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Research paper
Validation of the revised classification of cognitive and behavioural impairment in ALS
  1. Barbara Iazzolino1,
  2. Debora Pain2,
  3. Laura Peotta1,
  4. Andrea Calvo1,3,
  5. Cristina Moglia1,3,
  6. Antonio Canosa1,
  7. Umberto Manera1,
  8. Antonio Ilardi1,
  9. Alessandro Bombaci1,
  10. Jean Pierre Zucchetti1,
  11. Gabriele Mora2,
  12. Adriano Chio1,2,3
  1. 1 ALS Center, ‘Rita Levi Montalcini’ Department of Neuroscience, University of Turin, Torino, Italy
  2. 2 ALS Center, Istituti Clinici Scientifici Maugeri IRCCS, Milan, Italy
  3. 3 Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino, Italy
  1. Correspondence to Professor Adriano Chio, ‘Rita Levi Montalcini’ Department of Neuroscience, Torino I-10126, Italy; achio{at}


Objective In 2017, the diagnostic criteria for cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (ALSFTD-1) have been modified (ALSFTD-2) with the inclusion of a novel category (ALS with combined cognitive and behavioural impairment, ALScbi) and with changes of operational criteria of the other categories (ALS with cognitive impairment (ALSci), ALS with behavioural impairment (ALSbi) and ALS with frontotemporal dementia (ALS-FTD)). We compared the two sets of criteria to assess the effect of the revised criteria on the cognitive classification of patients with ALS.

Methods Two cohorts of patients with ALS were included in this study: a population-based cohort including patients identified through the Piemonte/Valle d’Aosta register for ALS in the 2014–2017 period (n=321), and a referral cohort recruited at the Turin ALS centre and at the ALS centre of the Maugeri Institute in Milan in the same period (n=205). Cognitive function was classified in blind by two neuropsychologists expert in ALS.

Results ALSFTD-2 criteria determined a shift of about 15% of patients from their original category to a new one. In both cohorts, about 9% of patients were reclassified to the novel category ALScbi. Among patients previously classified as cognitively normal, 14 (4.3%, population-based cohort) and 19 (9.3%, referral cohort) were reclassified as ALSbi or ALSci. The median survival of the different categories was significantly different with both with sets of criteria.

Conclusions The new ALSFTD-2 criteria, compared with the old ones, have positive effects on the clinical practice being more sensitive to the early cognitive impairment and having a better prognostic yield.

  • Amyotrophic lateral Sclerosis
  • Frontotemporal dementia
  • Revised Classification
  • Outcome
  • Clinical Characteristics

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  • GM and AC contributed equally.

  • Contributors Study concept and design: BI, DP, CM, ACalvo, GM, AChio. Analysis and interpretation of data: BI, DP, GM, AChio. Drafting of the manuscript: GM, AChio. Critical revision of the manuscript for important intellectual content: BI, DP, LP, ACalvo, CM, ACanosa, UM, AI, AB, JPZ, GM, AChio. Obtained funding: AChio. Administrative, technical and material support: LP, ACalvo, CM, ACanosa, UM, AI, AB, JPZ. Study supervision: GM, AChio. AChio has full access to data. The corresponding author confirm that all authors have read and approved the final draft of the manuscript and given written permission to include their names in the manuscript.

  • Funding This work was in part supported by the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata 2010, grants RF-2010-2309849, RF-2011-02351193 and GR-2011-02351217), the European Commission’s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867) and the Joint Programme—Neurodegenerative Disease Research (Strength, ALS-Care and Brain-Mend projects), granted by Italian Ministry of Education, University and Research. This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the ‘Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Italy.

  • Competing interests AC serves on scientific advisory boards for Mitsubishi Tanabe, Roche and Cytokinetics and has received a research grant from Italfarmaco. Andrea Calvo has received research grant from Cytokinetics.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.