The changes of cortical metabolism associated with the clinical response to donepezil therapy in traumatic brain injury

Clin Neuropharmacol. 2009 Mar-Apr;32(2):63-8. doi: 10.1097/WNF.0B013E31816F1BC1.


Objectives: To determine the effects of treatment with donepezil on cortical metabolism in patients with traumatic brain injury using F-fluorodeoxyglucose positron emission tomography.

Methods: Twenty-six patients with cognitive impairment after traumatic brain injury were enrolled and randomly assigned into the donepezil-treated group and the control group. There was no significant difference between 2 groups in age, sex, education, and postinjury duration. Donepezil 5 mg was administered daily for 3 weeks and then 10 mg/d for 3 weeks to patients in the experimental groups. For both groups, we evaluated cognitive function with Mini-Mental State Examination, Wechsler Memory Test, Boston Naming Test, Colored Progressive Matrices upon initial evaluation and at the 6-week follow-up. An 18F-fluorodeoxyglucose positron emission tomography of the brain was performed before and after 6 weeks of the donepezil-treated group. Effects of donepezil treatment on cortical metabolism were analyzed using Statistical Parametric Mapping software (Institute of Neurology, University College London, UK).

Results: There was no significance difference between the 2 groups in initial evaluation of cognitive functions. After 6 weeks, compared with the control group, donepezil-treated group showed enhanced cognitive functions (P < 0.05), and 18F-fluorodeoxyglucose positron emission tomography showed a statistically significant increase in the cerebral cortical metabolism for both of the frontal, parietal, occipital, and temporal cortices (P < 0.01) which are the key role of attention and object naming.

Conclusions: Cholinergic augmentation by donepezil therapy in traumatic brain injury shows a cortical metabolic effect on the both of the frontal, parietal, occipital, and temporal cortices associated with clinical response to treatment.

Publication types

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

MeSH terms

  • Adult
  • Brain Injuries / drug therapy
  • Brain Injuries / pathology*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism*
  • Donepezil
  • Drug Administration Schedule
  • Female
  • Fluorodeoxyglucose F18
  • Follow-Up Studies
  • Humans
  • Indans / pharmacology*
  • Indans / therapeutic use
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests
  • Nootropic Agents / pharmacology*
  • Nootropic Agents / therapeutic use
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Positron-Emission Tomography / methods


  • Indans
  • Nootropic Agents
  • Piperidines
  • Fluorodeoxyglucose F18
  • Donepezil