Skip to main content

Advertisement

Log in

The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Inflammation may contribute to cognitive decline and dementia. This study examined the cross-sectional relationships between markers of systemic inflammation (C-reactive protein, interleukins-1β, -6, -8, -10, -12, plasminogen activator inhibitor, serum amyloid A, tumour necrosis factor-α and vascular adhesion molecule-1) and cognitive function in 873 non-demented community-dwelling elderly participants aged 70–90 years. Regression analyses were performed to determine the relationships between cognitive domains and inflammatory markers, controlling for age, sex, education, cardiovascular risk factors, obesity and other metabolic factors, smoking, alcohol consumption, depression and presence of the apolipoprotein ε4 genotype. Regression analyses were repeated using four factors derived from a factor analysis of the cognitive tests. After Bonferroni correction for multiple testing, associations remained between raised levels of interleukin-12 and reduced performance in processing speed. Marked sex differences were noted in the abovementioned findings, with only females being significantly affected. Using the four factors derived from the factor analyses of cognitive test as dependent variables, interleukins-12 and -6 were both associated with the processing speed/executive function factor, even after controlling for relevant confounding factors. Thus, markers of systemic inflammation are related to cognitive deficits in a non-clinical community-dwelling elderly population, independent of depression, cardiovascular or metabolic risk factors, or presence of apolipoprotein ε4 genotype. Additional research is required to elucidate the pathophysiology and longitudinal development of these relationships.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Alley DE, Crimmins EM, Karlamangla A, Hu P, Seeman TE (2008) Inflammation and rate of cognitive change in high-functioning older adults. J Gerontol 63A(1):50–55

    Google Scholar 

  • Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M (2007) Serum TNF-α levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging 28:533–536

    Article  PubMed  CAS  Google Scholar 

  • American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington DC, International Version

    Google Scholar 

  • Anderson TM, Trollor JN, Sachdev PS, Brodaty H (2007) Effects of sociodemographic and health variables on Mini-Mental State Exam scores in older Australians. Am J Geriatr Psychiatry 15:467–476

    Article  PubMed  Google Scholar 

  • Azad NA, Al Bugami M, Loy-English I (2007) Gender differences in dementia risk factors. Gend Med 4:120–129

    Article  PubMed  Google Scholar 

  • Bagnoli S, Celline E, Tede A, Nacmias B, Piacentini S, Bessi V, Bracco L, Sorbi S (2007) Association of IL-10 promoter polymorphism in Italian Alzeimer's disease. Neurosci Lett 418:262–265

    Article  PubMed  CAS  Google Scholar 

  • Baune BT, Ponath G, Golledge J, Varga G, Arolt V, Rothermundt M, Berger K (2008) Association between IL-8 cytokine and cognitive performance in an elderly general population – The MEMO-Study. Neurobiol Aging 29:937–944

    Article  PubMed  CAS  Google Scholar 

  • Benton AL (1967) Problems of test construction in the field of aphasia. Cortex 3:32–58

    Google Scholar 

  • Benton Sivan AB, Spreen O (1996) Der Benton Test, 7th edn. Huber, Bern

    Google Scholar 

  • Bermejo P, Martin-Aragon S, Benedi J, Susin C, Felici E, Gil P, Ribera JM et al (2008) Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease. Immunol Lett 117:198–202

    Article  PubMed  CAS  Google Scholar 

  • Blom G (1958) Statistical estimates and transformed beta-variables. John Wiley and Sons, New York

    Google Scholar 

  • Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK (1999) A high plasma concentration of TNF-α is associated with dementia in centenarians. J Gerontol 54A(7):357–364

    Google Scholar 

  • Buckner RL (2004) Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 44:195–208

    Article  PubMed  CAS  Google Scholar 

  • Christensen H, Batterham PJ, Mackinnon AJ, Jorm AF, Mack HA et al (2008) The association of APOE genotype and cognitive decline in interaction with risk factors in a 65–69 year old community sample. BMC Geriatr 8:14

    Article  PubMed  Google Scholar 

  • Danesh J et al (2000) Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 321:199–204

