Cargando…

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

BACKGROUND: The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking....

Descripción completa

Detalles Bibliográficos
Autores principales: Pozzi, Federico Emanuele, Conti, Elisa, Appollonio, Ildebrando, Ferrarese, Carlo, Tremolizzo, Lucio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530658/
https://www.ncbi.nlm.nih.gov/pubmed/36203811
http://dx.doi.org/10.3389/fnins.2022.998224
_version_ 1784801732314791936
author Pozzi, Federico Emanuele
Conti, Elisa
Appollonio, Ildebrando
Ferrarese, Carlo
Tremolizzo, Lucio
author_facet Pozzi, Federico Emanuele
Conti, Elisa
Appollonio, Ildebrando
Ferrarese, Carlo
Tremolizzo, Lucio
author_sort Pozzi, Federico Emanuele
collection PubMed
description BACKGROUND: The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results. METHODS: We conducted a systematic review of the literature up to December 31(st), 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: predict(*) AND respon(*) AND (acetylcholinesterase inhibitors OR donepezil OR rivastigmine OR galantamine). The results were presented narratively. RESULTS: We identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included. DISCUSSION: The studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial.
format Online
Article
Text
id pubmed-9530658
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95306582022-10-05 Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review Pozzi, Federico Emanuele Conti, Elisa Appollonio, Ildebrando Ferrarese, Carlo Tremolizzo, Lucio Front Neurosci Neuroscience BACKGROUND: The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results. METHODS: We conducted a systematic review of the literature up to December 31(st), 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: predict(*) AND respon(*) AND (acetylcholinesterase inhibitors OR donepezil OR rivastigmine OR galantamine). The results were presented narratively. RESULTS: We identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included. DISCUSSION: The studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530658/ /pubmed/36203811 http://dx.doi.org/10.3389/fnins.2022.998224 Text en Copyright © 2022 Pozzi, Conti, Appollonio, Ferrarese and Tremolizzo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Pozzi, Federico Emanuele
Conti, Elisa
Appollonio, Ildebrando
Ferrarese, Carlo
Tremolizzo, Lucio
Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review
title Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review
title_full Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review
title_fullStr Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review
title_full_unstemmed Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review
title_short Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review
title_sort predictors of response to acetylcholinesterase inhibitors in dementia: a systematic review
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530658/
https://www.ncbi.nlm.nih.gov/pubmed/36203811
http://dx.doi.org/10.3389/fnins.2022.998224
work_keys_str_mv AT pozzifedericoemanuele predictorsofresponsetoacetylcholinesteraseinhibitorsindementiaasystematicreview
AT contielisa predictorsofresponsetoacetylcholinesteraseinhibitorsindementiaasystematicreview
AT appollonioildebrando predictorsofresponsetoacetylcholinesteraseinhibitorsindementiaasystematicreview
AT ferraresecarlo predictorsofresponsetoacetylcholinesteraseinhibitorsindementiaasystematicreview
AT tremolizzolucio predictorsofresponsetoacetylcholinesteraseinhibitorsindementiaasystematicreview