ArticleEuropean journal of neurology2026
Early Cognitive and Behavioral Changes in Primary Lateral Sclerosis: A Population-Based Study.
Article in European journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivePrimary lateral sclerosis (PLS) is a rare upper motor neuron neurodegenerative disorder whose cognitive profile, particularly at early stages, remains incompletely defined. We aimed to characterize cognitive and behavioral features of PLS at diagnosis and compare them with predominant upper motor neuron amyotrophic lateral sclerosis (PUMN-ALS) and healthy controls (HCs).
methodsPatients diagnosed with PLS between 2007 and 2021 were identified from the population-based Piemonte and Valle d'Aosta ALS Register. Diagnoses were established according to consensus criteria, including early, probable, and definite PLS. All patients underwent comprehensive neuropsychological and behavioral assessment within 3 months of their first ALS center visit. Cognitive-behavioral status was classified using ALS-frontotemporal dementia (FTD) consensus criteria.
resultsThirty-two PLS patients were included (mean disease duration, 25 months). Cognitive and/or behavioral impairment was identified in 29.3% of patients, most commonly affecting executive function, memory, and social cognition, including 21.1% early PLS. Compared with HCs, PLS patients showed poorer performance across several cognitive domains and higher anxiety and depression scores. Compared with matched PUMN-ALS patients, PLS patients demonstrated slightly worse executive performance, while the overall frequency of cognitive-behavioral impairment was similar. Behavioral profiles differed qualitatively, with apathy more frequent in PUMN-ALS. No PLS patient met criteria for frontotemporal dementia.
interpretationCognitive and behavioral impairments are already detectable at the time of diagnosis in a substantial proportion of patients with PLS, including early PLS, supporting the view of PLS as a multidimensional neurodegenerative disorder with early extramotor involvement.
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