European Journal of Epidemiology

, Volume 29, Issue 6, pp 419–427 | Cite as

Adverse outcomes of frailty in the elderly: the Rotterdam Study

  • Lies Lahousse
  • Bastiaan Maes
  • Gijsbertus Ziere
  • Daan W. Loth
  • Vincentius J. A. Verlinden
  • M. Carola Zillikens
  • André G. Uitterlinden
  • Fernando Rivadeneira
  • Henning Tiemeier
  • Oscar H. Franco
  • M. Arfan Ikram
  • Albert Hofman
  • Guy G. Brusselle
  • Bruno H. StrickerEmail author


To investigate the prevalence of frailty in a Dutch elderly population and to identify adverse health outcomes associated with the frailty phenotype independent of the comorbidities. Cross-sectional and longitudinal analyses within the Rotterdam Study (the Netherlands), a prospective population-based cohort study in persons aged ≥55 years. Frailty was defined as meeting three or more of five established criteria for frailty, evaluating nutritional status, physical activity, mobility, grip strength and exhaustion. Intermediate frailty was defined as meeting one or two frailty criteria. Comorbidities were objectively measured. Health outcomes were assessed by means of questionnaires, physical examinations and continuous follow-up through general practitioners and municipal health authorities for mortality. Of 2,833 participants (median age 74.0 years, inter quartile range 9) with sufficiently evaluated frailty criteria, 163 (5.8 %) participants were frail and 1,454 (51.3 %) intermediate frail. Frail elderly were more likely to be older and female, to have an impaired quality of life and to have fallen or to have been hospitalized. 108 (72.0 %) frail participants had ≥2 comorbidities, compared to 777 (54.4 %) intermediate frail and 522 (44.8 %) non-frail participants. Adjusted for age, sex and comorbidities, frail elderly had a significantly increased risk of dying within 3 years (HR 3.4; 95 % CI 1.9–6.4), compared to the non-frail elderly. This study in a general Dutch population of community-dwelling elderly able to perform the frailty tests, demonstrates that frailty is common and that frail elderly are at increased risk of death independent of comorbidities.


Frail elderly Weight loss Grip strength Physical activity Mortality 



Body mass index


Center for epidemiological studies depression


Confidence interval


Chronic obstructive pulmonary disease


Forced expiratory volume in 1 s


Forced vital capacity




Hazard ratio


Inter quartile range


Odds ratio


Quality of life


Rotterdam Study


White blood cells



The authors thank the study participants, the staff from the Rotterdam Study, J. Verkroost, F. van Rooij, M. Leening, R. Ruiter and the participating general practitioners. This study was supported by the Fund for Scientific Research Flanders (FWO) project G035014 N. The funding source had no involvement in the collection, analysis, writing, interpretation, nor in the decision to submit the paper for publication. Researchers were independent from funders for this work.

Conflict of interest

None of the authors has important conflicts of interest with relevance to the submitted work.

Supplementary material

10654_2014_9924_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 kb)


