research psychologist Walter Reed Army Institute of Research
Abstract Text: People serving in a variety of military occupational specialties operate and train with heavy weapons and explosives and are, consequently, exposed to repeated blast overpressure. Apart from rare mishaps, this routine occupational exposure to overpressure does not result in diagnosed injury to the brain but has been suspected to result in symptomology similar to concussion (e.g., headache, dizziness). In a series of studies conducted by Walter Reed Army Institute of Research (WRAIR) and collaborators, overpressure exposures have been measured for individuals during military training and then compared to concurrent measures of behavior and physiology. Associations between exposure and effects have been found and the study reported here is an exposition of findings from recently collected data and a comparison of behavioral and neurophysiological measures of effects.
A core behavioral measure in these studies is self-reported symptomology, either reported passively or reported in response to physical challenge, such as after subjects move their eyes left and right several times. A core physiological measure is peripheral blood draw and assay for proteomic biomarkers of neurotrauma, such as amyloid beta peptides (Aβ-40, Aβ-42). Behavioral and physiological measures have been observed to increase following occupational exposure to overpressure but not always in concert with each other. We report our observations of post-exposure changes in physical challenge-elicited symptoms, Aβ-40 concentrations, and Aβ-42/Aβ-40 ratio following exposure to repeated heavy weapons fires with particularly long duration overpressure phase.
In the first of three study evolutions, fourteen military service members completed research measures in the morning of a training day, were measured for overpressure exposure during training, and then completed parallel research measures at the end of the day. Blood samples were assayed for Aβ-40 and Aβ-42. Cumulative overpressure impulse exposures were calculated to range from 148 psi*ms to 590 psi*ms, symptomology increased by a mean of 2.6 symptoms (t(13)=3.45, p<.01), and Aβ-40 increased in concentration by a mean of 25.9 pg/mL (t(13)=2.60, p=.02). In consideration of the strength of association between overpressure exposure and symptom reporting change or Aβ-40 concentration change, we observed Aβ-40 concentration to be more consistently associated with overpressure magnitude (r=.60, p=.02) than was symptom reporting (r=.50, p=.10). The two overpressure effect measures tended to correlate with each other but did not meet statistical criterion in this small sample (r=.52, p=.06).
We examined also the Aβ-42/Aβ-40 ratio following exposure, given that this ratio has been shown to reflect greater amyloid cortical burden, cognitive decline, and risk of Alzheimer’s disease dementia. We found an association between overpressure exposure magnitude and Aβ-42/Aβ-40 ratio (r=-.55, p=.04) consistent with increased risk.
It may be of use to identify an acute exposure threshold associated with neurotrauma risk. In the present case, acute cumulative impulse exposures greater than 350 psi*ms (n=5) all resulted in Aβ-40 concentration increase, whereas lower magnitude exposures were less consistent with Aβ-40 concentration increase. However, if risk is better indicated by Aβ-42/Aβ-40 ratio, then an acute cumulative impulse exposure threshold in the range of 400-500 psi*ms might be more appropriate, as one individual with an exposure of 354 psi*ms showed the Aβ-42/Aβ-40 ratio suggesting the least risk in the overall sample, while the three individuals with Aβ-42/Aβ-40 ratios suggesting the most risk were all exposed to cumulative impulse at magnitudes greater than 500 psi*ms.
In sum, in this first dataset, the physiological marker of neurotrauma seems to be more closely associated with acute overpressure exposure than the behavioral measure and may be a better indicant of risk to brain health. This finding will need to be compared to other data sets already collected by WRAIR. If the pattern bears out, the Department of Defense may be able to use a bioassay in conjunction with overpressure exposure monitoring to manage neurotrauma risk among its populations with occupational overpressure exposure. We do not yet know what feature (or features) of overpressure exposure (e.g., peak, impulse, number, positive phase duration) is most responsible for driving amyloid beta increase, but identifying that relation is a goal of the research program at WRAIR.