The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. In parallel, dementia and cognitive disorders also represent major healthcare and social priorities. Although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. An International Consensus Group on “Cognitive Frailty” was organized by the International Academy on Nutrition and Aging (I.A.N.A) and the International Association of Gerontology and Geriatrics (I.A.G.G) on April 16th, 2013 in Toulouse (France). The present report describes the results of the Consensus Group and provides the first definition of a “Cognitive Frailty” condition in older adults. Specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. The consensus panel proposed the identification of the so-called “cognitive frailty” as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. In particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (CDR=0.5); and 2) exclusion of concurrent AD dementia or other dementias. Under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. A potential for reversibility may also characterize this entity. A psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors.
Beard J, Biggs S, Bloom D, et al. (2011) Global Population Ageing: Peril or Promise, Geneva: World Economic Forum, 2011.
Gonyea J (2005) The economic well-being of older Americans and the persistent divide. Public Health & Aging Report, 15 p. 1–11.
Morley JE (2011) Frailty: diagnosis and management. J Nutr Health Aging, 15(8): p. 667–670.
Cesari M, Vellas B and Gambassi G (2013) The stress of aging. Exp Gerontol, 48(4): p. 451–456.
Green R, Schneider L, Amato D, et al. (2009) Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild alzheimer disease: A randomized controlled trial. JAMA, 302(23): p. 2557–2564.
Bergman H, Ferrucci L, Guralnik J, et al. (2007) Frailty: an emerging research and clinical paradigm—issues and controversies. J Gerontol A Biol Sci Med Sci, 62(7): p. 731–737.
Rockwood K, Song X, MacKnight C, et al. (2005) A global clinical measure of fitness and frailty in elderly people. CMAJ, 173(5): p. 489–495.
Clegg A, Young J, Iliffe S, et al. (2013) Frailty in elderly people. Lancet, 381(9868): p. 752–762.
Buchman A, Yu L, Wilson R, et al. (2013) Association of brain pathology with the progression of frailty in older adults. Neurology, 80 p. 1–7.
Bandeen-Roche K, Xue QL, Ferrucci L, et al. (2006) Phenotype of frailty: characterization in the women’s health and aging studies. J Gerontol A Biol Sci Med Sci, 61(3): p. 262–266.
Fried LP, Tangen CM, Walston J, et al. (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci, 56(3): p. M146–M156.
Ensrud KE, Blackwell TL, Redline S, et al. (2009) Sleep disturbances and frailty status in older community-dwelling men. J Am Geriatr Soc, 57(11): p. 2085–2093.
Gill T, Gahbauer E, Allore H, et al. (2006) Transitions between frailty states among community-living older persons. Arch Intern Med, 166(4): p. 418–423.
Graham JE, Snih SA, Berges IM, et al. (2009) Frailty and 10-year mortality in communityliving Mexican American older adults. Gerontology, 55(6): p. 644–651.
Abellan van Kan G, Rolland Y, Bergman H, et al. (2008) The I.A.N.A Task Force on frailty assessment of older people in clinical practice. J Nutr Health Aging, 12(1): p. 29–37.
Abellan van Kan G, Rolland Y, Houles M, et al. (2010) The assessment of frailty in older people. Clin Geriatr Med, p. 275–286.
RodrÍguez-Mañas L, Féart C, Mann G, et al. (2013) Searching for an Operational Definition of Frailty: A Delphi Method Based Consensus Statement. The Frailty Operative Definition-Consensus Conference Project. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 68(1): p. 62–67.
Collard RM, Boter H, Schoevers RA, et al. (2012) Prevalence of frailty in communitydwelling older persons: a systematic review. J Am Geriatr Soc, 60(8): p. 1487–1492.
Fried LP, Ferrucci L, Darer J, et al. (2004) Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci, 59(3): p. 255–263.
Rothman MD, Leo-Summers L and Gill TM (2008) Prognostic significance of potential frailty criteria. J Am Geriatr Soc, 56(12): p. 2211–2116.
