Postoperative Cognitive Dysfunction

  • Suparna Bharadwaj
  • Sriganesh Kamath


Postoperative cognitive dysfunction (POCD) is a disturbing reality, the consequence of which may be significant morbidity and mortality. The spectrum of memory dysfunction, including acute delirium, postoperative decline, and dementia, is a source of anxiety for patients and their families. Comprehensive awareness about POCD may provide a direction to identify, manage, and prevent POCD in most vulnerable patients. POCD also has long-term consequences of costs involving the management of the cognitively debilitated. Persistent postoperative systemic inflammation is a key element that contributes to pathogenesis of COPD. Advanced age, metabolic syndromes, neurological disorders, and wrong choice of anesthetics/sedative drugs may each result in excessive and prolonged neuro-inflammatory response to surgery. By recognizing patients early enough in the occurrence of ongoing inflammation, interventions can be suitably executed. This chapter aims to discuss comprehensively the pathogenesis, risk factors, management, and prevention of POCD in patients after non-cardiac surgery.


Postoperative cognitive dysfunction Pathogenesis Risk factors Biomarkers Prevention Management 


  1. 1.
    Shugarman LR, Decker SL, Bercovitz A. Demographic and social characteristics and spending at the end of life. J Pain Symptom Manag. 2009;38(1):15–26.CrossRefGoogle Scholar
  2. 2.
    Bedford PD. Adverse cerebral effects of anaesthesia on old people. Lancet. 1955;2:259–63.CrossRefGoogle Scholar
  3. 3.
    Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1study. Lancet. 1998;351:857–61.CrossRefGoogle Scholar
  4. 4.
    Newman S, Stygall J, Hirani S, Shaefi S, Maze M. Postoperative cognitive dysfunction after noncardiac surgery: a systematic review. Anesthesiology. 2007;106(3):572–90.CrossRefGoogle Scholar
  5. 5.
    Krenk L, Rasmussen LS. Postoperative delirium and postoperative cognitive dysfunction in the elderly - what are the differences? Minerva Anestesiol. 2011;77:742–9.PubMedGoogle Scholar
  6. 6.
    Patel N, Minhas JS, Chung EM. Intraoperative embolization and cognitive decline after cardiac surgery: a systematic review. Semin Cardiothorac Vasc Anesth. 2016;20(3):225–31.CrossRefGoogle Scholar
  7. 7.
    Cropsey C, Kennedy J, Han J, Pandharipande P. Cognitive dysfunction, delirium, and stroke in cardiac surgery patients. Semin Cardiothorac Vasc Anesth. 2015;19(4):309–17.CrossRefGoogle Scholar
  8. 8.
    Savage H. Insanity following the use of anaesthetics in operations. Br Med J. 1887;2(1405):1199–200.CrossRefGoogle Scholar
  9. 9.
    Heyer EJ, Wilson DA, Sahlein DH, et al. APOE-epsilon4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy. Neurology. 2005;65:1759.CrossRefGoogle Scholar
  10. 10.
    Vizcaychipi MP, Watts HR, O’Dea KP, Lloyd DG, Penn JW, Wan Y, et al. The therapeutic potential of atorvastatin in a mouse model of postoperative cognitive decline. Ann Surg. 2014;259:1235–44.CrossRefGoogle Scholar
  11. 11.
    Gao L, Taha R, Gauvin D, Othmen LB, Wang Y, Blaise G. Postoperative cognitive dysfunction after cardiac surgery. Chest. 2005;128:3664–70.CrossRefGoogle Scholar
  12. 12.
    Chow WB, Rosenthal RA, Merkow RP, et al. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons national surgical quality improvement program and the American Geriatrics Society. J Am Coll Surg. 2012;215:453–66.CrossRefGoogle Scholar
  13. 13.
    Abildstrom H, Rasmussen LS, Rentowl P, et al. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. Acta Anaesthesiol Scand. 2000;44:1246–51.CrossRefGoogle Scholar
  14. 14.
    Steinmetz J, Siersma V, Kessing LV, Rasmussen LS. Is postoperative cognitive dysfunction a risk factor for dementia?A cohort follow-up study. Br J Anaesth. 2013;110:i92–7.CrossRefGoogle Scholar
  15. 15.
    Rockwood K, Cosway S, Carver D, Jarrett P, Stadnyk K, Fisk J. The risk of dementia and death after delirium. Age Ageing. 1999;28(6):551–6.CrossRefGoogle Scholar
  16. 16.
    Rasmussen LS. Postoperative cognitive decline: the extent of the problem. Acta Anaesthesialogica Belgica. 1999;50:199–204.Google Scholar
  17. 17.
    Rudolph JL, Marcantonio ER, Culley DJ, Silverstein JH, Rasmussen LS, et al. Delirium is associated with early postoperative cognitive dysfunction. Anaesthesia. 2008;63:941–7.CrossRefGoogle Scholar
  18. 18.
    Dijkstra JB, Jolles J. Postoperative cognitive dysfunction versus complaints: a discrepancy in long-term findings. Neuropsychol Rev. 2002;12:1–14.CrossRefGoogle Scholar
  19. 19.
    Ghoneim MM, Block RI. Clinical, methodological and theoretical issues in the assessment of cognition after anaesthesia and surgery: a review. Eur J Anaesthesiol. 2012;29:409–22.PubMedGoogle Scholar
  20. 20.
    Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefGoogle Scholar
  21. 21.
    Polunina AG, Golukhova EZ, Guekht AB, et al. Cognitive dysfunction after on-pump operations: neuropsychological characteristics and optimal core battery of tests. Stroke Res Treat. 2014;2014:302824.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major non-cardiac surgery. Anesthesiology. 2008;108(1):18–30.CrossRefGoogle Scholar
  23. 23.
