Traumatic brain injury and post-traumatic stress disorder are not associated with Alzheimer's disease pathology measured with biomarkers

Michael W Weiner; Danielle Harvey; Susan M Landau; Dallas P Veitch; Thomas C Neylan; Jordan H Grafman; Paul S Aisen; Ronald C Petersen; Clifford R Jack Jr; Duygu Tosun; Leslie M Shaw; John Q Trojanowski; Andrew J Saykin; Jacqueline Hayes; Charles De Carli; Alzheimer's Disease Neuroimaging Initiative and the Department of Defense Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.12712

Traumatic brain injury and post-traumatic stress disorder are not associated with Alzheimer's disease pathology measured with biomarkers

Alzheimers Dement. 2023 Mar;19(3):884-895. doi: 10.1002/alz.12712. Epub 2022 Jun 29.

Authors

Michael W Weiner^{1

2

3

4

5}, Danielle Harvey⁶, Susan M Landau⁷, Dallas P Veitch^{1

8}, Thomas C Neylan^{4

5}, Jordan H Grafman⁹, Paul S Aisen¹⁰, Ronald C Petersen¹¹, Clifford R Jack Jr¹², Duygu Tosun^{1

2}, Leslie M Shaw¹³, John Q Trojanowski¹³, Andrew J Saykin^{14

15}, Jacqueline Hayes^{1

8}, Charles De Carli¹⁶; Alzheimer's Disease Neuroimaging Initiative and the Department of Defense Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, USA.
² Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
³ Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
⁴ Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA.
⁵ Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
⁶ Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, Davis, California, USA.
⁷ Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, USA.
⁸ Northern California Institute for Research and Education (NCIRE), Department of Veterans Affairs Medical Center, San Francisco, California, USA.
⁹ Shirley Ryan AbilityLab, Northwestern University School of Medicine, Chicago, Illinois, USA.
¹⁰ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, La Jolla, California, USA.
¹¹ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹² Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹³ Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Research, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁴ Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁵ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁶ Department of Neurology and Center for Neuroscience, University of California Davis, Davis, California, USA.

Abstract

Introduction: Epidemiological studies report an association between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and clinically diagnosed Alzheimer's disease (AD). We examined the association between TBI/PTSD and biomarker-defined AD.

Methods: We identified 289 non-demented veterans with TBI and/or PTSD and controls who underwent clinical evaluation, cerebrospinal fluid (CSF) collection, magnetic resonance imaging (MRI), amyloid beta (Aβ) and tau positron emission tomography, and apolipoprotein E testing. Participants were followed for up to 5.2 years.

Results: Exposure groups (TBI, PTSD, and TBI + PTSD) had higher prevalence of mild cognitive impairment (MCI: P < .0001) and worse Mini-Mental State Examination scores (PTSD: P = .008; TBI & PTSD: P = .009) than controls. There were no significant differences in other cognitive scores, MRI volumes, Aβ or tau accumulation, or in most longitudinal measures.

Discussion: TBI and/or PTSD were not associated with elevated AD biomarkers. The poorer cognitive status of exposed veterans may be due to other comorbid pathologies.

Keywords: Alzheimer's disease; amyloid; cerebrovascular disease; cognitive decline; head injury; neurodegeneration; post‐traumatic stress disorder; tau; traumatic brain injury; veterans.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / pathology
Amyloid beta-Peptides* / cerebrospinal fluid
Apolipoproteins E / genetics
Biomarkers* / cerebrospinal fluid
Brain Injuries, Traumatic* / complications
Brain Injuries, Traumatic* / diagnostic imaging
Cognitive Dysfunction* / cerebrospinal fluid
Female
Humans
Magnetic Resonance Imaging*
Male
Middle Aged
Neuropsychological Tests / statistics & numerical data
Positron-Emission Tomography*
Stress Disorders, Post-Traumatic*
Veterans*
tau Proteins* / cerebrospinal fluid

Substances

Biomarkers
Amyloid beta-Peptides
tau Proteins
Apolipoproteins E

Grants and funding

U19 AG024904/AG/NIA NIH HHS/United States