Cytokines and Disability in Older Adults

  • David R. Thomas


A decline in functional status is a profound predictor of morbidity and mortality [1]. The mortality rate increases from 15% in individuals with only one impairment in an instrumental activity of daily living (IADL) to 21% in persons with one or two IADL impairments. In subjects with five or six IADL impairments, the mortality rate reaches 37% [2]. Disabled older adults are four to six times more likely to die than the nondisabled [3]. Up to half of the geriatric patients admitted to a hospital have either loss of or a diminished performance in at least one ADL during admission. This decline in functional status occurs as early as the second day of hospital admission [4, 5].


Functional Decline Older Adult Congestive Heart Failure Patient Nursing Home Admission Impaired Functional Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Thomas DR (2002) Focus on functional decline in hospitalized older adults. J Gerontol A Biol Sci Med Sci 57:M567–M568PubMedGoogle Scholar
  2. 2.
    Manton KG (1988) A longitudinal study of functional change and mortality in the United States. National Long Term Care Survey. J Gerontol 43:S153–S161Google Scholar
  3. 3.
    Corti MC, Salive ME, Guralnik J (1996) Serum albumin and physical function as predictors of coronary heart disease mortality and incidence in older persons. J Clin Epidemiol 49:519–526PubMedCrossRefGoogle Scholar
  4. 4.
    Hirsch CH, Sommers L, Olsen A et al (1990) The natural history of functional morbidity in hospitalized older patients. J Am Geriatr Soc 38:1296–1303PubMedGoogle Scholar
  5. 5.
    Warshaw GA, Sampson S, Matthias R et al (1982) Functional disability in the hospitalized elderly. J Am Med Assoc 248:847–850CrossRefGoogle Scholar
  6. 6.
    Fortinsky RH, Covinsky KE, Palmer RM, Landefeld CS (1999) Effects of functional status changes before and during hospitalization on nursing home admission of older patients. J Gerontol A Biol Sci Med Sci 54:M521–M526PubMedGoogle Scholar
  7. 7.
    Foley DJ, Ostfeld AM, Branch LG et al (1992) The risk of nursing home admission in three communities. J Aging Health 4:155–173PubMedCrossRefGoogle Scholar
  8. 8.
    Fried LP, Bush TL (1988) Morbidity as a focus of preventive health care in the elderly. Epidemiol Rev 10:48–64PubMedGoogle Scholar
  9. 9.
    Thomas DR (2001) The critical link between healthrelated quality of life and age-related changes in physical activity and nutrition. J Gerontol A Biol Sci Med Sci 56:M599–M602PubMedGoogle Scholar
  10. 10.
    Guralnik JM, Simonsick EM, Ferrucci L et al (1994) A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49:M85–M94PubMedGoogle Scholar
  11. 11.
    Buttar A, Blaum C, Fries B (2001 ) Clinical characteristics and six-month outcomes of nursing home residents with low activities of daily living dependency. J Gerontol A Biol Sci Med Sci 56:M292–M297PubMedGoogle Scholar
  12. 12.
    Donaldson LJ, Clayton DG, Clarke M (1980) The elderly in residential care: Mortality in relation to functional capacity. J Epidemiol Community Health 34:96–101PubMedGoogle Scholar
  13. 13.
    Guralnik JM, Ferrucci L, Simonsick EM et al (1995) Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 332:556–556PubMedCrossRefGoogle Scholar
  14. 14.
    Markides KS, Black SA, Ostir GV et al (2001) Lower body function and mortality in Mexican American elderly people. J Gerontol A Biol Sci Med Sci 56:M243–M247PubMedGoogle Scholar
  15. 15.
    Rogers A, Rogers RG, Belanger A (1990) Longer life but worse health? Measurement and dynamics. Gerontologist 30:640–649PubMedGoogle Scholar
  16. 16.
    Tinnetti ME, Speechley M, Ginter SF (1990) Risk factors for falls among elderly persons living in the community. N Engl J Med 322:286–290CrossRefGoogle Scholar
  17. 17.
    Nourhashemi F, Andrieu S, Gillette-Guyonnet S et al (2001) Instrumental activities of daily living as a potential marker of frailty: a study of 7364 community-dwelling elderly women (the EPIDOS Study). J Gerontol A Biol Sci Med Sci 56:M448–M453PubMedGoogle Scholar
  18. 18.
    Morley JE, Baumgartner RN, Roubenoff R et al (2001) Sarcopenia. J Lab Clin Med 137:231–243PubMedCrossRefGoogle Scholar
  19. 19.
    Morley JE (2001) Anorexia, sarcopenia, and aging. Nutrition 17:660–663PubMedCrossRefGoogle Scholar
  20. 20.
    Newman AB, Gottdiener JS, McBurnie MA et al (2001) Associations of subclinical cardiovascular disease with frailty. J Gerontol A Biol Sci Med Sci 56:M158–M166PubMedGoogle Scholar
  21. 21.
    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:M146–M156PubMedGoogle Scholar
  22. 22.
    Gillick M (2001) Pinning down frailty. J Gerontol A Biol Sci Med Sci 56:M134–M135PubMedGoogle Scholar
  23. 23.
    Fried TR, Bradley EH, Williams CS, Tinetti ME (2001) Functional disability and health care expenditures for older persons. Arch Intern Med 161:2602–2607PubMedCrossRefGoogle Scholar
  24. 24.
    Aniansson A, Sperling L, Rundgren A, Lehnberg E (1983) Muscle function in 75 year old men and women: a longitudinal study. Scand J Rehabil Med 9:92–102Google Scholar
  25. 25.
    Davies C, Thomas D, White M (1986) Mechanical properties of young and elderly human muscle. Acta Med Scand Suppl 711:219–226PubMedGoogle Scholar
  26. 26.
    Larron L, Grimby G, Karlsson J (1979) Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol 46:451–456Google Scholar
  27. 27.
    Aniansson A, Grimby G, Rundgren A (1980) Isometric and isokinetic quadriceps muscle strength in 70-year-old men and women. Scand J Rehabil Med 12:161–168PubMedGoogle Scholar
  28. 28.
    Jette AM, Branch LG (1985) Impairment and disability in the aged. J Chronic Dis 38:59–65PubMedCrossRefGoogle Scholar
  29. 29.
    Jette AM, Branch LG (1981) The Framingham Disability Study. II Physical disability among the aging. Am J Public Health 71:1211–1216PubMedGoogle Scholar
  30. 30.
    Astrand I (1960) Aerobic work capacity in men and women with special reference to age. Acta Physiol Scand 49:1–92CrossRefGoogle Scholar
  31. 31.
    Astrand I, Astrand P-O, Hallback I et al (1973) Reduction in maximal oxygen uptake with age. J Appl Physiol 35:649PubMedGoogle Scholar
  32. 32.
    Fleg JL, Lakatta EG (1985) Loss of muscle mass is a major determinant of the age-related decline in maximal aerobic capacity. Circulation 72:S464Google Scholar
  33. 33.
    Steinhaus LA, Dustman RE, Rubling RO et al (1988) Cardiorespiratory fitness of young and older active and sedentary men. Br J Sports Med 22:163–166PubMedGoogle Scholar
  34. 34.
    Moritani T, De Vries H (1980) Potential for gross muscle hypertrophy in older men. J Gerontol 35:672–682PubMedGoogle Scholar
  35. 35.
    Brown AB, McCartney N, Sale DG (1990) Positive adaptations to weightlifting training in the elderly. J Appl Physiol 69:1725–1733PubMedGoogle Scholar
  36. 36.
    Frontera WR, Meredith CN, O’Reilly KP et al (1988) Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J Appl Physiol 64:1038–1044PubMedGoogle Scholar
  37. 37.
    Charette SL, McEvoy L, Pyka G et al (1991) Muscle hypertrophy response to resistance training in older women. J Appl Physiol 70:1912–1916PubMedGoogle Scholar
  38. 38.
    Anniansson A, Gustafsson E (1981) Physical training in elderly men. Clin Physiol 1:87–98Google Scholar
  39. 39.
    Larsson L (1982) Physical training effects on muscle morphology in sedentary males of different ages. Med Sci Sports Exerc 14:203–206PubMedGoogle Scholar
  40. 40.
    Fiatarone MA, Evans WJ (1993) The etiology and reversibility of muscle dysfuntion in the aged. J Gerontol 48:77–83PubMedGoogle Scholar
  41. 41.
    Gardner EM, Murasko DM (2002) Age-related changes in Type 1 and Type 2 cytokine production in humans. Biogerontology 3:271–290PubMedCrossRefGoogle Scholar
  42. 42.
