.1093/ageing/26.4.315.
    1. Hamerman D. Toward an understanding of frailty. Ann Intern Med. 1999;130(11):945–950. doi: 10.7326/0003-4819-130-11-199906010-00022.
    1. Sager M.A., Rudberg M.A., Jalaluddin M., et al. Hospital admission risk profile (HARP): identifying older patients at risk for functional decline following acute medical illness and hospitalization. J Am Geriatr Soc. 1996;44(3):251–257. doi: 10.1111/j.1532-5415.1996.tb00910.x.
    1. Corti M.C., Guralnik J.M., Salive M.E., Sorkin J.D. Serum albumin level and physical disability as predictors of mortality in older persons. J Am Med Assoc. 1994;272(13):1036–1042. doi: 10.1001/jama.1994.03520130074036.
    1. Fried L.P., Tangen C.M., Walston J., et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–M156. doi: 10.1093/gerona/56.3.m146.
    1. Mitnitski A.B., Mogilner A.J., Rockwood K. Accumulation of deficits as a proxy measure of aging. Scientific World J. 2001;1:323–336. doi: 10.1100/tsw.2001.58.
    1. Rockwood K., Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722–727. doi: 10.1093/gerona/62.7.722.
    1. Buta B.J., Walston J.D., Godino J.G., et al. Frailty assessment instruments: systematic characterization of the uses and contexts of highly-cited instruments. Ageing Res Rev. 2016;26:53–61. doi: 10.1016/j.arr.2015.12.003.
    1. Morley J.E., Vellas B., van Kan G.A., et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392–397. doi: 10.1016/j.jamda.2013.03.022.
    1. Walston J., Robinson T.N., Zieman S., et al. Integrating frailty research into the medical specialties-report from a U13 conference. J Am Geriatr Soc. 2017;65(10):2134–2139. doi: 10.1111/jgs.14902.
    1. Turner G., Clegg A., British Geriatrics S., Age Uk, Royal College of General P. Best practice guidelines for the management of frailty: a British geriatrics society, age UK and royal college of general practitioners report. Age Ageing. 2014;43(6):744–747. doi: 10.1093/ageing/afu138.
    1. Baumann C.W., Kwak D., Thompson L.V. Assessing Onset, Prevalence and Survival in Mice Using a Frailty Phenotype. Aging (Albany NY) 2018;10(12):4042–4053. doi: 10.18632/aging.101692.
    1. Baumann C.W., Kwak D., Thompson L.V. Sex-specific Components of Frailty in C57BL/6 Mice. Aging (Albany NY) 2019;11:5206–5214. doi: 10.18632/aging.102114.
    1. Liu H., Graber T.G., Ferguson-Stegall L., Thompson L.V. Clinically relevant frailty index for mice. J Gerontol A Biol Sci Med Sci. 2014;69(12):1485–1491. doi: 10.1093/gerona/glt188.
    1. Kwak D., Baumann C.W., Thompson L.V. Identifying characteristics of frailty in female mice using a phenotype Assessment tool. J Gerontol A Biol Sci Med Sci. 2019 doi: 10.1093/gerona/glz092.
    1. Hadley E.C., Kuchel G.A., Newman A.B. Workshop S, participants. Report: NIA workshop on measures of physiologic resiliencies in human aging. J Gerontol A Biol Sci Med Sci. 2017;72(7):980–990. doi: 10.1093/gerona/glx015.
    1. Whitson H.E., Cohen H.J., Schmader K.E., Morey M.C., Kuchel G., Colon-Emeric C.S. Physical resilience: not simply the opposite of frailty. J Am Geriatr Soc. 2018;66(8):1459–1461. doi: 10.1111/jgs.15233.
    1. van Abbema R., Bielderman A., De Greef M., Hobbelen H., Krijnen W., van der Schans C. Building from a conceptual model of the resilience process during ageing, towards the Groningen Aging Resilience Inventory. J Adv Nurs. 2015;71(9):2208–2219. doi: 10.1111/jan.12685.
