Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method

Amber Nous, Laura Seynaeve, Odile Feys, Vincent Wens, Xavier De Tiège, Pieter Van Mierlo, Amir G Baroumand, Koenraad Nieboer, Gert-Jan Allemeersch, Shana Mangelschots, Veronique Michiels, Julie van der Zee, Christine Van Broeckhoven, Annemie Ribbens, Ruben Houbrechts, Sara De Witte, Mandy Melissa Jane Wittens, Maria Bjerke, Caroline Vanlersberghe, Sarah CeyssensGuy Nagels, Ilse Smolders, Sebastiaan Engelborghs

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Abstract

BACKGROUND: Epileptic seizures are an established comorbidity of Alzheimer's disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD.

AIMS: 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters.

METHODS: Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs.

RESULTS: We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher's exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall-Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann-Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without.

CONCLUSION: We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes.

TRIAL REGISTRATION: Clinicaltrials.gov, NCT04131491. 12/02/2020.

Original languageEnglish
Article number19
Number of pages20
JournalAlzheimer's Research & Therapy
Volume16
Issue number1
DOIs
Publication statusPublished - Dec 2024

Bibliographical note

Funding Information:
This work was supported by Fonds Wetenschappelijk Onderzoek (FWO), Flanders, grant number B040419N. We gratefully acknowledge the Brussels-Capital Region—Innoviris (Brussels Public Organisation for Research and Innovation) for financial support of the DetectDem research platform (2022-RPF-1). The funders had no role in study design, data collection, data analysis or interpretation of the data, nor in the writing of the report or decision to submit the article for publication.

Funding Information:
The MEG project at the CUB Hôpital Erasme and the Hôpital Universitaire de Bruxelles is financially supported by the Fonds Erasme (Brussels, Belgium; Research convention: “Les Voies du Savoir”). The PET-MR project at the CUB Hôpital Erasme is financially suppported by the Association Vinçotte Nuclear.

Funding Information:
O.F. is supported by a research grant from the Fonds pour la Formation à la Recherche dans l’Industrie et l’Agriculture (FRIA, Fonds de la Recherche Scientifique (FRS-FNRS), Brussels, Belgium).

Publisher Copyright:
© 2024, The Author(s).

Keywords

  • Alzheimer's Disease
  • High-density electroencephalography
  • Interictal epileptic discharges
  • Long-term electroencephalography
  • magnetoencephalography
  • Subclinical epileptiform activity

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