Systemic Inflammation and Cognition in the Elderly

Abstract

A complex inflammatory cascade is an established part of the pathophysiology of Alzheimer’s disease (AD), and preliminary studies have suggested a link between systemic inflammation and AD. Recent research has extended this theme by examining the influence of systemic inflammation on cognitive function in community-dwelling elderly. Preliminary findings suggest that elevated levels of some inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP) are associated with poorer cognition at cross-sectional assessment. Longitudinal studies suggest an impact of raised IL-6 and CRP, in terms of both cognitive decline and outcome of dementia. Although findings vary considerably between studies, systemic inflammation may have relevance for cognitive function and cognitive decline in late life. Further comprehensive studies are required to further explore the relationship between systemic inflammation and cognition in the elderly.

Keywords

Cognition Cytokines Dementia Inflammation Mild cognitive impairment 

References

  1. 1.
    Ishii T, Haga S, Shimizu F (1975) Identification of components of immunoglobulins in senile plaques by means of fluorescent antibody technique. Acta Neuropathol 32:157–162PubMedCrossRefGoogle Scholar
  2. 2.
    Rogers J, Luber-Narod J, Styren SD et al (1988) Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer’s disease. Neurobiol Aging 9:339–349PubMedCrossRefGoogle Scholar
  3. 3.
    McGeer PL, Rogers J, McGeer E (2006) Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years. J Alzheimers Dis 9:271–276PubMedGoogle Scholar
  4. 4.
    Akiyama H, Bargers S, Barnum S et al (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421PubMedCrossRefGoogle Scholar
  5. 5.
    Breitner JC (1996) Inflammatory processes and antiinflammatory drugs in Alzheimer’s disease: a current appraisal. Neurobiol Aging 17:789–794PubMedCrossRefGoogle Scholar
  6. 6.
    McGeer PL, Schulzer M, McGeer EG (1996) Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 47:425–432PubMedCrossRefGoogle Scholar
  7. 7.
    Wyss-Coray T (2006) Inflammation in Alzheimer’s disease: driving force, bystander or ­beneficial response? Nat Med 12(9):1005–1015PubMedGoogle Scholar
  8. 8.
    Bermejo P, Martin-Aragon S, Benedi J et al (2008) Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease. Immunol Lett 117(2):198–202PubMedCrossRefGoogle Scholar
  9. 9.
    Alvarez A, Cacabelos R, Sanpedro C et al (2007) Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer’s disease. Neurobiol Aging 28:533–536PubMedCrossRefGoogle Scholar
  10. 10.
    Dimopoulos N, Piperi C, Salonicioti A et al (2006) Indices of low-grade chronic inflammation correlate with early cognitive deterioration in an elderly Greek population. Neurosci Lett 398(1–2):118–123PubMedCrossRefGoogle Scholar
  11. 11.
    Zuliani G, Ranzini M, Guerra G et al (2007) Plasma cytokines profile in older subjects with late-onset Alzheimer’s disease or vascular dementia. J Psychiatr Res 41:686–693PubMedCrossRefGoogle Scholar
  12. 12.
    Licastro F, Pedrini S, Caputo L et al (2000) Increased plasma levels of interleukin-1, interleukin-6 and α1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals from the brain? J Neuroimmunol 103:97–102PubMedCrossRefGoogle Scholar
  13. 13.
    Singh VK, Guthikonda P (1997) Circulating cytokines in Alzheimer’s disease. J Psychiatr Res 31(6):657–660PubMedCrossRefGoogle Scholar
  14. 14.
    McGeer PL, McGeer EG (2001) Polymorphisms in inflammatory genes and the risk of Alzheimer disease. Arch Neurol 58:1790–1792PubMedCrossRefGoogle Scholar
  15. 15.
    Papassotiropolous A (1999) A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer’s disease. Ann Neurol 45:666–668CrossRefGoogle Scholar
  16. 16.
    Luterman JD, Haroutunian V, Yemul S et al (2000) Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Arch Neurol 57:1153–1160PubMedCrossRefGoogle Scholar
  17. 17.
    McCusker SM, Curran MD, Dynan KB (2001) Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer’s disease and vascular dementia: a case-control study. Lancet 357(9254):436–439PubMedCrossRefGoogle Scholar
  18. 18.
    Nicoll JA, Mrak RE, Graham DI et al (2000) Association of interleukin-1 gene polymorphisms with Alzheimer’s disease. Ann Neurol 47(3):365–368PubMedCrossRefGoogle Scholar
  19. 19.
    Franceschi C, Capri M, Monti D et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105PubMedCrossRefGoogle Scholar
  20. 20.
    Giunta B, Fernandez F, Nikolic WV et al (2008) Inflammaging as a prodrome to Alzheimer’s disease. J Neuroinflammation 5:51–66PubMedCrossRefGoogle Scholar
  21. 21.
    Sparkman NL, Johnson RW (2008) Neuroinflammation associated with aging sensitizes the brain to the effects of infection and stress. Neuroimmunomodulation 15:323–330PubMedCrossRefGoogle Scholar
  22. 22.
