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Brain Advance Access published online on November 17, 2004
Brain, doi:10.1093/brain/awh352
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Received April 29, 2004
Revised July 19, 2004
Accepted October 18, 2004

Article

Cognitive sequelae of head injury: involvement of basal forebrain and associated structures

C. H. Salmond 1*, D. A. Chatfield 2, D. K. Menon 3, J. D. Pickard 4, and B. J. Sahakian 5

1 Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, UK; Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
2 Department of Anaesthetics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
3 Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, UK; Department of Anaesthetics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
4 Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, UK; Department of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
5 Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

* To whom correspondence should be addressed.
C. H. Salmond, E-mail: chs20{at}wbic.cam.ac.uk


  Abstract

Summary Traumatic brain injury is the most common cause of death and disability in young people and survivors often suffer from chronic cognitive deficits. From animal, post-mortem and cognitive studies, there is now increased evidence that abnormalities in the cholinergic system may be underlying some of these deficits. This study investigated this hypothesis in a group of survivors of moderate-severe head injury (n = 31). Patients completed a comprehensive neuropsychological assessment and an MRI scan. Compared with a group of controls (matched on age, sex and premorbid intelligence quotient), the patients showed deficits in sustained attention, paired associate learning and reaction time, but comparative preservation of spatial working memory. Voxel-based morphometry revealed reduced grey matter density in the head injured group in the basal forebrain, the hippocampal formation and regions of the neocortex. These cognitive and structural results are consistent with cholinergic dysfunction. These preliminary findings suggest that cholinergic enhancers may be an effective treatment of cognitive deficits post head injury.

Keywords: head injury; acetylcholine; MRI; neuropsychology.
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