Neurology®
The most widely read and highly cited peer-reviewed Neurology journal
Quick Search
Advanced Search
This Article
Right arrow Full Text
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Friedman, G.
Right arrow Articles by Groswasser, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Friedman, G.
Right arrow Articles by Groswasser, Z.
Neurology 1999;52:244
© 1999 American Academy of Neurology
Articles

Apolipoprotein E-{epsilon}4 genotype predicts a poor outcome in survivors of traumatic brain injury

G. Friedman, MD, P. Froom, MD, MOccH, L. Sazbon, MD, I. Grinblatt, MD, M. Shochina, MD, J. Tsenter, MD, S. Babaey, BA, A. Ben Yehuda, MD and Z. Groswasser, MD, MPH

From the Division of Medicine, Geriatric Unit (Drs. Friedman, Grinblatt, and Ben Yehuda, and S. Babaey), and the Department of Rehabilitation (Drs. Shochina and Tsenter), Hadassah Hebrew University Medical Center, Jerusalem; the Loewenstein Rehabilitation Hospital (Drs. Groswasser and Sazbon), Ra’anana; and Department of Epidemiology and Preventive Medicine (Dr. Froom), Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Address correspondence and reprint requests to Dr. Zeev Groswasser, Department of Brain Injury Rehabilitation, Loewenstein Rehabilitation Hospital, 278 Achuza Street, Ra’anana 43100, Israel.

OBJECTIVE: To determine the ability of apolipoprotein E (APOE) genotypes to predict days of unconsciousness and a suboptimal functional outcome in traumatic brain injury (TBI) survivors.

BACKGROUND: TBI is known to be associated with neuropsychological deficits and functional disability. Recent evidence indicates that APOE plays a pivotal role in CNS response to injury.

METHODS: In this prospective study the authors determined the APOE genotypes and tested their ability to predict days of unconsciousness and functional outcome after at least 6 months in 69 survivors of TBI. A good functional outcome was defined as no dysarthria, behavioral abnormalities, or dysphasia; no severe cognitive abnormalities; and the ability to live independently.

RESULTS: The odds ratio of more than 7 days of unconsciousness was 5.69 in those with the APOE-{epsilon}4 allele compared with those without the {epsilon}4 allele (95% CI, 1.69 to 20.0; p = 0.001). Only 1 of 27 subjects (3.7%) with the {epsilon}4 allele had a good functional outcome compared with 13 of 42 (31.0%) of those without the {epsilon}4 allele (p = 0.006). The OR of a suboptimal outcome (fair or unfavorable) was 13.93 for those with the {epsilon}4 allele compared with those without the allele after controlling for age and time of unconsciousness (95% CI, 1.45 to 133.97; p = 0.02).

CONCLUSION: The results demonstrate a strong association between the APOE-{epsilon}4 allele and a poor clinical outcome, implying genetic susceptibility to the effect of brain injury. Additional studies of TBI patients are warranted to confirm their findings.




This article has been cited by other articles:


Home page
 StrokeHome page
M. L. James, P. M. Sullivan, C. D. Lascola, M. P. Vitek, and D. T. Laskowitz
Pharmacogenomic Effects of Apolipoprotein E on Intracerebral Hemorrhage
Stroke, February 1, 2009; 40(2): 632 - 639.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
W. P. Meehan III and R. G. Bachur
Sport-Related Concussion
Pediatrics, January 1, 2009; 123(1): 114 - 123.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. R. Riddell, H. Zhou, K. Atchison, H. K. Warwick, P. J. Atkinson, J. Jefferson, L. Xu, S. Aschmies, Y. Kirksey, Y. Hu, et al.
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
J. Neurosci., November 5, 2008; 28(45): 11445 - 11453.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
A H P W.-v. Son, G M Ribbers, W C J Hop, C M van Duijn, and H J Stam
Association between apolipoprotein-{varepsilon}4 and long-term outcome after traumatic brain injury
J. Neurol. Neurosurg. Psychiatry, April 1, 2008; 79(4): 426 - 430.
[Abstract] [Full Text] [PDF]

