Contributors: Institut Català de la Salut; [Borrego-Écija S] Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. [Turon-Sans J] Neurology department, Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. Center for Networked Biomedical Research into Neurodegenerative Diseases (CIBERNED), Madrid, Spain. [Ximelis T] Neurological Tissue Bank, Biobanc-Hospital Clínic-IDIBAPS, Barcelona, Spain. [Aldecoa I] Neurological Tissue Bank, Biobanc-Hospital Clínic-IDIBAPS, Barcelona, Spain. Pathology Department, CDB, Hospital Clinic Barcelona, Barcelona, Spain. [Molina-Porcel L] Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. Neurological Tissue Bank, Biobanc-Hospital Clínic-IDIBAPS, Barcelona, Spain. [Povedano M] Service of Neurology, Motor Neuron Unit, IDIBELL, Bellvitge University Hospital, Hospitalet de Llobregat, Spain. [Gámez J] Unitat d’Esclerosi Lateral Amiotròfica, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Vall d'Hebron Barcelona Hospital Campus
نبذة مختصرة : 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)
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