Objective The objective was to investigate changes in cognitive functioning in subjects with early multiple sclerosis (MS) over 5 years. Methodological issues associated with longitudinal cognitive research such as practice effects and drop-outs were also examined.

Methods Ninety subjects with a diagnosis of clinically isolated syndrome or MS and disease duration from a first symptom of ≤6 years participated in the study. Subjects were administered the Brief Repeatable Battery of Neuropsychological Tests in MS, which includes five measures assessing four cognitive domains. As a means of stabilising practice effects, the battery was administered 1–2 weeks apart at enrolment and then annually for up to 5 years.

Results Significant deterioration was found on a measure of working memory and speed of information processing. Significant deterioration was also found on measures of immediate and delayed visual spatial memory. Verbal memory was unchanged over the course of the study. Improved performance was observed on a second measure of speed of information processing and on a measure of verbal fluency. Among subjects with longitudinal follow-up, the drop-out rate was 30%, but subjects who dropped out did not differ from those who completed the study in terms of baseline cognitive performance or the change in cognitive performance from year 1 to year 2.

Conclusions Subjects with early MS showed a deterioration in working memory and visual spatial memory over a period of up to 5 years. Although significant practice effects were associated with several cognitive measures, the Symbol Digit Modality Test may be useful for longitudinal evaluations of cognitive functioning in MS.