Olfactory Dysfunction as a Predictive Biomarker for Postoperative Delirium Risk Assessment
Main Article Content
Abstract
Postoperative delirium is a common and serious complication of surgery, particularly in older adults. Despite its impact on outcomes and healthcare costs, effective preoperative tools to identify high-risk patients remain limited. This review evaluates the potential role of olfactory dysfunction as a noninvasive biomarker for predicting postoperative delirium, based on its strong association with brain vulnerability and neurodegenerative risk. Olfactory dysfunction is prevalent in patients with neurodegenerative and psychiatric disorders, as well as in aging populations—groups already at high risk for postoperative cognitive complications. It reflects key pathophysiological mechanisms shared with delirium, including neuroinflammation, cholinergic disruption, and corticolimbic network breakdown. Recent studies in surgical populations, including cardiac procedures, suggest that preoperative olfactory testing correlates with increased incidence and severity of postoperative delirium. Olfactory testing is inexpensive, rapid, and scalable, making it a feasible addition to preoperative evaluations. Its integration may enable personalized risk stratification and proactive cognitive management in perioperative care. Olfactory dysfunction offers a promising, biologically grounded strategy to identify patients at risk for postoperative delirium. Future studies should standardize testing protocols, validate its predictive value, and explore its role within multimodal perioperative risk models.
Keywords:
olfactory dysfunction, postoperative delirium, perioperative risk stratification, neurodegeneration, neuroinflammation
Article Details
How to Cite
LESSA, Marcos A.; SLAWKA, Eric.
Olfactory Dysfunction as a Predictive Biomarker for Postoperative Delirium Risk Assessment.
Medical Research Archives, [S.l.], v. 13, n. 9, oct. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6579>. Date accessed: 05 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i9.6579.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. Jul 28 2010;304(4):443-51. doi:10.1001/jam a.2010.1013
4. Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med. Jul 5 2012;367(1):30-9. doi:10.105 6/NEJMoa1112923
5. Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. Jan 14 2008;168(1):27-32. doi:10.1001/archinternmed.2007.4
6. Ross GW, Petrovitch H, Abbott RD, et al. Association of olfactory dysfunction with risk for future Parkinson's disease. Ann Neurol. Feb 2008; 63(2):167-73. doi:10.1002/ana.21291
7. Devanand DP, Michaels-Marston KS, Liu X, et al. Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up. Am J Psychiatry. Sep 2000;157(9):1399-405. doi:10.1176/appi.ajp.157.9.1399
8. Moberg PJ, Agrin R, Gur RE, Gur RC, Turetsky BI, Doty RL. Olfactory dysfunction in schizophrenia: a qualitative and quantitative review. Neuropsychopharmacology. Sep 1999;21(3):325-40. doi:10.1016/S0893-133X(99)00019-6
9. Eliyan Y, Wroblewski KE, McClintock MK, Pinto JM. Olfactory Dysfunction Predicts the Development of Depression in Older US Adults. Chem Senses. Jan 1 2021;46doi:10.1093/chemse/bjaa075
10. Doty RL. Olfactory dysfunction in neurodegenerative diseases: is there a common pathological substrate? Lancet Neurol. Jun 2017; 16(6):478-488. doi:10.1016/S1474-4422(17)30123-0
11. Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. Dec 2013;21 (12):1190-222. doi:10.1016/j.jagp.2013.09.005
12. Brown CHt, Morrissey C, Ono M, et al. Impaired olfaction and risk of delirium or cognitive decline after cardiac surgery. J Am Geriatr Soc. Jan 2015; 63(1):16-23. doi:10.1111/jgs.13198
13. Kamath V, Yanek LR, Neufeld KJ, et al. Poor olfaction prior to cardiac surgery: Association with cognition, plasma neurofilament light, and post-operative delirium. Int J Geriatr Psychiatry. Feb 2024;39(2):e6066. doi:10.1002/gps.6066
14. Aldecoa C, Bettelli G, Bilotta F, et al. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol. Apr 2017;34(4):192-214. doi:10.1097/EJA.0000000000000594
15. Hughes CG, Boncyk CS, Culley DJ, et al. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Delirium Prevention. Anesth Analg. Jun 2020;130(6):1572-1590. doi:10.1213/ANE.0000000000004641
16. Li C, Wei L, Gong H, Yuan X. Incidence and predictors of postoperative delirium following remimazolam administration: a systematic review and meta-analysis of 29 randomized trials. BMC Anesthesiol. Apr 23 2025;25(1):201. doi:10.1186/s 12871-025-03018-w
17. Suzuki R, Nakanishi A, Masuya M, Fukuroku K, Taneda Y, Matsuura Y. Risk factors for postoperative delirium in patients undergoing orthopedic procedures: a systematic review and meta-analysis. PLoS ONE. 2025;20(4):e0321025. doi:10.1371/jour nal.pone.0321025
18. Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. Dec 2009; 103 Suppl 1(Suppl 1):i41-46. doi:10.1093/bja/aep291
19. Smith JA, Das A, Ray SK, Banik NL. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull. Jan 4 2012; 87(1):10-20. doi:10.1016/j.brainresbull.2011.10.004
20. Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. Jul 25 2013;8(21):2003-14. doi:10.3969/j.issn.1673-5374.2013.21.009
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