    Cohen HJ, Pieper CF, Harris T et al (1997) The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J Gerontol 52:M201–M208Google Scholar
  43. 43.
    Cohen HJ, Harris T, Pieper CF (2003) Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med 114:180–187PubMedCrossRefGoogle Scholar
  44. 44.
    Reuben DB, Ferrucci L, Wallace R et al (2000) The prognostic value of serum albumin in healthy older persons with low and high serum interleukin-6 (IL-6) levels. J Am Geriatr Soc 48:1404–1407PubMedGoogle Scholar
  45. 45.
    Ferrucci L, 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 50:1947–1954PubMedCrossRefGoogle Scholar
  46. 46.
    Ferrucci L, Harris TB, Guralnik JM et al (1999) Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc 47:639–646PubMedGoogle Scholar
  47. 47.
    Vasan RS, Sullivan LM, Roubenoff R et al (2003) Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation 107:1486–1491PubMedCrossRefGoogle Scholar
  48. 48.
    Cicoira M, Bolger AP, Doehner W et al (2001) High tumor necrosis factor-alpha levels are associated with exercise intolerance and neurohormonal activation in chronic heart failure patients. Cytokine 15:80–86PubMedCrossRefGoogle Scholar
  49. 49.
    Tisdale MJ (1997) Biology of cachexia. J Natl Cancer Inst 89:1763–1773PubMedCrossRefGoogle Scholar
  50. 50.
    Banks WA, Farr SA, La Scola ME, Morley JE (2001) Intravenous human interleukin-1 alpha impairs memory processing in mice: dependence of blood-brain barrier transport in posterior division of the septum. J Pharmacol Exp Ther 299:536–541PubMedGoogle Scholar
  51. 51.
    Banks WA, Morley JE (2003) Memories of made of this: recent advances in understanding cognitive impairments and dementia. J Gerontol A Biol Sci Med Sci 58:314–321PubMedGoogle Scholar
  52. 52.
    Chan DC, Kasper JD, Black BS, Rabins PV (2003) Presence of behavioral and psychological symptoms predicts nursing home placement in conmmunity-dwelling elders with cognitive impairment in univariate but not multivariate analysis. J Gerontol A Biol Sci Med Sci 58:548–554PubMedGoogle Scholar
  53. 53.
    Sands LP, Yaffe K, Covinsky K et al (2003) Cognitive screening predicts magnitued of functional recovery from admission to 3 months after discharge in hospitalized elders. J Gerontol A Biol Sci Med Sci58:37–45PubMedGoogle Scholar
  54. 54.
    Blaum CS, Ofstedal MB, Liang J (2002) Low cognitive performance, comorbid disease, and task-specific disability: findings from a nationally representative survery. J Gerontol A Biol Sci Med Sci 57:523–531Google Scholar
  55. 55.
    Njegovan V, Man-Son-Hing M, Mitchell SL, Molnar FJ (2001) The hierarchy of functional loss associated with cognitive decline in older persons. J Gerontol A Biol Sci Med Sci 56:638–643Google Scholar
  56. 56.
    Royall DR, Chiodo LK, Polk MJ (2000) Correlates of disability among elderly retirees with’ subclinica’ cognitive impairment. J Gerontol A Biol Sci Med Sci 55:541–546Google Scholar
  57. 57.
    Shike M, Russell DM, Detsky AS et al (1984) Changes in body composition in patients with small-cell cancer. The effect of total parenteral nutrition as an adjunct to chemotherapy. Ann Intern Med 101:303–309PubMedGoogle Scholar
  58. 58.
    Mitch WE (1998) Mechanisms causing loss of lean body mass in kidney disease. Am J Clin Nutr 67:359–366PubMedGoogle Scholar
  59. 59.
    Hedlund J, Hansson LO, Ortqvist A (1995) Shortand long-term prognosis for middle-aged and elderly patients hospitalized with community-acquired pneumonia: impact of nutritional and inflammatory factors. Scand J Infect Dis 27:32–37PubMedGoogle Scholar
  60. 60.
    Toth MJ, Gottlieb SS, Goran MI et al (1997) Daily energy expenditure in free-living heart failure patients. Am J Physiol 272:469–475Google Scholar
  61. 61.
    Roubenoff R, Roubenoff RA, Cannon JG et al (1994) Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J Clin Invest 93:2379–2386PubMedCrossRefGoogle Scholar
  62. 62.
