Traumatic brain injury and risk of dementia in older veterans
Abstract
Objectives:
Traumatic brain injury (TBI) is common in military personnel, and there is growing concern about the long-term effects of TBI on the brain; however, few studies have examined the association between TBI and risk of dementia in veterans.
Methods:
We performed a retrospective cohort study of 188,764 US veterans aged 55 years or older who had at least one inpatient or outpatient visit during both the baseline (2000–2003) and follow-up (2003–2012) periods and did not have a dementia diagnosis at baseline. TBI and dementia diagnoses were determined using ICD-9 codes in electronic medical records. Fine-Gray proportional hazards models were used to determine whether TBI was associated with greater risk of incident dementia, accounting for the competing risk of death and adjusting for demographics, medical comorbidities, and psychiatric disorders.
Results:
Veterans were a mean age of 68 years at baseline. During the 9-year follow-up period, 16% of those with TBI developed dementia compared with 10% of those without TBI (adjusted hazard ratio, 1.57; 95% confidence interval: 1.35–1.83). There was evidence of an additive association between TBI and other conditions on risk of dementia.
Conclusions:
TBI in older veterans was associated with a 60% increase in the risk of developing dementia over 9 years after accounting for competing risks and potential confounders. Our results suggest that TBI in older veterans may predispose toward development of symptomatic dementia and raise concern about the potential long-term consequences of TBI in younger veterans and civilians.
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REFERENCES
1.
Institute of Medicine of the National Academies. Gulf War and Health: Volume 7: Long-Term Consequences of Traumatic Brain Injury. Washington, DC: National Academies Press; 2008.
2.
Breteler MM, de Groot RR, van Romunde LK, Hofman A. Risk of dementia in patients with Parkinson's disease, epilepsy, and severe head trauma: a register-based follow-up study. Am J Epidemiol 1995;142:1300–1305.
3.
Dams-O'Connor K, Gibbons LE, Bowen JD, McCurry SM, Larson EB, Crane PK. Risk for late-life re-injury, dementia and death among individuals with traumatic brain injury: a population-based study. J Neurol Neurosurg Psychiatry 2013;84:177–182.
4.
Fleminger S, Oliver DL, Lovestone S, Rabe-Hesketh S, Giora A. Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 2003;74:857–862.
5.
Guskiewicz KM, Marshall SW, Bailes J, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery 2005;57:719–726.
6.
Lee YK, Hou SW, Lee CC, Hsu CY, Huang YS, Su YC. Increased risk of dementia in patients with mild traumatic brain injury: a nationwide cohort study. PloS One 2013;8:e62422.
7.
Mayeux R, Ottman R, Maestre G, et al. Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease. Neurology 1995;45:555–557.
8.
Mehta KM, Ott A, Kalmijn S, et al. Head trauma and risk of dementia and Alzheimer's disease: the Rotterdam Study. Neurology 1999;53:1959–1962.
9.
Mortimer JA, van Duijn CM, Chandra V, et al. Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20(suppl 2):S28–S35.
10.
Nemetz PN, Leibson C, Naessens JM, et al. Traumatic brain injury and time to onset of Alzheimer's disease: a population-based study. Am J Epidemiol 1999;149:32–40.
11.
Plassman BL, Havlik RJ, Steffens DC, et al. Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 2000;55:1158–1166.
12.
Schofield PW, Tang M, Marder K, et al. Alzheimer's disease after remote head injury: an incidence study. J Neurol Neurosurg Psychiatry 1997;62:119–124.
13.
Sundstrom A, Nilsson LG, Cruts M, Adolfsson R, Van Broeckhoven C, Nyberg L. Increased risk of dementia following mild head injury for carriers but not for non-carriers of the APOE epsilon4 allele. Int Psychogeriatr 2007;19:159–165.
14.
Wang HK, Lin SH, Sung PS, et al. Population based study on patients with traumatic brain injury suggests increased risk of dementia. J Neurol Neurosurg Psychiatry 2012;83:1080–1085.
15.
Byers AL, Covinsky KE, Barnes DE, Yaffe K. Dysthymia and depression increase risk of dementia and mortality among older veterans. Am J Geriatric Psychiatry 2012;20:664–672.
16.
Yaffe K, Vittinghoff E, Lindquist K, et al. Posttraumatic stress disorder and risk of dementia among US veterans. Arch General Psychiatry 2010;67:608–613.
17.
Selassie AW, Zaloshnja E, Langlois JA, Miller T, Jones P, Steiner C. Incidence of long-term disability following traumatic brain injury hospitalization, United States, 2003. J Head Trauma Rehabil 2008;23:123–131.
18.
Krishnan LL, Petersen NJ, Snow AL, et al. Prevalence of dementia among Veterans Affairs medical care system users. Dement Geriatr Cogn Disord 2005;20:245–253.
19.
VA Dementia Registry Task Force. VA Dementia Registry Methods Report: Summary Data Tables on Demographics, Service Use and Costs. 2006. Available to researchers with VA network access at: http://vaww.arc.med.va.gov/gec/dementia/fy04/dementia2_reg_methods_report_2nov06.doc. Accessed June 3, 2014.
20.
(VIReC) VIRC. VHA Vital Status File [online]. Available to researchers with VA network access at: http://vaww.virec.research.va.gov/VSF/Overview.htm. Accessed June 3, 2014.
21.
Sohn MW, Arnold N, Maynard C, Hynes DM. Accuracy and completeness of mortality data in the Department of Veterans Affairs. Popul Health Metr 2006;4:2.
22.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999;94:496–509.
23.
Kim HT. Cumulative incidence in competing risks data and competing risks regression analysis. Clin Cancer Res 2007;13:559–565.
24.
Tremblay S, De Beaumont L, Henry LC, et al. Sports concussions and aging: a neuroimaging investigation. Cereb Cortex 2013;23:1159–1166.
25.
Lehman EJ, Hein MJ, Baron SL, Gersic CM. Neurodegenerative causes of death among retired National Football League players. Neurology 2012;79:1970–1974.
26.
Raymont V, Greathouse A, Reding K, Lipsky R, Salazar A, Grafman J. Demographic, structural and genetic predictors of late cognitive decline after penetrating head injury. Brain 2008;131:543–558.
27.
Kalkonde YV, Jawaid A, Qureshi SU, et al. Medical and environmental risk factors associated with frontotemporal dementia: a case-control study in a veteran population. Alzheimers Dement 2012;8:204–210.
28.
Blennow K, Hardy J, Zetterberg H. The neuropathology and neurobiology of traumatic brain injury. Neuron 2012;76:886–899.
29.
Smith DH, Johnson VE, Stewart W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol 2013;9:211–221.
30.
DeKosky ST, Blennow K, Ikonomovic MD, Gandy S. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat Rev Neurol 2013;9:192–200.
31.
Moretti L, Cristofori I, Weaver SM, Chau A, Portelli JN, Grafman J. Cognitive decline in older adults with a history of traumatic brain injury. Lancet Neurol 2012;11:1103–1112.
32.
Sayed N, Culver C, Dams-O'Connor K, Hammond F, Diaz-Arrastia R. Clinical phenotype of dementia after traumatic brain injury. J Neurotrauma 2013;30:1117–1122.
33.
Shively S, Scher AI, Perl DP, Diaz-Arrastia R. Dementia resulting from traumatic brain injury: what is the pathology? Arch Neurol 2012;69:1245–1251.
34.
Goldstein L, Fisher AM, Tagge CA, et al. Chronic traumatic encephalopathy in blast-exposed military veterans. Sci Transl Med 2012;4:1–16.
35.
Jawaid A, Rademakers R, Kass JS, Kalkonde Y, Schulz PE. Traumatic brain injury may increase the risk for frontotemporal dementia through reduced progranulin. Neurodegener Dis 2010;6:219–220.
36.
Cordts PR, Brosch LA, Holcomb JB. Now and then: combat casualty care policies for Operation Iraqi Freedom and Operation Enduring Freedom compared with those of Vietnam. J Trauma 2008;64:S14–S20.
37.
DePalma RG, Burris DG, Champion HR, Hodgson MJ. Blast injuries. N Engl J Med 2005;352:1335–1342.
38.
Coronado VG, McGuire LC, Sarmiento K, et al. Trends in traumatic brain injury in the U.S. and the public health response: 1995–2009. J Saf Res 2012;43:299–307.
39.
Faul M, Xu L, Wald MM, Coronado V. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths, 2002–2006. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.
Information & Authors
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© 2014 American Academy of Neurology.
Publication History
Received: October 22, 2013
Accepted: February 28, 2014
Published online: June 25, 2014
Published in print: July 22, 2014
Disclosure
D. Barnes reports research support from NCIRE/Department of Defense (W81XWH-11-2-0189, role: principal investigator [PI], 2011–2013); Department of Veterans Affairs (REA 01-097, role: scholar-in-residence, 2009–2013; 1IO1HX000694, role: coinvestigator, 2013–2018); NARSAD (role: PI, 2010–2013); S.D. Bechtel Jr., Foundation (role: senior investigator, 2010–2013; role: coinvestigator, 2011–2014); philanthropic support via Osher Center (role: PI, 2010–2014) and UCB Pharma, Inc. (role: study design and analytic consultant, 2012–2014). A. Kaup reports funding from the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs. K. Kirby reports no disclosures relevant to the manuscript. A. Byers reports support from the Department of Defense (W81XWH-11-2-0189, project 1614; role: PI, 2012–2014), the NIH (MD007019; role: PI, 2012–2015), and with resources from the San Francisco Veterans Affairs Medical Center. R. Diaz-Arrastia reports support from National Institute of Neurological Disorders and Stroke (R01 NS061860) and Department of Defense (ERMS 12109006). K. Yaffe reports serving on data safety monitoring boards for Takeda, Inc., and a study sponsored by the NIH and has served as a consultant for Novartis, Inc. Go to Neurology.org for full disclosures.
Study Funding
Supported by the Department of Defense/NCIRE (Barnes: W81XWH-11-2-0189, project 1610; Byers: W81XWH-11-2-0189, project 1614; Yaffe: W81XWH-12-1-0581) and the NIH (Yaffe: K24 AG031155). The funders did not contribute to the design of the study, analysis or interpretation of data, or decision to publish. The views expressed do not necessarily reflect those of the funders.
Authors
Author Contributions
Dr. Barnes oversaw the design of the study, obtained funding, oversaw data analyses, and drafted and revised the manuscript. Dr. Kaup contributed to the drafting and critical revision of the manuscript for content. Ms. Kirby performed the data analyses and contributed to the interpretation of the data. Dr. Byers contributed to the design of the study, analysis and interpretation of the data, and critical revision of the manuscript. Dr. Diaz-Arrastia contributed to the interpretation of the data and critical revision of the manuscript. Dr. Yaffe conceived the study, obtained funding, and contributed to the design of the study, analysis and interpretation of the data, and critical revision of the manuscript.
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