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Cited by 557Dementia and Cognitive Impairment ResearchEpilepsy research and treatmentAlzheimer's disease research and treatments

Incidence and impact of subclinical epileptiform activity in Alzheimer’s disease.

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Vossel, Keith A., Ranasinghe, Kamalini G., Beagle, Alexander J., Mizuiri, Danielle, Honma, Susanne M., Dowling, Anne F., Darwish, Sonja M., Van Berlo, Victoria +10 more·2016·Annals of Neurology
DOI 10.1002/ana.24794PMC PMC5177487
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Abstract

Objective: Seizures are more frequent in patients with Alzheimer's disease (AD) and can hasten cognitive decline. However, the incidence of subclinical epileptiform activity in AD and its consequences are unknown. Motivated by results from animal studies, we hypothesized higher than expected rates of subclinical epileptiform activity in AD with deleterious effects on cognition. Methods: We prospectively enrolled 33 patients (mean age, 62 years) who met criteria for AD, but had no history of seizures, and 19 age‐matched, cognitively normal controls. Subclinical epileptiform activity was assessed, blinded to diagnosis, by overnight long‐term video‐electroencephalography (EEG) and a 1‐hour resting magnetoencephalography exam with simultaneous EEG. Patients also had comprehensive clinical and cognitive evaluations, assessed longitudinally over an average period of 3.3 years. Results: Subclinical epileptiform activity was detected in 42.4% of AD patients and 10.5% of controls ( p = 0.02). At the time of monitoring, AD patients with epileptiform activity did not differ clinically from those without such activity. However, patients with subclinical epileptiform activity showed faster declines in global cognition, determined by the Mini–Mental State Examination (3.9 points/year in patients with epileptiform activity vs 1.6 points/year in patients without; p = 0.006), and in executive function ( p = 0.01). Interpretation: Extended monitoring detects subclinical epileptiform activity in a substantial proportion of patients with AD. Patients with this indicator of network hyperexcitability are at risk for accelerated cognitive decline and might benefit from antiepileptic therapies. These data call for more sensitive and comprehensive neurophysiological assessments in AD patient evaluations and impending clinical trials. Ann Neurol 2016;80:858–870

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  • It is possible that epileptic activity in primary tauopathies is clinically underrecognized due to being non-motor or subclinical in nature, as suggested by the detection of subclinical epileptic activity in over 40% of Alzheimer's disease patients during overnight electroencephalography and 1-h magnetoencephalogram recordings.

    “However, it is also possible that epileptic activity in these tauopathies is clinically underrecognized due to being non-motor or subclinical in nature, as suggested by the detection of subclinical epileptic activity in over 40% of AD patients during overnight electroencephalography and 1-h magnetoencephalogram recordings (Vossel et al., 2016).”

    From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Vossel et al., 2016

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Authors
Vossel, K. A., Ranasinghe, K. G., Beagle, A. J., Mizuiri, D., Honma, S. M., Dowling, A. F., Darwish, S. M., Van Berlo, V., Barnes, D. E., Mantle, M., Karydas, A. M., Coppola, G., Roberson, E. D., Miller, B. L., Garcia, P. A., Kirsch, H. E., Mucke, L., & Nagarajan, S. S.
Affiliations
  • Gladstone Institutes (US)
  • University of California, San Francisco (US)
  • Department of Neurology and Semel Institute for Neuroscience and Human Behavior in the Department of Psychiatry University of California Los Angeles Los Angeles CA
  • San Francisco VA Medical Center (US)
  • University of California, Los Angeles (US)
  • University of Alabama at Birmingham (US)
Corresponding author
Nagarajan, Srikantan S.
ORCID
Venue
Annals of Neurology
Publisher
Wiley
Published
2016-11-07
Volume
80
Issue
6
Pages
858-870
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.24794
PMC
PMC5177487
OpenAlex
W2527558243
Cited by
557
References
7
Citations by year
2026: 68 · 2025: 71 · 2024: 73 · 2023: 60 · 2022: 70 · 2021: 55 · 2020: 54 · 2019: 40 · 2018: 38 · 2017: 25 · 2016: 1
FWCI
30.81
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • NIH (K23 AG038357, P50 AG023501, P01 AG19724, R21 NS76171, R01 DC010145, NS066654, NS64060)
  • University of California San Francisco Alzheimer's Disease Research Center pilot project grant
  • National Science Foundation grant (BCS-1262297)
  • Alzheimer's Association (PCTRB-13-288476)
  • John Douglas French Alzheimer's Foundation
  • S.D. Bechtel Jr. Foundation
  • McBean Family Foundation
  • Larry L. Hillblom Foundation
  • National Center for Research Resources
  • National Center for Advancing Translational Sciences
  • University of California San Francisco-CTSI (UL1 RR024131, UL1 TR000004)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, cognitive decline, executive function, network hyperexcitability, seizures, anticonvulsant therapy, long-term video-EEG monitoring, magnetoencephalography, Mini-Mental State Examination
MeSH terms
Alzheimer Disease, California, Electroencephalography, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Seizures, Magnetoencephalography, Comorbidity, Incidence, Case-Control Studies, Neuroimaging, Prodromal Symptoms

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