2026-04-13T02:38:29Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1746752025-12-04T19:24:54Zcom_2072_1057col_2072_478858col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Borrego Écija, Sergi author Turon Sans, Janina author Ximelis, Teresa author Aldecoa Ansórregui, Iban author Molina Porcel, Laura author Povedano, Mònica author Rubio, Miguel Angel author Gámez, Josep author Cano, Antonio author Paré‐curell, Martí author Bajo, Lorena author Sotoca, Javier author Clarimón, Jordi author Balasa, Mircea author Antonell Boixader, Anna, 1978- author Lladó Plarrumaní, Albert author Sánchez Valle, Raquel author Rojas García, Ricard author Gelpi, Ellen author 2021-03-05T07:49:05Z 2021-03-05T07:49:05Z 2021-02-12 2021-03-04T09:03:58Z 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. Esclerosi lateral amiotròfica Neurociència cognitiva Amyotrophic lateral sclerosis Cognitive neuroscience Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants