Tau, β-amyloid, and glucose metabolism following service-related Traumatic Brain Injury in Vietnam war veterans: The AIBL-VETS study

Traumatic Brain Injury (TBI) is common amongst military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer’s disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 NIA-AA research framework[1][1], by measuring tau, β-amyloid and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI. Seventy male Vietnam war veterans — 40 with TBI (aged 68.0±2.5 years) and 30 controls (aged 70.1±5.3 years) — with no prior diagnosis of dementia or mild cognitive impairment underwent β-amyloid (18F-Florbetaben), tau (18F-Flortaucipir) and 18F-FDG PET. The TBI cohort included 15 participants with mild, 16 with moderate, and 9 with severe injury. β-amyloid level was calculated using the Centiloid (CL) method and tau was measured by Standardized Uptake Value Ratios (SUVR) using the cerebellar cortex as reference region. Analyses were adjusted for age and APOE-e4. The findings were validated in an independent cohort from the ADNI-DOD study. There were no significant nor trending differences in β-amyloid or tau levels or 18F-FDG uptake between the TBI and control groups before and after controlling for covariates. The β-amyloid and tau findings were replicated in the ADNI-DOD validation cohort and persisted when the AIBL-VETS and ADNI-DOD cohorts were combined (114 TBI vs 87 controls in total). These findings suggest that TBI is not associated with the later life accumulation of the neuropathological markers of AD. ### Competing Interest Statement Christopher C. Rowe has received research grants from NHMRC, Enigma Australia, Biogen, Eisai and Abbvie. He is on the scientific advisory board for Cerveau Technologies and has consulted for Prothena, Eisai, Roche, and Biogen Australia. Victor Villemagne is and has been a consultant or paid speaker at sponsored conference sessions for Eli Lilly, Life Molecular Imaging, GE Healthcare, IXICO, Abbvie, Lundbeck, Shanghai Green Valley Pharmaceutical Co Ltd, and Hoffmann La Roche. The other authors did not report any conflict of interest. ### Funding Statement The study was supported by grants from the National Health and Medical Research Council (NHMRC) (award numbers APP1127007, APP10475151), the US Department of Defense U.S. Army Medical Research and Materiel Command (award number W81XWH-14-1-0418) and Piramal Imaging who marketed Florbetaben at the time of the study. The funding sources had no input into the design of this study, the analysis of data, or writing of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approval for this study was obtained from the Austin Health Human Research Ethics Committee, the US Human Subjects Research Protection Office of the US Army Medical Research and Material Command, and the Australian Department of Veterans Affairs Ethics Committee. All participants provided consent prior to participating, and there were no direct incentives offered for participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Anonymized data from AIBL-VETS cohort may be shared upon request to the corresponding author from a qualified investigator, subject to restrictions according to participant consent and data protection legislation. [1]: #ref-1