(1) Background: Cognitive deterioration is an important marker of disease activity in multiple sclerosis (MS). It is vital to detect cognitive decline as soon as possible. Cognitive deterioration can take the form of isolated cognitive decline (ICD) with no other clinical signs of disease progression present. (2) Methods: We investigated 1091 MS patients from the longitudinal GQ (Grant Quantitative) study, assessing their radiological, neurological, and neuropsychological data. Additionally, the confirmatory analysis was conducted. Clinical disease activity was defined as the presence of new relapse or disability worsening. MRI activity was defined as the presence of new or enlarged T2 lesions on brain MRI. (3) Results: Overall, 6.4% of patients experienced cognitive decline and 4.0% experienced ICD without corresponding clinical activity. The vast majority of cognitively worsening patients showed concomitant progression in other neurological and radiologic measures. There were no differences in disease severity between completely stable patients and cognitively worsening patients but with normal cognition at baseline. (4) Conclusions: Only a small proportion of MS patients experience ICD over short-term follow-up. Patients with severe MS are more prone to cognitive decline; however, patients with normal cognitive performance and mild MS might benefit from the early detection of cognitive decline the most.

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY 14203 USA

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague 128 21 Prague Czech Republic

Department of Radiology 1st Faculty of Medicine and General University Hospital Prague Charles University Prague 128 08 Prague Czech Republic

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