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Multiple sclerosis
Research paper
Learning ability correlates with brain atrophy and disability progression in RRMS
  1. Maria Pia Sormani1,
  2. Nicola De Stefano2,
  3. Gavin Giovannoni3,
  4. Dawn Langdon4,
  5. Daniela Piani-Meier5,
  6. Dieter A Haering5,
  7. Ludwig Kappos6,
  8. Davorka Tomic5
  1. 1 Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy
  2. 2 Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
  3. 3 Barts and The London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK
  4. 4 Department of Psychology, Royal Holloway, University of London, Egham, UK
  5. 5 Novartis Pharma AG, Basel, Switzerland
  6. 6 Neurological Clinic and Polyclinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland
  1. Correspondence to Dr Maria Pia Sormani, Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa 16126, Italy; mariapia.sormani{at}unige.it

Abstract

Objective To assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis.

Methods We compared screening (day −14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years.

Results The mean PASAT score at screening was 45.38, increasing on average by 3.18 from day −14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates.

Conclusions Short-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

  • PASAT
  • learning effect
  • disability progression
  • fingolimod
  • multiple sclerosis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0

https://doi.org/10.1136/jnnp-2018-319129

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    Footnotes

    • Contributors MPS contributed to the conception, design and execution of the study, statistical analysis, and drafting of the manuscript's outline and critical revision of subsequent drafts of the manuscript, and is responsible for the overall content of the manuscript. NdS contributed to the conception of the study, interpretation of data and critical revision of the manuscript. GG contributed to the conception of the study, analysis and interpretation of data, and critical revision of the manuscript. DL contributed to the interpretation of data and critical revision of the manuscript. DP-M contributed to the conception of the study, interpretation of data, drafting and critical revision of the manuscript. DAH contributed to the execution of the study, statistical analysis and interpretation of data, and critical revision of the manuscript. LK, as the principal investigator of the FREEDOMS trial, was responsible for supervising the trial. He also contributed to the conception, design and execution of the study, interpretation of data, and critical review of manuscript. DT contributed to the conception, design and execution of the study, interpretation of data, and critical revision of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests This study was supported by Novartis Pharma AG, Basel, Switzerland. MPS received compensation for serving on the Scientific Advisory Boards of Teva, Genzyme, Novartis, Roche and Vertex; funding for travel or speaker honoraria from Merck Serono, Teva, Genzyme, Novartis, Biogen and Roche; consultancy from Merck Serono, Biogen, Teva, Genzyme, Roche, GeNeuro, MedDay and Novartis; Speakers' Bureaus from Teva, Merck Serono, Biogen, Novartis and Genzyme. NdS (University of Siena) has served on scientific advisory boards and steering committees of clinical trials for Merck Serono SA, Novartis Pharma AG and Teva, and has received support for congress participation or speaker honoraria from Bayer Schering AG, Biogen Idec, Merck Serono SA, Novartis Pharma AG, Sanofi-Aventis and Teva. GG has received compensation for serving as a consultant or speaker for or has received research support from AbbVie, Almirall, Atara Bio, Bayer Schering Healthcare, Biogen Idec, Canbex, Eisai, Elan, Five Prime Therapeutics, Genzyme, Genentech, GlaxoSmithKline, Ironwood Pharmaceuticals, Merck Serono, Novartis, Pfizer, Roche, Sanofi-Aventis, Synthon BV, Teva Pharmaceutical Industries, UCB and Vertex Pharmaceuticals. DL has participated on advisory boards/received consultancy/research grants or is in the Speaker Bureau for Bayer, Merck, Novartis, Teva, Excemed, Roche and Biogen. DP-M and DAH are employees of Novartis. LK has received no personal compensation. LK’s institution (University Hospital Basel) has received the following exclusively for research support: steering committee, advisory board and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB and Xenoport); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi and Teva); support for educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi and Teva); royalties (Neurostatus Products); licence fees for Neurostatus Products; and grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society and Swiss National Research Foundation). DT is an employee of Novartis.

    • Patient consent Not required.

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

    • Data sharing statement This is a post-hoc analysis of data from patients who had participated in the phase III clinical trial (FREEDOMS). Any data not provided in the article, including statistical analyses and assumptions, may be shared at the request of other investigators.

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