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

被引:34
作者
Boutte, Angela M. [1 ]
Thangavelu, Bharani [1 ]
Nemes, Jeffrey [2 ]
LaValle, Christina R. [2 ]
Egnoto, Mike [2 ]
Carr, Walter [2 ]
Kamimori, Gary H. [2 ]
机构
[1] Walter Reed Army Inst Res, Brain Trauma Neuroprotect Branch, Ctr Mil Psychiat & Neurosci, 503 Robert Grant Ave, Silver Spring, MD 20901 USA
[2] Walter Reed Army Inst Res, Blast Induced Neurotrauma Branch, Ctr Mil Psychiat & Neurosci, Silver Spring, MD USA
关键词
NEUROFILAMENT LIGHT PROTEIN; BLAST EXPOSURE; NEUROCOGNITIVE PERFORMANCE; PLASMA; TAU;
D O I
10.1001/jamanetworkopen.2021.6445
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 beta (A beta)-40, and A beta-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), A beta-40 (mean difference, 138.44; 95% CI, 116.32-160.56), and A beta-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 beta-42 levels were associated with ear ringing (F-1,F-72 = 7.40; P = .008) and memory problems (F-1,F-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.
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页数:10
相关论文
共 46 条
[21]   Neurocognitive Performance Deficits Related to Immediate and Acute Blast Overpressure Exposure [J].
LaValle, Christina R. ;
Carr, Walter S. ;
Egnoto, Michael J. ;
Misistia, Anthony C. ;
Salib, Jonathan E. ;
Ramos, Alejandro N. ;
Kamimori, Gary H. .
FRONTIERS IN NEUROLOGY, 2019, 10
[22]   Active duty service members who sustain a traumatic brain injury have chronically elevated peripheral concentrations of A40 and lower ratios of A42/40 [J].
Lejbman, Natasha ;
Olivera, Anlys ;
Heinzelmann, Morgan ;
Feng, Rebekah ;
Yun, Sijung ;
Kim, Hyung-Suk ;
Gill, Jessica .
BRAIN INJURY, 2016, 30 (12) :1436-1441
[23]   Serum Neurofilament Light Protein as a Marker for Diffuse Axonal Injury: Results from a Case Series Study [J].
Ljungqvist, Johan ;
Zetterberg, Henrik ;
Mitsis, Marios ;
Blennow, Kaj ;
Skoglund, Thomas .
JOURNAL OF NEUROTRAUMA, 2017, 34 (05) :1124-1127
[24]   Functional and Molecular Correlates after Single and Repeated Rat Closed-Head Concussion: Indices of Vulnerability after Brain Injury [J].
Mountney, Andrea ;
Boutte, Angela M. ;
Cartagena, Casandra M. ;
Flerlage, William F. ;
Johnson, Wyane D. ;
Rho, Chanyang ;
Lu, Xi-Chu ;
Yarnell, Angela ;
Marcsisin, Sean ;
Sousa, Jason ;
Chau Vuong ;
Zottig, Victor ;
Leung, Lai-Yee ;
Deng-Bryant, Ying ;
Gilsdorf, Janice ;
Tortella, Frank C. ;
Shear, Deborah A. .
JOURNAL OF NEUROTRAUMA, 2017, 34 (19) :2768-2789
[25]   Alzheimer's disease as oligomeropathy [J].
Ono, Kenjiro .
NEUROCHEMISTRY INTERNATIONAL, 2018, 119 :57-70
[26]   Expression and function of APP and its metabolites outside the central nervous system [J].
Puig, Kendra L. ;
Combs, Colin K. .
EXPERIMENTAL GERONTOLOGY, 2013, 48 (07) :608-611
[27]   Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease [J].
Roher, Alex E. ;
Esh, Chera L. ;
Kokjohn, Tyler A. ;
Castano, Eduardo M. ;
Van Vickle, Gregory D. ;
Kalback, Walter M. ;
Patton, R. Lyle ;
Luehrs, Dean C. ;
Daugs, Ian D. ;
Kuo, Yu-Min ;
Emmerling, Mark R. ;
Soares, Holly ;
Quinn, Joseph F. ;
Kaye, Jeffrey ;
Connor, Donald J. ;
Silverberg, Nina B. ;
Adler, Charles H. ;
Seward, James D. ;
Beach, Thomas G. ;
Sabbagh, Marwan N. .
ALZHEIMERS & DEMENTIA, 2009, 5 (01) :18-29
[28]   The Role of Very Low Level Blast Overpressure in Symptomatology [J].
Sajja, Venkata Siva Sai Sujith ;
LaValle, Christina ;
Salib, Jonathan E. ;
Misistia, Anthony C. ;
Ghebremedhin, Meron Y. ;
Ramos, Alejandro N. ;
Egnoto, Michael Joseph ;
Long, Joseph B. ;
Kamimori, Gary H. .
FRONTIERS IN NEUROLOGY, 2019, 10
[29]   Neurofilament light as a biomarker in traumatic brain injury [J].
Shahim, Pashtun ;
Politis, Adam ;
van der Merwe, Andre ;
Moore, Brian ;
Chou, Yi-Yu ;
Pham, Dzung L. ;
Butman, John A. ;
Diaz-Arrastia, Ramon ;
Gill, Jessica M. ;
Brody, David L. ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Chan, Leighton .
NEUROLOGY, 2020, 95 (06) :E610-E622
[30]   Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI [J].
Shahim, Pashtun ;
Politis, Adam ;
van der Merwe, Andre ;
Moore, Brian ;
Ekanayake, Vindhya ;
Lippa, Sara M. ;
Chou, Yi-Yu ;
Pham, Dzung L. ;
Butman, John A. ;
Diaz-Arrastia, Ramon ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Gill, Jessica M. ;
Brody, David L. ;
Chan, Leighton .
NEUROLOGY, 2020, 95 (06) :E623-E636