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

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Abstract
BackgroundEpileptic 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.Aims1. 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.Aims1. 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.Aims1. 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.MethodsSubjects (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.ResultsWe 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.ConclusionWe 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 registrationClinicaltrials.gov, NCT04131491. 12/02/2020.
Keywords
Cognitive Neuroscience, Neurology (clinical), Neurology, High-density electroencephalography, Long-term electroencephalography, Interictal epileptic discharges, Subclinical epileptiform activity, Alzheimer's disease

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MLA
Nous, Amber, et al. “Subclinical Epileptiform Activity in the Alzheimer Continuum : Association with Disease, Cognition and Detection Method.” ALZHEIMERS RESEARCH & THERAPY, vol. 16, no. 1, Springer Science and Business Media LLC, 2024, doi:10.1186/s13195-023-01373-9.
APA
Nous, A., Seynaeve, L., Feys, O., Wens, V., De Tiège, X., van Mierlo, P., … Engelborghs, S. (2024). Subclinical epileptiform activity in the Alzheimer continuum : association with disease, cognition and detection method. ALZHEIMERS RESEARCH & THERAPY, 16(1). https://doi.org/10.1186/s13195-023-01373-9
Chicago author-date
Nous, Amber, Laura Seynaeve, Odile Feys, Vincent Wens, Xavier De Tiège, Pieter van Mierlo, Amir Ghasemi Baroumand, et al. 2024. “Subclinical Epileptiform Activity in the Alzheimer Continuum : Association with Disease, Cognition and Detection Method.” ALZHEIMERS RESEARCH & THERAPY 16 (1). https://doi.org/10.1186/s13195-023-01373-9.
Chicago author-date (all authors)
Nous, Amber, Laura Seynaeve, Odile Feys, Vincent Wens, Xavier De Tiège, Pieter van Mierlo, Amir Ghasemi 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 Ceyssens, Guy Nagels, Ilse Smolders, and Sebastiaan Engelborghs. 2024. “Subclinical Epileptiform Activity in the Alzheimer Continuum : Association with Disease, Cognition and Detection Method.” ALZHEIMERS RESEARCH & THERAPY 16 (1). doi:10.1186/s13195-023-01373-9.
Vancouver
1.
Nous A, Seynaeve L, Feys O, Wens V, De Tiège X, van Mierlo P, et al. Subclinical epileptiform activity in the Alzheimer continuum : association with disease, cognition and detection method. ALZHEIMERS RESEARCH & THERAPY. 2024;16(1).
IEEE
[1]
A. Nous et al., “Subclinical epileptiform activity in the Alzheimer continuum : association with disease, cognition and detection method,” ALZHEIMERS RESEARCH & THERAPY, vol. 16, no. 1, 2024.
@article{01HNNQHNWERDW4984WA47X7MD2,
  abstract     = {{BackgroundEpileptic 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.Aims1. 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.Aims1. 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.Aims1. 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.MethodsSubjects (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.ResultsWe 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.ConclusionWe 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 registrationClinicaltrials.gov, NCT04131491. 12/02/2020.}},
  articleno    = {{19}},
  author       = {{Nous, Amber and Seynaeve, Laura and Feys, Odile and Wens, Vincent and De Tiège, Xavier and van Mierlo, Pieter and Ghasemi Baroumand, Amir and Nieboer, Koenraad and Allemeersch, Gert-Jan and Mangelschots, Shana and Michiels, Veronique and van der Zee, Julie and Van Broeckhoven, Christine and Ribbens, Annemie and Houbrechts, Ruben and De Witte, Sara and Wittens, Mandy Melissa Jane and Bjerke, Maria and Vanlersberghe, Caroline and Ceyssens, Sarah and Nagels, Guy and Smolders, Ilse and Engelborghs, Sebastiaan}},
  issn         = {{1758-9193}},
  journal      = {{ALZHEIMERS RESEARCH & THERAPY}},
  keywords     = {{Cognitive Neuroscience,Neurology (clinical),Neurology,High-density electroencephalography,Long-term electroencephalography,Interictal epileptic discharges,Subclinical epileptiform activity,Alzheimer's disease}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{20}},
  publisher    = {{Springer Science and Business Media LLC}},
  title        = {{Subclinical epileptiform activity in the Alzheimer continuum : association with disease, cognition and detection method}},
  url          = {{http://doi.org/10.1186/s13195-023-01373-9}},
  volume       = {{16}},
  year         = {{2024}},
}

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