Neurotrauma Biomarker Levels and Adverse Symptoms Among Military and Law Enforcement Personnel Exposed to Occupational Overpressure Without Diagnosed Traumatic Brain Injury

Abstract

This cohort study evaluates associations between exposure to low-level overpressure, elevated serum levels of neurotrauma biomarkers, and concussion-like symptoms in military and law enforcement personnel without a diagnosed traumatic brain injury.

Key Points

Question

Are neurotrauma biomarkers associated with adverse symptoms reported by military and law enforcement personnel exposed to low-level overpressure, an excess of normal atmospheric pressure, in the absence of a clinically defined brain injury?

Findings

In this cohort study of 106 male active-duty US Army or law enforcement personnel exposed to low-level atmospheric overpressure and 30 control individuals, serum levels of ubiquitin carboxyl hydrolase (UCH)–L1, tau, amyloid β (Aβ)–40, and Aβ-42 were elevated in personnel exposed to overpressure compared with control individuals; Aβ-42 was associated with self-reported ear ringing and memory problems.

Meaning

The findings suggest that elevated levels of neurotrauma biomarkers are associated with overpressure exposure and concussion-like symptoms among active-duty military and law enforcement personnel who are outwardly healthy and cleared to perform duties.

Abstract

Importance

There is a scientific and operational need to define objective measures of exposure to low-level overpressure (LLOP) and concussion-like symptoms among persons with specialized occupations.

Objective

To evaluate serum levels of neurotrauma biomarkers and their association with concussion-like symptoms reported by LLOP-exposed military and law enforcement personnel who are outwardly healthy and cleared to perform duties.

Design, Setting, and Participants

This retrospective cohort study, conducted from January 23, 2017, to October 21, 2019, used serum samples and survey data collected from healthy, male, active-duty military and law enforcement personnel assigned to operational training at 4 US Department of Defense and civilian law enforcement training sites. Personnel aged 18 years or older with prior LLOP exposure but no diagnosed traumatic brain injury or with acute blast exposure during sampling participated in the study. Serum samples from 30 control individuals were obtained from a commercial vendor.

Main Outcomes and Measures

Serum levels of glial fibrillary acidic protein, ubiquitin carboxyl hydrolase (UCH)-L1, neurofilament light chain, tau, amyloid β (Aβ)-40, and Aβ-42 from a random sample (30 participants) of the LLOP-exposed cohort were compared with those of 30 age-matched controls. Associations between biomarker levels and self-reported symptoms or operational demographics in the remainder of the study cohort (76 participants) were assessed using generalized linear modeling or Spearman correlations with age as a covariate.

Results

Among the 30 randomly sampled participants (mean [SD] age, 32 [7.75] years), serum levels of UCH-L1 (mean difference, 4.92; 95% CI, 0.71-9.14), tau (mean difference, 0.16; 95% CI, −0.06 to 0.39), Aβ-40 (mean difference, 138.44; 95% CI, 116.32-160.56), and Aβ-42 (mean difference, 4.97; 95% CI, 4.10-5.83) were elevated compared with those in controls. Among the remaining cohort of 76 participants (mean [SD] age, 34 [7.43] years), ear ringing was reported by 44 (58%) and memory or sleep problems were reported by 24 (32%) and 20 (26%), respectively. A total of 26 participants (34%) reported prior concussion. Amyloid β-42 levels were associated with ear ringing ( F _1,72 = 7.40; P = .008) and memory problems ( F _1,72 = 9.20; P = .003).

Conclusions and Relevance

The findings suggest that long-term LLOP exposure acquired during occupational training may be associated with serum levels of neurotrauma biomarkers. Assessment of biomarkers and concussion-like symptoms among personnel considered healthy at the time of sampling may be useful for military occupational medicine risk management.