Novel Imaging and Proteomic Markers as Predictors of Cognitive Status in at-Risk Veterans with Mild TBI Histories
Abstract
Background: Many people with histories of mild traumatic brain injury (mTBI) have long-lasting negative effects such as memory problems, brain changes seen on magnetic resonance imaging (MRI), and poor quality of life. A lot of studies have shown that people with mTBI histories have higher odds of having cognitive problems when they are older. Some data has shown that people who have had TBIs in the past—even mild head injuries dating as far back as childhood—are more at risk for dementia such as Alzheimer’s disease (AD), a disease that slowly kills brain cells where information is stored. AD is a medical condition that leads to severe memory loss, which is challenging not only for the patient but also for the families and caregivers of affected people. More recently, researchers have been interested in understanding why some people with TBI histories have worse outcomes later in life. Data suggests that a certain component of an important gene (apolipoprotein E) dramatically increases the odds for dementia in late life, especially in people who have had an mTBI event. Another risk factor for AD is whether someone has experienced more than one TBI in their lifetime. Indeed, studies show that people with repeated TBI tend to fare worse cognitively, and some studies show greater changes in the brain as well as even higher rates of neurological disorders like AD in late life. Unfortunately, many challenges remain in terms of accurate detection and diagnosis of mTBI, and our understanding of what happens in the brain—and how such changes may hasten or accelerate brain and cognitive changes in aging—is not well understood. More research looking at older adults with TBI histories is very much needed, especially since memory problems caused by TBI might not become obvious until someone is older. Objectives: There has been a lot of interest in blood flow in the brain as well as changes to the white matter, which has often been described as the “freeway” by which different brain regions communicate with each other. There is evidence that changes to brain blood flow and white matter may represent the earliest changes to occur in AD. At the same time, much of our work (and that of others) has shown that these brain changes are often seen after mTBI. What we hope to do with our research is focus in on those brain regions that we know are vulnerable to both TBI and early AD. These regions are seen in certain parts of the brain called the medial temporal lobe as well as the inferior parietal lobe. These areas of the brain take the hardest hits when the head is impacted by injury, and many autopsy and MRI studies have shown that AD brain changes begin in these areas, which is why they are often called “predilection sites.” We will use sophisticated, newer brain MRI tools and methods (arterial spin labeling [ASL] to examine brain blood flow, and diffusion tensor imaging [DTI] to examine white matter integrity), and then we will see whether brain changes using these tools can be mapped onto memory problems and other changes in cognition like processing speed. Major goals of this proposal are to see what the effects of repeated TBI and genetic risk are in our participants with and without TBI histories. An exciting aspect of our study that our exploratory aim, which will look at certain biomarkers in the blood of our participants, is very new and sophisticated. These markers are significant because they have been shown to be important predictors of AD, and newer work has begun to show that they may be very critical in TBI, as well. Rather than just looking at how much of these proteins are circulating in the blood at any one point in time, we are proposing to look at the exosomes that release different chemicals into the blood. Exosomes used to be thought of as just small sacs that get tossed from cells, but research has now shown that they are involved in health and disease. Exosomes are implicated in spreading diseases, including cancer
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110552
Entities
People
- Lisa Delano-wood
Organizations
- United States Army
- Veterans Medical Research Foundation of San Diego