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. 2025 Jan;32(1):e70027.
doi: 10.1111/ene.70027.

Education moderates the association between motor involvement and executive status in ALS

Edoardo Nicolò Aiello  1 , Barbara Poletti  1   2 , Monica Consonni  3 , Barbara Iazzolino  4 , Silvia Torre  1 , Veronica Faltracco  3 , Alessandra Telesca  5   6 , Francesca Palumbo  4 , Beatrice Curti  1 , Giulia De Luca  1 , Eleonora Dalla Bella  3 , Enrica Bersano  3   7 , Nilo Riva  3 , Federico Verde  1   8 , Stefano Messina  1 , Alberto Doretti  1 , Alessio Maranzano  1 , Claudia Morelli  1 , Andrea Calvo  4   9 , Vincenzo Silani  1   8 , Giuseppe Lauria  3   7 , Adriano Chiò  4   9   10 , Nicola Ticozzi  1   8
Affiliations

Education moderates the association between motor involvement and executive status in ALS

Edoardo Nicolò Aiello et al. Eur J Neurol. 2025 Jan.

Abstract

Background: This study aimed to determine whether educational attainment-a common proxy of cognitive reserve (CR)-influences the association between motor and cognitive/behavioural outcomes in a large cohort of ALS patients without dementia.

Methods: N = 726 ALS patients without FTD were assessed for motor (ALSFRS-R), cognitive (Edinburgh Cognitive and Behavioural ALS Screen, ECAS) and behavioural outcomes (ECAS-Carer Interview, ECAS-CI). CR was operationalized via educational attainment (in years). Moderation models were run on each subscale of the cognitive section of the ECAS and on the ECAS-CI by addressing ALSFRS-R as the predictor and education as the moderator.

Results: Education was associated with both the ALSFRS-R and all the cognitive subscales of the ECAS, while not with the ECAS-CI. As to moderation models, a significant Education*ALSFRS-R interaction was detected solely with regard to the ECAS-Executive-with its simple slope-based decomposition revealing that higher ALSFRS-R scores were associated with higher scores on the ECAS-Executive for patients with low (p < 0.001) and average (p = 0.007), while not high, levels of education.

Discussion: Education seems to moderate the association between motor involvement and executive status in ALS patients without dementia, thus possibly exerting a protective role towards both motor function and cognition in this population.

Keywords: amyotrophic lateral sclerosis; cognitive reserve; disease severity; executive functions; frontotemporal degeneration.

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Conflict of interest statement

V. S. received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l. and Novartis Pharma AG, receives or has received research support from the Italian Ministry of Health, AriSLA and E‐Rare Joint Transnational Call. He is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology. B.P. received compensation for consulting services and/or speaking activities from Liquidweb S.r.l. B.P. is an Associate Editor for Frontier in Neuroscience. N. T. received compensation for consulting services and/or speaking fees from Amylyx Pharmaceuticals, Biogen, Italfarmaco and Zambon Biotech SA. He is an Associate Editor for Frontiers in Aging Neuroscience. F.V. is an Associate Editor for Journal of Alzheimer's Disease. E.N.A. serves as an Editorial Board Member for BMC Neurology. A.Ch. is a member of the following Scientific Advisory Boards: Mitsubishi Tanabe, Roche, Biogen, Denali Pharma, Cytokinetics, Amylyx Pharmaceuticals, VectorY, Ferrer and Zambon Biotech; he received a scientific grant from Biogen; he is a member of the following Drug Safety and Monitoring Boards: AB Science, Verge, Corcept and Eli Lilly; A. Ca. has received a research grant from Cytokinetics. The other authors have nothing to declare.

Figures

FIGURE 1
FIGURE 1
Moderating effect of education on the association between ALSFRS‐R and ECAS‐Executive scores. ALSFRS‐R, Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised; ECAS, Edinburgh Cognitive and Behavioural ALS Screen. Regression slopes are depicted along with their 95% CI.
See this image and copyright information in PMC

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