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Journal of Neurology
Journal of Neurology
Volume 271, Issue 10 October 2024

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Barbara Poletti Edoardo Nicolò Aiello Nicola Ticozzi

Background This study aimed at (1) delivering generalizable estimates of the prevalence of frontotemporal-spectrum disorders (FTSDs) in non-demented ALS patients and (2) exploring their motor-functional correlates.

Methods N=808 ALS patients without FTD were assessed for motor-functional outcomes—i.e., disease duration, severity (ALSFRS-R), progression rate (FS), and stage (King’s and Milano–Torino—MiToS—systems)—cognition—via the cognitive section of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS)—and behaviour—via the ECAS-Carer Interview. Neuropsychological phenotypes were retrieved via Strong’s revised criteria—i.e., ALS cognitively and behaviourally normal (ALScbn) or cognitively and/or behaviourally impaired (ALSci/bi/cbi).

Results Defective ECAS-Total performances were detected in~29% of patients, with the ECAS-Executive being failed by the highest number of patients (~30%), followed by the ECAS-Language, -Fluency, and -Memory (~15–17%) and -Visuospatial (~%8). Apathy was the most frequent behavioural change (~28%), followed by loss of sympathy/empathy (~13%); remaining symptoms were reported in <4% of patients. The distribution of Strong’s classifications was as follows: ALScbn: 46.7%; ALSci/bi/cbi: 22.9%/20.0%/10.4%. Multinomial regressions on Strong’s classifications revealed that lower ALSFRS-R scores were associated with a higher probability of ALSbi and ALScbi classifications (p=/-.008). Higher King’s and MiToS stages were associated with a higher probability of ALSbi classification (p=/-.031).

Conclusions FTSDs affect~50% of non-demented ALS patients, with cognitive deficits being as frequent as behavioural changes. A higher degree of motor-functional involvement is associated with worse behavioural outcomes—with this link being weaker for cognitive deficits.