Skip to main content
AAN.com

Abstract

Background: The association between antecedent head injury and AD is inconsistent.
Objective: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE ε4 as risk factors for dementia.
Methods: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models.
Results: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE ε4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more ε4 alleles.
Conclusions: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
Salib E, Hillier V. Head injury and the risk of Alzheimer’s disease: a case control study. Int J Geriatr Psychiatry . 1997; 12: 363–368.
2.
van Duijn CM, Tanja TA, Haaxma R, et al. Head trauma and the risk of Alzheimer’s disease. Am J Epidemiol . 1992; 135: 775–782.
3.
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. Int J Epidemiol . 1991; 20 (suppl 2): S28–S35.
4.
Mayeux R, Ottman R, Tang M-X, et al. Genetic susceptibility and head injury as risk factors for Alzheimer’s disease among community-dwelling elderly persons and their first-degree relatives. Ann Neurol . 1993; 33: 494–501.
5.
O’Meara ES, Kukull WA, Sheppard L, et al. Head injury and risk of Alzheimer’s disease by apolipoprotein E genotype. Am J Epidemiol . 1997; 146: 373–384.
6.
Graves AB, White E, Koepsell TD, et al. The association between head trauma and Alzheimer’s disease. Am J Epidemiol . 1990; 131: 491–501.
7.
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.
8.
Heyman A, Wilkinson WE, Stafford JA, et al. Alzheimer’s disease: a study of epidemiological aspects. Ann Neurol . 1984; 15: 335–341.
9.
Williams DB, Annegers JF, Kokmen E, O’Brien PC, Kurland LT. Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology . 1991; 41: 1554–1557.
10.
Katzman R, Aronson M, Fuld P, et al. Development of dementing illnesses in an 80 year old volunteer cohort. Ann Neurol . 1989; 25: 317–324.
11.
Launer LJ, Andersen K, Dewey ME, et al. Rates and risk factors for dementia and Alzheimer’s disease. Neurology . 1999; 52: 78–84.
12.
Mehta KM, Ott A, Kalmijn S, et al. Head trauma and risk of dementia and Alzheimer’s disease. Neurology . 1999; 53: 1959–1962.
13.
Mayeux R. Apolipoprotein ε4 and head trauma: synergistic or additive risks? Neurology . 1996; 46: 889–891. Letter.
14.
Katzman R, Galasko DR, Saitoh T, et al. Apolipoprotein ε4 and head trauma: synergistic or additive risks? Neurology . 1996; 46: 889–891. Letter.
15.
Frankowski RF, Annegers JF, Whitman S. Epidemiological and descriptive studies. Part I: The descriptive epidemiology of head trauma in the United States. In: Becker DP, Povlishock JT, eds. Central nervous system trauma status report–1985. Bethesda, MD: National Institute of Neurological and Communicative Disorders and Stroke, 1985: 33–43.
16.
Brandt J, Spencer M, Folstein M. The Telephone Interview for Cognitive Status. Neuropsychiatry Neuropsychol Behav Neurol . 1988; 1: 111–117.
17.
Welsh KA, Breitner JCS, Magruder–Habib KM. Detection of dementia in the elderly using telephone screening of cognitive status. Neuropsychiatry Neuropsychol Behav Neurol . 1993; 6: 103–110.
18.
Folstein MF, Folstein SE, McHugh PR. Mini-Mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res . 1975; 12: 189–198.
19.
Jorm AF, Jacomb PA. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates, reliability, validity and some norms. Psychol Med . 1989; 19: 1015–1022.
20.
Gallo JJ, Breitner JCS. Alzheimer’s disease in the N.A.S.- N.R.C. registry of aging twin veterans. IV. Performance characteristics of a two-stage telephone screening procedure for Alzheimer’s dementia. Psychol Med . 1995; 25: 1211–1219.
21.
Silverman JM, Breitner JCS, Mohs RC, Davis KL. Reliability of the family history method in genetic studies of Alzheimer’s disease and related dementias. Am J Psychiatry . 1986; 143: 1279–1282.
22.
Kawas C, Segal J, Stewart WF, Corrada M, Thal LJ. A validation study of the dementia questionnaire. Arch Neurol . 1994; 51: 901–906.
23.
Breitner JCS, Wyse BW, Anthony JC, et al. APOE-ε4 count predicts age when prevalence of AD increases, then declines: the Cache County Study. Neurology . 1999; 53: 321–331.
24.
Breitner JCS, Welsh KA, Gau BA, et al. Alzheimer’s disease in the National Academy of Sciences–National Research Council Registry of aging twin veterans. III. Detection of cases, longitudinal results, and observations on twin concordance. Arch Neurol . 1995; 52: 763–771.
25.
McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology . 1984; 34: 939–944.
26.
Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology . 1993; 43: 250–260.
27.
Tatemichi TK, Sacktor N, Mayeux R. Dementia associated with cerebrovascular disease, other degenerative diseases, and metabolic disorders. In: Terry RD, Katzman R, Bick KL, eds. Alzheimer disease. New York, NY: Raven Press, 1994: 123–166.
28.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Third edition–revised. Washington, DC: American Psychiatric Association, 1987.
29.
Khachaturian AS, Gallo JJ, Breitner JCS. Performance characteristics of a two-stage dementia screen in a population sample. J Clin Epidemiol 2000 (in press).
30.
Tsuang D, Larson EB, Bowen J, et al. The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer’s disease in a community-based case series. Arch Neurol . 1999; 56: 1489–1495.
31.
Mayeux R, Saunders AM, Shea S, et al. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. N Engl J Med . 1998; 338: 506–511.
32.
Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer’s disease. Neurology . 1993; 43: 1467–1472.
33.
Hill AB. The environment and disease: association or causation? Proc R Soc Med . 1965; 58: 295–300.
34.
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.
35.
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.
36.
Gedye A, Beattie BL, Tuokko H, Horton A, Korsarek E. Severe head injury hastens age of onset of Alzheimer’s disease. J Am Geriatr Soc . 1989; 37: 970–973.
37.
National Institutes of Health. Rehabilitation of persons with traumatic brain injury. NIH Consensus Statement 1998, Oct 26–28;16:1–41.
38.
Breitner JCS. The end of Alzheimer’s disease. Int J Geriatr Psychiatry . 1999; 14: 577–586.
39.
Ghebremedhin E, Schultz C, Braak E, Braak H. High frequency of apolipoprotein E ε4 allele in young individuals with very mild Alzheimer’s disease-related neurofibrillary changes. Exp Neurol . 1998; 153: 152–155.
40.
McIntosh TK, Saatman KE, Raghupathi R, et al. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neurobiol . 1998; 24: 251–267.

