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cc by-nc-nd (c) Borrego Écija et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/174675

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

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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.

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BORREGO ÉCIJA, Sergi, TURON SANS, Janina, XIMELIS, Teresa, ALDECOA ANSÓRREGUI, Iban, MOLINA PORCEL, Laura, POVEDANO, Mònica, RUBIO, Miguel angel, GÁMEZ, Josep, CANO, Antonio, PARÉ‐CURELL, Martí, BAJO, Lorena, SOTOCA, Javier, CLARIMÓN, Jordi, BALASA, Mircea, ANTONELL BOIXADER, Anna, LLADÓ PLARRUMANÍ, Albert, SÁNCHEZ VALLE, Raquel, ROJAS GARCÍA, Ricard, GELPI, Ellen. Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants. _Brain Pathology_. 2021. [consulta: 29 de novembre de 2025]. [Disponible a: https://hdl.handle.net/2445/174675]

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