Alzheimer's disease (AD) is reported to affect at least 19% of individuals75-84 years old, and 47% of individuals over the age of 84 (Alzheimer's Association, 1996). Given the severe nature of the disease, the burden placed on caregivers, and the financial demands of the care of AD patients, there is growing interest in developing agents that not only reverse the cognitive deficits associated with AD, but also slow AD's progression. To date, however, there is only limited information about the aetiology and pathogenesis of AD (for a review, see Small, 1998), and this perhaps explains why only two drugs have been approved for the treatment of it.AD can be definitely diagnosed only by means of histopathological examination of brain tissue following a patient's death (Small, 1998). In the early stages of the disease, impairment in short-term memory is apparent. As the disease progresses, patients are unable to perform many basic activities needed for everyday living. They may show decreased knowledge of current and recent events, impaired concentration, and decreased ability to travel, handle finances, or perform complex tasks. Pathologically, the classical hallmarks of AD include neuritic plaques, neurofibrillary tangles, and significant neuronal loss in the basal forebrain area (Bowen & Davison, 1986). Various neurotransmitter systems may be affected, including the noradrenergic and serotonergic systems, but the involvement of the cholinergic system in AD has received the most attention. This is not surprising, given the marked impairment in memory performance following cholinergic system dysfunction. Over the last two decades, the hypothesis that the cholinergic system is the major neurotransmitter system involved in memory and learning has gained general acceptance (Bartus, 1978;Blokland, 1996;Everitt & Robbins, 1997). The evidence reviewed here reinforces the suggestion that AD is related to cholinergic system dysfunction.A recent comprehensive review by McDonald and Overmier (1998) describes a wide range of "animal models" for AD. Such models examine the effects of drugs such as scopolamine, of lesions (to the basal nucleus, medial septal area, fimbra/fornix, and hippocampus), and of betaamyloid administration, on performance in various delayed conditional-discrimination tasks in which subjects must rely on memory. The rationale for the "animal models" is that the effects of the drugs and lesions on task performance should resemble the deficits seen in AD patients. McDonald and Overmier suggest that for patients in the early stages of AD, the deficit is manifest primarily as an increase in the rate of forgetting, whereas for patients in the late stages of the disease, the deficit is attentional in nature, and that deficits in encoding ability may be related to poor cognitive function. Below we question the evidence for this distinction, and suggest that the overall performance deficit shown by AD patients (at any stage) is best characterized as an encoding deficit, with little effect on rate of forgetting.In ...