Late-Life Consequences of TBI and Military Service: A Population-Based Study

People who serve in the military have specific risk of exposure to head injury or traumatic brain injury (TBI) in addition to the typical risks faced by all people. TBIs can be fatal or cause severe disability, but many people survive TBI and recover well. The long-term consequences of survived TBIs are not entirely clear. Some studies suggest an association between TBI and dementia, while others do not. Both TBI and military service may increase the risk for medical problems in late life, but other studies suggest military service can have a positive impact on health. These questions are of great importance to society at large and to the Department of Defense (DoD) in particular. As medical care has improved, many people are surviving TBI and living to older adulthood, so determining the effects of survived head injuries on the aging brain becomes incredibly relevant. This information is needed to plan service needs for the numerous Service members and civilians who sustain a TBI. To learn more, the DoD seeks projects to study the epidemiology of Alzheimer's disease (AD), other dementias, and long-term health problems associated with TBI and military service.

We propose to address these important questions using data from the already-established Adult Changes of Thought (ACT) study. ACT is a prospective cohort study of older adults enrolled from Group Health, a Seattle area integrated health delivery system, who are followed over time to characterize their health and functioning, and also to identify incident cases of dementia, AD, and AD-related dementias (ADRD). We have decades of medical records and pharmacy data, plus neurocognitive and behavioral data collected at every biannual study visit. Many of ACT's participants have genome-wide genetic data available, and some also have neuroimaging data available. ACT participants can choose to participate in brain donation, and about one-third of participants have consented. The study has completed over 650 autopsies to date. In preparation for this proposal, we began asking detailed questions about lifetime history of TBI and other head trauma exposures, duration and branch(es) of military service, rank, and combat exposure. These new data suggest that 64% of ACT's 2,500 males (and 26% of the full cohort) served in the military. Over 46% of males (and 33% of the full cohort) sustained a TBI at some point in their lives. We have not been able to use these new data on military service or TBI history in any prior analyses.

The goal of our project is to study the late-life health associations of TBI and military service by using detailed data already available from a large-scale population-based longitudinal research study of Veterans and civilians. Our proposal addresses the hypothesis that TBI and military service have independent and joint effects on AD and other dementias, late-life cognition, medical health, functional independence, and mood.

We propose the following specific aims to address this hypothesis:

Aim 1: We will determine the impact of TBI and military service on clinical and pathological AD/ADRD outcomes. (a) We will test the hypothesis that TBI and military service are independently and jointly associated with risk for clinical AD, dementia, and Parkinson's disease. (b) We will use autopsy data to determine associations of TBI and military service with pathological markers of dementia. Certain proteins found in brain tissue are often considered a 'gold standard' for diagnosing specific types of dementia (such as AD or chronic traumatic encephalopathy [CTE]) and other aging-related brain changes. We will look at a wide variety of these markers (such as beta-amyloid, tau, alpha-synuclein, microinfarcts, and atrophy) and determine whether they are associated with TBI and military service.

Aim 2: We will determine the impact of TBI and military service on late-life cognitive, medical, functional, and emotional health. We will test the hypothesis that TBI and military service lead to faster cognitive decline, chronic disease comorbidity, functional decline, depression, and mood symptoms. We will use data gathered at ACT study visits to examine changes in these outcomes over time.

Aim 3: We will characterize clinical symptom profiles of individuals with and without TBI and military service. We will test the hypothesis that post-TBI and post-military service aging has features that are different from aging in people who did not serve or sustain a TBI. Our previous work suggests people aging with TBI have unique symptoms, and better understanding this will allow for more accurate diagnoses for people aging after TBI and military service.

Our project team will use rich data resources to significantly advance scientific knowledge about the impact of TBI and military service on aging in the U.S. Our investigations will allow us to better understand why some individuals have problems as they age while others do not. This information can inform care needs and treatments to benefit military, Veteran, and civilian communities.