Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury

Arch Phys Med Rehabil. 2004 Jul;85(7):1050-5. doi: 10.1016/j.apmr.2003.10.014.


Objective: To examine effects of donepezil on short-term memory and sustained attention in postacute patients with traumatic brain injury (TBI).

Design: A 24-week, randomized, placebo-controlled, double-blind crossover trial.

Setting: Outpatient clinics in 2 teaching hospitals.

Participants: Eighteen postacute TBI patients with cognitive impairment.

Intervention: Patients were randomly assigned to group A or group B. Patients in group A received donepezil for the first 10 weeks and then a placebo for another 10 weeks. The 2 treatment phases were separated by a washout period of 4 weeks. Patients in group B received the preparations in the opposite order.

Main outcome measures: Short-term memory and sustained attention were assessed by 2 indexes (Auditory Immediate Index [AII], Visual Immediate Index [VII]) of the Wechsler Memory Scale-III and the Paced Auditory Serial Addition Test (PASAT), at baseline, week 10, and week 24 of the trial.

Results: Intragroup comparison of different phases of the trial in both groups showed that donepezil significantly increased the testing scores of the AII and VII, as well as PASAT scores, compared with baseline. There was no significant change in the testing scores between assessment at baseline and the end of the placebo phase in group B. Intergroup comparison at the 10-week assessment showed significantly improved testing scores in group A with donepezil over group B with the placebo. The improved testing scores with donepezil in group A were sustained after the washout period and placebo phase, suggesting a carry-over effect of the medication.

Conclusions: Donepezil increased neuropsychologic testing scores in short-term memory and sustained attention in postacute TBI patients. Cholinergic augmentation may be a viable approach to restore memory and attention after TBI.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention / drug effects*
  • Brain Injuries / rehabilitation*
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Inhibitors / therapeutic use
  • Cognition / drug effects*
  • Cross-Over Studies
  • Donepezil
  • Double-Blind Method
  • Female
  • Humans
  • Indans / pharmacology*
  • Indans / therapeutic use
  • Male
  • Memory / drug effects*
  • Middle Aged
  • Neuropsychological Tests
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use


  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Donepezil