Related Experiment Video
Updated: Aug 23, 2026

Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after
Lei Zhang1, Rosette C Plotkin, Gary Wang
1Department of Rehabilitation Medicine, University of Texas Health Science Center, San Antonio, TX, USA. neurorehab@yahoo.com
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.
Related Concept Videos
Alzheimer's Disease: Treatment
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Indirect-Acting Cholinergic Agonists: Pharmacological Actions
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
Long-term Potentiation
Long-term Potentiation
Hebbian LTP
LTP can occur when presynaptic neurons...
Role of Neurotransmitters in Memory
Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is critical for...
