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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

The Postoperative Effects of Anesthesia Exposure on Cognitive Decline in Older Adults: A Narrative Review

Author(s): Kathleen Angela Willoughby-Dudley, Marielle L. Darwin and Deana B. Davalos*

Volume 21, Issue 1, 2024

Published on: 15 April, 2024

Page: [3 - 23] Pages: 21

DOI: 10.2174/0115672050288199240408035201


Background: As modern medicine continues to make strides in effective surgical treatments, we must also consider the critical impact of anesthesia on neuropsychological outcomes. Recent evidence suggests that anesthesia exposure may be a risk factor for postoperative cognitive decline and the eventual development of dementia.

Objectives: To explore the vulnerability of the aging brain in the context of anesthesia exposure in surgery, studies will be reviewed, and pertinent findings will be highlighted and explored to better understand risks and possible factors that need to be considered when contemplating surgery.

Methods: A narrative review was conducted using a combination of MEDLINE and APA PsycINFO databases to shed light on themes across studies assessing general trends regarding the influence of anesthesia on postoperative cognitive decline.

Results: A search of relevant literature identified 388 articles. Excluding results outside the parameters of this study, the review includes quality assessments for 24 articles.

Conclusion: While findings are inconclusive, suggestions for further investigation into the relationship between anesthesia exposure and increased risk for postoperative cognitive decline are discussed, in addition to factors that may allow for greater informed disclosure of potential risks of anesthesia in older adults.

Keywords: Anesthesia, dementia, general surgery, cognitive dysfunction, perioperative neurocognitive disorder, postoperative.

