Temporal course of cognitive and behavioural changes in motor neuron diseases

Caroline A McHutchison, Joanne Wuu, Corey T. McMillan, Rosa Rademakers, Jeffrey Statland, Gang Wu, Evadnie Rampersaud, Jessica P Hernandez, Jason Myers, Sharon Abrahams, Michael Benatar*, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: Cognitive and behavioural dysfunction may occur in people with motor neuron disease (MND), with some studies suggesting an association with the C9ORF72 repeat expansion. Their onset and progression, however, is poorly understood. We explored how cognition and behaviour change over time, and whether demographic, clinical and genetic factors impact these changes.

Methods: Participants with MND were recruited through the Phenotype-Genotype-Biomarker study. Every 3–6 months, the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was used to assess amyotrophic lateral sclerosis (ALS) specific (executive functioning, verbal fluency, language) and ALS non-specific (memory, visuospatial) functions. Informants reported on behaviour symptoms via semi-structured interview.Results Participants with neuropsychological data at ≥3 visits were included (n=237, mean age=59, 60% male), of which 18 (8%) were C9ORF72 positive. Baseline cognitive impairment was apparent in 18 (8%), typically in ALS specific domains, and associated with lower education, but not C9ORF72 status. Cognition, on average, remained stable over time, with two exceptions: (1) C9ORF72 carriers declined in all ECAS domains, (2) 8%–9% of participants with baseline cognitive impairment further declined, primarily in the ALS non-specific domain, which was associated with less education. Behavioural symptoms were uncommon.

Conclusions: In this study, cognitive dysfunction was less common than previously reported and remained stable over time for most. However, cognition declines longitudinally in a small subset, which is not entirely related to C9ORF72 status. Our findings raise questions about the timing of cognitive impairment in MND, and whether it arises during early clinically manifest disease or even prior to motor manifestations.
Original languageEnglish
Article numberjnnp-2023-331697
JournalJournal of Neurology, Neurosurgery & Psychiatry
Early online date12 Oct 2023
Publication statusE-pub ahead of print - 12 Oct 2023


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