β-Amyloid and Tau Imaging in Chronic Traumatic Brain Injury

Background and Objectives Traumatic brain injury (TBI) has been promoted as a risk factor for Alzheimer disease (AD). There is evidence of elevated β-amyloid (Aβ) and tau, the pathologic hallmarks of AD, immediately following TBI. It is not clear whether Aβ and tau remain elevated in the chronic period. To address this issue, we assessed Aβ and tau burden in long-term TBI survivors and healthy controls using PET imaging.

Methods Using a cross-sectional design, we recruited individuals following a single moderate to severe TBI at least 10 years previously from an inpatient rehabilitation program. A demographically similar healthy control group was recruited from the community. PET data were acquired using ¹⁸F-NAV4694 (Aβ) and ¹⁸F-MK6240 (tau) tracers. Aβ deposition was quantified using the Centiloid scale. Tau deposition was quantified using the standardized uptake value ratio (SUVR) in 4 regions of interest (ROIs). As a secondary measure, PET scans were also visually read as positive or negative. We examined PET data in relation to time since injury and age at injury. PET data were analyzed in a series of regression analyses.

Results The sample comprised 87 individuals with TBI (71.3% male; 28.7% female; mean 57.53 years, SD 11.53) and 59 controls (59.3% male; 40.7% female; mean 60.34 years, SD 11.97). Individuals with TBI did not have significantly higher ¹⁸F-NAV4694 Centiloid values (p = 0.067) or ¹⁸F-MK6240 tau SUVRs in any ROI (p ≤ 0.001; SUVR greater for controls). Visual assessment was consistent with the quantification; individuals with TBI were not more likely than controls to have a positive Aβ (p = 0.505) or tau scan (p = 0.221). No associations were identified for Aβ or tau burden with time since injury (p = 0.057 to 0.332) or age at injury.

Discussion A single moderate to severe TBI was not associated with higher burden of Aβ or tau pathologies in the chronic period relative to healthy controls. Aβ and tau burden did not show a significant increase with years since injury, and burden did not appear to be greater for those who were older at the time of injury.