Rockwood K, Stadnyk K, MacKnight C, et al. (1999) A brief clinical instrument to classify frailty in elderly people. Lancet, 353(9148): p. 205–206.
Ensrud KE, Ewing SK, Taylor BC, et al. (2008) Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med, 168(4): p. 382–389.
Yesavage JA, Brink TL, Rose TL, et al. (1982) Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res, 17(1): p. 37–49.
Gobbens RJ, van Assen MA, Luijkx KG, et al. (2010) Determinants of frailty. J Am Med Dir Assoc, 11(5): p. 356–364.
Gobbens RJJ, van Assen MALM, Luijkx KG, et al. (2012) The Predictive Validity of the Tilburg Frailty Indicator: Disability, Health Care Utilization, and Quality of Life in a Population at Risk. The Gerontologist, 52(5): p. 619–631.
Shim EY, Ma SH, Hong SH, et al. (2011) Correlation between Frailty Level and Adverse Health-related Outcomes of Community-Dwelling Elderly, One Year Retrospective Study. Korean J Fam Med, 32(4): p. 249–256.
Theou O, Rockwood M, Mitniski A, et al. (2012) Disability and co-morbidity in relation to frailty: How much do they overlap? Arch Gerontol Geriatr, 55(2): p. e1–e8.
Walston J, McBurnie MA, Newman A, et al. (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): p. 2333–2341.
Hubbard RE, O’Mahony MS, Savva GM, et al. (2009) Inflammation and frailty measures in older people. Journal of Cellular and Molecular Medicine, 13(9b): p. 3103–3109.
Jack CR, Jr., Knopman DS, Jagust WJ, et al. (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol, 12(2): p. 207–216.
Albert M, DeKosky S, Dickson D, et al. (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7(3): p. 270–279.
McKhann G, Knopman D, Chertkow H, et al. (2011) The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7 p. 263–269.
Sperling R, Aisen P, Beckett L, et al. (2011) Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7 p. 280–292.
Aisen P (2008) Treatment for MCI: is the evidence sufficient? Neurology, 70(22): p. 2020–2021.
Abdulrab K and Heun R (2008) Subjective memory impairement. A review of its definitions indicates the need for a comprehensive set of standardised and validated criteria. European Phychiatry, 23(5): p. 321–330.
Gillette-Guyonnet S, Andrieu S, Dantoine T, et al. (2009) Commentary on “A roadmap for the prevention of dementia II. Leon Thal Symposium 2008.” The Multidomain Alzheimer Preventive Trial (MAPT): A new approach to the prevention of Alzheimer’s disease. Alzheimer’s & Dementia, 5(2): p. 114–121.
Vellas B, Coley N, Ousset P-J, et al. (2012) Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebocontrolled trial. The Lancet Neurology, 11(10): p. 851–859.
Panza F, Frisardi V, Capurso C, et al. (2010) Late-life depression, mild cognitive impairment, and dementia: possible continuum? Am J Geriatr Psychiatry, 18(2): p. 98–116.
Mezuk B, Edwards L, Lohman M, et al. (2012) Depression and frailty in later life: a synthetic review. International Journal of Geriatric Psychiatry, 27(9): p. 879–892.
Lohman MC and Mezuk B (2013) Frailty and Depression: Comorbidity in the Context of Imperfect Measurement. Journal of the American Geriatrics Society, 61(3): p. 474–474.
Jefferson AL, Himali JJ, Au R, et al. (2011) Relation of left ventricular ejection fraction to cognitive aging (from the Framingham Heart Study). Am J Cardiol, 108(9): p. 1346–1351.
Jefferson AL, Himali JJ, Beiser AS, et al. (2010) Cardiac index is associated with brain aging: the Framingham Heart Study. Circulation, 122(7): p. 690–697.
Kamat SM, Kamat AS and Grossberg GT (2010) Dementia risk prediction: are we there yet? Clin Geriatr Med, 26(1): p. 113–123.
