BACKGROUND: Repeated administration of Paced Auditory Serial Addition Test (PASAT) results in a considerable learning effect in short- or long-term follow-up studies. However, the relationship between PASAT learning and changes in magnetic resonance imaging (MRI) parameters is yet to be investigated. OBJECTIVES: The aim of this study is to determine if change in brain MRI metrics predicts evolution of PASAT in high functioning clinically isolated syndrome (CIS) patients on disease-modifying treatment (DMT). METHODS: This prospective 48-month observational study examined 128 CIS patients treated with 30 μg of intramuscular interferon beta-1a once a week. The correlation between PASAT and MRI measures was assessed at baseline, at 6 months and then annually over the 48-month follow up. Linear mixed model analysis adjusted for age, gender, education and DMT was used to model the temporal association between MRI measures and PASAT performance. RESULTS: MRI revealed 2.5% gray matter (GM) volume loss and 4.3 point increase in PASAT score over 48 months. MS patients evidenced significantly greater PASAT score absolute change, had lower loss of GM volume (p=.008) but not significant change in cortical (p=.061), white matter (p=.086) or whole brain volumes (p=.879). CONCLUSIONS: The present study reveals a significant relationship between higher PASAT learning effect and less GM atrophy in CIS patients on DMT. These findings suggest that change in PASAT associated more with GM than WM pathology, and that treatment strategies oriented toward GM volume preservation may play an important role in prevention of cognitive deterioration in CIS patients.

Buffalo Neuroimaging Analysis Center Department of Neurology School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA

Buffalo Neuroimaging Analysis Center Department of Neurology School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA; IRCCS S Maria Nascente Don Gnocchi Foundation Milan Italy

Buffalo Neuroimaging Analysis Center Department of Neurology School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA; MR Imaging Clinical Translational Research Center School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA

Department of Neurology and Center of Clinical Neuroscience Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Department of Neurology and Center of Clinical Neuroscience Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Czech Republic; Buffalo Neuroimaging Analysis Center Department of Neurology School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA

Department of Radiology Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Czech Republic

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Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome