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 Alzheimers disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 NIA-AA research framework1, 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 (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 {beta}-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. {beta}-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 {beta}-amyloid or tau levels or 18F-FDG uptake between the TBI and control groups before and after controlling for covariates. The {beta}-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.