2026-04-17T02:53:25Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/70492024-12-13T09:46:59Zcom_2072_378071com_2072_378040col_2072_378097

Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants Borrego-Écija, Sergi Turon-Sans, Janina Ximelis, Teresa Aldecoa, Iban Molina-Porcel, Laura Povedano, Mónica Gamez Carbonell, Josep Trastorns de la cognició - Patogènesi Esclerosi lateral amiotròfica - Patogènesi DISEASES::Nervous System Diseases::Nervous System Diseases::Neurodegenerative Diseases::Nervous System Diseases::Neurodegenerative Diseases::TDP-43 Proteinopathies::Nervous System Diseases::Amyotrophic Lateral Sclerosis Other subheadings::Other subheadings::Other subheadings::/pathology PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Neurocognitive Disorders::Cognition Disorders::Cognitive Dysfunction Other subheadings::Other subheadings::Other subheadings::/pathology ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso::enfermedades neurodegenerativas::enfermedades del sistema nervioso::enfermedades neurodegenerativas::proteinopatías TDP-43::enfermedades del sistema nervioso::esclerosis lateral amiotrófica Otros calificadores::Otros calificadores::Otros calificadores::/patología PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos neurocognitivos::trastornos cognitivos::disfunción cognitiva Otros calificadores::Otros calificadores::Otros calificadores::/patología Proteïna TDP-43; Esclerosi lateral amiotròfica; Demència frontotemporal Proteína TDP-43; Esclerosis lateral amiotrófica; Demencia frontotemporal TDP-43 protein; Amyotrophic lateral sclerosis; Frontotemporal dementia 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 ε4 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. SBE is a recipient of the Rio-Hortega post-residency grant from the Instituto de Salud Carlos III, Spain. This study was partially funded by Fundació Marató de TV3 (grant no. 20141610 to EG and no. 20143710 to RRG) and Fondo Europeo de Desarrollo Regional (FEDER) (PI15/01618 to RRG). AA is funded by Departament de Salut de la Generalitat de Catalunya, Pla estratègic de recerca i innovació en salut (PERIS) 2016–2020 (SLT002/16/00329). JG is recipient of the Instituto de Salud Carlos III-FEDER grants (PI16/01673 and PI19/00593) 2023-11-08T15:23:39Z 2023-11-08T15:23:39Z 2023-11-08T15:23:39Z 2022-02-22T07:17:30Z 2022-02-22T07:17:30Z 2021-05 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/7049 Brain Pathology;31(3) https://doi.org/10.1111/bpa.12942 info:eu-repo/grantAgreement/ES/PE2013-2016/PI15%2F01618 info:eu-repo/grantAgreement/ES/PERIS2016-2020/SLT002%2F16%2F00329 info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F01673 info:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F00593 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Wiley Scientia