    1. Whitson H.E., Duan-Porter W., Schmader K.E., Morey M.C., Cohen H.J., Colon-Emeric C.S. Physical resilience in older adults: systematic review and development of an emerging construct. J Gerontol A Biol Sci Med Sci. 2016;71(4):489–495. doi: 10.1093/gerona/glv202.
    1. Kirkland J.L., Stout M.B., Sierra F. Resilience in aging mice. J Gerontol A Biol Sci Med Sci. 2016;71(11):1407–1414. doi: 10.1093/gerona/glw086.
    1. LeBrasseur N.K. Physical resilience: opportunities and challenges in translation. J Gerontol A Biol Sci Med Sci. 2017;72(7):978–979. doi: 10.1093/gerona/glx028.
    1. Pallis A.G., Hatse S., Brouwers B., et al. Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging? J Geriatr Oncol. 2014;5(2):204–218. doi: 10.1016/j.jgo.2013.09.001.
    1. Vina J., Borras C., Gomez-Cabrera M.C. A free radical theory of frailty. Free Radic Biol Med. 2018;124:358–363. doi: 10.1016/j.freeradbiomed.2018.06.028.
    1. Clegg A., Young J., Iliffe S., Rikkert M.O., Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–762. doi: 10.1016/S0140-6736(12)62167-9.
    1. Feng Z., Lugtenberg M., Franse C., et al. Risk factors and protective factors associated with incident or increase of frailty among community-dwelling older adults: a systematic review of longitudinal studies. PloS One. 2017;12(6) doi: 10.1371/journal.pone.0178383.
    1. Boxer R.S., Dauser D.A., Walsh S.J., Hager W.D., Kenny A.M. The association between vitamin D and inflammation with the 6-minute walk and frailty in patients with heart failure. J Am Geriatr Soc. 2008;56(3):454–461. doi: 10.1111/j.1532-5415.2007.01601.x.
    1. Carcaillon L., Garcia-Garcia F.J., Tresguerres J.A., Gutierrez Avila G., Kireev R., Rodriguez-Manas L. Higher levels of endogenous estradiol are associated with frailty in postmenopausal women from the toledo study for healthy aging. J Clin Endocrinol Metab. 2012;97(8):2898–2906. doi: 10.1210/jc.2012-1271.
    1. Carcaillon L., Blanco C., Alonso-Bouzon C., Alfaro-Acha A., Garcia-Garcia F.J., Rodriguez-Manas L. Sex differences in the association between serum levels of testosterone and frailty in an elderly population: the Toledo Study for Healthy Aging. PloS One. 2012;7(3) doi: 10.1371/journal.pone.0032401.
    1. Saedi A.A., Feehan J., Phu S., Duque G. Current and emerging biomarkers of frailty in the elderly. Clin Interv Aging. 2019;14:389–398. doi: 10.2147/CIA.S168687.
    1. Fontana L., Addante F., Copetti M., et al. Identification of a metabolic signature for multidimensional impairment and mortality risk in hospitalized older patients. Aging Cell. 2013;12(3):459–466. doi: 10.1111/acel.12068.
    1. Saum K.U., Dieffenbach A.K., Jansen E.H., et al. Association between oxidative stress and frailty in an elderly German population: results from the ESTHER cohort study. Gerontology. 2015;61(5):407–415. doi: 10.1159/000380881.
    1. Thompson L.V. Age-related muscle dysfunction. Exp Gerontol. 2009;44(1-2):106–111. doi: 10.1016/j.exger.2008.05.003.
    1. Marzetti E., Lees H.A., Wohlgemuth S.E., Leeuwenburgh C. Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. Biofactors. 2009;35(1):28–35. doi: 10.1002/biof.5.
    1. Marzetti E., Calvani R., Tosato M., et al. Sarcopenia: an overview. Aging Clin Exp Res. 2017;29(1):11–17. doi: 10.1007/s40520-016-0704-5.
    1. Lopez-Otin C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–1217. doi: 10.1016/j.cell.2013.05.039.
    1. Kennedy B.K., Berger S.L., Brunet A., et al. Geroscience: linking aging to chronic disease. Cell. 2014;159(4):709–713. doi: 10.1016/j.cell.2014.10.039.
    1. Cesari M., Demougeot L., Boccalon H., et al. A self-reported screening tool for detecting community-dwelling older persons with frailty syndrome in the absence of mobility disability: the FiND questionnaire. PloS One. 2014;9(7) doi: 10.1371/journal.pone.0101745.
    1. Cesari M., Gambassi G., van Kan G.A., Vellas B. The frailty phenotype and the frailty index: different instruments for different purposes. Age Ageing. 2014;43(1):10–12. doi: 10.1093/ageing/aft160.
    1. Dent E., Kowal P., Hoogendijk E.O. Frailty measurement in research and clinical practice: a review. Eur J Intern Med. 2016;31:3–10. doi: 10.1016/j.ejim.2016.03.007.
    1. Ma L. Current situation of frailty screening tools for older adults. J Nutr Health Aging. 2019;23(1):111–118. doi: 10.1007/s12603-018-1123-4.
    1. Walston J., Buta B., Xue Q.L. Frailty screening and interventions: considerations for clinical practice. Clin Geriatr Med. 2018;34(1):25–38. doi: 10.1016/j.cger.2017.09.004.
    1. Guralnik J.M., Simonsick E.M., Ferrucci L., et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–M94. doi: 10.1093/geronj/49.2.m85.
    1. Guralnik J.M., Ferrucci L., Simonsick E.M., Salive M.E., Wallace R.B. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med. 1995;332(9):556–561. doi: 10.1056/NEJM199503023320902.
    1. Ramirez-Velez R., Perez-Sousa M.A., Venegas-Sanabria L.C., et al. vol. 7. Front Med (Lausanne); 2020. Normative Values for the Short Physical Performance Battery (SPPB) and Their Association with Anthropometric Variables in Older Colombian Adults. The SABE Study, 2015; p. 52.
    1. Addison O., Kundi R., Ryan A.S., et al. Clinical relevance of the modified physical performance test versus the short physical performance battery for detecting mobility impairments in older men with peripheral arterial disease. Disabil Rehabil. 2018;40(25):3081–3085. doi: 10.1080/09638288.2017.1367966.
    1. Abellan van Kan G., Rolland Y., Andrieu S., et al. Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging. 2009;13(10):881–889. doi: 10.1007/s12603-009-0246-z.
    1. Podsiadlo D., Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142–148. doi: 10.1111/j.1532-5415.1991.tb01616.x.
    1. Ensrud K.E., Ewing S.K., Taylor B.C., et al. Frailty and risk of falls, fracture, and mortality in older women: the study of osteoporotic fractures. J Gerontol A Biol Sci Med Sci. 2007;62(7):744–751. doi: 10.1093/gerona/62.7.744.
    1. Bilotta C., Nicolini P., Case A., Pina G., Rossi S., Vergani C. Frailty syndrome diagnosed according to the Study of Osteoporotic Fractures (SOF) criteria and adverse health outcomes among community-dwelling older outpatients in Italy. A one-year prospective cohort study. Arch Gerontol Geriatr. 2012;54(2):e23–e28. doi: 10.1016/j.archger.2011.06.037.
    1. Ensrud K.E., Ewing S.K., Cawthon P.M., et al. A comparison of frailty indexes for the prediction of falls, disability, fractures, and mortality in older men. J Am Geriatr Soc. 2009;57(3):492–498. doi: 10.1111/j.1532-5415.2009.02137.x.
    1. Ensrud K.E., Ewing S.K., Taylor B.C., et al. Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med. 2008;168(4):382–389. doi: 10.1001/archinternmed.2007.113.
    1. Hyde Z., Flicker L., Almeida O.P., et al. Low free testosterone predicts frailty in older men: the health in men study. J Clin Endocrinol Metab. 2010;95(7):3165–3172. doi: 10.1210/jc.2009-2754.
    1. Ravindrarajah R., Lee D.M., Pye S.R., et al. The ability of three different models of frailty to predict all-cause mortality: results from the European Male Aging Study (EMAS) Arch Gerontol Geriatr. 2013;57(3):360–368. doi: 10.1016/j.archger.2013.06.010.
    1. Rolland Y.M., Hermabessiere S., Abellan G., et al. Stereotactic radiosurgery for trigeminal neuralgia in a 109-year-old woman. J Am Geriatr Soc. 2008;56(8):1586–1587. doi: 10.1111/j.1532-5415.2008.01793.x.
    1. Peters L.L., Boter H., Burgerhof J.G., Slaets J.P., Buskens E. Construct validity of the Groningen Frailty Indicator established in a large sample of home-dwelling elderly persons: evidence of stability across age and gender. Exp Gerontol. 2015;69:129–141. doi: 10.1016/j.exger.2015.05.006.
    1. Peters L.L., Boter H., Buskens E., Slaets J.P. Measurement properties of the Groningen Frailty Indicator in home-dwelling and institutionalized elderly people. J Am Med Dir Assoc. 2012;13(6):546–551. doi: 10.1016/j.jamda.2012.04.007.
    1. Peters L.L., Burgerhof J.G., Boter H., Wild B., Buskens E., Slaets J.P. Predictive validity of a frailty measure (GFI) and a case complexity measure (IM-E-SA) on healthcare costs in an elderly population. J Psychosom Res. 2015;79(5):404–411. doi: 10.1016/j.jpsychores.2015.09.015.
    1. Bielderman A., van der Schans C.P., van Lieshout M.R., et al. Multidimensional structure of the Groningen Frailty Indicator in community-dwelling older people. BMC Geriatr. 2013;13:86. doi: 10.1186/1471-2318-13-86.
    1. Vellas B., Balardy L., Gillette-Guyonnet S., et al. Looking for frailty in community-dwelling older persons: the gerontopole frailty screening tool (GFST) J Nutr Health Aging. 2013;17(7):629–631. doi: 10.1007/s12603-013-0363-6.
    1. Rolfson D.B., Majumdar S.R., Tsuyuki R.T., Tahir A., Rockwood K. Validity and reliability of the Edmonton frail scale. Age Ageing. 2006;35(5):526–529. doi: 10.1093/ageing/afl041.
    1. Hilmer S.N., Perera V., Mitchell S., et al. The assessment of frailty in older people in acute care. Australas J Ageing. 2009;28(4):182–188. doi: 10.1111/j.1741-6612.2009.00367.x.
    1. Perna S., Francis M.D., Bologna C., et al. Performance of Edmonton Frail Scale on frailty assessment: its association with multi-dimensional geriatric conditions assessed with specific screening tools. BMC Geriatr. 2017;17(1):2. doi: 10.1186/s12877-016-0382-3.
    1. Shumway-Cook A., Brauer S., Woollacott M. Predicting the probability for falls in community-dwelling older adults using the Timed up & Go Test. Phys Ther. 2000;80(9):896–903. doi: 10.1093/ptj/80.9.896.
    1. Stoicea N., Baddigam R., Wajahn J., et al. The gap between clinical research and standard of care: a review of frailty assessment scales in perioperative surgical settings. Front Public Health. 2016;4:150. doi: 10.3389/fpubh.2016.00150.
    1. Rockwood K., Song X., MacKnight C., et al. A global clinical measure of fitness and frailty in elderly people. CMAJ (Can Med Assoc J) 2005;173(5):489–495. doi: 10.1503/cmaj.050051.