Collerton J, Martin-Ruiz C, Davies K, et al. (2012) Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev, 133(6): p. 456–466.
Phan HM, Alpert JS and Fain M (2008) Frailty, inflammation, and cardiovascular disease: evidence of a connection. Am J Geriatr Cardiol, 17(2): p. 101–107.
Kalyani RR, Varadhan R, Weiss CO, et al. (2012) Frailty Status and Altered Glucose-Insulin Dynamics. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 67(12): p. 1300–1306.
Lu FP, Lin KP and Kuo HK (2009) Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. PLoS One, 4(1): p. e4144.
Morley JE (2010) Nutrition and the brain. Clin Geriatr Med, 26(1): p. 89–98.
Ho Y-Y, Matteini AM, Beamer B, et al. (2011) Exploring Biologically Relevant Pathways in Frailty. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 66A(9): p. 975–979.
Dato S, Montesanto A, Lagani V, et al. (2012) Frailty phenotypes in the elderly based on cluster analysis: a longitudinal study of two Danish cohorts. Evidence for a genetic influence on frailty. AGE, 34(3): p. 571–582.
Kaiser M, Bandinelli S and Lunenfeld B (2010) Frailty and the role of nutrition in older people. A review of the current literature. Acta Biomed, 81Suppl 1 p. 37–45.
Smit E, Winters-Stone KM, Loprinzi PD, et al. (2012) Lower nutritional status and higher food insufficiency in frail older US adults. British Journal of Nutrition, FirstView p. 1–7.
Gates N, Fiatarone Singh MA, Sachdev PS, et al. (2013) The Effect of Exercise Training on Cognitive Function in Older Adults with Mild Cognitive Impairment: A Meta-analysis of Randomized Controlled Trials. The American Journal of Geriatric Psychiatry, (0): In press.
Mi W, van Wijk N, Cansev M, et al. (2013) Nutritional approaches in the risk reduction and management of Alzheimer’s disease. Nutrition, 29(9): p. 1080–1089
Presse N, Belleville S, Gaudreau P, et al. (2013) Vitamin K status and cognitive function in healthy older adults. Neurobiology of Aging, (0): In press.
Boveris A and Navarro A (2008) Brain mitochondrial dysfunction in aging. IUBMB Life, 60(5): p. 308–314.
Bishop NA, Lu T and Yankner BA (2010) Neural mechanisms of ageing and cognitive decline. Nature, 464(7288): p. 529–535.
Panegyres PK (2004) The contribution of the study of neurodegenerative disorders to the understanding of human memory. QJM, 97(9): p. 555–567.
Rockwood K (2005) Frailty and its definition: a worthy challenge. J Am Geriatr Soc, 53(6): p. 1069–1070.
Ávila-Funes JA, Amieva H, Barberger-Gateau P, et al. (2009) Cognitive Impairment Improves the Predictive Validity of the Phenotype of Frailty for Adverse Health Outcomes: The Three-City Study. Journal of the American Geriatrics Society, 57(3): p. 453–461.
Buchman AS, Boyle PA, Wilson RS, et al. (2007) Frailty is Associated With Incident Alzheimer’s Disease and Cognitive Decline in the Elderly. Psychosomatic Medicine, 69(5): p. 483–489.
Boyle PA, Buchman AS, Wilson RS, et al. (2010) Physical Frailty Is Associated with Incident Mild Cognitive Impairment in Community-Based Older Persons. Journal of the American Geriatrics Society, 58(2): p. 248–255.
Samper-Ternent R, Al Snih S, Raji MA, et al. (2008) Relationship between frailty and cognitive decline in older Mexican Americans. J Am Geriatr Soc, 56(10): p. 1845–1852.
Auyeung TW, Lee JS, Kwok T, et al. (2011) Physical frailty predicts future cognitive decline — a four-year prospective study in 2737 cognitively normal older adults. J Nutr Health Aging, 15(8): p. 690–694.
