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

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.

PMID: 35768339
PMCID: PMC10269599
DOI: 10.1002/alz.12712

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

Michael W Weiner et al. Alzheimers Dement. 2023 Mar.

. 2023 Mar;19(3):884-895.

doi: 10.1002/alz.12712. Epub 2022 Jun 29.

Authors

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.

PMID: 35768339
PMCID: PMC10269599
DOI: 10.1002/alz.12712

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.

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Figures

**Figure 1.. Flow of DOD ADNI recruitment and enrollment.**
Abbreviations: ADAS-cog; Alzheimer’s Disease Assessment Scale – cognitive; CDR-SB, Clinical Dementia Rating – Sum of Boxes; CN, control; cort., cortical; CSF, cerebrospinal fluid; MMSE, Mini-Mental State Examination; MRI, magnetic resonance imaging; PET, positron emission tomography; PTSD, posttraumatic stress disorder; SCIDS, Structured Clinical Interview for DSM; TBI, traumatic brain injury.

**Figure 2.. Florbetapir and flortaucipir binding by participant group.**
Florbetapir cortical SUVRs are shown for each participant group, with a dotted line reflecting the positivity threshold at 1.17 and separate points for cognitively normal and MCI individuals (A). Flortaucipir entorhinal cortex and temporal metaROI SUVRs are shown for each participant group by amyloid status, with separate points for cognitively normal and MCI individuals (B). Abbreviations: C, controls; MCI, mild cognitive impairment; CN, cognitively unimpaired; PTSD, posttraumatic stress disorder; TBI, traumatic brain injury.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical