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BMC Geriatrics

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01-12-2022 | Alzheimer's Disease | Research

Association of cognitive enhancers and incident seizure risk in dementia: a population-based study

Authors: Junghee Ha, Nak-Hoon Son, Young Ho Park, Eun Lee, Eosu Kim, Woo Jung Kim

Published in: BMC Geriatrics | Issue 1/2022

Abstract

Background

Although individuals with dementia have a high risk of developing seizures, whether seizures are associated with cholinesterase inhibitors, which are commonly prescribed to treat individuals with dementia, remains unknown. This study investigated the risk of incident seizure following cholinesterase inhibitor use in patients with dementia.

Methods

A nationwide, nested case-control study was conducted using data from the Korean Health Insurance Review and Assessment Service (HIRA) from 2014 through 2018. A total of 13,767 participants aged 65–95 years who experienced incident seizure were propensity score-matched for medical comorbidities and drug exposure at a 1:3 ratio with a control group of 39,084 participants. The study examined the incidence of seizures in patients diagnosed with dementia within one year after receiving cognitive enhancers. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for seizure incidence according to cholinesterase inhibitor use were analyzed using a multivariable conditional logistic regression model.

Results

There was no statistically significant association between duration of cholinesterase inhibitors use and seizure risk. Although there was slight increased seizure risk in patient after receiving donepezil for 1 year compared to memantine, subgroup analyses stratified age and sex did not reveal any significant association between cholinesterase inhibitors use and late-onset seizure.

Conclusions

Our findings suggest no immediate increase in seizure risk is associated with cholinesterase inhibitor use, although the risk of seizure in patients with dementia did increase after one year of continued medication intake. Further study is required to obtain confirmatory results on the seizure-related safety of cognitive enhancers in patients with dementia.

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Baker J, Libretto T, Henley W, Zeman A. The prevalence and clinical features of epileptic seizures in a memory clinic population. Seizure. 2019;71:83–92. https://doi.org/10.1016/j.seizure.2019.06.016.CrossRefPubMed

Mendez M, Lim G. Seizures in elderly patients with dementia: epidemiology and management. Drugs Aging. 2003;20(11):791–803. https://doi.org/10.2165/00002512-200320110-00001.CrossRefPubMed

Nicolas N, Frédéric A, Margitta S. From here to epilepsy: the risk of seizure in patients with Alzheimer’s disease. Epileptic Disord. 2016;18(1):1–12. https://doi.org/10.1684/epd.2016.0808.CrossRef

Sen A, Capelli V, Husain M. Cognition and dementia in older patients with epilepsy. Brain. 2018;141(6):1592–608. https://doi.org/10.1093/brain/awy022.CrossRefPubMedPubMedCentral

Romoli M, Sen A, Parnetti L, Calabresi P, Costa C. Amyloid-β: a potential link between epilepsy and cognitive decline. Nat Rev Neurol. 2021;17(8):469–85. https://doi.org/10.1038/s41582-021-00505-9.CrossRefPubMed

Holmes GL. Cognitive impairment in epilepsy: the role of network abnormalities. Epileptic Disord. 2015;17(2):101–16. https://doi.org/10.1684/epd.2015.0739.CrossRefPubMedPubMedCentral

Giorgi FS, Saccaro LF, Busceti CL, Biagioni F, Fornai F. Epilepsy and Alzheimer’s Disease: Potential mechanisms for an association. Brain Res Bull. 2020;160:107–20. https://doi.org/10.1016/j.brainresbull.2020.04.009.CrossRefPubMed

Stefanidou M, Beiser AS, Himali JJ, Peng TJ, Devinsky O, Seshadri S, et al. Bi-directional association between epilepsy and dementia: The Framingham Heart Study. Neurology. 2020;95(24):e3241–7. https://doi.org/10.1212/wnl.0000000000011077.CrossRefPubMedPubMedCentral

Kumlien E, Lundberg PO. Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database. Seizure. 2010;19(2):69–73. https://doi.org/10.1016/j.seizure.2009.11.005.CrossRefPubMed

10.

Hamberger MJ, Palmese CA, Scarmeas N, Weintraub D, Choi H, Hirsch LJ. A randomized, double-blind, placebo-controlled trial of donepezil to improve memory in epilepsy. Epilepsia. 2007;48(7):1283–91. https://doi.org/10.1111/j.1528-1167.2007.01114.x.CrossRefPubMed

11.