    Article  PubMed  CAS  Google Scholar 

  • Deniz-Naranjo MC, Munoz-Fernandez C, Alemany-Rodriguez MJ, Perez-Vieitez MC, Aladro-Benito Y, Irurita-Latasa J, Sanchez-Garcia F (2008) Cytokine IL-1 beta but not IL-1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain. Eur J Neurol 15:1080–1084

    Article  PubMed  CAS  Google Scholar 

  • Dik MG, Jonker C, Hack CE, Smit JH, Comijs HC, Eikelenboom P (2005) Serum inflammatory proteins and cognitive decline in older persons. Neurology 64:1371–1377

    Article  PubMed  CAS  Google Scholar 

  • Dimopoulos N, Piperi C, Salonicioti A, Mitropoulos P, Kallai E, Liappas I et al (2006) Indicies of low-grade chronic inflammation correlate with early cognitive deterioration in an elderly Greek population. Neurosci Lett 398:118–123

    Article  PubMed  CAS  Google Scholar 

  • Engelhart M, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, Stijnen T, Hofman A, Witteman JCM, Breteler MMB (2004) Inflammatory proteins in plasma and the risk of dementia. Arch Neurol 61:668–672

    Article  PubMed  Google Scholar 

  • Fastenau PS, Denburg NL, Mauer BA (1998) Parallel short forms for the Boston Naming Test: psychometric properties and norms for older adults. J Clin Exp Neuropsychol 20(6):828–834

    Article  PubMed  CAS  Google Scholar 

  • Fischer P, Zehetmayer S, Bauer K, Huber K, Jungwirth S, Tragl KH (2006) Relation between vascular risk factors and cognition at age 75. Acta Neurol Scand 114:84–90

    Article  PubMed  CAS  Google Scholar 

  • Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–98

    Article  PubMed  CAS  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105

    Article  PubMed  CAS  Google Scholar 

  • Gimeno D, Marmot MG, Singh MA (2008) Inflammatory markers and cognitive function in middle-aged adults: the Whitehall II study. Psychoneuroendocrinology 33:1322–1334

    Article  PubMed  CAS  Google Scholar 

  • Giunta B, Fernandez F, Nikolic WV, Obregon D, Rrapo E, Town T, Tan J (2008) Inflammaging as a prodrome to Alzheimer's disease. J Neuroinflammation 5:51–66

    Article  PubMed  Google Scholar 

  • Gunning-Dixon FM, Brickman AM, Cheng JC, Alexopoulos GS (2009) Ageing of cerebral white matter: a review of MRI findings. Int J Geriatric Psychiatry 24:109–117

    Article  Google Scholar 

  • Henderson AS, Easteal S, Jorm AF, Mackinnon AJ, Korten AE et al (1995) Apolipoprotein E allele ε4, dementia, and cognitive decline in a population sample. Lancet 346(8987):1387–90

    Article  PubMed  CAS  Google Scholar 

  • Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with Hha1. J Lipid Res 31(3):545–8

    PubMed  CAS  Google Scholar 

  • Ishii T, Haga S, Shimizu F (1975) Identification of components of immunoglobins in senile plaques by means of fluorescent antibody technique. Acta Neuropath 32:157–162

    Article  PubMed  CAS  Google Scholar 

  • Jordanova V, Stewart R, Davies E, Sherwood R, Prince M (2008) Markers of inflammation and cognitive decline in an African-Caribbean population. Int J Geriatr Psychiatry 22:966–973

    Article  Google Scholar 

  • Kaplan E, Goodglass H, Weintraub S (2001) The Boston naming test. Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  • Klove H (1963) Clinical neuropsychology. In: Forster FM (ed) The Medical Clinics of North America. Saunders, New York

    Google Scholar 

  • Komulainen P, Lakka TA, Kivipelto M, Hassinen M, Penttila IM, Helkala E et al (2007) Serum high sensitivity C-reactive protein and cognitive function in elderly women. Age Aging 36:443–448

    Article  Google Scholar 

  • Kuo HK, Yen CJ, Chang CH, Kuo CK, Chen JH, Sorond F (2005) Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systemic review and meta-analysis. Lancet Neurol 4:371–380

    Article  PubMed  CAS  Google Scholar 

  • Lezak MD, Howieson DB, Loring DW (2004) Neuropsychological assessment, 4th edn. Oxford University Press, New York

    Google Scholar 

  • Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C et al (2000) Increased plasma levels of interleukin-1, interleukin-6 and α-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? J Neuroimmunology 103:97–102