Home page
 J. Neuropsychiatry Clin. Neurosi.Home page
M. Rapoport, U. Wolf, N. Herrmann, A. Kiss, P. Shammi, M. Reis, A. Phillips, and A. Feinstein
Traumatic Brain Injury, Apolipoprotein E-{epsilon}4, and Cognition in Older Adults: A Two-Year Longitudinal Study
J Neuropsychiatry Clin Neurosci, February 1, 2008; 20(1): 68 - 73.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
V. Raymont, A. Greathouse, K. Reding, R. Lipsky, A. Salazar, and J. Grafman
Demographic, structural and genetic predictors of late cognitive decline after penetrating head injury
Brain, February 1, 2008; 131(2): 543 - 558.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. O. Hopkins, L. K. Weaver, K. J. Valentine, C. Mower, S. Churchill, and J. Carlquist
Apolipoprotein E Genotype and Response of Carbon Monoxide Poisoning to Hyperbaric Oxygen Treatment
Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 1001 - 1006.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
S D. Han, A. I Drake, L. M Cessante, A. J Jak, W. S Houston, D. C Delis, J V. Filoteo, and M. W Bondi
Apolipoprotein E and traumatic brain injury in a military population: evidence of a neuropsychological compensatory mechanism?
J. Neurol. Neurosurg. Psychiatry, October 1, 2007; 78(10): 1103 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
M. Wilson and H. Montgomery
Impact of genetic factors on outcome from brain injury
Br. J. Anaesth., July 1, 2007; 99(1): 43 - 48.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H.-g. Lee, X. Zhu, R. J. Castellani, A. Nunomura, G. Perry, and M. A. Smith
Amyloid-beta in Alzheimer Disease: The Null versus the Alternate Hypotheses
J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 823 - 829.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. Ponsford, D. Rudzki, K. Bailey, and K. T. Ng
Impact of apolipoprotein gene on cognitive impairment and recovery after traumatic brain injury
Neurology, February 20, 2007; 68(8): 619 - 620.
[Full Text] [PDF]

Home page
 SEMIN CARDIOTHORAC VASC ANESTHHome page
R. B. Yates and M. Stafford-Smith
The genetic determinants of renal impairment following cardiac surgery.
Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2006; 10(4): 314 - 326.
[Abstract] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
M Ariza, R Pueyo, M d. M Matarin, C Junque, M Mataro, I Clemente, P Moral, M A Poca, A Garnacho, and J Sahuquillo
Influence of APOE polymorphism on cognitive and behavioural outcome in moderate and severe traumatic brain injury
J. Neurol. Neurosurg. Psychiatry, October 1, 2006; 77(10): 1191 - 1193.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
H. Isoniemi, T. Kurki, O. Tenovuo, V. Kairisto, and R. Portin
Hippocampal volume, brain atrophy, and APOE genotype after traumatic brain injury.
Neurology, September 12, 2006; 67(5): 756 - 760.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. W. Mahley, K. H. Weisgraber, and Y. Huang
Inaugural Article: Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer's disease
PNAS, April 11, 2006; 103(15): 5644 - 5651.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. A. Gay, R. C. Klein, and J. L. Yakel
Apolipoprotein E-Derived Peptides Block {alpha}7 Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes
J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 835 - 842.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
G. Bartzokis, P. H. Lu, D. H. Geschwind, N. Edwards, J. Mintz, and J. L. Cummings
Apolipoprotein E Genotype and Age-Related Myelin Breakdown in Healthy Individuals: Implications for Cognitive Decline and Dementia
Arch Gen Psychiatry, January 1, 2006; 63(1): 63 - 72.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
G. M. Teasdale, G. D. Murray, and J. A. R. Nicoll
The association between APOE {varepsilon}4, age and outcome after head injury: a prospective cohort study
Brain, November 1, 2005; 128(11): 2556 - 2561.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Sports. Med.Home page
P McCrory, K Johnston, W Meeuwisse, M Aubry, R Cantu, J Dvorak, T Graf-Baumann, J Kelly, M Lovell, and P Schamasch
Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague 2004
Br. J. Sports Med., August 1, 2005; 39(suppl_1): i78 - i86.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Sports. Med.Home page
P McCrory, K Johnston, W Meeuwisse, M Aubry, R Cantu, J Dvorak, T Graf-Baumann, J Kelly, M Lovell, and P Schamasch
Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague 2004
Br. J. Sports Med., April 1, 2005; 39(4): 196 - 204.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
P D Leclercq, L S Murray, C Smith, D I Graham, J A R Nicoll, and S M Gentleman
Cerebral amyloid angiopathy in traumatic brain injury: association with apolipoprotein E genotype
J. Neurol. Neurosurg. Psychiatry, February 1, 2005; 76(2): 229 - 233.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
N. Pomara, L. Willoughby, K. Wesnes, D. J. Greenblatt, and J. J. Sidtis
Apolipoprotein E {varepsilon}4 Allele and Lorazepam Effects on Memory in High-Functioning Older Adults
Arch Gen Psychiatry, February 1, 2005; 62(2): 209 - 216.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
A. Collie, P. Maruff, M. Falleti, A. Sundstrom, and L. Nyberg
APOE influences on neuropsychological function after mild head injury: Within-person comparisons
Neurology, December 28, 2004; 63(12): 2460 - 2460.
[Full Text] [PDF]

Home page
 BrainHome page
L. Chamelian, M. Reis, and A. Feinstein
Six-month recovery from mild to moderate Traumatic Brain Injury: the role of APOE-{varepsilon}4 allele
Brain, December 1, 2004; 127(12): 2621 - 2628.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
A. Sundstrom, P. Marklund, L. -G. Nilsson, M. Cruts, R. Adolfsson, C. Van Broeckhoven, and L. Nyberg
APOE influences on neuropsychological function after mild head injury: Within-person comparisons
Neurology, June 8, 2004; 62(11): 1963 - 1966.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Sports. Med.Home page
P McCrory, M Turner, and J Murray
A punch drunk jockey?
Br. J. Sports Med., June 1, 2004; 38(3): e3 - e3.
[Abstract] [Full Text] [PDF]

Home page
 Br J OphthalmolHome page
S Lake, E Liverani, M Desai, R Casson, B James, A Clark, and J F Salmon
Normal tension glaucoma is not associated with the common apolipoprotein E gene polymorphisms
Br J Ophthalmol, April 1, 2004; 88(4): 491 - 493.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
J-C Lambert, N Coyle, and C Lendon
The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease
J. Med. Genet., February 1, 2004; 41(2): 104 - 112.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. R. Lynch, W. Tang, H. Wang, M. P. Vitek, E. R. Bennett, P. M. Sullivan, D. S. Warner, and D. T. Laskowitz
APOE Genotype and an ApoE-mimetic Peptide Modify the Systemic and Central Nervous System Inflammatory Response
J. Biol. Chem., December 5, 2003; 278(49): 48529 - 48533.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
J. W. Gaynor, M. Gerdes, E. H. Zackai, J. Bernbaum, G. Wernovsky, R. R. Clancy, M. F. Newman, A. M. Saunders, P. J. Heagerty, J. A. D'Agostino, et al.
Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery
J. Thorac. Cardiovasc. Surg., December 1, 2003; 126(6): 1736 - 1745.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
C. L. Lendon, J. M. Harris, A. L. Pritchard, J. A.R. Nicoll, G. M. Teasdale, and G. Murray
Genetic variation of the APOE promoter and outcome after head injury
Neurology, September 9, 2003; 61(5): 683 - 685.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
K Millar, J A R Nicoll, S Thornhill, G D Murray, and G M Teasdale
Long term neuropsychological outcome after head injury: relation to APOE genotype
J. Neurol. Neurosurg. Psychiatry, August 1, 2003; 74(8): 1047 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pathol.Home page
N Nathoo, R Chetty, J R van Dellen, and G H Barnett
Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E
Mol. Pathol., June 1, 2003; 56(3): 132 - 136.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
R. Diaz-Arrastia, Y. Gong, S. Fair, K. D. Scott, M. C. Garcia, M. C. Carlile, M. A. Agostini, and P. C. Van Ness
Increased Risk of Late Posttraumatic Seizures Associated With Inheritance of APOE{epsilon}4 Allele
Arch Neurol, June 1, 2003; 60(6): 818 - 822.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
J. S. Burgos, C. Ramirez, I. Sastre, M. J. Bullido, and F. Valdivieso
Involvement of Apolipoprotein E in the Hematogenous Route of Herpes Simplex Virus Type 1 to the Central Nervous System
J. Virol., December 1, 2002; 76(23): 12394 - 12398.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. E. Hartman, H. Laurer, L. Longhi, K. R. Bales, S. M. Paul, T. K. McIntosh, and D. M. Holtzman
Apolipoprotein E4 Influences Amyloid Deposition But Not Cell Loss after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease
J. Neurosci., December 1, 2002; 22(23): 10083 - 10087.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Interv.Home page
K.R. Bales, J.C. Dodart, R.B. DeMattos, D.M. Holtzman, and S.M. Paul
Apolipoprotein E, Amyloid, and Alzheimer Disease
Mol. Interv., October 1, 2002; 2(6): 363 - 375.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. N. Liberman, W. F. Stewart, K. Wesnes, and J. Troncoso
Apolipoprotein E {epsilon}4 and short-term recovery from predominantly mild brain injury
Neurology, April 9, 2002; 58(7): 1038 - 1044.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
F. C. Crawford, R. D. Vanderploeg, M. J. Freeman, S. Singh, M. Waisman, L. Michaels, L. Abdullah, D. Warden, R. Lipsky, A. Salazar, et al.
APOE genotype influences acquisition and recall following traumatic brain injury
Neurology, April 9, 2002; 58(7): 1115 - 1118.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Sports. Med.Home page
P McCrory
Boxing and the brain
Br. J. Sports Med., February 1, 2002; 36(1): 2 - 2.
[Full Text] [PDF]

