DOI QR코드

DOI QR Code

Comparison of electroencephalogram waveforms in older patients with/without dementia after administration of midazolam: a prospective, observational comparative study

  • Megumi Hayashi (Department of Geriatric Dentistry, Kanagawa Dental University) ;
  • Yoshinari Morimoto (Department of Geriatric Dentistry, Kanagawa Dental University) ;
  • Lou Mikuzuki (Department of Geriatric Dentistry, Kanagawa Dental University)
  • Received : 2025.10.18
  • Accepted : 2025.12.14
  • Published : 2026.02.01

Abstract

Background: Sedation with midazolam in older patients with severe dementia can cause reactions that differ from those encountered in healthy individuals. We hypothesized that one reason for this is that electroencephalogram (EEG) responses to midazolam in patients with severe dementia may differ from those encountered in healthy individuals. In this study, we aimed to examine the effects of midazolam on EEG findings in older patients with severe dementia and compare them with those observed in older adults without dementia. Methods: We included 25 patients aged ≥ 60 years, and allocated them to either the dementia (13 patients) or non-dementia (12 patients) group. Participants with a Mini-Mental State Examination score of ≤ 23, Functional Assessment Staging of Alzheimer's disease stage 6 or 7, and/or Clinical Dementia Rating of being "severe" were considered to have severe dementia. EEG electrodes were attached to patients' frontal pole (Fp2). Midazolam was administered until a modified Observer's Assessment of Alertness/Sedation (OAA/S) score of 2 was attained. Chi-square test, Mann-Whitney U test, and Wilcoxon signed-rank test were performed to assess between-group differences. Differences were considered statistically significant at P < 0.05. Results: The power of the delta wave at baseline and immediately before treatment was higher in patients with dementia than that in the patients without dementia. Conversely, the power of the alpha wave was lower in the dementia group in the sedated state of the OAA/S 2. Regarding the changes within each group, the theta and beta waves in the dementia group decreased after midazolam administration. Conclusion: Regarding EEG waveforms in the frontal pole, administration of midazolam significantly decreased the power of the fast wave (alpha wave) and increased the power of the slow wave (delta wave) in older patients with severe dementia compared with that in older patients without cognitive decline.

Keywords

Acknowledgement

This study was partly sponsored by a Grant-in-Aid for Scientific Research C (20K10061) from the Japan Society for the Promotion of Science.

References

  1. Working Group on Guidelines Development for Intravenous Sedation in Dentistry, the Japanese Dental Society of Anesthesiology. Practice guidelines for intravenous conscious sedation in dentistry- developed by the Japanese Dental Society of Anesthesiology for dentists practicing sedation in Japan, 2nd ed. Anesth Prog 2018; 65: e1-18. https://doi.org/10.2344/anpr-65-04-15w
  2. White S, Griffiths R, Baxter M, Beanland T, Cross J, Dhesi J, et al. Guidelines for the perioperative care of people with dementia. Anaesthesia 2019; 74: 357-72. https://doi.org/10.1111/anae.2019.74.issue-3
  3. Nishizaki H, Morimoto Y, Hayashi M, Iida T. Analysis of intravenous sedation for dental treatment in elderly patients with severe dementia-a retrospective cohort study of a Japanese population. J Dent Sci 2021; 16: 101-7. https://doi.org/10.1016/j.jds.2020.06.027
  4. Tatsuno Y, Morimoto Y, Hayashi M, Iida T. Comparison of intravenous sedation using midazolam during dental treatment in elderly patients with/without dementia: a prospective, controlled clinical trial. Sci Rep 2021; 11: 3617. https://doi.org/10.1038/s41598-021-83122-2
  5. Morimoto Y, Hayashi M, Yao Y, Nishizaki H, Ishii H, Mikuzuki L, et al. Comparison of intravenous sedation using midazolam versus dexmedetomidine in elderly patients with dementia: a randomized cross-over trial. Sci Rep 2022; 12: 6293. https://doi.org/10.1038/s41598-022-10167-2
  6. Obrist WD. Electroencephalogram of normal-aged adults. Electroencephalogr Clin Neurophysiol 1954; 6: 235-44. https://doi.org/10.1016/0013-4694(54)90025-5
  7. Gibbs EL, Lorimer FM, Gibbs FA. Clinical correlates of exceedingly fast activity in the electroencephalogram. Dis Nerv Syst 1950; 11: 323-6.
  8. Silverman AJ, Busse EW, Barnes RH. Studies on the processes of aging: electroencephalographic findings in 400 elderly subjects. Electroencephalogr Clin Neurophysiol 1955; 7: 67-74. https://doi.org/10.1016/0013-4694(55)90060-2
  9. Wang R, Wang J, Yu H, Wei X, Yang C, Deng B. Power spectrum density and coherence analysis of Alzheimer's EEG. Cogn Neurodyn 2015; 9: 291-304. https://doi.org/10.1007/s11571-014-9325-x
  10. Choi J, Ku B, You YG, Jo M, Kwon M, Choi Y, et al. Resting-state prefrontal EEG biomarkers correlate with MMSE scores in elderly individuals. Sci Rep 2019; 9: 10468. https://doi.org/10.1038/s41598-019-46789-2
  11. Touchard C, Cartailler J, Levé C, Serrano J, Sabbagh D, Manquat E. Propofol requirement and EEG alpha band power during general anesthesia provide complementary views on preoperative cognitive decline. Front Aging Neurosci 2020; 12: 593320. https://doi.org/10.3389/fnagi.2020.593320
  12. Gutiérrez RG, Egaña JI, Maldonado FA, Sáez IA, Reyes FI, Soulat H, et al. Association between lower preoperative cognition with intraoperative electroencephalographic features consistent with deep states of anesthesia in older patients: an observational cohort study. Anesth Analg 2021; 133: 205-14. https://doi.org/10.1213/ANE.0000000000005262
  13. Kim J, Park S, Kim KN, Ha Y, Shin SJ, Cha W, et al. Resting-state prefrontal EEG biomarker in correlation with postoperative delirium in elderly patients. Front Aging Neurosci 2023; 15: 1224264. https://doi.org/10.3389/fnagi.2023.1224264
  14. Tsoi KKF, Chan JYC, Hirai HW, Wong SYS, Kwok TCY. Cognitive tests to detect dementia: a systematic review and meta-analysis. JAMA Intern Med 2015; 175: 1450-8. https://doi.org/10.1001/jamainternmed.2015.2152
  15. GMS Co., Ltd. Manufacturer's instructions and specifications. Tokyo, GMS Co., Ltd. 2020.
  16. Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86: 836-47. https://doi.org/10.1097/00000542-199704000-00014
  17. Choi J, Ku B, Doan DNT, Park J, Cha W, Kim JU, et al. Prefrontal EEG slowing, synchronization, and ERP peak latency in association with predementia stages of Alzheimer's disease. Front Aging Neurosci 2023; 15: 1131857. https://doi.org/10.3389/fnagi.2023.1131857
  18. Koch S, Feinkohl I, Chakravarty S, Windmann V, Lichtner G, Pischon T, et al. Cognitive impairment is associated with absolute intraoperative frontal α-band power but not with baseline α-band power: a pilot study. Dement Geriatr Cogn Disord 2019; 48: 83-92. https://doi.org/10.1159/000502950
  19. Vuyk J, Sitsen E, Reekers M. Intravenous anesthetics. In: Miller's Anesthesia. 8th ed. Edited by Miller RD. Philadelphia, Elsevier Publishers. 2015, pp 838-43, 854-9.
  20. Saito M, Hashimoto M. Drug-induced changes in EEG, anxiolytics, anti-depressives and anti-psychotics. Rinsho Noha 1997; 39: 648-52.
  21. Hotz MA, Ritz R, Linder L, Scollo-Lavizzari G, Haefeli WE. Auditory and electroencephalographic effects of midazolam and a-hydroxy-midazolam in healthy subjects. Br J Clin Pharmacol 2000; 49: 72-9. https://doi.org/10.1046/j.1365-2125.2000.00104.x
  22. Numan T, van Dellen E, Vleggaar FP, van Vlieberghe P, Stam CJ, Slooter AJC. Resting state EEG characteristics during sedation with midazolam or propofol in older subjects. Clin EEG Neurosci 2019; 50: 436-43. https://doi.org/10.1177/1550059419838938
  23. Guessous K, Touchard C, Glezerson B, Levé C, Sabbagh D, Mebazaa A, et al. Intraoperative electroencephalography alpha-band power is a better proxy for preoperative low MoCA under propofol compared with sevoflurane. Anesth Analg 2023; 137: 1084-92. https://doi.org/10.1213/ANE.0000000000006422
  24. Kondo T, Suzuki N, Beppu S, Okumura H, Uematsu H, Kubota Y, et al. Intravenous sedation with midazolam-part 1. Sedative effect. J Jap Dent Soc Anesth 1983; 11: 296-308.
  25. Sieber F, Pauldine R. Geriatric anesthesia. In: Miller's Anesthesia. 8th ed. Edited by Miller RD. Philadelphia, Elsevier Publishers. 2015, p 2418.
  26. Ohkuma T, ed. Clinical electroencephalography. 6th ed. Tokyo, Igakushoin. 2016, pp 13-77.