title: Effect of cholinergic neurotransmission modulation on visual spatial paired associate learning in healthy human adults.
abstract: BACKGROUND
  Use of cross-species neuropsychological paradigms such as visual-spatial paired associate learning (PAL) may allow for a better understanding of underlying neural substrates of memory. Such paradigms, which are often used to guide models of memory in animals, can then be carried forward into humans to provide a basis for evaluation of pharmacologic compounds designed to ameliorate learning and memory impairments in neurologic and psychiatric morbidities.
  
  
  OBJECTIVE
  This double-blind, randomized, crossover trial investigated effects of donepezil, an acetylcholinesterase (AChE) inhibitor, in attenuating scopolamine-induced cognitive impairment using a novel, "process-based" computerized measure of visual-spatial PAL.
  
  
  RESULTS
  In healthy male volunteers, scopolamine (0.6 mg) induced a time-dependent reduction in visual-spatial PAL, with the greatest impairment (Cohen's d = 1.37) observed 2 h after dosing. Cotreatment with donepezil (10 mg) significantly ameliorated scopolamine-induced impairment at the 2-h time point (Cohen's d = 0.66). Process-based analyses revealed a significant impairment in both memory (Cohen's d = 1.37 to 0.50) and executive (Cohen's d = 1 .21 to 0.62) aspects of visual-spatial PAL performance following acute scopolamine challenge, and these reductions were ameliorated by donepezil.
  
  
  CONCLUSIONS
  Acute scopolamine challenge can produce large and robust deficits in visual-spatial PAL, which reflect impairments in both memory and executive processes. Coadministration of a single dose of donepezil can ameliorate these deficits. These results provide support for the use of a visual-spatial PAL test as a pharmacodynamic cognitive marker of central nervous system (CNS)-mediating compounds in humans.
authors.affiliation: CogState, Ltd, 195 Church St., 8th Floor, New Haven, CT 06510, USA. bharel@cogstate.com
authors.forename: Brian T
authors.initials: BT
authors.lastname: Harel
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000293:Adolescent; D000328:Adult; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy*; D018592:Cross-Over Studies; D000077265:Donepezil; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010153:Paired-Associate Learning / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D012601:Scopolamine / Q000633:toxicity; D013997:Time Factors; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D012601:Scopolamine