Home page
 Br. J. Sports. Med.Home page
P. McCrory
When to retire after concussion?
Br. J. Sports Med., December 1, 2001; 35(6): 380 - 382.
[Full Text] [PDF]

Home page
 J Gerontol A Biol Sci Med SciHome page
D. G. Blazer, G. Fillenbaum, and B. Burchett
The APOE-E4 Allele and the Risk of Functional Decline in a Community Sample of African American and White Older Adults
J Gerontol A Biol Sci Med Sci, December 1, 2001; 56(12): M785 - M789.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. Chapman, A. D. Korczyn, D. M. Karussis, and D. M. Michaelson
The effects of APOE genotype on age at onset and progression of neurodegenerative diseases
Neurology, October 23, 2001; 57(8): 1482 - 1485.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Kipnis, E. Yoles, H. Schori, E. Hauben, I. Shaked, and M. Schwartz
Neuronal Survival after CNS Insult Is Determined by a Genetically Encoded Autoimmune Response
J. Neurosci., July 1, 2001; 21(13): 4564 - 4571.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
T. Niskakangas, J. Ohman, M. Niemela, E. Ilveskoski, T. A. Kunnas, and P. J. Karhunen
Association of Apolipoprotein E Polymorphism With Outcome After Aneurysmal Subarachnoid Hemorrhage : A Preliminary Study
Stroke, May 1, 2001; 32(5): 1181 - 1184.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
D. Malaspina, R. R. Goetz, J. H. Friedman, C. A. Kaufmann, S. V. Faraone, M. Tsuang, C. R. Cloninger, J. I. Nurnberger Jr., and M. C. Blehar
Traumatic Brain Injury and Schizophrenia in Members of Schizophrenia and Bipolar Disorder Pedigrees
Am J Psychiatry, March 1, 2001; 158(3): 440 - 446.
[Abstract] [Full Text]

Home page
 Arch NeurolHome page
S. A. Small
Age-Related Memory Decline: Current Concepts and Future Directions
Arch Neurol, March 1, 2001; 58(3): 360 - 364.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
J. R. Saper
Posttraumatic Headache: A Neurobehavioral Disorder
Arch Neurol, December 1, 2000; 57(12): 1776 - 1778.
[Full Text] [PDF]

Home page
 NeurologyHome page
S. W. Lichtman, G. Seliger, B. Tycko, and K. Marder
Apolipoprotein E and functional recovery from brain injury following postacute rehabilitation
Neurology, November 28, 2000; 55(10): 1536 - 1539.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
M. O. McCarron, K. W. Muir, J. A. R. Nicoll, J. Stewart, Y. Currie, K. Brown, and I. Bone
Prospective Study of Apolipoprotein E Genotype and Functional Outcome Following Ischemic Stroke
Arch Neurol, October 1, 2000; 57(10): 1480 - 1484.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
D. T. Laskowitz, D. M. Lee, D. Schmechel, and H. F. Staats
Altered immune responses in apolipoprotein E-deficient mice
J. Lipid Res., April 1, 2000; 41(4): 613 - 620.
[Abstract] [Full Text]

Home page
 NeurologyHome page
Z. Guo, L. A. Cupples, A. Kurz, S. H. Auerbach, L. Volicer, H. Chui, R. C. Green, A. D. Sadovnick, R. Duara, C. DeCarli, et al.
Head injury and the risk of AD in the MIRAGE study
Neurology, March 28, 2000; 54(6): 1316 - 1323.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
M. O. McCarron, D. Delong, and M. J. Alberts
APOE genotype as a risk factor for ischemic cerebrovascular disease: A meta-analysis
Neurology, October 1, 1999; 53(6): 1308 - 1308.
[Abstract] [Full Text]

Home page
 Evid. Based Ment. HealthHome page
J. Price
APOE {{varepsilon}}4 allele, age, and duration of unconsciousness were associated with unfavourable outcomes in traumatic brain injury
Evid. Based Ment. Health, August 1, 1999; 2(3): 94 - 94.
[Full Text]