Traumatic Brain Injury, PTSD and Alzheimer’s Disease-Related Biomarkers: Is There a Link?

There is no association between increased levels of Alzheimer’s disease (AD)-related biomarkers and veterans who experienced post-traumatic stress disorder (PTSD) and/or traumatic brain injury (TBI). Although veterans exposed to TBI, PTSD, or both showed poorer cognitive status, researchers believe it’s attributed to other comorbid pathologies. These are the findings of a study published in Alzheimer’s & Dementia.

PTSD and TBI are often comorbid and linked with later-in-life all-cause dementia, though studies are more ambiguous about the association of PTSD with this later life disorder. For this study, the researchers tested the association between TBI/PTSD and biomarker-defined AD in a group of older veterans without dementia.

Researchers conducted a cohort study between 2013 and 2020 and used military and Veterans Benefits Administration records to identify US Vietnam veterans with military service-related TBI and/or ongoing PTSD who did not have dementia and control individuals with no record of TBI/PTSD before, during, or after the Vietnam War. Participants were also recruited by advertisements. All participants underwent clinical evaluation, cerebrospinal fluid (CSF) collection, magnetic resonance imaging (MRI), amyloid-beta and tau positron emission tomography (PET), and apolipoprotein E (APOE) testing. The average follow-up was up to 5.2 years.

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Of the 289 study participants, PTSD (N=81; 20% mild cognitive impairment [MCI]), TBI (N=43; 21% MCI), and PTSD and TBI (N=94; 25% MCI), all showed significantly greater prevalence of MCI than control individuals (N=71; 3% MCI) (MCI: P <.0001).

Tests results for the Mini-Mental State Examination (MMSE) scores (testing naming, spatial, memory, attention, orientation, and concentration skills; possible total score of 30 points) revealed virtually identical mean scores for all groups at study initiation; Control (28.8, 96.0%), PTSD (28.0, 93.3%), TBI (28.5, 95.0%), TBI and PTSD (27.9, 93.0%) and interpreted in the current study as “worse MMSE scores” for the exposure groups ( PTSD, TBI, TBI and PTSD) than for control individuals.

Researchers reported no significant differences in amyloid-beta or tau accumulation, MRI volumes, or other cognitive scores. Longitudinal testing was carried out on a subset of veterans (N=225) over an average of 1.8 years and showed no significant difference between groups for MMSE, except for Clinical Dementia Rating-Sum of Boxes, which was much worse in the TBI group compared with control individuals. Among veterans aged at least 65 years with 12 years of education and no APOE ε alleles, who were also considered to be cognitively unimpaired, hippocampal volume significantly declined in the TBI group by 0.01% (standard error [SE], 0.004; P=.01).

Study limitations included the insensitivity of the radiotracers used, some self-reported TBI not documented with medical records, the use of alternative definitions of TBI aging study results, selection bias, 20% failed quality control of MRI scans, more than 50% of tau PET data unavailable, and only 2 women participated.

“Our data showing comparable degree of abnormality in biomarkers of [amyloid-beta], tau, and neurodegeneration between exposure and control groups do not support the hypothesis that TBI and PTSD are associated with biomarker-defined AD,” the researchers stated. They also noted that the high frequency of abnormal AD biomarkers in participants with dementia, and those veterans were excluded from results.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Weiner MW, Harvey D, Landau SM, et al; for the Alzheimer’s Disease Neuroimaging Initiative and the Department of Defense Alzheimer’s Disease Neuroimaging Initiative. Traumatic brain injury and post-traumatic stress disorder are not associated with Alzheimer’s disease pathology measured with biomarkers. Alzheimer’s dementia. Published online June 29, 2022. doi:10.1002/alz.12712

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