Designing Randomized, Controlled Trials Aimed at Preventing or Delaying Functional Decline and Disability in Frail, Older Persons: A Consensus Report
Abstract
The discovery of effective interventions to prevent or delay disability in older persons is a public health priority. Most likely to benefit from such interventions are frail individuals who are not yet disabled and those with early disability who are at high risk of progression. In spite of this frail older persons have often been excluded from research on the assumption that they would not tolerate testing or benefit from treatment. The Interventions on Frailty Working Group developed recommendations to screen, recruit, evaluate, and retain frail older persons in clinical trials. Specific recommendations are: Eligibility screening should include a multistage process, to quickly exclude those who are too well and those who are too sick. Inclusion criteria should target those most likely to benefit, be meaningful to clinicians, and reflect advancements in the frailty research area. Disability outcome measures should include self‐reported, objective, and proxy measures. Strategies to improve retention and compliance and to monitor their effectiveness should be an integral part of the study design. Estimation of cost and sample size should contemplate high dropout rates and interference bycompeting outcomes. Additional research is needed to refine criteria for screening frail older persons, identify objective measures of disability that are reliable and valid in frail older persons, and improve the informed consent process for high‐risk participants, recognizing that research in this subgroup is essential to improving their health outcomes.
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An index with 30-40 variables has been shown to be sufficiently accurate for predicting adverse outcomes.
“Even so, an index with 30–40 variables has been shown to be sufficiently accurate for predicting adverse outcomes [6,14].”
From A standard procedure for creating a frailty index (2008) · cites this paper as [14]
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“Sarcopenia also plays a predominant role in the etiology and pathogenesis of frailty, which is highly predictive of adverse events such as hospitalization, associated morbidity and disability and mortality (215, 216).”
BackgroundFugate Woods, N., LaCroix, A. Z., Gray, S. L., Aragaki, A., Cochrane, B. B., Brunner, R. L., Masaki, K., Murray, A., & Newman, A. B. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53405.x · Cited by 1,040 · see citing works
“The ability to identify a set of readily measured indicators of frailty can serve as a foundation for further research about the mechanisms of frailty and interventions to modify it.(3) In addition, identification of a set of simply measured indicators could enable clinicians to identify those at risk in community set…”
BackgroundEnsrud, K. E. (2008) · Archives of Internal Medicine · doi:10.1001/archinternmed.2007.113 · Cited by 975 · see citing works
“Individual SOF index components Weight lossb 1017 (15) Inability to rise from chairc 779 (12)”
BackgroundAcute Coronary Care in the Elderly, Part I
Alexander, K. P., Newby, L. K., Cannon, C. P., Armstrong, P. W., Gibler, W. B., Rich, M. W., de Werf, F. V., White, H. D., Weaver, W. D., Naylor, M. D., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.182615 · Cited by 913 · see citing works
Evidence for the Domains Supporting the Construct of Intrinsic Capacity
Cesari, M., Araujo de Carvalho, I., Amuthavalli Thiyagarajan, J., Cooper, C., Martin, F. C., Reginster, J.-Y., Vellas, B., & Beard, J. R. (2018) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gly011 · Cited by 745 · see citing works
The Identification of Frailty: A Systematic Literature Review
Sternberg, S. A., Schwartz, A. W., Karunananthan, S., Bergman, H., & Mark Clarfield, A. (2011) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2011.03597.x · Cited by 703 · see citing works
“Whether exploring the etiologies and predictors of frailty, or interventions to prevent and treat frailty, researchers need a clear definition to define their study populations and measure their results.(8,9,16) Similarly, policy decisions regarding the distribution of scarce resources to help frail older adults and p…”
BackgroundFrailty Syndrome: A Transitional State in a Dynamic Process
Lang, P. O., Michel, J., & Zekry, D. (2009) · Gerontology · doi:10.1159/000211949 · Cited by 672 · see citing works
Association of frailty with survival: A systematic literature review
Shamliyan, T., Talley, K. M., Ramakrishnan, R., & Kane, R. L. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.03.001 · Cited by 667 · see citing works
“We used the framework proposed by the Interventions on Frailty Working Group to identify criteria of frailty in epidemiologic studies (Ferrucci et al., 2004).”
MethodThe effectiveness of exercise interventions for the management of frailty: a systematic review
Theou, O., Stathokostas, L., Roland, K. P., Jakobi, J. M., Patterson, C., Vandervoort, A. A., & Jones, G. R. (2011) · Journal of Aging Research · doi:10.4061/2011/569194 · Cited by 652 · see citing works
“However, there is broad support for the understanding that frailty is a state of vulnerability, caused by multisystem reduction, ranging in severity from mild to severe, that places the individual at increased risk of adverse health outcomes [2, 3].”
BackgroundEnsrud, K. E., Ewing, S. K., Cawthon, P. M., Fink, H. A., Taylor, B. C., Cauley, J. A., Dam, T., Marshall, L. M., Orwoll, E. S., Cummings, S. R., et al. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02137.x · Cited by 636 · see citing works
Significance of Frailty among Dialysis Patients
Johansen, K. L., Chertow, G. M., Jin, C., & Kutner, N. G. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007020221 · Cited by 644 · see citing works
Hamaker, M. E., Jonker, J. M., de Rooij, S. E., Vos, A. G., Smorenburg, C. H., & Munster, B. C. V. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70259-0 · Cited by 644 · see citing works
Role of Frailty in Patients With Cardiovascular Disease
Afilalo, J., Karunananthan, S., Eisenberg, M. J., Alexander, K. P., & Bergman, H. (2009) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2009.01.375 · Cited by 616 · see citing works
Bagshaw, S. M., Stelfox, H. T., McDermid, R. C., Rolfson, D. B., Tsuyuki, R. T., Baig, N., Bobranska-Artiuch, B., Ibrahim, Q. I., Stollery, D. E., Rokosh, E., et al. (2013) · Canadian Medical Association Journal · doi:10.1503/cmaj.130639 · Cited by 551 · see citing works
“For frail critically ill patients, such an integrated program may have elements addressing the minimization of unnecessary sedation,(28) screening for delirium,(29) early assessment for weaning from mechanical ventilation, nutritional support,(30) medication reconciliation(31) and early mobilization.(32,33) In additio…”
BackgroundMitnitski, A., Song, X., Skoog, I., Broe, G., Cox, J. L., Grunfeld, E., & Rockwood, K. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.00506.x · Cited by 547 · see citing works
Boyle, P. A., Buchman, A. S., Wilson, R. S., Leurgans, S. E., & Bennett, D. A. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02671.x · Cited by 510 · see citing works
Geriatric Care Management for Low-Income Seniors
Counsell, S. R., Callahan, C. M., Clark, D. O., Tu, W., Buttar, A. B., Stump, T. E., & Ricketts, G. D. (2007) · JAMA · doi:10.1001/jama.298.22.2623 · Cited by 521 · see citing works
“Initial team conference, mean (range), d 25 (4-162)”
BackgroundÁvila‐Funes, J. A., Amieva, H., Barberger‐Gateau, P., Goff, M. L., Raoux, N., Ritchie, K. A., Carrière, I., Tavernier, B., Tzourio, C., Gutiérrez‐Robledo, L. M., et al. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.02136.x · Cited by 520 · see citing works
“The Interventions on Frailty Working Group has supported the consensus that criteria to define physical frailty should be based on the physiological domains most frequently cited in the frailty literature: mobility, muscle strength, motor processing, cognition, nutrition, endurance, and physical activity.(23) Nonethel…”
BackgroundFaber, M. J., Bosscher, R. J., Chinapaw, M. J. M., & van Wieringen, P. C. W. (2006) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2006.04.005 · Cited by 518 · see citing works
Low Nutrient Intake Is an Essential Component of Frailty in Older Persons
Bartali, B., Frongillo, E. A., Bandinelli, S., Lauretani, F., Semba, R. D., Fried, L. P., & Ferrucci, L. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.6.589 · Cited by 495 · see citing works
Self-citationTopinková, E. (2008) · Annals of Nutrition and Metabolism · doi:10.1159/000115340 · Cited by 483 · see citing works
Sarcopenia and Physical Frailty: Two Sides of the Same Coin
Cesari, M., Landi, F., Vellas, B., Bernabei, R., & Marzetti, E. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00192 · Cited by 468 · see citing works
“Nevertheless, there is an overall agreement about the key role that physical function (in particular, mobility) plays in the determination of the status of extreme vulnerability (Ferrucci et al., 2004; Daniels et al., 2008; Abellan van Kan et al., 2009).”
BackgroundShimada, H., Makizako, H., Doi, T., Yoshida, D., Tsutsumimoto, K., Anan, Y., Uemura, K., Ito, T., Lee, S., Park, H., et al. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.03.010 · Cited by 451 · see citing works
Towards an integral conceptual model of frailty
Gobbens, R. J. J., Luijkx, K. G., Wijnen-Sponselee, M. T., & Schols, J. M. G. A. (2010) · The journal of nutrition health & aging · doi:10.1007/s12603-010-0045-6 · Cited by 449 · see citing works
Frailty is associated with incident Alzheimer's disease and cognitive decline in the elderly
Buchman, A. S., Boyle, P. A., Wilson, R. S., Tang, Y., & Bennett, D. A. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e318068de1d · Cited by 420 · see citing works
“Body composition was based on BMI weight/height (2).”
BackgroundMethodInfluential. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty.
Desquilbet, L., Jacobson, L. P., Fried, L. P., Phair, J. P., Jamieson, B. D., Holloway, M., Margolick, J. B., & Study, F. T. M. A. C. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.11.1279 · Cited by 420 · see citing works
“Because of the physiologic parallels between aging and HIV infection, and because of clinical parallels in symptoms and signs of frailty (19,21) and HIV infection (35), we hypothesized that HIV infection might be causally associated with a frailty-like clinical presentation.”
BackgroundSelf-citationMultidimensional Frailty Score for the Prediction of Postoperative Mortality Risk
Kim, S., Han, H., Jung, H., Kim, K., Hwang, D. W., Kang, S., & Kim, C. (2014) · JAMA Surgery · doi:10.1001/jamasurg.2014.241 · Cited by 418 · see citing works
Impact of frailty on outcomes in surgical patients: A systematic review and meta-analysis
Panayi, A. C., Orkaby, A. R., Sakthivel, D., Endo, Y., Varon, D. E., Roh, D. S., Orgill, D. P., Neppl, R. L., Javedan, H., Bhasin, S., et al. (2018) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2018.11.020 · Cited by 417 · see citing works
Frailty syndrome: implications and challenges for health care policy
Kojima, G., Liljas, A. E. M., & Iliffe, S. (2019) · Risk Management and Healthcare Policy · doi:10.2147/rmhp.s168750 · Cited by 413 · see citing works
“Given the multidimensional and heterogeneous nature of frailty and the complex care needs of frail older adults, a multidisciplinary collaborative approach is needed between researchers, clinicians, policy makers, and older people themselves to improve the health and well-being of this subgroup of older adults.(109,11…”
BackgroundGitlin, L. N., Winter, L., Dennis, M. P., Corcoran, M., Schinfeld, S., & Hauck, W. W. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00703.x · Cited by 402 · see citing works
“Thus, it remains an important public health priority to identify effective interventions to manage ongoing and long-term functional consequences of chronic disease and improve life quality of older community members.(4,19) A promising new direction involves targeting modifiable behavioral and environmental contributor…”
BackgroundFrailty Among Community-Dwelling Elderly People in France: The Three-City Study
Ávila‐Funes, J. A., Helmer, C., Amieva, H., Barberger‐Gateau, P., Goff, M. L., Ritchie, K. A., Portet, F., Carrière, I., Tavernier, B., Gutiérrez‐Robledo, L. M., et al. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.10.1089 · Cited by 392 · see citing works
“Nevertheless, important advances have occurred in the field with the proposal of methodological guidelines to include frail people in future research (38).”
