Interictal Epileptiform Discharges in Alzheimer's Disease: Prevalence, Relevance, and Controversies

Overview

Journal Front Neurol

Specialty Neurology

Date 2023 Oct 9

PMID 37808503

Authors

Hernan Nicolas Lemus

Rani A Sarkis

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is the most common type of dementia and remains an incurable, progressive disease with limited disease-modifying interventions available. In patients with AD, interictal epileptiform discharges (IEDs) have been identified in up to 54% of combined cohorts of mild cognitive impairment (MCI) or mild dementia and are a marker of a more aggressive disease course. Studies assessing the role of IEDs in AD are limited by the lack of standardization in the definition of IEDs or the different neurophysiologic techniques used to capture them. IEDs are an appealing treatment target given the availability of EEG and anti-seizure medications. There remains uncertainty regarding when to treat IEDs, the optimal drug and dose for treatment, and the impact of treatment on disease course. This review covers the state of knowledge of the field of IEDs in AD, and the steps needed to move the field forward.

Citing Articles

Alzheimer's Disease and Epilepsy: Exploring Shared Pathways and Promising Biomarkers for Future Treatments.

Kalyvas A, Dimitriou M, Ioannidis P, Grigoriadis N, Afrantou T J Clin Med. 2024; 13(13).

PMID: 38999445 PMC: 11242231. DOI: 10.3390/jcm13133879.

Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction.

Olkhova E, Smith L, Dennis B, Ng Y, LeBeau F, Gorman G Biochem Soc Trans. 2024; 52(2):553-565.

PMID: 38563502 PMC: 11088917. DOI: 10.1042/BST20230191.

References

Geva-Sagiv M, Mankin E, Eliashiv D, Epstein S, Cherry N, Kalender G . Augmenting hippocampal-prefrontal neuronal synchrony during sleep enhances memory consolidation in humans. Nat Neurosci. 2023; 26(6):1100-1110. PMC: 10244181. DOI: 10.1038/s41593-023-01324-5. View

Landi S, Petrucco L, Sicca F, Ratto G . Transient Cognitive Impairment in Epilepsy. Front Mol Neurosci. 2019; 11:458. PMC: 6330286. DOI: 10.3389/fnmol.2018.00458. View

Lambert I, Tramoni-Negre E, Lagarde S, Roehri N, Giusiano B, Trebuchon-Da Fonseca A . Hippocampal Interictal Spikes during Sleep Impact Long-Term Memory Consolidation. Ann Neurol. 2020; 87(6):976-987. DOI: 10.1002/ana.25744. View

Kleen J, Scott R, Holmes G, Roberts D, Rundle M, Testorf M . Hippocampal interictal epileptiform activity disrupts cognition in humans. Neurology. 2013; 81(1):18-24. PMC: 3770206. DOI: 10.1212/WNL.0b013e318297ee50. View

Gelinas J, Khodagholy D, Thesen T, Devinsky O, Buzsaki G . Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy. Nat Med. 2016; 22(6):641-8. PMC: 4899094. DOI: 10.1038/nm.4084. View

Rao S, Dove G, Cascino G, Petersen R . Recurrent seizures in patients with dementia: frequency, seizure types, and treatment outcome. Epilepsy Behav. 2008; 14(1):118-20. PMC: 2875670. DOI: 10.1016/j.yebeh.2008.08.012. View

Horvath A, Szucs A, Barcs G, Kamondi A . Sleep EEG Detects Epileptiform Activity in Alzheimer's Disease with High Sensitivity. J Alzheimers Dis. 2017; 56(3):1175-1183. DOI: 10.3233/JAD-160994. View

Rae-Grant A, BLUME W, Lau C, Hachinski V, Fisman M, Merskey H . The electroencephalogram in Alzheimer-type dementia. A sequential study correlating the electroencephalogram with psychometric and quantitative pathologic data. Arch Neurol. 1987; 44(1):50-4. DOI: 10.1001/archneur.1987.00520130042015. View

Vossel K, Ranasinghe K, Beagle A, Mizuiri D, Honma S, Dowling A . Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Ann Neurol. 2016; 80(6):858-870. PMC: 5177487. DOI: 10.1002/ana.24794. View

10.

Sanchez Fernandez I, Loddenkemper T, Galanopoulou A, Moshe S . Should epileptiform discharges be treated?. Epilepsia. 2015; 56(10):1492-504. PMC: 6294573. DOI: 10.1111/epi.13108. View

11.

Shewmon D, Erwin R . Focal spike-induced cerebral dysfunction is related to the after-coming slow wave. Ann Neurol. 1988; 23(2):131-7. DOI: 10.1002/ana.410230205. View

12.

Hautecloque-Raysz G, Sellal F, Bousiges O, Phillipi N, Blanc F, Cretin B . Epileptic Prodromal Alzheimer's Disease Treated with Antiseizure Medications: Medium-Term Outcome of Seizures and Cognition. J Alzheimers Dis. 2023; 94(3):1057-1074. DOI: 10.3233/JAD-221197. View

13.

Musaeus C, Frederiksen K, Andersen B, Hogh P, Kidmose P, Fabricius M . Detection of subclinical epileptiform discharges in Alzheimer's disease using long-term outpatient EEG monitoring. Neurobiol Dis. 2023; 183:106149. DOI: 10.1016/j.nbd.2023.106149. View

14.

Sarkis R, Goksen Y, Mu Y, Rosner B, Lee J . Cognitive and fatigue side effects of anti-epileptic drugs: an analysis of phase III add-on trials. J Neurol. 2018; 265(9):2137-2142. DOI: 10.1007/s00415-018-8971-z. View

15.

Brunetti V, DAtri A, Della Marca G, Vollono C, Marra C, Vita M . Subclinical epileptiform activity during sleep in Alzheimer's disease and mild cognitive impairment. Clin Neurophysiol. 2020; 131(5):1011-1018. DOI: 10.1016/j.clinph.2020.02.015. View

16.

Horvath A, Papp A, Zsuffa J, Szucs A, Luckl J, Radai F . Subclinical epileptiform activity accelerates the progression of Alzheimer's disease: A long-term EEG study. Clin Neurophysiol. 2021; 132(8):1982-1989. DOI: 10.1016/j.clinph.2021.03.050. View

17.

Lam A, Sarkis R, Pellerin K, Jing J, Dworetzky B, Hoch D . Association of epileptiform abnormalities and seizures in Alzheimer disease. Neurology. 2020; 95(16):e2259-e2270. PMC: 7713786. DOI: 10.1212/WNL.0000000000010612. View

18.

Kural M, Duez L, Sejer Hansen V, Larsson P, Rampp S, Schulz R . Criteria for defining interictal epileptiform discharges in EEG: A clinical validation study. Neurology. 2020; 94(20):e2139-e2147. PMC: 7526669. DOI: 10.1212/WNL.0000000000009439. View

19.

Trejo-Lopez J, Yachnis A, Prokop S . Neuropathology of Alzheimer's Disease. Neurotherapeutics. 2021; 19(1):173-185. PMC: 9130398. DOI: 10.1007/s13311-021-01146-y. View

20.

Noorlag L, van Klink N, Kobayashi K, Gotman J, Braun K, Zijlmans M . High-frequency oscillations in scalp EEG: A systematic review of methodological choices and clinical findings. Clin Neurophysiol. 2022; 137:46-58. DOI: 10.1016/j.clinph.2021.12.017. View