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Changes in plasma and cerebrospinal fluid biomarkers in aged patients with early postoperative cognitive dysfunction following total hip-replacement surgery

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Abstract

Purpose

We hypothesized that different patterns of biomarkers of brain injury and inflammation exist in aged patients with postoperative cognitive dysfunction (POCD) after total hip-replacement with spinal anesthesia.

Methods

Eighty-three patients older than 65 years undergoing elective total hip-replacement surgery were enrolled in this prospective observational study. The CSF levels of Tau, phosphorylated-tau (pTau), amyloidβ1–42 (Aβ1–42), Tau/Aβ1–42, pTau/Aβ1–42, BDNF, IL-6, and IL-1β were measured preoperatively. Perioperative plasma levels of IL-1β, IL-6, brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), and malonaldehyde (MDA) as well as neurocognitive tests were determined preoperatively and seven days postoperatively.

Results

Sixty-one patients completed both the CSF and blood samples collection and the neurocognitive tests. POCD occurred in 24.6 % of patients at seven days after surgery. Patients with POCD had significantly higher IL-1β, Tau/Aβ1–42, pTau/Aβ1–42, and a lower level of Aβ1–42 in CSF when compared with the Non-POCD group (P < 0.05). Furthermore, POCD patients displayed significantly higher plasma levels of MDA when compared with Non-POCD patients at seven days after surgery (P < 0.05). There was no difference in preoperative CSF levels of Tau, IL-6, and pTau as well as plasma levels of IL-1β, IL-6, BDNF and CRP between POCD and Non-POCD groups (P > 0.05).

Conclusion

The POCD patients were associated with higher postoperative plasma levels of MDA, and higher IL-1β and lower Aβ1–42 levels in preoperative CSF that might predispose the development of POCD in aged patients following total hip-replacement surgery with spinal anesthesia.

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References

  1. Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009;110(3):548–55.

    Article  PubMed  Google Scholar 

  2. Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010;68(3):360–8.

    Article  PubMed  CAS  Google Scholar 

  3. Sauër AM, Kalkman C, van Dijk D. Postoperative cognitive decline. J Anesth. 2009;23(2):256–9.

    Article  PubMed  Google Scholar 

  4. Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008;108(1):18–30.

    Article  PubMed  Google Scholar 

  5. Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet. 1998;351(9106):6857–61.

    Article  Google Scholar 

  6. McDonagh DL, Mathew JP, White WD, Phillips-Bute B, Laskowitz DT, Podgoreanu MV, Newman MF, Neurologic Outcome Research Group. Cognitive function after major noncardiac surgery, apolipoprotein E4 genotype, and biomarkers of brain injury. Anesthesiology. 2010;112(4):852–9.

    Article  PubMed  CAS  Google Scholar 

  7. Li YC, Xi CH, An YF, Dong WH, Zhou M. Perioperative inflammatory response and protein S-100β concentrations—relationship with post-operative cognitive dysfunction in elderly patients. Acta Anaesthesiol Scand. 2012;56(5):595–600.

    Article  PubMed  CAS  Google Scholar 

  8. Fodale V, Santamaria LB, Schifilliti D, Mandal PK. Anaesthetics and postoperative cognitive dysfunction: a pathological mechanism mimicking Alzheimer’s disease. Anaesthesia. 2010;65(4):388–95.

    Article  PubMed  CAS  Google Scholar 

  9. Seidenberg M, O’Leary DS, Berent S, Boll T. Changes in seizure frequency and test-retest scores on the Wechsler Adult Intelligence Scale. Epilepsia. 1981;22:75–83.

    Article  PubMed  CAS  Google Scholar 

  10. Brickenkamp R. Test d2: Aufmerksamkeits-Belastungs-test manual. Gottingen: Hogrefe; 1994.

    Google Scholar 

  11. Oswald WD, Roth E. Der Zahlen-Verbindungs-Test (ZVT). Gottingen: Hogrefe; 1997.

    Google Scholar 

  12. Krenk L, Rasmussen LS, Kehlet H. New insights into the pathophysiology of postoperative cognitive dysfunction. Acta Anaesthesiol Scand. 2010;54(8):951–6.

    Article  PubMed  CAS  Google Scholar 

  13. Johnson T, Monk T, Rasmussen LS, Abildstrom H, Houx P, Korttila K, Kuipers HM, Hanning CD, Siersma VD, Kristensen D, Canet J, Ibañaz MT, Moller JT, ISPOCD2 Investigators. Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology. 2002;96(6):1351–7.

    Article  PubMed  Google Scholar 

  14. Tang JX, Baranov D, Hammond M, Shaw LM, Eckenhoff MF, Eckenhoff RG. Human Alzheimer and inflammation biomarkers after anesthesia and surgery. Anesthesiology. 2011;115(4):727–32.

    Article  PubMed  CAS  Google Scholar 

  15. Humpel C. Identifying and validating biomarkers for Alzheimer’s disease. Trends Biotechnol. 2011;29(1):26–32.

    Article  PubMed  CAS  Google Scholar 

  16. Mulder C, Verwey NA, van der Flier WM, Bouwman FH, Kok A, van Elk EJ, Scheltens P, Blankenstein MA. Amyloid-beta(1–42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin Chem. 2010;56(2):248–53.

    Article  PubMed  CAS  Google Scholar 

  17. Hudetz JA, Gandhi SD, Iqbal Z, Patterson KM, Pagel PS. Elevated postoperative inflammatory biomarkers are associated with short- and medium-term cognitive dysfunction after coronary artery surgery. J Anesth. 2011;25(1):1–9.

    Article  PubMed  Google Scholar 

  18. Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA. 2010;107(47):20518–22.

    Article  PubMed  CAS  Google Scholar 

  19. Rudolph JL, Ramlawi B, Kuchel GA, McElhaney JE, Xie D, Sellke FW, Khabbaz K, Levkoff SE, Marcantonio ER. Chemokines are associated with delirium after cardiac surgery. J Gerontol A Biol Sci Med Sci. 2008;63(2):184–9.

    Article  PubMed  Google Scholar 

  20. Torres LL, Quaglio NB, de Souza GT, Bouwman FH, Kok A, van Elk EJ, Scheltens P, Blankenstein MA. Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2011;26(1):59–68.

    PubMed  CAS  Google Scholar 

  21. Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EH, Geschwind D, Masliah E, Chiba AA, Tuszynski MH. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med. 2009;15(3):331–7.

    Article  PubMed  CAS  Google Scholar 

  22. Gunstad J, Benitez A, Smith J, Glickman E, Spitznagel MB, Alexander T, Juvancic-Heltzel J, Murray L. Serum brain-derived neurotrophic factor is associated with cognitive function in healthy older adults. J Geriatr Psychiatry Neurol. 2008;21(3):166–70.

    Article  PubMed  Google Scholar 

  23. Wang Y, Sands LP, Vaurio L, Mullen EA, Leung JM. The effects of postoperative pain and its management on postoperative cognitive dysfunction. Am J Geriatr Psychiatry. 2007;15(1):50–9.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Jiangsu Province’s Key Provincial Talents Program (No. RC2011136) and the Natural Science Foundation of Jiangsu Province (No. BK2012778) and attributed to Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

Conflict of interest

The authors have no potential conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China

    Mu-Huo Ji, Guang-Fen Zhang, Xiao-Min Li, Lin Dong, Wei-Yan Li, Zhi-Qiang Zhou & Jian-Jun Yang

  2. Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China

    Hong-Mei Yuan

Authors
  1. Mu-Huo Ji
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  2. Hong-Mei Yuan
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  3. Guang-Fen Zhang
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  4. Xiao-Min Li
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  5. Lin Dong
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  6. Wei-Yan Li
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  7. Zhi-Qiang Zhou
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Corresponding author

Correspondence to Jian-Jun Yang.

Additional information

M.-H. Ji and H.-M. Yuan contributed equally to this work.

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Ji, MH., Yuan, HM., Zhang, GF. et al. Changes in plasma and cerebrospinal fluid biomarkers in aged patients with early postoperative cognitive dysfunction following total hip-replacement surgery. J Anesth 27, 236–242 (2013). https://doi.org/10.1007/s00540-012-1506-3

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  • DOI: https://doi.org/10.1007/s00540-012-1506-3

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