Brain Amyloid Seen in Young Men With Subconcussive Trauma

Early brain amyloid accumulation was found in otherwise healthy young men exposed to repetitive subconcussive blast injuries, a pilot study showed.

Military instructors routinely exposed to repeated blast events had significantly increased amyloid-beta deposition in four brain regions -- the inferomedial frontal lobe (P=0.004), precuneus (P=0.02), anterior cingulum (P=0.002), and superior parietal lobule (P=0.003) -- compared with controls, reported Carlos Leiva-Salinas, MD, PhD, MBA, of the University of Missouri School of Medicine in Columbia, and co-authors.

Discriminant analysis based on regional amyloid PET changes over time correctly identified all the control participants and 78% of military instructors exposed to subconcussive blasts, the researchers wrote in Radiology.

"Amyloid-beta is a molecule not normally found in the brains of young patients," Leiva-Salinas said in a statement.

"Further research needs to be done to establish the relationship between the frequency and the severity of traumatic brain injury and the degree of amyloid changes in the brain, the natural course of the observed accumulation, and other potential biologic risk factors for amyloid plaque deposition and the development of cognitive decline," he added.

Pathologic evidence of chronic traumatic encephalopathy (CTE) has been identified in deceased military veterans and civilians after recurrent head trauma, but how CTE occurs is not fully understood. Repetitive head trauma, including indirect impact from military blasts or direct hits from contact sports like American football, have been linked with CTE.

Brain scans have identified tau in CTE regions in former National Football League players, but have not shown amyloid. PET could be used to identify early-stage amyloid accumulation in people exposed to mild brain trauma and may shed light on mechanisms causing CTE, Leiva-Salinas and colleagues suggested.

The researchers evaluated nine military grenade or breacher instructors at Fort Leonard Wood Military Base in Missouri from January 2020 to December 2021. They also assessed nine age-matched healthy civilians as controls. All participants had no previous history of concussion.

The median age in both groups was 33. PET exams were performed with florbetapir F 18 (Amyvid) injection.

Participants were evaluated at baseline, then 5 months later. During that period, the military instructors recorded the number of breacher or demolition events and blasts they were exposed to, including fire weapons.

The median number of overall blast events was 54 and the median number of breacher blasts was 54. Military participants reported no concussions or loss of consciousness in their exposure logs.

None of the controls showed abnormal amyloid accumulation at any time point. However, the blast-exposed participants showed evidence of amyloid deposition in follow-up imaging, most frequently in the superior parietal lobules and precuneus but also in the cingulum, paracentral lobules, and anteromesial temporal and occipital lobes.

Six of the nine blast-exposed participants (67%) had abnormal amyloid uptake in one or more anatomic locations from baseline. Three had one brain region with increased amyloid uptake, two had two brain regions, and one had three brain regions. No correlation emerged between amyloid deposition and the number of overall or breacher blast events.

An obvious limitation of the study is its small sample size, noted Sven Haller, MD, MSc, of the Centre d'Imagerie Médicale de Cornavin in Geneva, Switzerland, in an accompanying editorial but "the observation of an obvious and important effect despite the small sample sizes" underlines the sensitivity of these scans, he pointed out.

"Although we do not yet know how to handle the clinical information of early amyloid accumulation in the brain, a better understanding of this mechanism is fundamental and could serve to hopefully develop preventive and therapeutic strategies in the future," Haller wrote.

"Additionally, this method may likely be applicable to other situations with subconcussive head trauma, including various contact sports (e.g., American football, ice hockey) or other professional exposure (e.g., mine workers, heavy equipment operators)," he added.

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