    Abildstrom H, Rasmussen LS, Rentowl P, et al. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand. 2000;44(10):1246–51.CrossRefGoogle Scholar
  24. 24.
    Abildstrom H, Christiansen M, Siersma VD, Rasmussen LS, ISPOCD2 Investigators. Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery. Anesthesiology. 2004;101(4):855–61.CrossRefGoogle Scholar
  25. 25.
    Goldstein MZ, Young BL, Fogel BS, Benedict RH. Occurrence and predictors of short-term mental and functional changes in older adults undergoing elective surgery under general anesthesia. Am J Geriatr Psychiatr. 1998;6(1):42–52.Google Scholar
  26. 26.
    Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, et al. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010;68:360–8.CrossRefGoogle Scholar
  27. 27.
    Buvanendran A, Kroin JS, Berger RA, et al. Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology. 2006;104:403–10.CrossRefGoogle Scholar
  28. 28.
    Vizcaychipi MP, Vizcaychipi MP, Xu L, et al. Heat shock protein 72 overexpression prevents early postoperative memory decline after orthopedic surgery under general anesthesia in mice. Anesthesiology. 2011;114:891–900.CrossRefGoogle Scholar
  29. 29.
    Flink BJ, Rivelli SK, Cox EA, White WD, Falcone G, Vail TP, et al. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the non-demented elderly. Anesthesiology. 2012;116:788–96.CrossRefGoogle Scholar
  30. 30.
    Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104–7.CrossRefGoogle Scholar
  31. 31.
    Terrando N, Monaco C, Ma D, et al. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A. 2010;107(47):20518–22.CrossRefGoogle Scholar
  32. 32.
    Lotze MT, Zeh HJ, Rubartelli A, et al. The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol Rev. 2007;220:60–81.CrossRefGoogle Scholar
  33. 33.
    Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9(6):418–28.CrossRefGoogle Scholar
  34. 34.
    de Jonge WJ, van der Zanden EP, The FO, et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol. 2005;6(8):844–51.CrossRefGoogle Scholar
  35. 35.
    Bartus RT, Dean RL 3rd, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217(4558):408–14.CrossRefGoogle Scholar
  36. 36.
    Parnet P, Amindari S, Wu C, Brunke-Reese D, Goujon E, Weyhenmeyer JA, et al. Expression of type I and type II interleukin-1 receptors in mouse brain. Brain Res Mol Brain Res. 1994;27(1):63–70.CrossRefGoogle Scholar
  37. 37.
    Rothwell NJ, Hopkins SJ. Cytokines and the nervous system II: actions and mechanisms of action. Trends Neurosci. 1995;18(3):130–6.CrossRefGoogle Scholar
  38. 38.
    Tang JX, Eckenhoff MF, Eckenhoff RG. Anesthetic modulation of neuroinflammation in Alzheimer’s disease. Curr Opin Anaesthesiol. 2011;24(4):389–94.CrossRefGoogle Scholar
  39. 39.
    Cirelli C. Sleep, synaptic homeostasis and neuronal firing rates. Curr Opin Neurobiol. 2017;44:72–9.CrossRefGoogle Scholar
  40. 40.
    Sanders RD, Maze M. Contribution of sedative-hypnotic agents to delirium via modulation of the sleep pathway. Can J Anaesth. 2011;58(2):149–56.CrossRefGoogle Scholar
  41. 41.
    da Silva AA, de Mello RG, Schaan CW, Fuchs FD, Redline S, Fuchs SC. Sleep duration and mortality: a systematic review and meta-analysis. BMJ Open. 2016;6(2):e008119.CrossRefGoogle Scholar
  42. 42.
    Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008;108(1):18–30.CrossRefGoogle Scholar
  43. 43.
    Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Pagel PS. Metabolic syndrome exacerbates short-term postoperative cognitive dysfunction in patients undergoing cardiac surgery: results of a pilot study. J Cardiothorac Vasc Anesth. 2011;25(2):282–7.CrossRefGoogle Scholar
  44. 44.
    An N, Yu WF. Difficulties in understanding postoperative cognitive dysfunction. J Anesth Perioper Med. 2017;4:87–94.Google Scholar
  45. 45.
    Tomaszewski D. Biomarkers of brain damage and postoperative cognitive disorders in orthopedic patients: an update. Biomed Res Int. 2015;2015:402959.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Wang W, Wang Y, Wu H, et al. Postoperative cognitive dysfunction: current developments in mechanism and prevention. Med Sci Monit. 2014;20:1908–12.CrossRefGoogle Scholar
  47. 47.
    van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012;67(3):280–93.CrossRefGoogle Scholar
  48. 48.
    Tuffiash E, Tamargo RJ, Hillis AE. Craniotomy for treatment of unruptured aneurysms is not associated with long-term cognitive dysfunction. Stroke. 2003;34(9):2195–9.CrossRefGoogle Scholar
  49. 49.
    Mahajan C, Chouhan RS, Rath GP, et al. Effect of intraoperative brain protection with propofol on postoperative cognition in patients undergoing temporary clipping during intracranial aneurysm surgery. Neurol India. 2014;62(3):262–8.CrossRefGoogle Scholar
  50. 50.
    Heyer EJ, Mergeche JL, Anastasian ZH, et al. Arterial blood pressure management during carotid endarterectomy and early cognitive dysfunction. Neurosurgery. 2014;74(3):245–51.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Suparna Bharadwaj
    • 1
  • Sriganesh Kamath
    • 1
  1. 1.Department of Neuroanaesthesia and Neurocritical CareNational Institute of Mental Health and NeurosciencesBengaluruIndia

Personalised recommendations