Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants
Por:
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
Publicada:
1 may 2021
Ahead of Print:
1 feb 2021
Resumen:
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.
Filiaciones:
Borrego-Ecija, S:
Univ Barcelona, Hosp Clin, Neurol Dept, Alzheimers Dis & Other Cognit Disorders Unit,Inst, Barcelona, Spain
Turon-Sans, J:
Univ Autonoma Barcelona, Res Inst, Neurol Dept, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Ximelis, T:
Biobanc Hosp Clin IDIBAPS, Neurol Tissue Bank, Barcelona, Spain
Aldecoa, I:
Biobanc Hosp Clin IDIBAPS, Neurol Tissue Bank, Barcelona, Spain
Hosp Clin Barcelona, Pathol Dept, CDB, Barcelona, Spain
Molina-Porcel, L:
Univ Barcelona, Hosp Clin, Neurol Dept, Alzheimers Dis & Other Cognit Disorders Unit,Inst, Barcelona, Spain
Biobanc Hosp Clin IDIBAPS, Neurol Tissue Bank, Barcelona, Spain
Povedano, M:
Bellvitge Univ Hosp, Serv Neurol, Motor Neuron Unit, Lhospitalet De Llobregat, Spain
Rubio, MA:
Hosp Mar, Dept Neurol, Neuromuscular Unit, Barcelona, Spain
Gamez, J:
Vall dHebron Univ Hosp, Vall dHebron Res Inst VHIR, Neurol Dept, ALS Unit, Barcelona, Spain
UAB, Dept Med, European Reference Network Rare Neuromuscular Dis, Barcelona, Spain
Cano, A:
Hosp Mataro, Neurol Dept, Mataro, Spain
Pare-Curell, M:
Hosp Badalona Germans Trias & Pujol, Neurol Dept, Badalona, Spain
Bajo, L:
Hosp Univ Santa Creu Vic, Fundacio Hosp Santa Creu, Serv Geriatria, Vic, Spain
Sotoca, J:
Hosp Mutua Terrassa, Neurol Dept, Terrassa, Spain
Clarimon, J:
Univ Autonoma Barcelona, Res Inst, Neurol Dept, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Balasa, M:
Univ Barcelona, Hosp Clin, Neurol Dept, Alzheimers Dis & Other Cognit Disorders Unit,Inst, Barcelona, Spain
Antonell, A:
Univ Barcelona, Hosp Clin, Neurol Dept, Alzheimers Dis & Other Cognit Disorders Unit,Inst, Barcelona, Spain
Llado, A:
Univ Barcelona, Hosp Clin, Neurol Dept, Alzheimers Dis & Other Cognit Disorders Unit,Inst, Barcelona, Spain
Sanchez-Valle, R:
Univ Barcelona, Hosp Clin, Neurol Dept, Alzheimers Dis & Other Cognit Disorders Unit,Inst, Barcelona, Spain
Biobanc Hosp Clin IDIBAPS, Neurol Tissue Bank, Barcelona, Spain
Rojas-Garcia, R:
Univ Autonoma Barcelona, Res Inst, Neurol Dept, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Gelpi, E:
Biobanc Hosp Clin IDIBAPS, Neurol Tissue Bank, Barcelona, Spain
Med Univ Vienna, Dept Neurol, Div Neuropathol & Neurochem, Vienna, Austria
Green Published, gold
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