Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants

Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concom...

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Autores: Borrego-Ecija, S, Turon-Sans, J, Ximelis, T, Aldecoa, I, Molina-Porcel, L, Povedano, M, Rubio, MA, Gamez, J, Cano, A, Pare-Curell, M, Bajo, L, Sotoca, J, Clarimon, J, Balasa, M, Antonell, A, Llado, A, Sanchez-Valle, R, Rojas-Garcia, R, Gelpi, E
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p5763
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5763
Access Level:acceso abierto
Palabra clave:Alzheimer&#8217
s disease
amyotrophic lateral sclerosis
ALS&#8208
FTD
frontotemporal dementia
neuropathology
TDP&#8208
43 protein
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spelling Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinantsBorrego-Ecija, STuron-Sans, JXimelis, TAldecoa, IMolina-Porcel, LPovedano, MRubio, MAGamez, JCano, APare-Curell, MBajo, LSotoca, JClarimon, JBalasa, MAntonell, ALlado, ASanchez-Valle, RRojas-Garcia, RGelpi, EAlzheimer&#8217s diseaseamyotrophic lateral sclerosisALS&#8208FTDfrontotemporal dementianeuropathologyTDP&#820843 proteinCognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE epsilon 4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP-43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP-43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer's disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non-FTLD related findings can influence the cognitive status, particularly in older age groups.WILEY2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5763BRAIN PATHOLOGYISSN: 10156305ISSNe: 17503639reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p57632026-06-14T12:41:47Z
dc.title.none.fl_str_mv Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
title Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
spellingShingle Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
Borrego-Ecija, S
Alzheimer&#8217
s disease
amyotrophic lateral sclerosis
ALS&#8208
FTD
frontotemporal dementia
neuropathology
TDP&#8208
43 protein
title_short Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
title_full Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
title_fullStr Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
title_full_unstemmed Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
title_sort Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
dc.creator.none.fl_str_mv Borrego-Ecija, S
Turon-Sans, J
Ximelis, T
Aldecoa, I
Molina-Porcel, L
Povedano, M
Rubio, MA
Gamez, J
Cano, A
Pare-Curell, M
Bajo, L
Sotoca, J
Clarimon, J
Balasa, M
Antonell, A
Llado, A
Sanchez-Valle, R
Rojas-Garcia, R
Gelpi, E
author Borrego-Ecija, S
author_facet Borrego-Ecija, S
Turon-Sans, J
Ximelis, T
Aldecoa, I
Molina-Porcel, L
Povedano, M
Rubio, MA
Gamez, J
Cano, A
Pare-Curell, M
Bajo, L
Sotoca, J
Clarimon, J
Balasa, M
Antonell, A
Llado, A
Sanchez-Valle, R
Rojas-Garcia, R
Gelpi, E
author_role author
author2 Turon-Sans, J
Ximelis, T
Aldecoa, I
Molina-Porcel, L
Povedano, M
Rubio, MA
Gamez, J
Cano, A
Pare-Curell, M
Bajo, L
Sotoca, J
Clarimon, J
Balasa, M
Antonell, A
Llado, A
Sanchez-Valle, R
Rojas-Garcia, R
Gelpi, E
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer&#8217
s disease
amyotrophic lateral sclerosis
ALS&#8208
FTD
frontotemporal dementia
neuropathology
TDP&#8208
43 protein
topic Alzheimer&#8217
s disease
amyotrophic lateral sclerosis
ALS&#8208
FTD
frontotemporal dementia
neuropathology
TDP&#8208
43 protein
description Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE epsilon 4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP-43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP-43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer's disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non-FTLD related findings can influence the cognitive status, particularly in older age groups.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5763
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5763
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv BRAIN PATHOLOGY
ISSN: 10156305
ISSNe: 17503639
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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