    1. McPhee J.S., French D.P., Jackson D., Nazroo J., Pendleton N., Degens H. Physical activity in older age: perspectives for healthy ageing and frailty. Biogerontology. 2016;17(3):567–580. doi: 10.1007/s10522-016-9641-0.
    1. Hamer M., Lavoie K.L., Bacon S.L. Taking up physical activity in later life and healthy ageing: the English longitudinal study of ageing. Br J Sports Med. 2014;48(3):239–243. doi: 10.1136/bjsports-2013-092993.
    1. Manini T.M., Everhart J.E., Patel K.V., et al. Daily activity energy expenditure and mortality among older adults. J Am Med Assoc. 2006;296(2):171–179. doi: 10.1001/jama.296.2.171.
    1. Stessman J., Hammerman-Rozenberg R., Cohen A., Ein-Mor E., Jacobs J.M. Physical activity, function, and longevity among the very old. Arch Intern Med. 2009;169(16):1476–1483. doi: 10.1001/archinternmed.2009.248.
    1. Romero S.A., Minson C.T., Halliwill J.R. The cardiovascular system after exercise. J Appl Physiol. 1985;122(4):925–932. doi: 10.1152/japplphysiol.00802.2016.
    1. Wilson M.G., Ellison G.M., Cable N.T. Basic science behind the cardiovascular benefits of exercise. Br J Sports Med. 2016;50(2):93–99. doi: 10.1136/bjsports-2014-306596rep.
    1. Cholewa J., Guimaraes-Ferreira L., da Silva Teixeira T., et al. Basic models modeling resistance training: an update for basic scientists interested in study skeletal muscle hypertrophy. J Cell Physiol. 2014;229(9):1148–1156. doi: 10.1002/jcp.24542.
    1. Archer T., Ricci S., Massoni F., Ricci L., Rapp-Ricciardi M. Cognitive benefits of exercise intervention. Clin Ter. 2016;167(6):e180–e185. doi: 10.7417/CT.2016.1965.
    1. Lautenschlager N.T., Cox K.L., Flicker L., et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. J Am Med Assoc. 2008;300(9):1027–1037. doi: 10.1001/jama.300.9.1027.
    1. Dipietro L., Campbell W.W., Buchner D.M., et al. Physical activity, injurious falls, and physical function in aging: an umbrella review. Med Sci Sports Exerc. 2019;51(6):1303–1313. doi: 10.1249/MSS.0000000000001942.
    1. Piercy K.L., Troiano R.P., Ballard R.M., et al. The physical activity guidelines for Americans. J Am Med Assoc. 2018;320(19):2020–2028. doi: 10.1001/jama.2018.14854.
    1. Gine-Garriga M., Roque-Figuls M., Coll-Planas L., Sitja-Rabert M., Salva A. Physical exercise interventions for improving performance-based measures of physical function in community-dwelling, frail older adults: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2014;95(4):753–769. doi: 10.1016/j.apmr.2013.11.007.
    1. Studenski S., Perera S., Patel K., et al. Gait speed and survival in older adults. J Am Med Assoc. 2011;305(1):50–58. doi: 10.1001/jama.2010.1923.
    1. Chou C.H., Hwang C.L., Wu Y.T. Effect of exercise on physical function, daily living activities, and quality of life in the frail older adults: a meta-analysis. Arch Phys Med Rehabil. 2012;93(2):237–244. doi: 10.1016/j.apmr.2011.08.042.
    1. Lopez P., Pinto R.S., Radaelli R., et al. Benefits of resistance training in physically frail elderly: a systematic review. Aging Clin Exp Res. 2018;30(8):889–899. doi: 10.1007/s40520-017-0863-z.
    1. Cadore E.L., Rodriguez-Manas L., Sinclair A., Izquierdo M. Effects of different exercise interventions on risk of falls, gait ability, and balance in physically frail older adults: a systematic review. Rejuvenation Res. 2013;16(2):105–114. doi: 10.1089/rej.2012.1397.

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