title: Effect of cholinergic stimulation in early Alzheimer's disease - functional imaging during a recognition memory task.
abstract: Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (AChEI) enhances cholinergic activity and alleviates clinical symptoms. In the present functional magnetic resonance imaging (fMRI) study, we investigated the effect of the AChEI rivastigmine on cognitive function and brain activation patterns during a face recognition memory task. Twenty patients with newly-diagnosed mild AD were administered a single oral dose of placebo, a single dose of rivastigmine (acute), and twice-daily treatment with rivastigmine for 4 weeks (chronic). After each treatment, the patients underwent a facial recognition task during fMRI. The prefrontal areas known to be involved in face recognition memory processing demonstrated greater fMRI activity in both the acute and chronic rivastigmine conditions compared to the placebo condition. In the same brain areas, differences in both fMRI activation at the map level and regional fMRI signal intensity measures between the placebo and chronic treatment conditions correlated negatively with the Mini- Mental State Examination score. In the chronic rivastigmine condition, patients with better preserved cognitive abilities demonstrated less enhanced prefrontal activity, whereas patients with poorer cognition showed greater prefrontal activity. These findings suggest that the prefrontal attention/working memory systems are already impaired in the early stages of AD and that the effect of cholinergic medication in the brain areas involved in recognition memory, i.e., increased or decreased fMRI activation patterns, depends on the severity of the disease. These findings also suggest the importance of early AChEI treatment in the course of AD, at the point when there is still some cognitive reserve available and the therapy has the highest potential efficacy.
authors: Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Pekka S
authors: PS
authors: Miettinen
authors: Maija
authors: M
authors: Pihlajamäki
authors: Anne M
authors: AM
authors: Jauhiainen
authors: Ina M
authors: IM
authors: Tarkka
authors: Heidi
authors: H
authors: Gröhn
authors: Eini
authors: E
authors: Niskanen
authors: Tuomo
authors: T
authors: Hänninen
authors: Ritva
authors: R
authors: Vanninen
authors: Hilkka
authors: H
authors: Soininen