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Vol. 29, No. 3, 2010
Issue release date: April 2010
Section title: Original Research Article
Free Access
Dement Geriatr Cogn Disord 2010;29:233–239
(DOI:10.1159/000295114)

Spine Surgery under General Anesthesia May Not Increase the Risk of Alzheimer’s Disease

Zuo C.a · Zuo Z.b
aDuke University, Durham, N.C., and bDepartment of Anesthesiology, University of Virginia, Charlottesville, Va., USA
email Corresponding Author

Abstract

Background:Volatile anesthetics cause Alzheimer’s disease (AD)-like neuropathology in animals. We determined whether spine surgery under general anesthesia and anesthetic choice contributed to AD development. Methods: We searched the Clinical Data Repository of the University of Virginia for patients receiving spine surgery from January 1, 1992 to March 1, 2004. Patients with newly-diagnosed AD after the surgery but before March 1, 2009 (a minimal 5-year follow-up time after the surgery) were identified. Results: Among 10,161 spine surgery patients, 26 patients had new-onset AD. Univariate and multivariate logistic regression analyses of the data from these 26 patients and from 161 randomly selected spine surgery patients without new-onset AD suggest that increasing age is a risk factor for new-onset AD. Gender, anesthesia/surgery time, use of volatile anesthetics versus propofol (an intravenous anesthetic) and length of hospital stay were not different between patients with and without new-onset AD. Similar results were found with the case-control study. The frequency of new-onset AD in spine surgery patients was similar to that of patients who had never had a surgery. Conclusion: These results suggest that increasing age is a risk factor for AD in patients after spine surgery. Anesthesia/surgery may not be independent factors for AD development.

© 2010 S. Karger AG, Basel


  

Key Words

  • Alzheimer’s disease
  • Anesthesia
  • Anesthetics
  • Spine surgery

References

  1. Rocchi A, Pellegrini S, Siciliano G, Murri L: Causative and susceptibility genes for Alzheimer’s disease: a review. Brain Res Bull 2003;61:1–24.
  2. Higgins GA, Jacobsen H: Transgenic mouse models of Alzheimer’s disease: phenotype and application. Behav Pharmacol 2003;14:419–438.
  3. Hofman A, Rocca WA, Brayne C, Breteler MM, Clarke M, Cooper B, Copeland JR, Dartigues JF, da Silva Droux A, Hagnell O, et al: The prevalence of dementia in Europe: a collaborative study of 1980–1990 findings. Eurodem Prevalence Research Group. Int J Epidemiol 1991;20:736–748.
  4. Lahiri DK: Unraveling nature’s secrets, from neurons and memory to brain disorders: exploring the new frontier of Alzheimer’s disease (preface). Curr Alz Res 2004;1:1–3.
  5. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA: Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 2003;60:1119–1122.
  6. Abildstrom H, Rasmussen LS, Rentowl P, Hanning CD, Rasmussen H, Kristensen PA, Moller JT: 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;44:1246–1251.
  7. Ancelin ML, de Roquefeuil G, Ledesert B, Bonnel F, Cheminal JC, Ritchie K: Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly. Br J Psychiatry 2001;178:360–366.
  8. 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. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998;351:857–861.
  9. Johnson T, Monk T, Rasmussen LS, Abildstrom H, Houx P, Korttila K, Kuipers HM, Hanning CD, Siersma VD, Kristensen D, Canet J, Ibanaz MT, Moller JT: Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology 2002;96:1351–1357.
  10. Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS: Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology 2008;108:18–30.
  11. Eckenhoff RG, Johansson JS, Wei H, Carnini A, Kang B, Wei W, Pidikiti R, Keller JM, Eckenhoff MF: Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 2004;101:703–709.
  12. Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, Moir RD, Frosch MP, Crosby G, Tanzi RE: The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann Neurol 2008;64:618–627.
  13. Selkoe DJ: Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 2001;81:741–766.
  14. Hall MJ, Kozak LJ: Ambulatory and inpatient surgery: national patterns for the elderly. Stat Bull Metrop Insur Co 1999;80:22–31.
  15. Bohnen NI, Warner MA, Kokmen E, Beard CM, Kurland LT: Alzheimer’s disease and cumulative exposure to anesthesia: a case-control study. J Am Geriatr Soc 1994;42:198–201.
  16. Breteler MM, van Duijn CM, Chandra V, Fratiglioni L, Graves AB, Heyman A, Jorm AF, Kokmen E, Kondo K, Mortimer JA, et al: Medical history and the risk of Alzheimer’s disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20(suppl 2):S36–S42.
  17. Gasparini M, Vanacore N, Schiaffini C, Brusa L, Panella M, Talarico G, Bruno G, Meco G, Lenzi GL: A case-control study on Alzheimer’s disease and exposure to anesthesia. Neurol Sci 2002;23:11–14.
  18. Knopman DS, Petersen RC, Cha RH, Edland SD, Rocca WA: Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease. Neurology 2005;65:986–990.
  19. Bohnen N, Warner MA, Kokmen E, Kurland LT: Early and midlife exposure to anesthesia and age of onset of Alzheimer’s disease. Int J Neurosci 1994;77:181–185.
  20. Lee TA, Wolozin B, Weiss KB, Bednar MM: Assessment of the emergence of Alzheimer’s disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. J Alzheimers Dis 2005;7:319–324.
  21. Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA: Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001;344:395–402.
  22. Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS: Long-term consequences of postoperative cognitive dysfunction. Anesthesiology 2009;110:548–555.
  23. Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A, Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller JT: Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand 2003;47:260–266.
  24. Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME: Cognitive effects after epidural vs general anesthesia in older adults: a randomized trial. JAMA 1995;274:44–50.
  25. Nielson WR, Gelb AW, Casey JE, Penny FJ, Merchant RN, Manninen PH: Long-term cognitive and social sequelae of general versus regional anesthesia during arthroplasty in the elderly. Anesthesiology 1990;73:1103–1109.
  26. Avidan MS, Searleman AC, Storandt M, Barnett K, Vannucci A, Saager L, Xiong C, Grant EA, Kaiser D, Morris JC, Evers AS: Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology 2009;111:964–970.
  27. Culley DJ, Baxter MG, Yukhananov R, Crosby G: Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology 2004;100:309–314.
  28. Planel E, Bretteville A, Liu L, Virag L, Du AL, Yu WH, Dickson DW, Whittington RA, Duff KE: Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia. FASEB J 2009;23:2595–2604.
  29. Planel E, Richter KE, Nolan CE, Finley JE, Liu L, Wen Y, Krishnamurthy P, Herman M, Wang L, Schachter JB, Nelson RB, Lau LF, Duff KE: Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia. J Neurosci 2007;27:3090–3097.
  30. Cottrell JE: We care, therefore we are: anesthesia-related morbidity and mortality: the 46th Rovenstine Lecture. Anesthesiology 2008;109:377–388.