    Article  CAS  Google Scholar 

  • Luciano M, Marioni RE, Gow AJ, Starr JM, Deary IJ (2009) Reverse causation in the association between C-reactive protein and fibrinogen levels and cognitive abilities in an aging sample. Psychosom Med 71:404–9

    Article  PubMed  CAS  Google Scholar 

  • Marsland AL, Petersen KL, Sathanoori R, Muldoon MF, Neumann SA, Ryan C, Flory JD, Manuck SB (2006) Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers. Psychosom Med 68:895–903

    Article  PubMed  CAS  Google Scholar 

  • Motta M, Imbesi R, Di Rosa M, Stivala F, Malaguarnera L (2007) Altered plasma cytokine levels in Alzheimer's disease: correlation with the disease progression. Immunol Lett 114:46–51

    Article  PubMed  CAS  Google Scholar 

  • Paganelli R, Di Iorio A, Patricelli L, Ripani F, Sparvieri E, Faricelli R, Iarlori C, Porreca E, Di Gioacchino M, Abate G (2002) Proinflamatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer's disease patients. Exp Gerontol 37:257–263

    Article  PubMed  CAS  Google Scholar 

  • Phillips AC, Batty GD, van Zanten JJ, Mortensen LH, Deary IJ, Calvin CM, Carroll D (2011) Cognitive ability in early adulthood is associated with systemic inflammation in middle age: the Vietnam experience study. Brain Behav Immun 25:298–301

    Article  PubMed  Google Scholar 

  • Ravaglia G, Forti P, Mailoi F, Brunetti N, Martelli M, Servadei L et al (2005) Serum C-reactive protein and cognitive function in healthy elderly Italian community dwellers. J Gerontol: Med Sci 60A(8):1017–1021

    Article  CAS  Google Scholar 

  • Reitan RM, Wolfson D (1993) The Halstead–Reitan neuropsycholgical test battery: theory and clinical interpretation. Neuropsychological Press, Tucson

    Google Scholar 

  • Rey A (1964) L'examen clinique en psychologie. Presses Universitaires de France, Paris

    Google Scholar 

  • Rogers J, Luber-Narod J, Styren SD, Civin WH (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 9:339–349

    Article  PubMed  CAS  Google Scholar 

  • Sachdev P, Brodaty H, Reppermund S, Kochan NA, Trollor JN, Draper B, Slavin M, Crawford J, Kang K, Broe A, Mather K, Lux O, Memory and Ageing Study Team (2010) The Sydney Memory and Ageing Study (MAS): methodology and baseline medical and neuropsychiatric characteristics of an elderly epidemiological non-demented cohort of Australians aged 70–90 years. Int Psychogeriatr 19:1–17

    Google Scholar 

  • Schram MT, Euser SM, de Craen AJM, Witteman JC, Frolich M, Hofman A, Jolles J, Breteler MMB, Westendorp RGJ (2007) Systemic markers of inflammation and cognitive decline in old age. J Am Geriatr Soc 55:708–716

    Article  PubMed  Google Scholar 

  • Sheikh JI, Yesavage JA (1986) Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. In: Brink TL (ed) Clinical gerontology: a guide to assessment and intervention. The Hawthorn Press, NY, pp 165–173

    Google Scholar 

  • Soeda S, Koyanagi S, Kuramoto Y, Kimura M, Oda M, Kozako T, Hayashida S, Shimeno H (2008) Anti-apoptotic roles of the plasminogen activator inhibitor-1 as a neurotropic factor in the central nervous system. Thromb Hemost 100:1014–1020

    CAS  Google Scholar 

  • Spreen O, Benton AL (1969) Neurosensory center comprehensive examination for Aphasia: manual of instructions (NCCEA). University of Victoria, Victoria

    Google Scholar 

  • SPSS Statistics (2008) Rel. 17.0.0. SPSS Inc, Chicago

    Google Scholar 

  • Strachan MWJ, Reynolds RM, Frier BM, Mitchell RJ, Price JF (2008) The relationship between type 2 diabetes and dementia. Br Med Bull 88:131–146

