Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer’s disease

Abstract

Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer’s disease (AD) indicate that the short and long term actions of ChEIs are dissimilar. fMRI studies of the ChEI rivastigmine have focused on its short term action. In this exploratory study the effect of prolonged (20 weeks) rivastigmine treatment on regional brain activity was measured with fMRI in patients with mild AD. Eleven patients with probable AD and nine age-matched controls were assessed with a Pyramids and Palm Trees semantic association and an n-back working memory fMRI paradigm. In the patient group only, the assessment was repeated after 20 weeks of treatment. There was an increase in task-related brain activity after treatment with activations more like those of normal healthy elderly. Behaviorally, however, there were no significant differences between baseline and retest scores, with a range of performance probably reflecting variation in drug efficacy across patients. Variable patient response and drug dynamic/kinetic factors in small patient groups will inevitably bias (either way) the effect size of any relevant drug related changes in activation. Future studies should take drug response into account to provide more insight into the benefits of ChEI drugs at the individual level.

Keywords:

• fMRI
• rivastigmine
• treatment
• dementia
• Alzheimer’s disease

Acknowledgements

The authors thank Katrina E Forbes-McKay, Gordon D Waiter, Mario Ries and Iain Elrich for their assistance throughout the project. This study was supported partially through a grant from Novartis Pharma AG to AV and MFS and by a grant from MIUR to AV.