    Kotier DP, Wang J, Pierson RN (1985) Body composition studies in patients with the acquired immunodeficiency syndrome. Am J Clin Nutr 42:1255–1265Google Scholar
  63. 63.
    Baez-Franceschi D, Morley JE (1999) Physio-pathology of the catabolism associated with malnutrition in the elderly. Z Gerontol Geriatr 32:12–19CrossRefGoogle Scholar
  64. 64.
    Thomas DR (2002) Distinguishing starvation from cachexia. Clin Geriatr Med 18:883–891PubMedCrossRefGoogle Scholar
  65. 65.
    Thomas DR (2002) Dietary prescription for chronic obstructive pulmonary disease. Clin Geriatr Med 18:835–839PubMedCrossRefGoogle Scholar
  66. 66.
    Ershler WB (2003) Biological interactions of aging and anemia: a focus on cytokines. J Am Geriatr Soc 51:S18–S21PubMedCrossRefGoogle Scholar
  67. 67.
    Wilkinson TJ, Warren MR (2003) What is the prognosis of mild normocytic anemia in older people? Intern Med J 33:14–17PubMedCrossRefGoogle Scholar
  68. 68.
    Hung AM, Chertow GM, Young BS et al (2002) Inflammatory markers are unrelated to physical activity, performance, and functioning in hemodialysis. J Ren Nutr 12:170–176PubMedCrossRefGoogle Scholar
  69. 69.
    Rubenstein LZ, Josephson KR, Wieland GD et al (1987) Geriatric assessment on a subacute hospital ward. Clin Geriatr Med 3:131–143PubMedGoogle Scholar
  70. 70.
    Applegate WB, Akins D, Van der Zwaag R et al (1983) A geriatric rehabilitation and assessment unit in a community hospital. J Am Geriatr Soc 31:206–210PubMedGoogle Scholar
  71. 71.
    Landefeld CS, Palmer RM, Kresevic DM et al (1995) A randomized trial of care in a hospital medical unit especially designed to improve the functional outcomes of acutely ill older patients. N Engl J Med 332:1338–1344PubMedCrossRefGoogle Scholar
  72. 72.
    Wanich CK, Sullivan-Marx EM, Gottlieb GL, Johnson JC (1992) Functional status outcomes of nursing intervention in hospitalized elderly. Image J Nurs Sch 24:201–207PubMedCrossRefGoogle Scholar
  73. 73.
    Rich MW (2001) Heart failure in the 21st century: a cardiogeriatric syndrome. J Gerontol A Biol Sci Med Sci 56:M88–M96PubMedGoogle Scholar
  74. 74.
    Kirk-Sanchez NJ, Roach KE (2001) Relationship between duration of therapy services in a comprehensive rehabilitation program and mobility at discharge in patients with orthopedic problems. Phys Ther 81:888–895PubMedGoogle Scholar
  75. 75.
    Stuck AE, Egger M, Hammer A et al (2000) Home visits to prevent nursing home admission and functional decline in elderly people. Systematic review and meta-regression analysis. JAMA 287:1022–1028CrossRefGoogle Scholar
  76. 76.
    Li FZ, Harmer P, McAuley E et al (2001) An evaluation of the effects of Tai Chi exercise on physical function among older persons: a randomized controlled trial. Ann Behav Med 23:139–146PubMedCrossRefGoogle Scholar
  77. 77.
    Paffenbarger RSJr, Hyde RT, Wing AL, Hsieh CC (1986) Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 314:605–613PubMedCrossRefGoogle Scholar
  78. 78.
    Kujala UM, Kaprio J, Sarna S, Koskenvuo M (1998) Relationship of leisure-time physical activity and mortality: the Finnish twin cohort. JAMA 279:440–444PubMedCrossRefGoogle Scholar
  79. 79.
    Fiatarone MA, Marks EC, Ryan ND et al (1990) High-intensity strength training in nonagenarians. Effects on skeletal muscle. JAMA 263:3029–3034PubMedCrossRefGoogle Scholar
  80. 80.
    Fiatarone MA, O’Neill EF, Ryan ND et al (1994) Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330:1769–1775PubMedCrossRefGoogle Scholar
  81. 81.
    Meredith CN, Frontera WR, O’Reilly KP, Evans WJ (1992) Body composition in elderly men: effect of dietary modification during strength training. J Am Geriatr Soc 40:155–162PubMedGoogle Scholar
  82. 82.