    Article  PubMed  CAS  Google Scholar 

  • Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18:643–662

    Article  Google Scholar 

  • Sheikh JI, Yesavage JA, Brooks JO 3rd, Friedman L, Gratzinger P, Hill RD, Zadeik A, Crook T (1991) Proposed factor structure of the Geriatric Depression Scale. Int Psychogeriatr 3(1):23–8

    Article  PubMed  CAS  Google Scholar 

  • Salthouse TA (1996) The processing-speed theory of adult age differences in cognition. Psychol Rev 103:403–428

    Article  PubMed  CAS  Google Scholar 

  • Trollor JN, Smith E, Baune BT, Kochan NA, Campbell L, Samaras K, Crawford J, Brodaty H, Sachdev P (2010) Systemic inflammation is associated with MCI and its subtypes - the Sydney Memory and Aging Study. Dement Geriatr Cogn Disord 30(6):569–578

    Article  PubMed  Google Scholar 

  • Uhlar CM, Whitehead AS (1999) Serum amyloid A, the major vertabrate acute-phase reactant. Eur J Biochem 265:501–523

    Article  PubMed  CAS  Google Scholar 

  • van den Biggelaar AHJ, Gussekloo J, de Craen AJM, Frolich M, Stek ML, van der Mast RC, Westendorp RGJ (2007) Inflammation and interleukin-1 signalling network contribute to depressive symptoms but not cognitive decline in old age. Exp Gerontol 42:693–701

    Article  PubMed  Google Scholar 

  • Wright CB, Sacco RL, Rundek TR, Delman JB, Rabbani LE, Elkind MSV (2006) Interleukin-6 is associated with cognitive function: the Northern Manhattan Study. J Stroke Cerebrovasc Dis 15:34–38

    Article  PubMed  Google Scholar 

  • van Dijk EJ, Prins ND, Vermeer SE, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MMB (2005) C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation 112:900–905

    Article  PubMed  Google Scholar 

  • Warnberg J, Gomez-Martinez S, Romeo J, Diaz LE, Marcos A (2009) Nutrition, inflammation and cognitive function. Neuroimmunomodulation: annuals New York Academy Sci 1153:164–175

    Article  CAS  Google Scholar 

  • Weaver JD, Huang MH, Albert M, Harris T, Rowe JW, Seeman TE (2002) Interleukin-6 and risk of cognitive decline: MacArthur Studies of Successful Aging. Neurology 59:371–378

    Article  PubMed  CAS  Google Scholar 

  • Wechsler D (1997) Wechsler adult intelligence scale-III. The Psychological Corporation, San Antonio

    Google Scholar 

  • Wechsler D (1981) Wechsler adult intelligence scale — Revised: Manual. Psychological Corporation: New York

  • Wilson CJ, Finch CE, Cohen HJ (2002) Cytokines and cognition: the case for a head-to-toe paradigm. J Am Geriatr Soc 50:2041–2056

    Article  PubMed  Google Scholar 

  • Zuliani G, Cavalieri M, Galvani M, Passaro A, Munani MR, Bosi C et al (2008) Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia. J Neurological Sci 272:164–170

    Article  CAS  Google Scholar 

  • Zuliani G, Ranzini M, Guerra G, Rossi L, Munari MR, Zurlo A, Volpato S, Atti AR, Ble A, Fellin R (2007) Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. J Psychiatr Res 41:686–693

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a Dementia Research Grant through the Australian National Health and Medical Research Council (Grant ID 510124).

The Sydney MAS is supported by the Australian National Health and Medical Research Council Program Grant (Grant ID 350833). The authors wish to acknowledge the contributions of Brain and Ageing Research Program Staff especially Kristan Kang, Simone Reppermund and Melissa Slavin as well all MAS participants.

DNA was extracted by Genetic Repositories Australia, which is supported by an Australian National Health and Medical Research Council Grant (grant ID 401184). Arezoo Assareh and Karen Mather undertook the APOE genotyping in the laboratory of Peter Schofield and John Kwok at Neuroscience Research Australia.

We would also like to acknowledge and thank the accredited laboratory SEALS for their contribution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Julian N. Trollor.

About this article

Cite this article

Trollor, J.N., Smith, E., Agars, E. et al. The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study. AGE 34, 1295–1308 (2012). https://doi.org/10.1007/s11357-011-9301-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-011-9301-x

Keywords

Navigation