Cholinergic enhancement of episodic memory in healthy young adults.
BACKGROUND
Acetylcholine esterase (AchE) inhibitors are known to remediate symptoms of Alzheimer's disease. However, only few systematic data exist on the effects of cholinergic treatment on cognitive functions in normal subjects.


OBJECTIVE
This study evaluated the effects of donepezil, an inhibitor of AchE, on cognitive performance in young and healthy subjects.


METHODS
We used a randomised double-blind parallel group placebo-controlled repeated measures design to investigate changes of cognitive functions in a group of 30 young healthy male subjects (mean age 23.9 years+/-2.24 SD) upon application of donepezil or placebo for 30 days. Attentional and executive functions, visual and verbal short-term and working memory, semantic memory, as well as verbal and visual episodic memory were investigated using an extensive neuropsychological test battery.


RESULTS
Time-by-group interactions demonstrated significant drug effects that were specific to episodic memory in both the verbal and visual domain. Additionally, donezepil significantly improved long-term visual episodic recall. In none of the other functions under investigation any significant treatment effects were observed.


CONCLUSIONS
Given this specific drug effect and the well-known relevance of the hippocampal region for episodic memory, we conclude that this region appears to be the major target of cholinergic enhancement in healthy subjects due to long-term inhibition of AchE.
Grön
Georg
G
Department of Psychiatry, University of Ulm, Leimgrubenweg 12, 89075 Ulm, Germany. georg.groen@medizin.uni-ulm.de
Kirstein
Matthias
M
Thielscher
Axel
A
Riepe
Matthias W
MW
Spitzer
Manfred
M
D000328:Adult; D001288:Attention / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects*; D009483:Neuropsychological Tests; D009949:Orientation / Q000187:drug effects; D010364:Pattern Recognition, Visual / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011214:Practice, Psychological; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects; D012691:Serial Learning / Q000187:drug effects; D014706:Verbal Learning / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil