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Quantifying a significant cognitive change on a neuropsychological battery is essential to assess patients’ decline or recovery and offer appropriate care. The reliability of change indices is particularly important in multiple sclerosis (MS), as the course of cognitive impairment is quite unpredictable, due at least in part to substantial interindividual variability. The main objective of this study was to compare six different methods for assessing cognitive change in an MS sample: the SD method, two reliable change indices, two standardized regression-based methods (SRB), and the generalized regression-based method (GSRB). One hundred and twenty-three patients with clinically definite MS and 89 healthy controls underwent a battery of standardized neuropsychological tests assessing cognitive functions that are frequently affected in this disease (i.e., verbal episodic memory, working memory, processing speed and verbal fluency). We observed fairly similar proportions of improvement, decline or stability in the control group whatever the method. By contrast, in the MS sample, regression-based methods with one predictor (i.e., score at T1) and four predictors (i.e., score at T1 and demographic factors: age, sex, education level) detected a significant worsening more often than the reliable change indices while the GSRB method was more consistent with the RCI methods in tasks associated with ceiling effects. The interpretation of a patient’s cognitive changes depends on which method is used. The (G)SRB methods appear to be relevant indicators for assessing cognitive change in MS. The addition of demographic factors does not seem to play an important role in the prediction of significant worsening in the MS sample, regardless of cognitive domain. For clinicians, an easy-to-use free shiny app is provided.

Assessing cognitive changes in multiple sclerosis: criteria for a reliable decision