Tau, beta-Amyloid, and Glucose Metabolism Following Service-Related Traumatic Brain Injury in Vietnam War Veterans: The Australian Imaging Biomarkers and Lifestyle Study of Aging-Veterans Study (AIBL-VETS)

Traumatic brain injury (TBI) is common among 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 National Institute on Aging - Alzheimer's Association (NIA-AA) research framework, by measuring tau, beta-amyloid, and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI. Seventy male Vietnam war veterans-40 with TBI (age 68.0 +/- 2.5 years) and 30 controls (age 70.1 +/- 5.3 years)-with no prior diagnosis of dementia or mild cognitive impairment underwent beta-amyloid (F-18-Florbetaben), tau (F-18-Flortaucipir), and fluorodeoxyglucose (F-18-FDG) PET. The TBI cohort included 15 participants with mild, 16 with moderate, and nine with severe injury. beta-Amyloid level was calculated using the Centiloid (CL) method and tau was measured by standardized uptake value ratios (SUVRs) 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 Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DOD ADNI) study. There were no significant nor trending differences in beta-amyloid or tau levels or F-18-FDG uptake between the TBI and control groups before and after controlling for covariates. The beta-amyloid and tau findings were replicated in the DOD ADNI validation cohort and persisted when the Australian Imaging Biomarkers and Lifestyle study of aging-Veterans study (AIBL-VETS) and DOD ADNI cohorts were combined (114 TBI vs. 87 controls in total). In conclusion, no increase in the later life accumulation of the neuropathological markers of AD in veterans with a remote history of TBI was identified.

Automated summary

This case control study used positron emission tomography (PET) to investigate the risk of Alzheimer's disease (AD) in veterans with traumatic brain injury (TBI). The results showed no significant differences in beta-amyloid, tau, or brain metabolism between the TBI and control groups. These findings were validated in other independent cohorts. Therefore, it can be concluded that there is no increase in neuropathological markers of AD in veterans with a history of TBI.