Ageing: the cholinergic hypothesis of cognitive decline

Abstract

The concept that memory loss in ageing might be attributable to deficiencies in cholinergic function was first proposed two decades ago. This proposal gained additional definition when pathology was found in the basal forebrain cholinergic system of patients with Alzheimer's disease, and substantial deterioration of these neurons was detected in several animal models of ageing. A recently developed method for selectively removing basal forebrain cholinergic neurons using an immunotoxin provides a powerful tool for examining the function of the basal forebrain cholinergic system. This review will address new information that has come from this approach, with an emphasis on understanding the contribution of basal forebrain cholinergic neurons to age-related cognitive impairment.