  1. 1.
    Mitnitski AB, Graham JE, Mogilner AJ, et al. Frailty, fitness and late-life mortality in relation to chronological and biological age. BMC Geriatr. 2002;2:1.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Collard RM, Boter H, Schoevers RA, et al. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012;60(8):1487–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet. 2013;381(9868):752–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol Ser A Biol Sci Med Sci. 2001;56(3):M146–56.CrossRefGoogle Scholar
  5. 5.
    Rockwood K, Stadnyk K, MacKnight C, et al. A brief clinical instrument to classify frailty in elderly people. Lancet. 1999;353(9148):205–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Puts MT, Lips P, Deeg DJ. Sex differences in the risk of frailty for mortality independent of disability and chronic diseases. J Am Geriatr Soc. 2005;53(1):40–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Ensrud KE, Ewing SK, Cawthon PM, 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):492–8.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Ensrud KE, Ewing SK, Taylor BC, et al. Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med. 2008;168(4):382–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Bouillon K, Kivimaki M, Hamer M, et al. Measures of frailty in population-based studies: an overview. BMC Geriatr. 2013;13:64.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Fried LP, Ferrucci L, Darer J, et al. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol Ser A Biol Sci Med Sci. 2004;59(3):255–63.CrossRefGoogle Scholar
  11. 11.
    Cawthon PM, Marshall LM, Michael Y, et al. Frailty in older men: prevalence, progression, and relationship with mortality. J Am Geriatr Soc. 2007;55(8):1216–23.PubMedCrossRefGoogle Scholar
  12. 12.
    Sternberg SA, Wershof Schwartz A, Karunananthan S, et al. The identification of frailty: a systematic literature review. J Am Geriatr Soc. 2011;59(11):2129–38.PubMedCrossRefGoogle Scholar
  13. 13.
    Hofman A, van Duijn CM, Franco OH, et al. The Rotterdam Study: 2012 objectives and design update. Eur J Epidemiol. 2011;26(8):657–86.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Hofman A, Grobbee DE, de Jong PT, et al. Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. Eur J Epidemiol. 1991;7(4):403–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Hofman A, Breteler MM, van Duijn CM, et al. The Rotterdam Study: objectives and design update. Eur J Epidemiol. 2007;22(11):819–29.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Hofman A, Breteler MMB, van Duijn CM, et al. The Rotterdam Study: 2010 objectives and design update. Eur J Epidemiol. 2009;24(9):553–72.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Ikram MA, van der Lugt A, Niessen WJ, et al. The Rotterdam Scan Study: design and update up to 2012. Eur J Epidemiol. 2011;26(10):811–24.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Hofman A, Darwish Murad S, van Duijn CM, et al. The Rotterdam Study: 2014 objectives and design update. Eur J Epidemiol. 2013;28(11):889–926.PubMedCrossRefGoogle Scholar
  19. 19.
    de Vries NM, Staal JB, van Ravensberg CD, et al. Outcome instruments to measure frailty: a systematic review. Ageing Res Rev. 2011;10(1):104–14.PubMedCrossRefGoogle Scholar
  20. 20.
    Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1(3):385–401.CrossRefGoogle Scholar
  21. 21.
    Taylor HL, Jacobs DR Jr, Schucker B, et al. A questionnaire for the assessment of leisure time physical activities. J Chronic Dis. 1978;31(12):741–55.PubMedCrossRefGoogle Scholar
  22. 22.
    Executive summary: standards of medical care in diabetes–2013. Diabetes Care. 2013;36(Suppl 1):S4–S10.Google Scholar
  23. 23.
    Lahousse L, van den Bouwhuijsen Q, Loth DW, et al. Chronic obstructive pulmonary disease and lipid core carotid artery plaques in the Elderly: the Rotterdam Study. Am J Respir Crit Care Med. 2013;187(1):58–64.PubMedCrossRefGoogle Scholar
  24. 24.
    European Society of Hypertension. European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003;21(6):1011–53.CrossRefGoogle Scholar
  25. 25.
    WHO. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organization Technical Report Series. 1994;843:1–129.Google Scholar
  26. 26.
    Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139(2):137–47.PubMedCrossRefGoogle Scholar
  27. 27.
    Levey AS, Coresh J, Greene T, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53(4):766–72.PubMedCrossRefGoogle Scholar
  28. 28.
    World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System, Geneva. 2011.Google Scholar
  29. 29.
    Kiely DK, Cupples LA, Lipsitz LA. Validation and comparison of two frailty indexes: the MOBILIZE Boston Study. J Am Geriatr Soc. 2009;57(9):1532–9.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Morley JE, Haren MT, Rolland Y, et al. Frailty. Med Clin North Am. 2006;90(5):837–47.PubMedCrossRefGoogle Scholar
  31. 31.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412–23.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Chaves PH, Semba RD, Leng SX, et al. 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. 2005;60(6):729–35.PubMedCrossRefGoogle Scholar
  33. 33.
    Leng SX, Xue QL, Tian J, et al. Inflammation and frailty in older women. J Am Geriatr Soc. 2007;55(6):864–71.PubMedCrossRefGoogle Scholar
  34. 34.
    Ershler WB, Keller ET. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med. 2000;51:245–70.PubMedCrossRefGoogle Scholar
  35. 35.
    Gill TM, Gahbauer EA, Allore HG, et al. Transitions between frailty states among community-living older persons. Arch Intern Med. 2006;166(4):418–23.PubMedCrossRefGoogle Scholar
  36. 36.
    Hamerman D. Toward an understanding of frailty. Ann Intern Med. 1999;130(11):945–50.PubMedCrossRefGoogle Scholar
  37. 37.
    Verdery RB. Failure to thrive in older people. J Am Geriatr Soc. 1996;44(4):465–6.PubMedGoogle Scholar
  38. 38.
    Gill TM, Baker DI, Gottschalk M, et al. A program to prevent functional decline in physically frail, elderly persons who live at home. N Engl J Med. 2002;347(14):1068–74.PubMedCrossRefGoogle Scholar
  39. 39.
    Ganz DA, Higashi T, Rubenstein LZ. Monitoring falls in cohort studies of community-dwelling older people: effect of the recall interval. J Am Geriatr Soc. 2005;53(12):2190–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Lies Lahousse
    • 1
    • 2
  • Bastiaan Maes
    • 1
    • 2
  • Gijsbertus Ziere
    • 2
  • Daan W. Loth
    • 2
  • Vincentius J. A. Verlinden
    • 2
    • 3
  • M. Carola Zillikens
    • 4
    • 7
  • André G. Uitterlinden
    • 2
    • 4
    • 7
  • Fernando Rivadeneira
    • 2
    • 4
    • 7
  • Henning Tiemeier
    • 2
    • 7
  • Oscar H. Franco
    • 2
    • 7
  • M. Arfan Ikram
    • 2
    • 3
    • 5
    • 7
  • Albert Hofman
    • 2
    • 7
  • Guy G. Brusselle
    • 1
    • 2
    • 6
  • Bruno H. Stricker
    • 2
    • 7
    • 8
    Email author
  1. 1.Department of Respiratory Medicine, Ghent University HospitalGhent UniversityGhentBelgium
  2. 2.Departments of EpidemiologyErasmus Medical CenterRotterdamThe Netherlands
  3. 3.Departments of RadiologyErasmus Medical CenterRotterdamThe Netherlands
  4. 4.Departments of Internal MedicineErasmus Medical CenterRotterdamThe Netherlands
  5. 5.Departments of NeurologyErasmus Medical CenterRotterdamThe Netherlands
  6. 6.Departments of Respiratory MedicineErasmus Medical CenterRotterdamThe Netherlands
  7. 7.Netherlands Consortium on Healthy Aging (NCHA)LeidenThe Netherlands
  8. 8.Inspectorate of HealthcareThe HagueThe Netherlands

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