    Posner JD, Gorman KM, Gitlin LN et al (1990) Effects of exercise training in the elderly on the occurrence and time to onset of cardiovascular diagnoses. J Am Geriatr Soc 38:205–210PubMedGoogle Scholar
  83. 83.
    Arraiz GA, Wigle DT, Mao Y (1992) Risk assessment of physical activity and physical fitness in the Canada Health Survey Mortality follow-up Study. J Clin Epidemiol 45:419–428PubMedCrossRefGoogle Scholar
  84. 84.
    Kannel WB, Sorlie P (1979) Some health benefits of physical activity: the Framingham Study. J Clin Epidemiol 139:857–861Google Scholar
  85. 85.
    Lapidus L, Bengtsson C (1986) Socioeconomic factors and physical activity in relation to cardiovascular disease and death: a 12-year follow-up of participants in a population study of women in Gothenburg, Sweden. Br Heart J 55:295–301PubMedCrossRefGoogle Scholar
  86. 86.
    Adamopoulos S, Parissis J, Karatzas D et al (2002) Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure. J Am Coll Cardiol 39:653–663PubMedCrossRefGoogle Scholar
  87. 87.
    Matsumoto AM (2002) Andropause: clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol A Biol Sci Med Sci 57:M76–M79PubMedGoogle Scholar
  88. 88.
    Morley JE, Perry HM (2003) Androgens and women at the menopause and beyond. J Gerontol A Biol Sci Med Sci 58:409–416Google Scholar
  89. 89.
    Wittert GA, Chapman IM, Haren MT et al (2003) Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 2003;58:618–625Google Scholar
  90. 90.
    Kenny AM, Dawson L, Kleppinger A et al (2003) Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy. J Gerontol A Biol Sci Med Sci 58:M436–M440PubMedGoogle Scholar
  91. 91.
    Iannuzzi-Sucich M, Prestwood KM, Kenny AM (2002) Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 57:772–777Google Scholar
  92. 92.
    Kenny AM, Prestwood KM, Gruman CA et al (2001) Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 56:266–272Google Scholar
  93. 93.
    Morley JE (2001) Andropause: is it time for the geriatrician to treat it? J Gerontol A Biol Sci Med Sci 56:263–265Google Scholar
  94. 94.
    Wittert GA, Chapman IM, Haren MT et al (2003) Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 58:618–625PubMedGoogle Scholar
  95. 95.
    Morley JE (2003) The need for a men’s health initiative. J Gerontol A Biol Sci Med Sci 58:614–617PubMedGoogle Scholar
  96. 96.
    Bhasin S (2003) Testosterone supplementation for aging-associated sarcopenia. J Gerontol A Biol Sci Med Sci 58:1002–1008PubMedGoogle Scholar
  97. 97.
    Morley JE, Kaiser FE, Sih R et al (1997) Testosterone and frailty. Clin Geriatr Med 13:685–695PubMedGoogle Scholar
  98. 98.
    Perry HM, Miller DK, Patrick P, Morley JE (2000) Testosterone and leptin in older African-American men: relationship to age, strength, function and season. Metabolism 49:1085–1091PubMedCrossRefGoogle Scholar
  99. 99.
    Yeh SS, Wu SY, Levine DM et al (2001) The correlation of cytokine levels with body weight after megestrol acetate treatment in geriatric patients. J Gerontol A Biol Sci Med Sci 56:48–54Google Scholar
  100. 100.
    Lambert CP, Sullivan DH, Evans WJ (2003) Effects of testosterone replacement and/or resistance training on interleukin-6, tumor necrosis factor alpha, and leptin in elderly men ingesting megastrol acetate: a randomized controlled trial. J Gerontol A Biol Sci Med Sci 58:165–170PubMedGoogle Scholar
  101. 101.
    Mantovani G, Macciò A, Lai P et al (1998) Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 9:99–106PubMedGoogle Scholar
  102. 102.
    Mantovani G, Macciò A, Massa E, Madeddu C (2001) Managing cancer related anorexia/cachexia. Drugs 61:499–514PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2006

Authors and Affiliations

  • David R. Thomas
    • 1
  1. 1.Division of Geriatric MedicineSaint Louis University Health Sciences CenterSaint LouisUSA

Personalised recommendations