    Wilson CJ, Finch CE, Cohen HJ (2002) Cytokines and cognition: the case for a head-to-toe paradigm. J Am Geriatr Soc 50:2041–2056PubMedCrossRefGoogle Scholar
  23. 23.
    Alley DE, Crimmins EM, Karlamangla A et al (2008) Inflammation and rate of cognitive change in high-functioning older adults. J Gerontol A Biol Sci Med Sci 63A(1):50–55CrossRefGoogle Scholar
  24. 24.
    Baune BT, Ponath G, Golledge J et al (2008) Association between IL-8 cytokine and cognitive performance in an elderly general population: the MEMO-study. Neurobiol Aging 29:937–944PubMedCrossRefGoogle Scholar
  25. 25.
    Sweat V, Starr V, Bruehl H (2008) C-reactive protein is linked to lower cognitive performance in overweight and obese women. Inflammation 31(3):198–207PubMedCrossRefGoogle Scholar
  26. 26.
    Schram MT, Euser SM, de Craen AJM et al (2007) Systemic markers of inflammation and cognitive decline in old age. J Am Geriatr Soc 55:708–716PubMedCrossRefGoogle Scholar
  27. 27.
    Fischer P, Zehetmayer S, Bauer K et al (2006) Relation between vascular risk factors and cognition at age 75. Acta Neurol Scand 114:84–90PubMedCrossRefGoogle Scholar
  28. 28.
    Dik MG, Jonker C, Hack CE et al (2005) Serum inflammatory proteins and cognitive decline in older persons. Neurology 64:1371–1377PubMedCrossRefGoogle Scholar
  29. 29.
    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 60A(8):1017–1021CrossRefGoogle Scholar
  30. 30.
    Elwan O, Madkour O, Elwan F et al (2003) Brain aging in normal Egyptians: cognition, ­education, personality, genetic and immunological study. J Neurol Sci 211:15–22PubMedCrossRefGoogle Scholar
  31. 31.
    Teunissen CE, van Boxtel MPJ, Bosma H et al (2003) Inflammation markers in relation to cognition in a healthy aging population. J Neuroimmunol 134:142–150PubMedCrossRefGoogle Scholar
  32. 32.
    Weaver JD, Huang MH, Albert M et al (2002) Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 59:371–378PubMedCrossRefGoogle Scholar
  33. 33.
    Bruunsgaard H, Andersen-Ranberg K, Jeune B et al (1999) A high plasma concentration of TNF-α is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci 54A(7):357–364CrossRefGoogle Scholar
  34. 34.
    Haan MN, Aiello AE, West NA et al (2008) C-reactive protein and rate of dementia in carriers and non carriers of apolipoprotein APOE4 genotype. Neurobiol Aging 29:1774–1782PubMedCrossRefGoogle Scholar
  35. 35.
    Jordanova V, Stewart R, Davies E et al (2007) Markers of inflammation and cognitive decline in an African-Caribbean population. Int J Geriatr Psychiatry 22:966–973PubMedCrossRefGoogle Scholar
  36. 36.
    Komulainen P, Lakka TA, Kivipelto M et al (2007) Serum high sensitivity C-reactive protein and cognitive function in elderly women. Age Ageing 36:443–448PubMedCrossRefGoogle Scholar
  37. 37.
    Rafnsson SB, Deary IJ, Smith FB et al (2007) Cognitive decline and markers of inflammation and hemostasis: the Edinburgh artery study. J Am Geriatr Soc 55:700–707PubMedCrossRefGoogle Scholar
  38. 38.
    Ravaglia G, Forti P, Maioli F et al (2007) Blood inflammatory markers and risk of dementia: the Conselice study of brain aging. Neurobiol Aging 28:1810–1820PubMedCrossRefGoogle Scholar
  39. 39.
    Tan ZS, Beiser AS, Vasan RS et al (2007) Inflammatory markers and the risk of Alzheimer’s disease: the Framingham study. Neurology 68:1902–1908PubMedCrossRefGoogle Scholar
  40. 40.
    Van den Biggelaar AHJ, Gussekloo J, de Craen AJM et al (2007) Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. Exp Gerontol 42:693–701PubMedCrossRefGoogle Scholar
  41. 41.
    Weuve J, Ridker PM, Cook NR et al (2006) High-sensitivity C-reactive protein and cognitive function in older women. Epidemiology 17:183–189PubMedCrossRefGoogle Scholar
  42. 42.
    Tilvis RS, Kahonen-Vare MH, Jolkkonen J et al (2004) Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol A Biol Sci Med Sci 59A(3):268–274CrossRefGoogle Scholar
  43. 43.
    Yaffe K, Kanaya A, Lindquist K et al (2004) The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 292(18):2237–2242PubMedCrossRefGoogle Scholar
  44. 44.
    Engelhart M, Geerlings MI, Meijer J et al (2004) Inflammatory proteins in plasma and the risk of dementia. Arch Neurol 61:668–672PubMedCrossRefGoogle Scholar
  45. 45.
    Schmidt R, Schmidt H, Curb D et al (2002) Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia aging study. Ann Neurol 52:168–174PubMedCrossRefGoogle Scholar
  46. 46.
    Gimeno D, Marmot MG, Singh et al (2008) Inflammatory markers and cognitive function in middle-aged adults: the Whitehall II study. Psychoneuroendocrinology 33:1322–1334PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  1. 1.Brain and Ageing Program, School of PsychiatryUniversity of New South WalesSydneyAustralia
  2. 2.Department of Developmental Disability Neuropsychiatry, School of PsychiatryUniversity of New South WalesSydneyAustraliaand
  3. 3.University of New South WalesUNSW,SydneyAustraliae-mail: j.trollor@unsw.edu.au

Personalised recommendations