Effect of prior traumatic brain injury on Alzheimer's disease blood biomarkers in Vietnam Veterans

ImportanceTraumatic brain injury (TBI) is a risk factor for dementia and is known to impact levels of several Alzheimers disease (AD) blood biomarkers. Plasma pTau217/ A{beta}42 ratio has been reported to be 90% accurate for detection of brain amyloid in civilian cohorts. ObjectiveTo evaluate the accuracy of emerging AD blood biomarkers in Veterans with and without TBI history. DesignWe assessed the performance of the FDA-approved plasma pTau217/A{beta}42 ratio and plasma levels of pTau217 and A{beta}42/40 ratio for detecting brain amyloid-{beta} positivity (e.g., amyloid-PET consensus visual read). We compared biomarkers accuracy in Veterans with no TBI (N=93), TBI with loss of consciousness (LOC) 0-5 minutes (N=89), and TBI with LOC >5 minutes (N=90). SettingCross-sectional cohort study using existing data and banked plasma from the Alzheimers Disease Neuroimaging Initiative Department of Defense (ADNI-DOD) study. Participants272 older Vietnam Veterans without dementia (83% cognitively unimpaired, 17% mild cognitive impairment), median (IQR) age 69 (67,72) years, 270/272 male, who had amyloid-PET and concurrently collected banked plasma available for analysis. ResultsAmyloid-PET positivity prevalence was 30.5%. Plasma pTau217/A{beta}42 ratio was highly accurate (90%) in Veterans with no TBI, but not in Veterans with TBI with LOC 0-5 minutes (78% accuracy, P=0.027 vs no TBI) nor in Veterans with TBI with LOC>5 minutes (63% accuracy, P<0.001 vs no TBI). Results were similar for plasma pTau217 alone and plasma A{beta}42/40 ratio. Results were also similar after excluding Veterans with TBI within the past 10 years, or when amyloid-PET positivity was defined using a quantitative threshold rather than consensus visual read. DiscussionPrior TBI is a modifier of AD biomarkers accuracy in prediction of brain amyloid-PET positivity. Caution is advised in interpreting AD blood test results in this context. Further research is warranted to refine precision AD diagnosis in Veterans and civilians with TBI history. Key points QuestionWhat is the accuracy of the plasma pTau217/A{beta}42 ratio test for detecting amyloid-PET positivity for Alzheimers disease (AD) diagnosis in older Veterans with and without a history of traumatic brain injury (TBI)? FindingsIn this cross-sectional study (n=272), plasma pTau217/A{beta}42 ratio test accuracy was 90% in Veterans without TBI history, but was significantly lower (63-78% accuracy) in Veterans with TBI history, with lowest accuracy in those with greater TBI severity. MeaningTBI history and severity is a modifier of AD blood test accuracy in prediction of brain amyloid-PET positivity.AD blood tests should be interpreted with caution in Veterans and civilians with TBI history.