Modelling dementia: effects of scopolamine on memory and attention

Scopolamine, a muscarinic cholinergic antagonist, is capable of inducing transient memory impairment in normal subjects. Against the background of the cholinergic hypothesis of Alzheimer's disease (AD) the present study was designed to investigate the effects of low oral doses of scopolamine on a range of cognitive functions known or hypothesized to be affected in AD. Twenty healthy volunteers (18-48 yr) performed a battery of automated cognitive tasks under each of five treatments: oral scopolamine 0.3 mg, 0.6 mg, 1.2 mg; oral methylscopolamine 0.6 mg; placebo. Alongside analogous tests of verbal and non-verbal memory, the battery enabled assessments of a range of attentional functions: alerting, sustained attention, selective attention, and covert orientation. A profile of effects was observed within and beyond the realm of memory. While some functions were unaffected by the drug (e.g. alerting) and others were impaired at the highest dose (e.g. verbal learning) still others were affected in a linear dose-dependent manner (sustained attention; visual contrast sensitivity). These observations are discussed in the context of the "scopolamine model" of AD.