THE CHOLINERGIC HYPOTHESIS—TEN YEARS ON

Abstract

The cholinergic hypothesis of Alzheimer's disease originally postulated a connection between some of the cognitive impaiments of this disorder, particularly memory, and a disturbance in cerebral cholinergic neurotransmission. A decade of neurochemical, anatomical, pathological and psychopharmacological research has since reinforced and refined the hypothesis. Current evidence suggests a critical role for cortical cholinergic projections, originating in the basal forebrain, in the memory component (possibly via activation of encoding mechanisms) of both Alzheimer and Parkinson types of dementia. In more advanced stages of Alzheimer's disease, the involvement of other transmitters extends the search for potential long-term therapy beyound the cholinergic system. Nevertheless, the cholinergic hypothesis still merits investigation today with a view to obtaining more precise information on the role of the human cerebral cholinergic system memory and, with the advent of novel approaches to cholinergic therapy, to improving the management of at least mildly demented patients.