Effects of Donepezil on Cognitive Functioning and Memory

Author/Year/ Country/Study Design/ PEDro Score/N



Khateb et al. (2005)
Ninitial=15, Nfinal=10



Population: TBI; Mean age=43yr; Gender: Male=8, Female=7; Mean Time Post Injury=42mo.
Treatment:  Patients were administered donepezil 5 mg/day for 1 month, followed by 10 mg/day for 2 months.
Outcome Measure: Stroop test, trail making test (TMT), Rey Auditory Verbal Memory Test (RAVMT) and Test for Attentional Performance (TAP).

  1. 4 of 15 participants stopped due to side effects within the first week (e.g., nausea, sleep disorders, anxiety, dizziness, etc.).
  2. Changes on the neuropsychological evaluation show modest improvement, the comparison of the global score of all questionnaires before and after therapy was marginally significant (p=0.058).
  3. A significant improvement in executive function was only found for the Stroop Colour naming test (87.3±22.9 to 79.5±19.1, p=0.03); for learning and memory the RAVMT-learning (47.7±6.9 to 53.5±5.0, p=0.05); and for attention, the errors subsection of divided attention (5.8±3.3 to 2.9±2.7, p=0.03).

Zhang et al. (2004)


Population: TBI; Group A (n=9): Mean Age=33yr; Gender: Male=6, Female=3; Mean GCS=9.3; Mean Time Post Injury=4.6mo; Group B (n=9): Mean Age=31yr; Gender: Male=7, Female=2; Mean GCS=8.9; Mean Time Post Injury=3.9.
Treatment: In a randomized crossover trial, Group A received oral donepezil for the first 10wk, followed by a washout period of 4wk, then followed by 10wk of placebo. Group B received the treatments in the opposite order. Donepezil was administered at 5mg/d for the first 2wk, and at 10mg/d for the remaining 8wk.
Outcome Measure: Auditory (AII) and Visual (VII) subtests of Wechsler Memory Scale-III, and the Paced Auditory Serial Addition Test (PASAT).

  1. At week 10, Group A achieved significantly better scores in AII (95.4±4.5 vs. 73.6±4.5; p=0.002), VII (93.5±3.0 vs. 64.9±3.0; p<0.001), and in the PASAT (p≤0.001) compared to Group B.
  2. This increase in scores in Group A were sustained after washout and placebo treatment (week 24), leading to no significant differences in AII (105.9±4.5 vs. 102.4±4.5; p=0.588), VII (91.3±3.0 vs. 94.9±3.0; p=0.397), and PASAT (p>0.1) compared to Group B at study end.
  3. Within-group comparisons showed that patients in both Group A and Group B improved significantly in AII and VII (p<0.05), as well as in PASAT (p<0.001), after receiving donepezil.

Morey et al. (2003)
Case Series


Population: TBI; Mean Age=30.7yr; Gender: Male=5, Female=2; Mean Time Post Injury=33.3mo.
Treatment: Following baseline cognitive testing (T1), each participant began a 6mo treatment phase with 5mg/d donepezil for the first 4wk, then with 10mg/d for the final 5mo (T2). Washout period then occurred for 6wk (T3). Another 6mo treatment period took place with participants receiving 5mg/d donepezil for the entire period (T4).
Outcome Measure: Brief Visual Memory Test-Revised (BVMT-R), Hopkins Verbal Learning Test, digit span and letter-number sequence subtests of Wechsler Adult Intelligence Scale-Revised III, Controlled Oral Word Association Test, and Memory Functioning Questionnaires.

  1. Significant improvements (p<0.05) from T1 to T2 were observed for the following: Trial 1 of the BVMT-R, Trial 3 of the BVMT-R, total score of the BVMT-R, and delayed recall trial of the BVMT-R. No significant differences were identified for other measures, or across other testing intervals.

Masanic et al. (2001)

Population: TBI; Age Range=24-35yr; Gender: Male=4, Female=0; GCS Range=3-8; Time Post Injury Range=35-46mo.
Treatment: Participants received 5mg donepezil daily for 8wk, followed by 10mg daily for 4wk. Washout period then occurred for 4wk. Assessments occurred at baseline, and at weeks 4, 8, 12, and 16.
Outcome Measure: Rey Auditory Verbal Learning Test (RAVLT), Complex Figure Test (CFT), Rivermead Behavioural Memory Test (RBMT).

  1. Mean scores for short-term and long-term recall on the RAVLT improved by 1.03 (1.25±1.89 at baseline to 3.00±2.70 at week 12) and 0.83 (0.50±0.58 at baseline to 2.50±2.38 at week 12) standard deviations above baseline, respectively.
  2. Mean scores for short-term and long-term recall on the CFT improved also by 1.56 (13.88±8.45 at baseline to 20.13±12.93 at week 12) and 1.38 (14.00±5.60 at baseline to 19.38±11.46 at week 12) standard deviations above baseline, respectively.
  3. Perceived memory deficit (RBMT) showed a trend toward improvement over the first 12wk, followed by deterioration after the washout period.

PEDro=Physiotherapy Evidence Database rating scale score (Moseley et al. 2002).