Department of Defense Alzheimer s Disease Blood-Testing Initiative (DOD-ADBI): A Study to Accelerate Blood-Based Diagnosis of Alzheimer s in Veterans
Abstract
Background: With the recent U.S. Food and Drug Administration (FDA) approval of Aducanumab, a new drug for Alzheimer’s disease (AD), the treatments for this disease have a entered new era in which brain scans and blood tests will be used to decide who gets what medicines, and whether or not the medicines are working. FDA approval of other similar drugs is expected soon. Screening patients for the abnormal proteins associated with AD such as amyloid and tau will inform allocation of these costly new drugs. Current gold standard tests for diagnosing AD require spinal taps or expensive brain imaging studies, which can only be performed as specialized centers. These tests will not be feasible for community-based screening in the primary care clinics where Veterans with AD often present first. New blood tests may be important for screening for and diagnosing AD. Unfortunately, prior studies of accuracy of these blood tests were done in non-Veterans. Traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), and cerebral small vessel disease (CSVD) are common in Veterans and may decrease accuracy of blood tests for AD. While these military-relevant exposures (MREs) are associated with increased risk for dementia, the clinical and pathological features are more consistent with diseases other than AD. For example, the major finding of the Department of Defense (DoD) Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) study in Vietnam Veterans is that TBI and PTSD are associated with high rates of cognitive impairment but are not associated with AD biomarkers in spinal tap tests or brain scans. It is unknown whether or how these highly prevalent MREs will effect blood tests for AD diagnosis in Veterans. Because AD in Veterans is often atypical, it is also unclear which Veterans should be prioritized for AD biomarker testing in the first place. Goals: To address these gaps, we will validate accuracy of leading AD blood tests in Veterans and determine whether MREs impact accuracy of these tests. We will cost-efficiently leverage and extend the prior DoD-ADNI study, led by Dr. Weiner (co-investigator on this proposal), which collected brain scans and blood on 280 Vietnam Veterans with normal cognition (80%) and mild cognitive impairment (MCI). To expand generalizability to more symptomatic Veterans, we will also recruit 100 Veterans with MCI and mild dementia from two Department of Veterans Affairs (VA) Memory Clinics. Both cohorts will have high rates of prior TBI, PTSD, and CSVD. We hypothesize that C2N’s FDA-approved PrecivityAD™ test will be very accurate for diagnosing AD (e.g., identifying a positive amyloid-PET positron emission tomography scan) in Veterans, regardless of military relevant exposures. We hypothesize that some p-tau tests will accurately diagnose AD in some Veterans, but will be less accurate in Veterans with a high burden of CSVD or multiple or severe TBIs, given evidence that CSVD and repetitive/severe TBI is associated with brain tau independent of AD pathology. We hypothesize that Veterans who are older, have more memory impairment, and have less PTSD symptoms will be more likely to have signs of AD on PET scan. Aim 1–DoD Alzheimer’s Disease Blood-testing Initiative (DoD-ADBI) Cohort: Assemble a new cohort of 100 Veterans with MCI and mild dementia who will undergo brain scans and blood-draw. Aim 2–Validation of AD blood tests in Vietnam Veterans with mostly normal cognition (N=280): 2a: Determine accuracy of all of the leading commercially available blood tests for detecting AD-associated proteins (amyloid and tau) in DoD-ADNI cohort using brain scans as gold standards. 2b: Assess for interaction with TBI, PTSD, and CSVD. Aim 3–Validation of AD blood tests in all-era Veterans with normal cognition, MCI, and mild dementia (N=380): 3a: Determine accuracy of Aim 2 blood biomarkers for detecting AD-associated proteins in combined DoD-ADNI+DoD-ADBI cohort using brain scans as gold
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211081
Entities
People
- Raquel C Gardner
Organizations
- United States Army