Effects of therapy with the acetylcholinesterase inhibitor rivastigmine on spatial and verbal working memory in Alzheimer's disease: A H2150PET study

Objective: Impairments of spatial and verbal memory are early and common symptoms in Alzheimer’s disease (AD). Cognitive impairment may result from cholinergic dysfunctions and can be improved by cholinergic therapies. The current study was designed to determine how a cholinergic therapy affects neural responses during different working memory tasks. Methods: In eight patients with mild AD (NINCDS-ADRDA criteria), regional cerebral blood flow (rCBF) was measured using H215O and PET prior to and three months after therapy with the acetylcholinesterase inhibitor rivastigmine (6–9 mg p.o., daily) in two consecutive series of four scans each. rCBF was measured in a rest condition and while patients were performing a verbal, a spatial or a more demanding verbalspatial working memory task. Results: Rivastigmine therapy speeded up reaction times across conditions but altered rCBF responses in a task-specific manner. Rivastigmine therapy enhanced rCBF activation in a left temporal area and rCBF deactivation in left parietal areas during verbal working memory. Furthermore, rivastigmine increased rCBF activation in the cerebellum and rCBF deactivation of the left temporal area during spatial working memory. Finally, rivastigmine enhanced rCBF activation in the right frontal and occipital areas and rCBF deactivation in posterior frontal, temporal and occipital areas during verbal/ spatial working memory. Conclusions: The results indicate that rivastigmine modulates neural responses in brain areas that are differentially activated by different working memory tasks. The results further suggest that rivastigmine may improve cognition in Alzheimer’s disease by facilitating the attentional allocation of neural resources during effortful cognitive tasks.