Jacobs J, Cohen A, Ein-Mor E, et al. (2011) Frailty, cognitive impairment and mortality among the oldest old. The journal of nutrition, health & aging, 15(8): p. 678–682.
Gray SL, Anderson ML, Hubbard RA, et al. (2013) Frailty and Incident Dementia. J Gerontol A Biol Sci Med Sci, 68(9): 1083–1090
Mitnitski A, Fallah N, Rockwood MRH, et al. (2011) Transitions in cognitive status in relation to frailty in older adults: A Comparison of three frailty measures. The journal of nutrition, health & aging, 15(10): p. 863–867.
Macuco CRM, Batistoni SST, Lopes A, et al. (2012) Mini-Mental State Examination performance in frail, pre-frail, and non-frail community dwelling older adults in Ermelino Matarazzo, São Paulo, Brazil. International Psychogeriatrics, 24(11): p. 1725–1731.
Yassuda M, Lopes A, Cachioni M, et al. (2012) Frailty criteria and cognitive performance are related: Data from the Fibra study in Ermelino Matarazzo, Sao Paulo, Brazil. The journal of nutrition, health & aging, 16(1): p. 55–61.
Houles M, Canevelli M, Abellan van Kan G, et al. (2012) Frailty and Cognition. The Journal of Frailty & Aging, 1(2): p. 56–63.
Subra J, Gillette-Guyonnet S, Cesari M, et al. (2012) The integration of frailty into clinical practice: Preliminary results from the Gérontopôle. The journal of nutrition, health & aging, 16(8): p. 714–720.
Abellan van Kan G, Rolland Y, Andrieu S, et al. (2009) Gait speed at usual pace as apredictor of adverse outcomes in community-dwelling plder people. An International Academy on Nutrition and Aging (IANA) Task Force.. The Journal of Nutrition & Aging, 13(10): p. 881–889.
David R, Mulin E, Friedman L, et al. (2012) Decreased daytime motor activity associated with apathy in Alzheimer disease: an actigraphic study. Am J Geriatr Psychiatry, 20(9): p. 806–814.
Semanik P, Lee J, Manheim L, et al. (2011) Relationship between accelerometer-based measures of physical activity and the Yale Physical Activity Survey in adults with arthritis. Arthritis Care & Research, 63(12): p. 1766–1772.
Leng S, Chaves P, Koenig K, et al. (2002) Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc, 50(7): p. 1268–1271.
Wilson CJ, Finch CE and Cohen HJ (2002) Cytokines and cognition—the case for a headto- toe inflammatory paradigm. J Am Geriatr Soc, 50(12): p. 2041–2056.
Engelhart MJ, Geerlings MI, Meijer J, et al. (2004) Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol, 61(5): p. 668–672.
Ravaglia G, Forti P, Maioli F, et al. (2005) Serum C-reactive protein and cognitive function in healthy elderly Italian community dwellers. J Gerontol A Biol Sci Med Sci, 60(8): p. 1017–1021.
Albert MS, DeKosky ST, Dickson D, et al. (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7(3): p. 270–279.
Desai AK, Grossberg GT and Chibnall JT (2010) Healthy brain aging: a road map. Clin Geriatr Med, 26(1): p. 1–16.
Dubois B, Feldman HH, Jacova C, et al. (2010) Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol, 9(11): p. 1118–1127.
Aisen PS, Petersen RC, Donohue MC, et al. (2010) Clinical Core of the Alzheimer’s Disease Neuroimaging Initiative: progress and plans. Alzheimer’s & Dementia, 6(3): p. 239–246.
About this article
Cite this article
Kelaiditi, E., Cesari, M., Canevelli, M. et al. Cognitive frailty: Rational and definition from an (I.A.N.A./I.A.G.G.) International Consensus Group. J Nutr Health Aging 17, 726–734 (2013). https://doi.org/10.1007/s12603-013-0367-2
- cognitive frailty
- neurodegenerative disease
- clinical markers
- biological markers