Detecting effects of donepezil on visual selective attention using signal detection parameters in Alzheimer's disease

Abstract

Attentional function is impaired in Alzheimer's disease (AD). Moreover, attention is mediated by acetylcholine. But, despite the widespread use of acetylcholinesterase inhibitors (AChE-I) to augment available acetylcholine in AD, measures of attentional function have not been used to assess the drug response. We hypothesized that as cholinergic augmentation impacts directly on the attentional system, higher-order measures of visual selective attention would be sensitive to effects of treatment using an AChE-I (donepezil hydrochloride). We also sought to determine whether these attentional measures were more sensitive to treatment than other measures of cognitive function. Seventeen patients with AD (8 untreated, 9 treated with donepezil) were contrasted on performance of a selective cancellation task. Two signal detection parameters were used as outcome measures: decision strategy (beta, beta) and discriminability (d-prime, d'). Standard screening and cognitive domain measures of vigilance, language, memory, and executive function were also contrasted. Treated patients judged stimuli more conservatively (p = 0.29) by correctly endorsing targets and rejecting false alarms. They also discriminated targets from distractors more easily (p = 0.58). The screening and neuropsychological measures failed to differentiate the groups. Higher-order attentional measures captured the effects of donepezil treatment in small groups of patients with AD. The results suggest that cholinergic availability may directly affect the attentional system, and that these selective attention measures are sensitive markers to detect treatment response.