Relationship Between Alzheimer’s Disease Risk Score and Outcomes of Mild Repetitive Neurotrauma

Conceptualization of the causal mechanisms of Alzheimer’s Disease (AD) acknowledges the importance of interactions between biological, genetic, and environmental risk factors, including exposure to neurotrauma, as well as the recognition that the neuropathological processes of AD start several decades prior to obvious clinical manifestations of the illness (“preclinical AD”). Moderate and severe traumatic brain injury (TBI) is a known risk factor for AD, but it is unclear if this holds true for milder forms of TBI (mTBI or concussion) and repetitive head impact exposure (RHIE) encountered in contact/collision sports and in military training or combat. Deeper understanding of this relationship, and the early identification of those at greater risk for preclinical AD has become more important with the emergence of disease-modifying therapies. The Concussion Assessment, Research, and Education (CARE) Consortium effort, with its large, diverse, richly characterized cohort of participants, provides a unique opportunity to detect the earliest possible signals of AD in individuals exposed to neurotrauma. The overarching goal of this project is to characterize the relationship between degree of exposure to concussion, RHIE, known risk factors for AD, and trajectory of neurobehavioral function up to 10 years following neurotrauma exposure in military service members and former collegiate athletes. We propose to integrate neurotrauma exposure, neurocognitive, neuroimaging, proteomic, and genetic data prospectively collected from our cohort over the past decade to derive a quantitative AD Relative-risk and Resilience Scale (ADRRS) that we hypothesize will effectively classify individuals with neurocognitive and neurobehavioral features consistent with preclinical AD.