Cargando…

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

Epilepsy and Alzheimer’s disease (AD) incidence increases with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age, and abnormal AD biomarkers in PET and/or CSF are frequen...

Descripción completa

Detalles Bibliográficos
Autores principales: Altuna, Miren, Olmedo-Saura, Gonzalo, Carmona-Iragui, María, Fortea, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030029/
https://www.ncbi.nlm.nih.gov/pubmed/35457126
http://dx.doi.org/10.3390/ijms23084307
_version_ 1784692044483002368
author Altuna, Miren
Olmedo-Saura, Gonzalo
Carmona-Iragui, María
Fortea, Juan
author_facet Altuna, Miren
Olmedo-Saura, Gonzalo
Carmona-Iragui, María
Fortea, Juan
author_sort Altuna, Miren
collection PubMed
description Epilepsy and Alzheimer’s disease (AD) incidence increases with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age, and abnormal AD biomarkers in PET and/or CSF are frequently found in late-onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes, including neuronal hyperexcitability and an early excitatory–inhibitory dysregulation, leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies, suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy, share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology, such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate the progression of cognitive decline, and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly patients without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with an altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASMs). There is also a potential role for ASMs to be used as disease-modifying drugs in AD.
format Online
Article
Text
id pubmed-9030029
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90300292022-04-23 Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications Altuna, Miren Olmedo-Saura, Gonzalo Carmona-Iragui, María Fortea, Juan Int J Mol Sci Review Epilepsy and Alzheimer’s disease (AD) incidence increases with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age, and abnormal AD biomarkers in PET and/or CSF are frequently found in late-onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes, including neuronal hyperexcitability and an early excitatory–inhibitory dysregulation, leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies, suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy, share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology, such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate the progression of cognitive decline, and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly patients without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with an altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASMs). There is also a potential role for ASMs to be used as disease-modifying drugs in AD. MDPI 2022-04-13 /pmc/articles/PMC9030029/ /pubmed/35457126 http://dx.doi.org/10.3390/ijms23084307 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Altuna, Miren
Olmedo-Saura, Gonzalo
Carmona-Iragui, María
Fortea, Juan
Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications
title Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications
title_full Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications
title_fullStr Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications
title_full_unstemmed Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications
title_short Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications
title_sort mechanisms involved in epileptogenesis in alzheimer’s disease and their therapeutic implications
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030029/
https://www.ncbi.nlm.nih.gov/pubmed/35457126
http://dx.doi.org/10.3390/ijms23084307
work_keys_str_mv AT altunamiren mechanismsinvolvedinepileptogenesisinalzheimersdiseaseandtheirtherapeuticimplications
AT olmedosauragonzalo mechanismsinvolvedinepileptogenesisinalzheimersdiseaseandtheirtherapeuticimplications
AT carmonairaguimaria mechanismsinvolvedinepileptogenesisinalzheimersdiseaseandtheirtherapeuticimplications
AT forteajuan mechanismsinvolvedinepileptogenesisinalzheimersdiseaseandtheirtherapeuticimplications