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

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Researchers sought to assess the association between traumatic brain injury/posttraumatic stress disorder and biomarker-defined Alzheimer disease in veterans.

There is no association between increased levels of Alzheimer disease (AD)-related biomarkers and veterans who experienced posttraumatic 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.

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 altering 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 posttraumatic stress disorder are not associated with Alzheimer’s disease pathology measured with biomarkers. Alzheimers Dement. Published online June 29, 2022. doi:10.1002/alz.12712