BackgroundPrevalence of frailty in Japan: A systematic review and meta-analysis
Kojima, G., Iliffe, S., Taniguchi, Y., Shimada, H., Rakugi, H., & Walters, K. R. (2016) · Journal of Epidemiology · doi:10.1016/j.je.2016.09.008 · Cited by 394 · see citing works
Giné-Garriga, M., Roqué-Fíguls, M., Coll-Planas, L., Sitjà-Rabert, M., & Salvà, A. (2014) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2013.11.007 · Cited by 468 · see citing works
Relationships Between Housing and Healthy Aging in Very Old Age
Oswald, F., Wahl, H., Schilling, O. K., Nygren, C., Fänge, A. M., Sixsmith, A. J., Sixsmith, J., Széman, Z., Tomsone, S., & Iwarsson, S. (2007) · The Gerontologist · doi:10.1093/geront/47.1.96 · Cited by 391 · see citing works
“…studies have focused on the impact of home hazards on negative health events particularly, such as falls (Gitlin, 2003; Oswald & Wahl, 2004), but generally the evidence about a link between housing and health is limited (Ferrucci et al., 2004; Gitlin et al., 2006; Oswald & Wahl; Spillman, 2004).”
BackgroundVasunilashorn, S. M., Coppin, A. K., Patel, K. V., Lauretani, F., Ferrucci, L., Bandinelli, S., & Guralnik, J. M. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/gln022 · Cited by 383 · see citing works
Self-citationWhat would make a definition of frailty successful?
Rockwood, K. J. (2005) · Age and Ageing · doi:10.1093/ageing/afi146 · Cited by 382 · see citing works
“A consensus group of the American Geriatrics Society has settled on defining frailty as a physiological syndrome characterised by decreased reserve and diminished resistance to stressors, resulting from cumulative decline across multiple physiological systems, and causing vulnerability to adverse outcomes [5].”
BackgroundPeterson, M. J., Giuliani, C. A., Morey, M. C., Pieper, C. F., Evenson, K. R., Mercer, V. S., Cohen, H. J., Visser, M., Brach, J. S., Kritchevsky, S. B., et al. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/gln001 · Cited by 374 · see citing works
“Frailty, a primary pathway to disability, has been defi ned as a pathological condition that results in a constellation of signs and symptoms and is characterized by high susceptibility to adverse health outcomes, impending decline in physical function, and high risk of death (6,7).”
BackgroundFrailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study
Cesari, M., Leeuwenburgh, C., Lauretani, F., Onder, G., Bandinelli, S., Maraldi, C., Guralnik, J. M., Pahor, M., & Ferrucci, L. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.5.1142 · Cited by 365 · see citing works
Self-citationFrailty in older adults: insights and interventions.
Espinoza, S. E., & Walston, J. D. (2005) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.72.12.1105 · Cited by 362 · see citing works
“5,7,8 Many definitions of physical frailty use measures of function and performance as markers of the changes in mobility and strength found in frail older adults.”
BackgroundSelf-citationBuurman, B. M., Hoogerduijn, J. G., de Haan, R. J., Abu–Hanna, A., Lagaay, A. M., Verhaar, H. J. J., Schuurmans, M. J., Levi, M. M., & de Rooij, S. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026951 · Cited by 358 · see citing works
“Limitations of this type are frequently encountered in studies of acutely hospitalized older patients and could account for lower inclusion rates than in other studies involving older patients [40].”
Sayer, A. A., Syddall, H. E., Martin, H. J., Dennison, E. M., Roberts, H. C., & Cooper, C. C. (2006) · Age and Ageing · doi:10.1093/ageing/afl024 · Cited by 353 · see citing works
“The Short Form-36 (SF-36) has gained widespread acceptance as a HRQoL measure and has been recommended as the optimum outcome measure across a range of ages, participant characteristics and illness conditions [10, 11].”
BackgroundThe Assessment of Frailty in Older Adults
van Kan, G. A., Rolland, Y., Houles, M., Guyonnet, S., Soto, M. E., & Vellas, B. J. (2010) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.02.002 · Cited by 351 · see citing works
Stolk, R. P., Rosmalen, J. G. M., Postma, D. S., de Boer, R. A., Navis, G., Slaets, J. P. J., Ormel, J., & Wolffenbuttel, B. H. R. (2008) · European Journal of Epidemiology · doi:10.1007/s10654-007-9204-4 · Cited by 391 · see citing works
“Frailty is defined as a state of increased physiologic vulnerability for adverse health outcomes, characterized by wasting, loss of endurance, decreased mobility and potentially decreased cognitive function [33].”
BackgroundBenefits of resistance training in physically frail elderly: a systematic review
Lopez, P., Pinto, R. S., Radaelli, R., Rech, A., Grazioli, R., Izquierdo, M., & Cadore, E. L. (2018) · Aging Clinical and Experimental Research · doi:10.1007/s40520-017-0863-z · Cited by 338 · see citing works
Stress, age, and immune function: toward a lifespan approach
Graham, J. E., Christian, L. M., & Kiecolt-Glaser, J. K. (2006) · Journal of Behavioral Medicine · doi:10.1007/s10865-006-9057-4 · Cited by 329 · see citing works
“ularly those already experiencing functional decline and disability (Ferrucci et al., 2004).”
BackgroundSex differences in stroke: Challenges and opportunities
Bushnell, C., Chaturvedi, S., Gage, K. R., Herson, P. S., Hurn, P. D., Jiménez, M. C., Kittner, S. J., Madsen, T. E., McCullough, L. D., McDermott, M., et al. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18793324 · Cited by 309 · see citing works
Interventions to prevent disability in frail community-dwelling elderly: a systematic review
Daniëls, R., van Rossum, E., de Witte, L., Kempen, G. I. J. M., & van den Heuvel, W. J. (2008) · BMC Health Services Research · doi:10.1186/1472-6963-8-278 · Cited by 303 · see citing works
“Based on recent studies into riskfactors for adverse outcomes in frail elderly there appears to be a growing consensus for acknowledging physical frailty as a construct that can be identified by frailty components [14].”
BackgroundMethodInfluentialFrom Bedside to Bench: Research Agenda for Frailty
Fried, L. P., Hadley, E. C., Walston, J. D., Newman, A. B., Guralnik, J. M., Studenski, S. A., Harris, T. B., Ershler, W. B., & Ferrucci, L. (2005) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2005.31.pe24 · Cited by 299 · see citing works
Self-citationPRISMA-7: A case-finding tool to identify older adults with moderate to severe disabilities
Raı̂che, M., Hébert, R., & Dubois, M. (2007) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2007.06.004 · Cited by 295 · see citing works
Comparing models of frailty: the Health and Retirement Study
Cigolle, C. T., Ofstedal, M. B., Tian, Z., & Blaum, C. S. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02225.x · Cited by 286 · see citing works
Frailty and Its Definition: A Worthy Challenge
Rockwood, K. J. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53312.x · Cited by 288 · see citing works
Loss of motor function in preclinical Alzheimer's disease
Buchman, A. S., & Bennett, D. A. (2011) · Expert Review of Neurotherapeutics · doi:10.1586/ern.11.57 · Cited by 311 · see citing works
Chaves, P. H. M., Semba, R. D., Leng, S. X., Woodman, R. C., Ferrucci, L., Guralnik, J. M., & Fried, L. P. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.6.729 · Cited by 263 · see citing works
Self-citationPhysical frailty in older persons is associated with Alzheimer disease pathology
Buchman, A. S., Schneider, J. A., Leurgans, S. E., & Bennett, D. A. (2008) · Neurology · doi:10.1212/01.wnl.0000324864.81179.6a · Cited by 260 · see citing works
Kenny, R. A., Kleppinger, A., Annis, K., Rathier, M., Browner, B., Judge, J. O., & McGee, D. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02865.x · Cited by 251 · see citing works
Neri, A. L., Yassuda, M. S., de Araújo, L. F., Eulálio, M. D. C., Cabral, B. E., de Siqueira, M. E. C., dos Santos, G. A., & Moura, J. G. D. A. (2013) · Cadernos de Saúde Pública · doi:10.1590/s0102-311x2013000400015 · Cited by 251 · see citing works
How should we grade frailty in nursing home patients?
Rockwood, K., Abeysundera, M. J., & Mitnitski, A. (2007) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2007.07.012 · Cited by 249 · see citing works
Transitions between States of Disability and Independence among Older Persons
Hardy, S. E., Dubin, J. A., Holford, T. R., & Gill, T. M. (2005) · American Journal of Epidemiology · doi:10.1093/aje/kwi083 · Cited by 249 · see citing works
Measurement of Disability-free Survival after Surgery
Shulman, M. A., Myles, P. S., Chan, M. T. V., McIlroy, D. R., Wallace, S. K. A., & Ponsford, J. (2015) · Anesthesiology · doi:10.1097/aln.0000000000000586 · Cited by 245 · see citing works
Amini, N., Spolverato, G., Gupta, R., Margonis, G. A., Kim, Y., Wagner, D., Rezaee, N., Weiss, M. J., Wolfgang, C. L., Makary, M. M., et al. (2015) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-015-2835-y · Cited by 246 · see citing works
“Frailty, defined as decreased physiologic reservoir, has been proposed as a more global metric of the patient’s health status.(15,16) In fact, 7 to 12 % of individuals in the USA suffer from frailty, with women being at greater risk than men.”
Emergency General Surgery in the Elderly: Too Old or Too Frail?
Joseph, B. A., Zangbar, B., Pandit, V., Fain, M. J., Mohler, M. J., Kulvatunyou, N., Jokar, T. O., O’Keeffe, T., Friese, R., & Rhee, P. (2016) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2016.01.063 · Cited by 246 · see citing works
Motives for and Barriers to Physical Activity among Older Adults with Mobility Limitations
Rasinaho, M., Hirvensalo, M. H., Leinonen, R., Lintunen, T., & Rantanen, T. (2007) · Journal of Aging and Physical Activity · doi:10.1123/japa.15.1.90 · Cited by 234 · see citing works
“Observational studies have shown that older adults who engage in physical exercise have a lower risk of disability and mortality, regardless of the presence of other disability risk factors such as mobility limitation (Bokovoy & Blair, 1994; Ferrucci et al., 2004; Hirvensalo, Rantanen, & Heikkinen, 2000; LaCroix, Gura…”
BackgroundFragility Fractures: Risk Factors and Management in the Elderly
Migliorini, F., Giorgino, R., Hildebrand, F., Spiezia, F., Peretti, G. M., Bonetti, M. A., Eschweiler, J., & Maffulli, N. (2021) · Medicina · doi:10.3390/medicina57101119 · Cited by 233 · see citing works
“In addition to the parameters used to monitor the specific risk of falling, a previous fall also significantly impacts the patient’s functional decline [41].”
BackgroundBuch, A., Carmeli, E., Boker, L. K., Marcus, Y., Shefer, G., Kis, O., Berner, Y., & Stern, N. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.01.008 · Cited by 227 · see citing works
Weiss, E. P., Racette, S. B., Villareal, D. T., Fontana, L., Steger-May, K., Schechtman, K. B., Klein, S., Ehsani, A. A., Holloszy, J. O., & Washington University School of Medicine CALERIE Group (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00853.2006 · Cited by 218 · see citing works
“Although the preservation of strength and V̇O2 max may not be important in modern society for the purposes of avoiding predators, for example, decrements in strength and V̇O2 max may be predisposing factors for physical frailty in late life (3, 4).”
BackgroundFrailty and Chronic Diseases in Older Adults
Weiss, C. O. (2010) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.08.003 · Cited by 219 · see citing works
“The major barrier to gaining such an understanding from randomized trials is a failure to measure frailty as an outcome in large trials of older adults.(30,59) In particular, frailty holds promise as a treatment effect modifier that identifies a small but vulnerable subset in whom treatment can be more or less efficac…”
BackgroundExercise as an Intervention for Frailty
Liu, C., & Fielding, R. A. (2010) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.08.001 · Cited by 214 · see citing works
“impairments in mobility, balance, strength, motor processing, cognition, nutrition, endurance (fatigue), and physical activity.(4) In 1992, Buchner and Wagner(5) first proposed a formal definition of frailty as a syndrome of weakness, impaired mobility, balance, and minimal reserve.”
Should elderly patients be admitted to the intensive care unit?
Boumendil, A., Somme, D., Garrouste-Orgeas, M., & Guidet, B. (2007) · Intensive Care Medicine · doi:10.1007/s00134-007-0621-3 · Cited by 211 · see citing works
Vellas, B. J., Balardy, L., Guyonnet, S., van Kan, G. A., Ghisolfi-Marque, A., Subra, J., Bismuth, S., Oustric, S., & Cesari, M. (2013) · The journal of nutrition health & aging · doi:10.1007/s12603-013-0363-6 · Cited by 211 · see citing works
The prevalence of subjective frailty and factors associated with frailty in Taiwan
Chen, C., Wu, S., Chen, L.-J., & Lue, B. (2010) · Archives of Gerontology and Geriatrics · doi:10.1016/s0167-4943(10)70012-1 · Cited by 209 · see citing works
The Association Between Geriatric Syndromes and Survival
Kane, R. L., Shamliyan, T., Talley, K. M., & Pacala, J. T. (2012) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2012.03942.x · Cited by 208 · see citing works
“Frailty definitions were categorized as phenotype and accumulation of deficits.(15) Phenotype definitions use the biological syndrome model of frailty, measuring weight loss, fatigue, exhaustion, weakness, low physical activity, slowness, and mobility impairment.”
BackgroundFrailty and nutrition: Searching for evidence
Bonnefoy, M., Berrut, G., Lesourd, B., Ferry, M., Gilbert, T., Guérin, O., Hanon, O., Jeandel, C., Paillaud, É., Raynaud-Simon, A., et al. (2014) · The journal of nutrition health & aging · doi:10.1007/s12603-014-0568-3 · Cited by 207 · see citing works
“Frail elderly are at increased risk for physical or functional decline, disability and death (1–3).”
Fried, L. F., Lee, J. S., Shlipak, M. G., Chertow, G. M., Green, C., Ding, J., Harris, T. B., Newman, A. B., & for the Health, A. A. B. C. S. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00727.x · Cited by 204 · see citing works
“Moreover, older individuals with CKD are more likely to be frail (a clinical syndrome of decreased functional reserve due to decline in multiple physiological systems), suggesting that they are at greater risk of developing functional limitation and disability.(11,12) The current study evaluated CKD, across the broad…”
BackgroundSelf-citationRelationship Between Frailty and Cognitive Decline in Older Mexican Americans
Samper‐Ternent, R., Snih, S. A., Raji, M. A., Markides, K. S., & Ottenbacher, K. J. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.01947.x · Cited by 204 · see citing works
“The relationship between cognition and frailty is complex, and some investigators have argued that cognitive function should be included in the definition of frailty.(46) In the meantime, rehabilitation and pharmacological treatments targeted toward the different components of frailty should be considered simultaneous…”
BackgroundBrain Pathology Contributes to Simultaneous Change in Physical Frailty and Cognition in Old Age
Buchman, A. S., Yu, L., Wilson, R. S., Boyle, P. A., Schneider, J. A., Bennett, D. A., & Kritchevsky, S. B. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu117 · Cited by 203 · see citing works
Szanton, S. L., Thorpe, R. J., Boyd, C. M., Tanner, E. K., Leff, B. A., Agree, E. M., Xue, Q., Allen, J. K., Seplaki, C. L., Weiss, C. O., et al. (2011) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2011.03698.x · Cited by 201 · see citing works
“These measures were selected based on the following criteria: known reliability and validity with low-income samples, sensitivity to change, and clinical relevance to quality of life.(27) The primary outcome was reduction in ADL and IADL difficulty; secondary focuses were health-related quality of life and falls effic…”
MethodSelf-citationEklund, K., & Wilhelmson, K. (2009) · Health & Social Care in the Community · doi:10.1111/j.1365-2524.2009.00844.x · Cited by 201 · see citing works
Missing Data: A Special Challenge in Aging Research
Hardy, S. E., Allore, H. G., & Studenski, S. A. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.02168.x · Cited by 200 · see citing works
Self-citationThe SF-36: A simple, effective measure of mobility-disability for epidemiological studies
Syddall, H. E., Martin, H., Harwood, R., Cooper, C. C., & Sayer, A. A. (2009) · The journal of nutrition health & aging · doi:10.1007/s12603-009-0010-4 · Cited by 193 · see citing works
“[9,10] It has been used extensively in observational and randomised studies for a range of illness conditions and validated across a range of ages and participant characteristics.[11,12] Its use extends beyond people with specific disease states, to determine HRQL in populations.”
MethodBiritwum, R. B., Minicuci, N., Yawson, A. E., Theou, O., Mensah, G. P., Naidoo, N., Wu, F., Guo, Y., Zheng, Y., Jiang, Y., et al. (2016) · Maturitas · doi:10.1016/j.maturitas.2016.05.012 · Cited by 187 · see citing works
Grip Strength and the Risk of Incident Alzheimer’s Disease
Buchman, A. S., Wilson, R. S., Boyle, P. A., Bienias, J. L., & Bennett, D. A. (2007) · Neuroepidemiology · doi:10.1159/000109498 · Cited by 189 · see citing works
Kim, C.-O., & Lee, K.-R. (2013) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/gls167 · Cited by 184 · see citing works
Incontinence in the frail elderly: Report from the 4th international consultation on incontinence
DuBeau, C. E., Kuchel, G. A., Johnson, T. M., Palmer, M. H., & Wagg, A. (2009) · Neurourology and Urodynamics · doi:10.1002/nau.20842 · Cited by 181 · see citing works
“Frailty overlaps with but is not identical to disability and comorbidity.(1) UI is related to the severity of comorbidity and functional impairment and may be an early marker of frailty.”
BackgroundHigher levels and blunted diurnal variation of cortisol in frail older women
Varadhan, R., Walston, J., Cappola, A. R., Carlson, M. C., Wand, G. S., & Fried, L. P. (2008) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/63.2.190 · Cited by 182 · see citing works
“Such a connection is biologically plausible, because chronic exposure to elevated cortisol is known to magnify its catabolic effects (10,33,34), leading to loss of muscle mass and strength, loss of appetite, weight loss, and decreased energy, all of which are classic symptoms of frailty (4,35).”
BackgroundSelf-citationThe prediction of functional decline in older hospitalised patients
Hoogerduijn, J. G., Buurman, B. M., Korevaar, J. C., Grobbee, D. E., de Rooij, S. E., & Schuurmans, M. J. (2012) · Age and Ageing · doi:10.1093/ageing/afs015 · Cited by 183 · see citing works
Wong, C. H., Weiss, D. R., Sourial, N., Karunananthan, S., Quail, J. M., Wolfson, C. M., & Bergman, H. (2010) · Aging Clinical and Experimental Research · doi:10.1007/bf03324816 · Cited by 181 · see citing works
Clinical strategies and animal models for developing senolytic agents
Kirkland, J. L., & Tchkonia, T. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.10.012 · Cited by 168 · see citing works
“Subjects with mild or moderate degrees of frailty or sarcopenia (i.e., Fried class 2 or 3 (Ferrucci et al., 2004)) would likely be better candidates for initial trials of effects of senolytics on frailty-related outcomes than would be subjects with advanced, potentially irreversible frailty.”
BackgroundFrailty and 10-Year Mortality in Community-Living Mexican American Older Adults
Graham, J. E., Snih, S. A., Berges, I. M., Ray, L. A., Markides, K. S., & Ottenbacher, K. J. (2009) · Gerontology · doi:10.1159/000235653 · Cited by 172 · see citing works
- Authors
- Ferrucci, L., Guralnik, J. M., Studenski, S., Fried, L. P., Cutler, G. B., Walston, J. D., & The Interventions on Frailty Working Group
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 2004-03-30
- Volume
- 52
- Issue
- 4
- Pages
- 625-634
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- OpenAlex
- W1562992882
- Cited by
- 1,027
- References
- 79
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 24 · 2023: 22 · 2022: 22 · 2021: 31 · 2020: 48 · 2019: 58 · 2018: 49 · 2017: 49 · 2016: 51 · 2015: 55 · 2014: 62 · 2013: 72 · 2012: 70
- FWCI
- 18.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Keywords
- frailty, older adults, disability prevention, functional decline, clinical trial design, participant recruitment, participant retention, sample size determination, dropout, informed consent
- MeSH terms
- Activities of Daily Living, Aged, Chronic Disease, Geriatrics, Persons with Disabilities, Health Priorities, Humans, Mass Screening, Periodicals as Topic, Planning Techniques, Primary Prevention, Public Health, Publishing, Research Design, Risk Factors, Geriatric Assessment, Randomized Controlled Trials as Topic, Frail Elderly, Outcome Assessment, Health Care, Sample Size, Disease Progression, Patient Selection
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