Effects of donepezil on verbal memory after semantic processing in healthy older adults

Cogn Behav Neurol. 2008 Jun;21(2):57-64. doi: 10.1097/WNN.0b013e3181799df1.


Objective: To learn if acetylcholinesterase inhibitors alter verbal recall by improving semantic encoding in a double-blind randomized placebo-controlled trial.

Background: Cholinergic supplementation has been shown to improve delayed recall in adults with Alzheimer disease. With functional magnetic resonance imaging, elderly adults, when compared with younger participants, have reduced cortical activation with semantic processing. There have been no studies investigating the effects of cholinergic supplementation on semantic encoding in healthy elderly adults.

Method: Twenty elderly participants (mean age 71.5, SD+/-5.2) were recruited. All underwent memory testing before and after receiving donepezil (5 mg, n=11 or 10 mg, n=1) or placebo (n=8) for 6 weeks. Memory was tested using a Levels of Processing task, where a series of words are presented serially. Subjects were either asked to count consonants in a word (superficially process) or decide if the word was "pleasant" or "unpleasant" (semantically process).

Results: After 6 weeks of donepezil or placebo treatment, immediate and delayed recall of superficially and semantically processed words was compared with baseline performance. Immediate and delayed recall of superficially processed words did not show significant changes in either treatment group. With semantic processing, both immediate and delayed recall performance improved in the donepezil group.

Conclusions: Our results suggest that when using semantic encoding, older normal subjects may be aided by anticholinesterase treatment. However, this treatment does not improve recall of superficially encoded words.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Attention / drug effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Comprehension
  • Donepezil
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Indans / therapeutic use*
  • Male
  • Memory, Short-Term / drug effects
  • Mental Recall / drug effects*
  • Neuropsychological Tests
  • Nootropic Agents / therapeutic use*
  • Pattern Recognition, Visual
  • Piperidines / therapeutic use*
  • Retention, Psychology / drug effects
  • Semantics*
  • Serial Learning / drug effects
  • Verbal Learning / drug effects*


  • Cholinesterase Inhibitors
  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil