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

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Foundation of Epileptology

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VOLUME 23 , ISSUE 2 (December 2015) > List of articles

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

Krzysztof Sendrowski * / Wojciech Sobaniec

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

Citation Information : Journal of Epileptology. Volume 23, Issue 2, Pages 139-147, DOI: https://doi.org/10.1515/joepi-2015-0035

License : (CC BY 4.0)

Received Date : 17-November-2015 / Accepted: 08-December-2015 / Published Online: 10-December-2015

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ABSTRACT

Introduction. Excessive accumulation of amyloid-beta (A_) 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.

Aim. 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.

Methods. A literature review of publications published within the last fifteen years, was conducted using the PubMed database.

Review. The authors describe A_-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.

Conclusions. The majority of the studied AEDs improve cognitive dysfunction in various experimental models of A_-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 welltolerated 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 A_-associated brain pathology.

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