  

Author Contacts

Prof. Zhiyi Zuo
Department of Anesthesiology, University of Virginia Health System
1 Hospital Drive, PO Box 800710
Charlottesville, VA 22908-0710 (USA)
Tel. +1 434 924 2283, Fax +1 434 924 2105, E-Mail zz3c@virginia.edu

  

Article Information

Accepted: February 26, 2010
Published online: April 6, 2010
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 4, Number of References : 30

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 29, No. 3, Year 2010 (Cover Date: April 2010)

Journal Editor: Chan-Palay V. (New York, N.Y.)
ISSN: 1420-8008 (Print), eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background:Volatile anesthetics cause Alzheimer’s disease (AD)-like neuropathology in animals. We determined whether spine surgery under general anesthesia and anesthetic choice contributed to AD development. Methods: We searched the Clinical Data Repository of the University of Virginia for patients receiving spine surgery from January 1, 1992 to March 1, 2004. Patients with newly-diagnosed AD after the surgery but before March 1, 2009 (a minimal 5-year follow-up time after the surgery) were identified. Results: Among 10,161 spine surgery patients, 26 patients had new-onset AD. Univariate and multivariate logistic regression analyses of the data from these 26 patients and from 161 randomly selected spine surgery patients without new-onset AD suggest that increasing age is a risk factor for new-onset AD. Gender, anesthesia/surgery time, use of volatile anesthetics versus propofol (an intravenous anesthetic) and length of hospital stay were not different between patients with and without new-onset AD. Similar results were found with the case-control study. The frequency of new-onset AD in spine surgery patients was similar to that of patients who had never had a surgery. Conclusion: These results suggest that increasing age is a risk factor for AD in patients after spine surgery. Anesthesia/surgery may not be independent factors for AD development.

© 2010 S. Karger AG, Basel


  

Author Contacts

Prof. Zhiyi Zuo
Department of Anesthesiology, University of Virginia Health System
1 Hospital Drive, PO Box 800710
Charlottesville, VA 22908-0710 (USA)
Tel. +1 434 924 2283, Fax +1 434 924 2105, E-Mail zz3c@virginia.edu

  

Article Information

Accepted: February 26, 2010
Published online: April 6, 2010
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 4, Number of References : 30

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 29, No. 3, Year 2010 (Cover Date: April 2010)

Journal Editor: Chan-Palay V. (New York, N.Y.)
ISSN: 1420-8008 (Print), eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Accepted: 2/26/2010
Published online: 4/6/2010
Issue release date: April 2010

Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 4

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Rocchi A, Pellegrini S, Siciliano G, Murri L: Causative and susceptibility genes for Alzheimer’s disease: a review. Brain Res Bull 2003;61:1–24.
  2. Higgins GA, Jacobsen H: Transgenic mouse models of Alzheimer’s disease: phenotype and application. Behav Pharmacol 2003;14:419–438.
  3. Hofman A, Rocca WA, Brayne C, Breteler MM, Clarke M, Cooper B, Copeland JR, Dartigues JF, da Silva Droux A, Hagnell O, et al: The prevalence of dementia in Europe: a collaborative study of 1980–1990 findings. Eurodem Prevalence Research Group. Int J Epidemiol 1991;20:736–748.
  4. Lahiri DK: Unraveling nature’s secrets, from neurons and memory to brain disorders: exploring the new frontier of Alzheimer’s disease (preface). Curr Alz Res 2004;1:1–3.
  5. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA: Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 2003;60:1119–1122.
  6. Abildstrom H, Rasmussen LS, Rentowl P, Hanning CD, Rasmussen H, Kristensen PA, Moller JT: 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;44:1246–1251.
  7. Ancelin ML, de Roquefeuil G, Ledesert B, Bonnel F, Cheminal JC, Ritchie K: Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly. Br J Psychiatry 2001;178:360–366.
  8. 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. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998;351:857–861.
  9. Johnson T, Monk T, Rasmussen LS, Abildstrom H, Houx P, Korttila K, Kuipers HM, Hanning CD, Siersma VD, Kristensen D, Canet J, Ibanaz MT, Moller JT: Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology 2002;96:1351–1357.
  10. Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS: Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology 2008;108:18–30.
  11. Eckenhoff RG, Johansson JS, Wei H, Carnini A, Kang B, Wei W, Pidikiti R, Keller JM, Eckenhoff MF: Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 2004;101:703–709.
  12. Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, Moir RD, Frosch MP, Crosby G, Tanzi RE: The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann Neurol 2008;64:618–627.
  13. Selkoe DJ: Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 2001;81:741–766.
  14. Hall MJ, Kozak LJ: Ambulatory and inpatient surgery: national patterns for the elderly. Stat Bull Metrop Insur Co 1999;80:22–31.
  15. Bohnen NI, Warner MA, Kokmen E, Beard CM, Kurland LT: Alzheimer’s disease and cumulative exposure to anesthesia: a case-control study. J Am Geriatr Soc 1994;42:198–201.
  16. Breteler MM, van Duijn CM, Chandra V, Fratiglioni L, Graves AB, Heyman A, Jorm AF, Kokmen E, Kondo K, Mortimer JA, et al: Medical history and the risk of Alzheimer’s disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20(suppl 2):S36–S42.
  17. Gasparini M, Vanacore N, Schiaffini C, Brusa L, Panella M, Talarico G, Bruno G, Meco G, Lenzi GL: A case-control study on Alzheimer’s disease and exposure to anesthesia. Neurol Sci 2002;23:11–14.
  18. Knopman DS, Petersen RC, Cha RH, Edland SD, Rocca WA: Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease. Neurology 2005;65:986–990.
  19. Bohnen N, Warner MA, Kokmen E, Kurland LT: Early and midlife exposure to anesthesia and age of onset of Alzheimer’s disease. Int J Neurosci 1994;77:181–185.
  20. Lee TA, Wolozin B, Weiss KB, Bednar MM: Assessment of the emergence of Alzheimer’s disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. J Alzheimers Dis 2005;7:319–324.
  21. Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA: Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001;344:395–402.
  22. Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS: Long-term consequences of postoperative cognitive dysfunction. Anesthesiology 2009;110:548–555.
  23. Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A, Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller JT: Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand 2003;47:260–266.
  24. Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME: Cognitive effects after epidural vs general anesthesia in older adults: a randomized trial. JAMA 1995;274:44–50.
  25. Nielson WR, Gelb AW, Casey JE, Penny FJ, Merchant RN, Manninen PH: Long-term cognitive and social sequelae of general versus regional anesthesia during arthroplasty in the elderly. Anesthesiology 1990;73:1103–1109.
  26. Avidan MS, Searleman AC, Storandt M, Barnett K, Vannucci A, Saager L, Xiong C, Grant EA, Kaiser D, Morris JC, Evers AS: Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology 2009;111:964–970.
  27. Culley DJ, Baxter MG, Yukhananov R, Crosby G: Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology 2004;100:309–314.
  28. Planel E, Bretteville A, Liu L, Virag L, Du AL, Yu WH, Dickson DW, Whittington RA, Duff KE: Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia. FASEB J 2009;23:2595–2604.
  29. Planel E, Richter KE, Nolan CE, Finley JE, Liu L, Wen Y, Krishnamurthy P, Herman M, Wang L, Schachter JB, Nelson RB, Lau LF, Duff KE: Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia. J Neurosci 2007;27:3090–3097.
  30. Cottrell JE: We care, therefore we are: anesthesia-related morbidity and mortality: the 46th Rovenstine Lecture. Anesthesiology 2008;109:377–388.