Kim, C.T.; Myung, W.; Lewis, M.; Lee, H.; Kim, S.E.; Lee, K.; Lee, C.; Choi, J.; Kim, H.; Carroll, B.J.; Kim, D.K. Exposure to general anesthesia and risk of dementia: A nationwide population-based cohort study. J. Alzheimers Dis., 2018, 63(1), 395-405.
[] [PMID: 29614656]
Jiang, J.; Dong, Y.; Huang, W.; Bao, M. General anesthesia exposure and risk of dementia: A meta-analysis of epidemiological studies. Oncotarget, 2017, 8(35), 59628-59637.
[] [PMID: 28938666]
Evered, L.; Silbert, B.; Knopman, D.S.; Scott, D.A.; DeKosky, S.T.; Rasmussen, L.S.; Oh, E.S.; Crosby, G.; Berger, M.; Eckenhoff, R.G. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery—2018. Anesthesiology, 2018, 129(5), 872-879.
[] [PMID: 30325806]
Patel, D.; Lunn, A.D.; Smith, A.D.; Lehmann, D.J.; Dorrington, K.L. Cognitive decline in the elderly after surgery and anaesthesia: Results from the oxford project to investigate memory and ageing (OPTIMA) cohort. Anaesthesia, 2016, 71(10), 1144-1152.
[] [PMID: 27501155]
Steinmetz, J.; Rasmussen, L.S. Anesthesia and the risk of dementia in the elderly. Presse Med., 2018, 47(4), e45-e51.
[] [PMID: 29661618]
O’ Brien, H.; Mohan, H.; Hare, C.O.; Reynolds, J.V.; Kenny, R.A. Mind over matter? the hidden epidemic of cognitive dysfunction in the older surgical patient. Ann. Surg., 2017, 265(4), 677-691.
[] [PMID: 27537541]
Velkers, C.; Berger, M.; Gill, S.S.; Eckenhoff, R.; Stuart, H.; Whitehead, M.; Austin, P.C.; Rochon, P.A.; Seitz, D. Association between exposure to general versus regional anesthesia and risk of dementia in older adults. J. Am. Geriatr. Soc., 2021, 69(1), 58-67.
[] [PMID: 33025584]
Dhesi, J.K.; Moppett, I.K. Anaesthesia and the older brain: What should we do? Anaesthesia, 2022, 77(S1), 8-10.
[] [PMID: 35001379]
Jiang, J.; Jiang, H. Effect of the inhaled anesthetics isoflurane, sevoflurane and desflurane on the neuropathogenesis of Alzheimer’s disease (Review). Mol. Med. Rep., 2015, 12(1), 3-12.
[] [PMID: 25738734]
Sun, M.; Chen, W.M.; Wu, S.Y.; Zhang, J. Dementia risk after major elective surgery based on the route of anaesthesia: A propensity score-matched population-based cohort study. EClinicalMedicine, 2023, 55, 101727.
[] [PMID: 36386032]
Bademosi, A.T.; Steeves, J.; Karunanithi, S.; Zalucki, O.H.; Gormal, R.S.; Liu, S.; Lauwers, E.; Verstreken, P.; Anggono, V.; Meunier, F.A.; van Swinderen, B. Trapping of syntaxin1a in presynaptic nanoclusters by a clinically relevant general anesthetic. Cell Rep., 2018, 22(2), 427-440.
[] [PMID: 29320738]
Kwon, Y.S.; Lee, S.H.; Kim, C.; Yu, H.; Sohn, J.H.; Lee, J.J.; Kim, D.K. Risk of dementia according to surgery type: A nationwide cohort study. J. Pers. Med., 2022, 12(3), 468.
[] [PMID: 35330467]
Kim, J.H.; Jung, H.; Lee, Y.; Sohn, J.H. Surgery performed under propofol anesthesia induces cognitive impairment and amyloid pathology in ApoE4 knock-in mouse model. Front. Aging Neurosci., 2021, 13, 658860.
[] [PMID: 33981208]
Steinmetz, J; Rasmussen, LS Long-term consequences of postoperative cognitive dysfunction. Anesthesiology, 2009, 110(3), 548-555.
van Sinderen, K.; Schwarte, L.A.; Schober, P. Diagnostic criteria of postoperative cognitive dysfunction: A focused systematic review. Anesthesiol. Res. Pract., 2020, 2020, 1-13.
[] [PMID: 33281900]
Daiello, L.A.; Racine, A.M.; Yun Gou, R.; Marcantonio, E.R.; Xie, Z.; Kunze, L.J.; Vlassakov, K.V.; Inouye, S.K.; Jones, R.N.; Alsop, D.; Travison, T.; Arnold, S.; Cooper, Z.; Dickerson, B.; Fong, T.; Metzger, E.; Leone, P.A.; Schmitt, E.M.; Shafi, M.; Cavallari, M.; Dai, W.; Dillon, S.T.; McElhaney, J.; Guttmann, C.; Hshieh, T.; Kuchel, G.; Libermann, T.; Ngo, L.; Press, D.; Saczynski, J.; Vasunilashorn, S.; O’Connor, M.; Kimchi, E.; Strauss, J.; Wong, B.; Belkin, M.; Ayres, D.; Callery, M.; Pomposelli, F.; Wright, J.; Schermerhorn, M.; Abrantes, T.; Albuquerque, A.; Bertrand, S.; Brown, A.; Callahan, A.; D’Aquila, M.; Dowal, S.; Fox, M.; Gallagher, J.; Anna Gersten, R.; Hodara, A.; Helfand, B.; Inloes, J.; Kettell, J.; Kuczmarska, A.; Nee, J.; Nemeth, E.; Ochsner, L.; Palihnich, K.; Parisi, K.; Puelle, M.; Rastegar, S.; Vella, M.; Xu, G.; Bryan, M.; Guess, J.; Enghorn, D.; Gross, A.; Gou, Y.; Habtemariam, D.; Isaza, I.; Kosar, C.; Rockett, C.; Tommet, D.; Gruen, T.; Ross, M.; Tasker, K.; Gee, J.; Kolanowski, A.; Pisani, M.; de Rooij, S.; Rogers, S.; Studenski, S.; Stern, Y.; Whittemore, A.; Gottlieb, G.; Orav, J.; Sperling, R. Postoperative delirium and postoperative cognitive dysfunction. Anesthesiology, 2019, 131(3), 477-491.
[] [PMID: 31166241]
Davis, D.H.J.; Muniz-Terrera, G.; Keage, H.A.D.; Stephan, B.C.M.; Fleming, J.; Ince, P.G.; Matthews, F.E.; Cunningham, C.; Ely, E.W.; MacLullich, A.M.J.; Brayne, C. Association of delirium with cognitive decline in late life. JAMA Psychiatr., 2017, 74(3), 244-251.
[] [PMID: 28114436]
Devinney, MJ; Mathew, JP; Berger, M Postoperative delirium and postoperative cognitive dysfunction: Two sides of the same coin? Anesthesiology, 2018, 129, 389-391.
PRB, Fact Sheet: Aging in the United States. Available from:
Prince, M.J.; Wu, F.; Guo, Y.; Robledo, G.L.M.; O’Donnell, M.; Sullivan, R.; Yusuf, S. The burden of disease in older people and implications for health policy and practice. Lancet, 2015, 385(9967), 549-562.
[] [PMID: 25468153]
Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; Chou, R.; Glanville, J.; Grimshaw, J.M.; Hróbjartsson, A.; Lalu, M.M.; Li, T.; Loder, E.W.; Mayo-Wilson, E.; McDonald, S.; McGuinness, L.A.; Stewart, L.A.; Thomas, J.; Tricco, A.C.; Welch, V.A.; Whiting, P.; Moher, D. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 2021, 372(71), n71.
[] [PMID: 33782057]
Peisah, C. Practical geriatrics: Persistent postoperative cognitive decline in an elderly woman with preexisting neuropathology. Psychiatr. Serv., 2002, 53(3), 277-279.
[] [PMID: 11875219]
Sprung, J.; Abcejo, A.S.A.; Knopman, D.S.; Petersen, R.C.; Mielke, M.M.; Hanson, A.C.; Schroeder, D.R.; Schulte, P.J.; Martin, D.P.; Weingarten, T.N.; Pasternak, J.J.; Warner, D.O. Anesthesia with and without nitrous oxide and long-term cognitive trajectories in older adults. Anesth. Analg., 2020, 131(2), 594-604.
[] [PMID: 31651458]
Bickel, H.; Gradinger, R.; Kochs, E.; Förstl, H. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement. Geriatr. Cogn. Disord., 2008, 26(1), 26-31.
[] [PMID: 18577850]
Sprung, J.; Roberts, R.O.; Weingarten, T.N.; Cavalcante, N.A.; Knopman, D.S.; Petersen, R.C.; Hanson, A.C.; Schroeder, D.R.; Warner, D.O. Postoperative delirium in elderly patients is associated with subsequent cognitive impairment. Br. J. Anaesth., 2017, 119(2), 316-323.
[] [PMID: 28854531]
Suraarunsumrit, P.; Pathonsmith, C.; Srinonprasert, V.; Sangarunakul, N.; Jiraphorncharas, C.; Siriussawakul, A. Postoperative cognitive dysfunction in older surgical patients associated with increased healthcare utilization: A prospective study from an upper-middle-income country. BMC Geriatr., 2022, 22(1), 213.
[] [PMID: 35296258]
Neufeld, K.J.; Leoutsakos, J.M.S.; Oh, E.; Sieber, F.E.; Chandra, A.; Ghosh, A.; Schretlen, D.J.; Needham, D.M. Long-term outcomes of older adults with and without delirium immediately after recovery from general anesthesia for surgery. Am. J. Geriatr. Psychiatry, 2015, 23(10), 1067-1074.
[] [PMID: 25912784]
Bowles, A.E.J.; Larson, E.B.; Pong, R.P.; Walker, R.L.; Anderson, M.L.; Yu, O.; Gray, S.L.; Crane, P.K.; Dublin, S. Anesthesia exposure and risk of dementia and alzheimer’s disease: A prospective study. J. Am. Geriatr. Soc., 2016, 64(3), 602-607.
[] [PMID: 26865152]
Ancelin, M.L.; De Roquefeuil, G.; Ledésert, B.; Bonnel, F.; Cheminal, J.C.; Ritchie, K. Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly. Br. J. Psychiatry, 2001, 178(4), 360-366.
[] [PMID: 11282816]
Schulte, P.J.; Roberts, R.O.; Knopman, D.S.; Petersen, R.C.; Hanson, A.C.; Schroeder, D.R.; Weingarten, T.N.; Martin, D.P.; Warner, D.O.; Sprung, J. Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: Report from the mayo clinic study of aging. Br. J. Anaesth., 2018, 121(2), 398-405.
[] [PMID: 30032878]
Zhang, D.; Ying, J.; Ma, X.; Gao, Z.; Chen, H.; Zhu, S.; Shi, L.; Lu, X. Social cognitive dysfunction in elderly patients after anesthesia and surgery. Front. Psychol., 2020, 11, 541161.
[] [PMID: 33071859]
Sprung, J.; Roberts, R.O.; Knopman, D.S.; Olive, D.M.; Gappa, J.L.; Sifuentes, V.L.; Behrend, T.L.; Farmer, J.D.; Weingarten, T.N.; Hanson, A.C.; Schroeder, D.R.; Petersen, R.C.; Warner, D.O. Association of mild cognitive impairment with exposure to general anesthesia for surgical and nonsurgical procedures. Mayo Clin. Proc., 2016, 91(2), 208-217.
[] [PMID: 26803349]
Sprung, J.; Roberts, R.O.; Knopman, D.S.; Price, L.L.; Schulz, H.P.; Tatsuyama, C.L.; Weingarten, T.N.; Schroeder, D.R.; Hanson, A.C.; Petersen, R.C.; Warner, D.O. Mild cognitive impairment and exposure to general anesthesia for surgeries and procedures: A population-based case–control study. Anesth. Analg., 2017, 124(4), 1277-1290.
[] [PMID: 28291057]
Yoshimoto, A.; Inoue, T.; Morizumi, S.; Nishi, S.; Shimizu, T.; Kurahashi, K.; Suematsu, Y. Analysis of the perioperative change in cognitive function of patients with risk factors for cognitive impairment in cardiovascular surgery. Gen. Thorac. Cardiovasc. Surg., 2019, 67(2), 214-218.
[] [PMID: 30143959]
Fischer, P.; Wallner, H.; Jungwirth, S.; Weissgram, S.; Krampla, W.; Bauer, P.; Tragl, K.H. Cumulative exposure to general anesthesias and cognitive dysfunction at age 75 in the vienna transdanube aging “VITA” study. J. Neuropsychiatry Clin. Neurosci., 2007, 19(1), 21-26.
[] [PMID: 17308223]
Ackenbom, M.F.; Butters, M.A.; Davis, E.M.; Abebe, K.Z.; Baranski, L.; Zyczynski, H.M. Incidence of postoperative cognitive dysfunction in older women undergoing pelvic organ prolapse surgery. Int. Urogynecol. J. Pelvic Floor Dysfunct., 2021, 32(2), 433-442.
[] [PMID: 32827107]
Sprung, J.; Schulte, P.J.; Knopman, D.S.; Mielke, M.M.; Petersen, R.C.; Weingarten, T.N.; Martin, D.P.; Hanson, A.C.; Schroeder, D.R.; Warner, D.O. Cognitive function after surgery with regional or general anesthesia: A population-based study. Alzheimers Dement., 2019, 15(10), 1243-1252.
[] [PMID: 31495602]
Strand, A.K.; Nyqvist, F.; Ekdahl, A.; Wingren, G.; Eintrei, C. Is there a relationship between anaesthesia and dementia? Acta Anaesthesiol. Scand., 2019, 63(4), 440-447.
[] [PMID: 30511411]
Xie, H.; Zhou, J.; Du, W.; Zhang, S.; Huang, R.; Han, Q.; Guo, Q. Impact of thoracic paravertebral block combined with general anesthesia on postoperative cognitive function and serum adiponectin levels in elderly patients undergoing lobectomy. Wideochir. Inne Tech. Malo Inwazyjne, 2019, 14(4), 538-544.
[] [PMID: 31908700]
Geng, Y.; Wu, Q.; Zhang, R. Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial. J. Clin. Anesth., 2017, 38, 165-171.
[] [PMID: 28372661]
Chrisinger, A.A.; Avidan, M.S. Postoperative delirium portends descent to dementia. Br. J. Anaesth., 2017, 119(2), 285-288.
[] [PMID: 28854545]
Ishii, K.; Makita, T.; Yamashita, H.; Matsunaga, S.; Akiyama, D.; Toba, K.; Hara, K.; Sumikawa, K.; Hara, T. Total intravenous anesthesia with propofol is associated with a lower rate of postoperative delirium in comparison with sevoflurane anesthesia in elderly patients. J. Clin. Anesth., 2016, 33, 428-431.
[] [PMID: 27555205]
Chan, C.S.; Chan, M.T.V. Use of nitrous oxide in contemporary anesthesia—an ongoing tug of war. Can. J. Anaesth., 2021, 68(11), 1597-1600.
[] [PMID: 34448128]
Myles, P.S.; Chan, M.T.V.; Kaye, D.M.; McIlroy, D.R.; Lau, C.W.; Symons, J.A.; Chen, S. Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function. Anesthesiology, 2008, 109(4), 657-663.
[] [PMID: 18813045]
Chen, Y.; Liu, X.; Cheng, C.H.K.; Gin, T.; Leslie, K.; Myles, P.; Chan, M.T.V. Leukocyte DNA damage and wound infection after nitrous oxide administration: A randomized controlled trial. Anesthesiology, 2013, 118(6), 1322-1331.
[] [PMID: 23549382]
Leung, J.M.; Sands, L.P.; Vaurio, L.E.; Wang, Y. Nitrous oxide does not change the incidence of postoperative delirium or cognitive decline in elderly surgical patients. Br. J. Anaesth., 2006, 96(6), 754-760.
[] [PMID: 16670110]
Vacas, S.; Cole, D.J.; Cannesson, M. Cognitive decline associated with anesthesia and surgery in older patients. JAMA, 2021, 326(9), 863-864.
[] [PMID: 34338712]
Ding, D.; Wang, P.; Jiang, Y.; Zhang, X.; Shi, W.; Luo, Y. Effects of apolipoprotein Ε ε4 allele on early postoperative cognitive dysfunction after anesthesia. Anaesthesist, 2021, 70(S1), 60-67.
[] [PMID: 34143234]
Deiner, S.; Baxter, M.G.; Mincer, J.S.; Sano, M.; Hall, J.; Mohammed, I.; O’Bryant, S.; Zetterberg, H.; Blennow, K.; Eckenhoff, R. Human plasma biomarker responses to inhalational general anaesthesia without surgery. Br. J. Anaesth., 2020, 125(3), 282-290.
[] [PMID: 32536445]
Baxter, M.G.; Mincer, J.S.; Brallier, J.W.; Schwartz, A.; Ahn, H.; Nir, T.; McCormick, P.J.; Ismail, M.; Sewell, M.; Allore, H.G.; Ramsey, C.M.; Sano, M.; Deiner, S.G. Cognitive recovery by decade in healthy 40- to 80-year-old volunteers after anesthesia without surgery. Anesth. Analg., 2022, 134(2), 389-399.
[] [PMID: 34889804]
Chen, L.; Au, E.; Saripella, A.; Kapoor, P.; Yan, E.; Wong, J.; Tang-Wai, D.F.; Gold, D.; Riazi, S.; Suen, C.; He, D.; Englesakis, M.; Nagappa, M.; Chung, F. Postoperative outcomes in older surgical patients with preoperative cognitive impairment: A systematic review and meta-analysis. J. Clin. Anesth., 2022, 80, 110883.
[] [PMID: 35623265]
Li, L.; Dohan, D.; Smith, A.K.; Whitlock, E.L. ‘It was a great brain, and I miss it’: Lay perspectives on postoperative cognitive dysfunction. Br. J. Anaesth., 2023, 130(5), 567-572.
[] [PMID: 36868965]
Han, C.; Ji, H.; Guo, Y.; Fei, Y.; Wang, C.; Yuan, Y.; Ruan, Z.; Ma, T. Effect of subanesthetic dose of esketamine on perioperative neurocognitive disorders in elderly undergoing gastrointestinal surgery: A randomized controlled trial. Drug Des. Devel. Ther., 2023, 17, 863-873.
[] [PMID: 36974331]
Hu, L.; Luo, M.; Huang, H.; Wu, L.; Ouyang, W.; Tong, J.; Le, Y. Perioperative probiotics attenuates postoperative cognitive dysfunction in elderly patients undergoing hip or knee arthroplasty: A randomized, double-blind, and placebo-controlled trial. Front. Aging Neurosci., 2023, 14, 1037904.
[] [PMID: 36688164]
Wang, P.; Yin, X.; Chen, G.; Li, L.; Le, Y.; Xie, Z.; Ouyang, W.; Tong, J. Perioperative probiotic treatment decreased the incidence of postoperative cognitive impairment in elderly patients following non-cardiac surgery: A randomised double-blind and placebo-controlled trial. Clin. Nutr., 2021, 40(1), 64-71.
[] [PMID: 32451125]
Olotu, C.; Ascone, L.; Wiede, J.; Manthey, J.; Kuehn, S.; Scherwath, A.; Kiefmann, R. The effect of delirium preventive measures on the occurrence of postoperative cognitive dysfunction in older adults undergoing cardiovascular surgery. The DelPOCD randomised controlled trial. J. Clin. Anesth., 2022, 78, 110686.
[] [PMID: 35190345]
Wasef, S.; Laksono, I.; Kapoor, P.; Tang-Wei, D.; Gold, D.; Saripella, A.; Riazi, S.; Islam, S.; Englesakis, M.; Wong, J.; Chung, F. Screening for subjective cognitive decline in the elderly via subjective cognitive complaints and informant-reported questionnaires: A systematic review. BMC Anesthesiol., 2021, 21(1), 277.
[] [PMID: 34753428]
Carter, J.; Story, D.A. Veterinary and human anaesthesia: An overview of some parallels and contrasts. Anaesth. Intensive Care, 2013, 41(6), 710-718.
[] [PMID: 24180711]
Drummond, E.; Wisniewski, T. Alzheimer’s disease: Rxperimental models and reality. Acta Neuropathol., 2017, 133(2), 155-175.
[] [PMID: 28025715]
Cho, S.A.; Lee, S.J.; Sung, T.Y.; Kim, D.K.; Cho, C.K. Comparative analysis of anesthetic legal disputes between older and younger patients referred to the korean society of anesthesiologists in 2009–2018. Ann Geriatr Med Res, 2019, 23(4), 204-211.
[] [PMID: 32743313]

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