The purpose of this study was to investigate the effects of donepezil, a cholinergic agent, on chronic cognitive impairment due to traumatic brain injury (TBI). Chronic patients underwent two standardized neuropsychological evaluations – one before and the other 3 months following treatment with donepezil. Together with global inventories that appraised behaviour, fatigue, anxiety and depression, these evaluations also assessed executive functioning, memory and attention. Of the 10 patients who followed the therapy, 8 reported subjective improvement in at least one cognitive domain following therapy and most of them reported better functioning in everyday activities. This effect was supported by a slight global improvement when considering the global score of the different affectivo-behavioural scales. At the neuropsychological level, although we could observe a slight improvement in the majority of the considered tests, significant positive changes were mainly found in tests assessing speed of processing, learning and divided attention. These findings suggest that donepezil may lead to better general functioning and improve attentional skills in patients with chronic TBI.

1.
Lezak MD: Assessment of the behavioral consequences of head trauma. Front Clin Neurosci 1989;7:1–143.
2.
Masanic CA, Bayley MT, VanReekum R, Simard M: Open-label study of donepezil in traumatic brain injury. Arch Phys Med Rehabil 2001;82:896–901.
3.
Arciniegas D, Adler L, Topkoff J, Cawthra E, Filley CM, Reite M: Attention and memory dysfunction after traumatic brain injury: cholinergic mechanisms, sensory gating, and a hypothesis for further investigation. Brain Inj 1999;13:1–13.
4.
Dikmen SS, Bombardier CH, Machamer JE, Fann JR, Temkin NR: Natural history of depression in traumatic brain injury. Arch Phys Med Rehabil 2004;85:1457–1464.
5.
Oquendo MA, Friedman JH, Grunebaum MF, Burke A, Silver JM, Mann JJ: Suicidal behavior and mild traumatic brain injury in major depression. J Nerv Ment Dis 2004;192:430–434.
6.
Prigatano GP, Fordyce DJ, Zeiner HK, Roueche JR, Pepping M, Wood BC: Neuropsychological rehabilitation after closed head injury in young adults. J Neurol Neurosurg Psychiatry 1984;47:505–513.
7.
Zhang L, Plotkin RC, Wang G, Sandel ME, Lee S: Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil 2004;85:1050–1055.
8.
Dixon CE, Ma X, Marion DW: Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release. J Neurotrauma 1997;14:161–169.
9.
Griffin SL, van Reekum R, Masanic C: A review of cholinergic agents in the treatment of neurobehavioral deficits following traumatic brain injury. J Neuropsychiatry Clin Neurosci 2003;15:17–26.
10.
Levin HS, Peters BH, Kalisky Z, High WM Jr, von Laufen A, Eisenberg HM, et al: Effects of oral physostigmine and lecithin on memory and attention in closed head-injured patients. Cent Nerv Syst Trauma 1986;3:333–342.
11.
Cardenas DD, McLean A Jr, Farrell-Roberts L, Baker L, Brooke M, Haselkorn J: Oral physostigmine and impaired memory in adults with brain injury. Brain Inj 1994;8:579–587.
12.
Lawrence AD, Sahakian BJ: The cognitive psychopharmacology of Alzheimer’s disease: focus on cholinergic systems. Neurochem Res 1998;23:787–794.
13.
Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT: A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Donepezil Study Group. Neurology 1998;50:136–145.
14.
Cummings JL: Cholinesterase inhibitors: A new class of psychotropic compounds. Am J Psychiatry 2000;157:4–15.
15.
Taverni JP, Seliger G, Lichtman SW: Donepezil medicated memory improvement in traumatic brain injury during post acute rehabilitation. Brain Inj 1998;12:77–80.
16.
Whitlock JA Jr: Brain injury, cognitive impairment, and donepezil. J Head Trauma Rehabil 1999;14:424–427.
17.
Whelan FJ, Walker MS, Schultz SK: Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Ann Clin Psychiatry 2000;12:131–135.
18.
Bourgeois JA, Bahadur N, Minjares S: Donepezil for cognitive deficits following traumatic brain injury: a case report. J Neuropsychiatry Clin Neurosci 2002;14:463–464.
19.
Giacobini E, Spiegel R, Enz A, Veroff AE, Cutler NR: Inhibition of acetyl- and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer’s disease by rivastigmine: correlation with cognitive benefit. J Neural Transm 2002;109:1053–1065.
20.
López-Pousaa S, Vilalta-Francha J, Garre-Omoa J, Lozano-Gallegoa M, Hernandez-Ferrandiza M, Fajardo-Tibaua C, et al: Effectiveness of donepezil on several cognitive functions in patients with Alzheimer’s disease over 12 months. Neurologia 2001;6:342–347.
21.
Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–370.
22.
Wilson BA, Aldermann N, Burgess PW, Emslie H, Evans JJ: Behavioral Assessment of the Dysexecutive Syndrome. Bury St Edmunds, Thames Valley Test Company, 1996.
23.
Schwartz JE, Jandorf L, Krupp LB: The measurement of fatigue: a new instrument. J Psychosom Res 1993;37:753–762.
24.
Cardebat D, Doyon B, Puel M, Goulet P, Joanette Y: Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level (in French). Acta Neurol Belg 1990;90:207–217.
25.
Regard M, Strauss E, Knapp P: Children’s production on verbal and non-verbal fluency tasks. Percept Mot Skills 1982;55:839–844.
26.
Stroop JR: Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643–661.
27.
Spreen O, Strauss E: A Compendium of Neuropsychological Testing: Administration, Norms and Commentary. New York, Oxford University Press, 1998.
28.
Zimmermann P, Fimm B: Test for attentional performance (French version). Freiburg, Psytest, 1994.
29.
Tenovuo O: Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury-clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:61–67.
30.
Jackson S, Ham RJ, Wilkinson D: The safety and tolerability of donepezil in patients with Alzheimer’s disease. Br J Clin Pharmacol 2004;58(suppl 1):1–8.
31.
Beglinger LJ, Gaydos BL, Kareken DA, Tangphao-Daniels O, Siemers ER, Mohs RC: Neuropsychological test performance in healthy volunteers before and after donepezil administration. J Psychopharmacol 2004;18:102–108.
32.
Olazaran-Rodriguez J, Cruz-Orduna I, Jimenez-Martin I: Donepezil therapy in patients with vascular and post-traumatic cognitive impairment: some clinical observations (in Spanish). Rev Neurol 2004;38:938–943.
33.
Staub F, Bogousslavsky J: Fatigue after stroke: a major but neglected issue. Cerebrovasc Dis 2001;12:75–81.
34.
Azouvi P, Couillet J, Leclercq M, Martin Y, Asloun S, Rousseaux M: Divided attention and mental effort after severe traumatic brain injury. Neuropsychologia 2004;42:1260–1268.
35.
Pepeu G, Giovannini MG: Changes in acetylcholine extracellular levels during cognitive processes. Learn Mem 2004;11:21–27.
36.
Muir JL: Attention and stimulus processing in the rat. Brain Res Cogn Brain Res 1996;3:215–225.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.