The effects of rivastigmine on processing speed and brain activation in patients with multiple sclerosis and subjective cognitive fatigue

Background: Cognitive decline and fatigue are typical in multiple sclerosis (MS). However, there is no official medication for either of these symptoms. Objective: The purpose of this study was to estimate the effects of a single dose of rivastigmine on processing speed and associated brain activity in patients with MS and subjective cognitive fatigue. Methods: Fifteen patients with MS and subjective cognitive fatigue and 13 healthy controls (HCs) matched for age, gender and education performed a neuropsychological assessment and functional (f)MRI. A modified version of the Paced Visual Serial Addition Test (mPVSAT) was used as the behavioural task during fMRIs. After the first scanning session, both groups were randomly divided into two subgroups receiving either rivastigmine or placebo. A single dose of rivastigmine or placebo was administrated double-blindly and 2.5 hours later the scanning was repeated. Results: At baseline, the patients with MS showed slower processing speed in mPVSAT compared with the HCs. They also demonstrated stronger bilateral frontal activation after sustained cognitive effort than the HCs. Performance improvement and a further activation increase in the left anterior frontal cortex and additional activation in the right cerebellum were observed in patients who received rivastigmine but not in patients on placebo, or in HCs with placebo or rivastigmine. Conclusion: These preliminary findings suggest that rivastigmine may improve cognitive processing speed by enhancing compensatory brain activation in patients with MS.