Information & Authors

Information

Published In

Neurology®
Volume 55Number 8October 24, 2000
Pages: 1158-1166
PubMed: 11071494

Publication History

Accepted: June 23, 2000
Published online: October 24, 2000
Published in print: October 24, 2000
Received: October 26, 2000

Permissions

Request permissions for this article.

Authors

Affiliations & Disclosures

B.L. Plassman, PhD
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
R.J. Havlik, MD, MPH
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
D.C. Steffens, MD
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
M.J. Helms, MS
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
T.N. Newman, BS
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
D. Drosdick
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
C. Phillips, MS
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
B.A. Gau, MSW
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
K.A. Welsh–Bohmer, PhD
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
J.R. Burke, MD, PhD
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
J.M. Guralnik, MD, PhD
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
J.C. S. Breitner, MD, MPH
From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.

Notes

Address correspondence and reprint requests to Dr. Brenda L. Plassman, Box 41, 905 W. Main Street, Suite 25D, Durham, NC 27701; e-mail: [email protected]

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke, Brain, Behavior, and Immunity, 115, (43-63), (2024).https://doi.org/10.1016/j.bbi.2023.09.015
    Crossref
  2. Single Versus Repetitive Traumatic Brain Injury: Current Knowledge on the Chronic Outcomes, Neuropathology and the Role of TDP-43 Proteinopathy, Experimental Neurobiology, 32, 4, (195-215), (2023).https://doi.org/10.5607/en23008
    Crossref
  3. Investigation into the vascular contributors to dementia and the associated treatments, Exploration of Neuroscience, (224-237), (2023).https://doi.org/10.37349/en.2023.00023
    Crossref
  4. Phytochemicals: A Promising Alternative for the Prevention of Alzheimer’s Disease, Life, 13, 4, (999), (2023).https://doi.org/10.3390/life13040999
    Crossref
  5. Potential Biomarkers in Experimental Animal Models for Traumatic Brain Injury, Journal of Clinical Medicine, 12, 12, (3923), (2023).https://doi.org/10.3390/jcm12123923
    Crossref
  6. Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory, International Journal of Molecular Sciences, 24, 10, (8967), (2023).https://doi.org/10.3390/ijms24108967
    Crossref
  7. Preliminary Observations of Personalized Repetitive Magnetic Stimulation (PrTMS) Guided by EEG Spectra for Concussion, Brain Sciences, 13, 8, (1179), (2023).https://doi.org/10.3390/brainsci13081179
    Crossref
  8. Traumatic brain injury-associated epigenetic changes and the risk for neurodegenerative diseases, Frontiers in Neuroscience, 17, (2023).https://doi.org/10.3389/fnins.2023.1259405
    Crossref
  9. An exhaustive analysis of post-traumatic brain injury dementia using bibliometric methodologies, Frontiers in Neurology, 14, (2023).https://doi.org/10.3389/fneur.2023.1165059
    Crossref
  10. How Traumatic Brain Injury History Relates to Brain Health MRI Markers and Dementia Risk: Findings from the 3C Dijon Cohort, Journal of Alzheimer's Disease, 92, 1, (183-193), (2023).https://doi.org/10.3233/JAD-220658
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share