ReviewJournal of Alzheimer's disease : JAD2023
Etiology and Clinical Significance of Network Hyperexcitability in Alzheimer's Disease: Unanswered Questions and Next Steps.
Review in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Mapping new pharmacological interventions for cognitive function in Alzheimer's disease: a systematic review of randomized clinical trials.Frontiers in pharmacology · 2023Pooled it
- Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.The EMBO journal · 2026Article
- Impairment of hippocampal long-term potentiation by soluble amyloid-β oligomers is mediated by glutamate transporter 1 expressed in neurons.Neural regeneration research · 2026Article
- Human P301L tau expression in mice alters neuronal excitability independent of neurodegeneration.Frontiers in neuroscience · 2026Article
- The impact of long-term antiseizure treatment on cognitive decline in late-onset epileptic prodromal Alzheimer's disease: an exploratory study.Frontiers in aging neuroscience · 2026Article
- Epilepsy and EEG abnormalities in neurodegenerative dementias: toward a system epilepsy framework.Frontiers in aging neuroscience · 2026Review
- Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study.Frontiers in pharmacology · 2026Article
- Epilepsy, seizures and hyperexcitability-a challenge in neurology.Neurological research and practice · 2025Article
- Longitudinal excitation-inhibition balance altered by sex and APOE-ε4.Communications biology · 2025Article
- High-frequency oscillations in epileptic and non-epileptic Alzheimer's disease patients and the differential effect of levetiracetam on the oscillations.Brain communications · 2025Article
- Development of a three-dimensional organoid model to explore early retinal phenotypes associated with Alzheimer's disease.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cortical network hyperexcitability related to synaptic dysfunction in Alzheimer's disease (AD) is a potential target for therapeutic intervention. In recent years, there has been increased interest in the prevalence of silent seizures and interictal epileptiform discharges (IEDs, or seizure tendency), with both entities collectively termed "subclinical epileptiform activity" (SEA), on neurophysiologic studies in AD patients. SEA has been demonstrated to be common in AD, with prevalence estimates ranging between 22-54%. Converging lines of basic and clinical evidence imply that modifying a hyperexcitable state results in an improvement in cognition. In particular, though these results require further confirmation, post-hoc findings from a recent phase II clinical trial suggest a therapeutic effect with levetiracetam administration in patients with AD and IEDs. Here, we review key unanswered questions as well as potential clinical trial avenues. Specifically, we discuss postulated mechanisms and treatment of hyperexcitability in patients with AD, which are of interest in designing future disease-modifying therapies. Criteria to prompt screening and optimal screening methodology for hyperexcitability have yet to be defined, as does timing and personalization of therapeutic intervention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.