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Brain Advance Access originally published online on December 19, 2007
Brain 2008 131(2):543-558; doi:10.1093/brain/awm300
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Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Demographic, structural and genetic predictors of late cognitive decline after penetrating head injury

Vanessa Raymont1,2, Amanda Greathouse1,2, Katherine Reding1,2, Robert Lipsky3, Andres Salazar2 and Jordan Grafman2

1Vietnam Head Injury Study, Henry M. Jackson Foundation, National Naval Medical Center, 20889, 2Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke and 3Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA

Correspondence to: Jordan Grafman, PhD, Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, Building 10; Room 7D43; MSC 1440, Bethesda, MD 20892-1440, USA E-mail: grafmanj{at}ninds.nih.gov

We examined the relationship of pre-injury intelligence, demographic variables, lesion location, brain tissue volume loss and a number of genetic markers to long-term cognitive decline in a group of Vietnam veterans with predominantly penetrating head injury (PHI) suffered more than 30 years ago. Using linear and stepwise regression procedures, we found that those with PHI demonstrated a greater degree of cognitive decline overall during the years following recovery from injury compared with a control group of uninjured Vietnam veterans. This became increasingly significant later in life. We also found that pre-injury intelligence was the most consistent predictor of cognitive outcome across all phases of potential recovery and decline after such injuries. While laterality of lesion was not a factor, we did find some associations between atrophy and specific regions of tissue loss and long-term cognitive functioning. Finally, we found evidence for an association between level of cognitive decline following PHI and the possession of certain genetic markers that have been linked with brain injury and neurodegeneration. Thus exacerbated decline does occur in Vietnam veterans with PHI and it is apparently unrelated to dementia and is determined by multiple factors (most notably pre-injury intelligence).

Key Words: cognitive decline; brain injury; penetrating brain injury; genetics; predictors

Abbreviations: ATP, adenosine triphosphate; AD, Alzheimer's disease; ANOVA, analysis of variance; AFQT, Armed Forces Qualification Test; AIR, Automated Image Registration; BDNF, brain-derived neurotrophic factor; COMT, catechol-O-methyl transferase; CHI, closed head injury; DBH, dopamine beta-hydroxylase; GABA, gamma-amino butyric acid; GAD, glutamic acid decarboxylase; MMSE, Mini-Mental State Examination; NMDA, N-methyl-D-aspartate; PHI, penetrating head injury; P1, phase 1; P2, phase 2; P3, phase 3; TVL, total volume loss; TBI, traumatic brain injury; VA, Veterans Affairs; VHIS, Vietnam Head Injury Study

Received August 7, 2007. Revised October 17, 2007. Accepted November 19, 2007.


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