<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_joepi-2015-0035_s_001"><h3>Introduction</h3><p>Excessive accumulation of amyloid-beta (Aβ) peptides in the brain results initially in mild cognitive impairment (MCI) and finally in Alzheimer’s disease (AD). Evidences from experimental and clinical studies show that pathological hyperexcitability of hippocampal neurons is a very early functional impairment observed in progressive memory dysfunctions. Therefore, antiepileptic drugs (AEDs) whose mechanism of action is aimed at inhibition of such neuronal hyperexcitability, seems to be an rationale choice for MCI and AD treatment.</p></sec><sec id="j_joepi-2015-0035_s_002"><h3>Aim</h3><p>To provide data from experimental and clinical studies on: 1. The unfavorable impact of neuronal hyperexcitability, mainly within the hippocampus, on cognitive processes. 2. Efficacy of AEDs against such abnormally elevated neuronal activity for the prevention of progressive cognitive impairment.</p></sec><sec id="j_joepi-2015-0035_s_003"><h3>Methods</h3><p>A literature review of publications published within the last fifteen years, was conducted using the PubMed database.</p></sec><sec id="j_joepi-2015-0035_s_004"><h3>Review</h3><p>The authors describe Aβ-induced hyperexcitability of hippocampal nerve cells as the cause of cognitive deficits, the connection of such activity with an increased risk of seizures and epilepsy in patients with MCI/AD, and finally the efficacy of AEDs: valproic acid (VPA), phenytoin (PHT), topiramate (TPM), lamotrigine (LTG), ethosuximide (ESM) and levetiracetam (LEV) in the prevention of cognitive impairment in experimental models and patients with MCI/AD.</p></sec><sec id="j_joepi-2015-0035_s_005"><h3>Conclusions</h3><p>The majority of the studied AEDs improve cognitive dysfunction in various experimental models of Aβ-induced brain pathology with accompanied neuronal hyperexcitability. The promising results achieved for LEV in animal models of cognitive impairment were also confirmed in patients with MCI/AD. LEV was well-tolerated and it’s beneficial antidementive effect was confirmed by memory tests and fMRI examination. In conclusion, the use of AEDs could be a novel therapeutic concept for preventing cognitive impairment in patients with Aβ-associated brain pathology.</p></sec></abstract>

IntroductionExcessive accumulation of amyloid-beta (Aβ) peptides in the brain results initially in mild cognitive impairment (MCI) and finally in Alzheimer’s disease (AD). Evidences from experimental and clinical studies show that pathological hyperexcitability of hippocampal neurons is a very early functional impairment observed in progressive memory dysfunctions. Therefore, antiepileptic drugs (AEDs) whose mechanism of action is aimed at inhibition of such neuronal hyperexcitability, seems to be an rationale choice for MCI and AD treatment.AimTo provide data from experimental and clinical studies on: 1. The unfavorable impact of neuronal hyperexcitability, mainly within the hippocampus, on cognitive processes. 2. Efficacy of AEDs against such abnormally elevated neuronal activity for the prevention of progressive cognitive impairment.MethodsA literature review of publications published within the last fifteen years, was conducted using the PubMed database.ReviewThe authors describe Aβ-induced hyperexcitability of hippocampal nerve cells as the cause of cognitive deficits, the connection of such activity with an increased risk of seizures and epilepsy in patients with MCI/AD, and finally the efficacy of AEDs: valproic acid (VPA), phenytoin (PHT), topiramate (TPM), lamotrigine (LTG), ethosuximide (ESM) and levetiracetam (LEV) in the prevention of cognitive impairment in experimental models and patients with MCI/AD.ConclusionsThe majority of the studied AEDs improve cognitive dysfunction in various experimental models of Aβ-induced brain pathology with accompanied neuronal hyperexcitability. The promising results achieved for LEV in animal models of cognitive impairment were also confirmed in patients with MCI/AD. LEV was well-tolerated and it’s beneficial antidementive effect was confirmed by memory tests and fMRI examination. In conclusion, the use of AEDs could be a novel therapeutic concept for preventing cognitive impairment in patients with Aβ-associated brain pathology.

Antiepileptic drugs as a new therapeutic concept for the prevention of cognitive impairment and Alzheimer’s disease. Recent advances

Journal of Epileptology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

IntroductionExcessive accumulation of amyloid-beta (Aβ) peptides in the brain results initially in mild cognitive impairment (MCI) and finally in Alzheimer’s...

Antiepileptic drugs as a new therapeutic concept for the prevention of cognitive impairment and Alzheimer’s disease. Recent advances

Published Online: Dec 10, 2015

Page range: 139 - 147

Received: Nov 17, 2015

Accepted: Dec 08, 2015

DOI: https://doi.org/10.21307/joepi-2015-0035

Keywords
antiepileptic drugs, neuronal hyperexcitability, cognitive impairment, amyloid-beta

© 2015 Krzysztof Sendrowski et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Antiepileptic drugs as a new therapeutic concept for the prevention of cognitive impairment and Alzheimer’s disease. Recent advances

Published Online: Dec 10, 2015

Page range: 139 - 147

Received: Nov 17, 2015

Accepted: Dec 08, 2015

DOI: https://doi.org/10.21307/joepi-2015-0035

Keywordsantiepileptic drugs, neuronal hyperexcitability, cognitive impairment, amyloid-beta

© 2015 Krzysztof Sendrowski et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
antiepileptic drugs, neuronal hyperexcitability, cognitive impairment, amyloid-beta