Functional studies of cholinergic activity in normal and Alzheimer disease states by imaging technique

Abstract

This chapter presents the current developments based on novel technologies, such as positron emission tomography (PET), for directly imaging cholinergic neuroreceptors, enzymes or amyloid plaques, in addition to measuring cerebral blood flow and metabolic changes in the brain of Alzheimer's disease (AD) patients. The cholinergic neurotransmitter system, which is involved in cognitive processes, is severely impaired in AD. Functional imaging allows measurement of acetylcholinesterase (AchE) and butyrylcholinesterase (BuChE) activities, nicotinic, muscarinic receptor binding, and vesicular acetylcholine transporter in normal subjects and AD patients. These cholinergic surrogate markers are more sensitive to early changes in brain than cerebral glucose metabolism. In order to explore the anatomical patterns of activation associated with cognitive processing in normal and diseased brain, PET and functional magnetic resonance imaging (fMRI) are presently used for functional imaging studies. With both techniques, changes in cerebral blood flow can be measured as an index of neural activity. Because episodic memory and attention are affected early in AD, functional brain imaging focuses on the regional brain activation patterns for the mental performances in AD patients.