ArticleBrain pathology (Zurich, Switzerland)2021
Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants.
Article in Brain pathology (Zurich, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The contribution of brain banks to knowledge discovery in amyotrophic lateral sclerosis: A systematic review.Neuropathology and applied neurobiology · 2022Pooled it
- Proteomic analysis of cerebrospinal fluid of amyotrophic lateral sclerosis patients in the presence of autologous bone marrow derived mesenchymal stem cells.Stem cell research & therapy · 2024Trial
- Methodological insights and clinical outcomes in ALS and FTLD: lessons from the SPIN cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Associations of cognitive and behavioural impairment in ALS with brain pathology: pTDP-43 versus microglial activation.Journal of neurology · 2026Article
- Targeting dysregulated CB1 receptors in a Down syndrome mouse model improves neurological outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Genetic and Clinical Insights into ALS/FTD: Profiling a Rare Cohort to Explore Spectrum Heterogeneity.Journal of personalized medicine · 2025Article
- Restoration of CB1 receptor function in hippocampal GABAergic neurons rescues memory deficits in Huntington's disease models.Translational neurodegeneration · 2025Article
- Frequency and Early Predictors of Cognitive Deterioration in Amyotrophic Lateral Sclerosis: A Longitudinal Population-Based Study.Annals of neurology · 2025Article
- Impact of APOE and MAPT genetic profile on the cognitive functions among Amyotrophic Lateral Sclerosis Tunisian patients.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Identification of a pathogenic mutation inJournal of neurology, neurosurgery, and psychiatry · 2025Article
- The Basis of Cognitive and Behavioral Dysfunction in Amyotrophic Lateral Sclerosis.Brain and behavior · 2024Review
- Association of APOE genotype and cerebrospinal fluid Aβ and tau biomarkers with cognitive and motor phenotype in amyotrophic lateral sclerosis.European journal of neurology · 2024Article
- Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum.Brain : a journal of neurology · 2024Observational
- Clinical heterogeneity within the ALS-FTD spectrum in a family with a homozygous optineurin mutation.Annals of clinical and translational neurology · 2024Article
- Cognitive function in amyotrophic lateral sclerosis: a cross-sectional and prospective pragmatic clinical study with review of the literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Mitochondrial complex I deficiency stratifies idiopathic Parkinson's disease.Nature communications · 2024Article
- The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update.International journal of molecular sciences · 2023Review
- Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study.Journal of neurology · 2023Article
- The role of neurofilament light in genetic frontotemporal lobar degeneration.Brain communications · 2023Review
- Sensory Involvement in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
19 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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