Fisher RS, Bortz JJ, Blum DE, Duncan B, Burke H. A pilot study of donepezil for memory problems in epilepsy. Epilepsy Behav. 2001;2(4):330–4. https://doi.org/10.1006/ebeh.2001.0221.CrossRefPubMed

12.

Mares P, Mikulecká A. Different effects of two N-methyl-D-aspartate receptor antagonists on seizures, spontaneous behavior, and motor performance in immature rats. Epilepsy Behav. 2009;14(1):32–9. https://doi.org/10.1016/j.yebeh.2008.08.013.CrossRefPubMed

13.

Marimuthu P, Varadarajan S, Krishnan M, Shanmugam S, Kunjuraman G, Ravinder JR, et al. Evaluating the efficacy of memantine on improving cognitive functions in epileptic patients receiving anti-epileptic drugs: A double-blind placebo-controlled clinical trial (Phase IIIb pilot study). Ann Indian Acad Neurol. 2016;19(3):344–50. https://doi.org/10.4103/0972-2327.179971.CrossRefPubMedPubMedCentral

14.

Dunn NR, Pearce GL, Shakir SA. Adverse effects associated with the use of donepezil in general practice in England. J Psychopharmacol. 2000;14(4):406–8. https://doi.org/10.1177/026988110001400410.CrossRefPubMed

15.

Griffith HR, Martin R, Andrews S, LeBron PA, Ware J, Faught E, et al. The safety and tolerability of galantamine in patients with epilepsy and memory difficulties. Epilepsy Behav. 2008;13(2):376–80. https://doi.org/10.1016/j.yebeh.2008.05.006.CrossRefPubMed

16.

Kim JA, Yoon S, Kim LY, Kim DS. Towards Actualizing the Value Potential of Korea Health Insurance Review and Assessment (HIRA) Data as a Resource for Health Research: Strengths, Limitations, Applications, and Strategies for Optimal Use of HIRA Data. J Korean Med Sci. 2017;32(5):718–28. https://doi.org/10.3346/jkms.2017.32.5.718.CrossRefPubMedPubMedCentral

17.

Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130–9. https://doi.org/10.1097/01.mlr.0000182534.19832.83.CrossRefPubMed

18.

Schneeweiss S, Maclure M. Use of comorbidity scores for control of confounding in studies using administrative databases. Int J Epidemiol. 2000;29(5):891–8. https://doi.org/10.1093/ije/29.5.891.CrossRefPubMed

19.

Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: A systematic review. Neurology. 2015;85(15):1332–41. https://doi.org/10.1212/wnl.0000000000002023.CrossRefPubMed

20.

Wu CS, Liu HY, Tsai HJ, Liu SK. Seizure Risk Associated With Antidepressant Treatment Among Patients With Depressive Disorders: A Population-Based Case-Crossover Study. J Clin Psychiatry. 2017;78(9):e1226–32. https://doi.org/10.4088/JCP.16m11377.CrossRefPubMed

21.

Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011;46(3):399–424. https://doi.org/10.1080/00273171.2011.568786.CrossRefPubMedPubMedCentral

22.

Amatniek JC, Hauser WA, DelCastillo-Castaneda C, Jacobs DM, Marder K, Bell K, et al. Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia. 2006;47(5):867–72. https://doi.org/10.1111/j.1528-1167.2006.00554.x.CrossRefPubMed

23.

McAreavey MJ, Ballinger BR, Fenton GW. Epileptic seizures in elderly patients with dementia. Epilepsia. 1992;33(4):657–60. https://doi.org/10.1111/j.1528-1157.1992.tb02343.x.CrossRefPubMed

24.

Turski L, Ikonomidou C, Turski WA, Bortolotto ZA, Cavalheiro EA. Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse. 1989;3(2):154–71. https://doi.org/10.1002/syn.890030207.

25.

Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain : a journal of neurology. 2018;141(7):1917–33. https://doi.org/10.1093/brain/awy132.CrossRef

26.

Craig LA, Hong NS, Kopp J, McDonald RJ. Reduced cholinergic status in hippocampus produces spatial memory deficits when combined with kainic acid induced seizures. Hippocampus. 2008;18(11):1112–21. https://doi.org/10.1002/hipo.20471.CrossRefPubMed

27.

Serra M, Dazzi L, Cagetti E, Chessa MF, Pisu MG, Sanna A, et al. Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats. J Neurochem. 1997;68(1):313–8. https://doi.org/10.1046/j.1471-4159.1997.68010313.x.CrossRefPubMed

28.

Fernández de Sevilla D, Núñez A, Borde M, Malinow R, Buño W. Cholinergic-mediated IP3-receptor activation induces long-lasting synaptic enhancement in CA1 pyramidal neurons. J Neurosci. 2008;28(6):1469–78. https://doi.org/10.1523/jneurosci.2723-07.2008.

29.

Babic T, Zurak N. Convulsions induced by donepezil. J Neurol Neurosurg Psychiatry. 1999;66(3):410. https://doi.org/10.1136/jnnp.66.3.410.CrossRefPubMedPubMedCentral

30.

Shareef J, Joseph J, Adithi K. A single case report on hyponatremia seizure induced by acetylcholinesterase inhibitors. Int J Pharm Pharm Sci. 2017;9(7):165–216. https://doi.org/10.22159/ijpps.2017v9i7.19057.CrossRef

31.

Cutler NR, Sramek JJ, Murphy MF, Nash RJ. Implications of the study population in the early evaluation of anticholinesterase inhibitors for Alzheimer’s disease. Ann Pharmacother. 1992;26(9):1118–22.CrossRef

32.

Lebert F, Hasenbroekx C, Pasquier F, Petit H. Convulsive effects of tacrine. Lancet (London, England). 1996;347(9011):1339–40.CrossRef

33.

Jeong JH, Choi BY, Kho AR, Lee SH, Hong DK, Lee SH, et al. Diverse Effects of an Acetylcholinesterase Inhibitor, Donepezil, on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure. Int J Mol Sci. 2017;18(11):2311. https://doi.org/10.3390/ijms18112311.CrossRefPubMedCentral

34.

Rogers SL, Friedhoff LT. The efficacy and safety of donepezil in patients with Alzheimer’s disease: results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. The Donepezil Study Group Dementia. 1996;7(6):293–303. https://doi.org/10.1159/000106895.CrossRef

35.

Cummings JL, Vinters HV, Cole GM, Khachaturian ZS. Alzheimer's disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology. 1998;51(1 Suppl 1):S2–17; discussion S65–7. https://doi.org/10.1212/wnl.51.1_suppl_1.s2.

36.

Park JK, Kim KS, Lee TY, Lee KS, Lee DH, Lee SH, et al. The accuracy of ICD codes for cerebrovascular diseases in medical insurance claims. J Prev Med Public Health. 2000;33(1):76–82.

37.

Ha J, Choi D-W, Kim KJ, Cho SY, Kim H, Kim KY, et al. Association of metformin use with Alzheimer’s disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study. Sci Rep. 2021;11(1):24069. https://doi.org/10.1038/s41598-021-03406-5.CrossRefPubMedPubMedCentral

38.

Lyou HJ, Seo K-D, Lee JE, Pak HY, Lee JH. Association of Alzheimer’s Disease with the Risk of Developing Epilepsy: a 10-Year Nationwide Cohort Study. Dement Neurocogn Disord. 2018;17(4):156–62. https://doi.org/10.12779/dnd.2018.17.4.156.

39.

Mbizvo GK, Schnier C, Simpson CR, Duncan SE, Chin RFM. Validating the accuracy of administrative healthcare data identifying epilepsy in deceased adults: A Scottish data linkage study. Epilepsy Res. 2020;167: 106462. https://doi.org/10.1016/j.eplepsyres.2020.106462.CrossRefPubMed

Title: Association of cognitive enhancers and incident seizure risk in dementia: a population-based study
Authors: Junghee Ha
Nak-Hoon Son
Young Ho Park
Eun Lee
Eosu Kim
Woo Jung Kim
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Alzheimer's Disease
Dementia
Epilepsy
Alzheimer's Disease
Dementia
Published in: BMC Geriatrics / Issue 1/2022
Electronic ISSN: 1471-2318
DOI: https://doi.org/10.1186/s12877-022-03120-5

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