Abstract Details

Title Traumatic Brain Injury Warfighters with Poor Sleep have Increased Plasma Biomarkers of Neurodegeneration

Topic Sleep

Presentation(s) P1 - Poster Session 1 (12:00 PM-1:00 PM)

Poster/Presentation
Number 5-008

Objective We hypothesized that warfighters with traumatic brain injury (TBI) and comorbid sleep dysfunction would have increased evidence of neuronal injury, revealing a potential mechanistic connection between TBI-related sleep disorders and neurodegeneration . We measured plasma biomarkers and surveyed sleep dysfunction in addition to basic demographics for analysis.

Background Increasing evidence links neurodegeneration to TBI, and a separate body of literature links neurodegeneration to sleep dysfunction, implicating increased toxin production and decreased glymphatic clearance. Comorbid sleep disorders affect 40-70% of TBI patients, yet the sleep-neurodegeneration connection in these patients remains unexplored.

Design/Methods A retrospective cross-sectional review of warfighters from the in the Chronic Effects of Neurotrauma Consortium (n=113 chronic mild TBI patients) were administered the Pittsburgh sleep quality index (PSQI) and we compared it with measurements of Aβ42, NFL, tau, and phospho-tau (threonine 181) isolated from plasma and exosomes. Exosome isolation was achieved via precipitation from plasma. Protein quantification was achieved with the Single Molecule Array (Quanterix). Generalized linear models were constructed with gaussian distributions and were adjusted for age, ApoE, and number of TBIs.

Results Poor sleepers with TBI (PSQI>8) had elevated NFL compared to good sleepers both from plasma (p=0.007) or exosomes (p=0.00017), and PSQI strongly correlated with NFL (plasma: Beta=0.23, p=0.0079; exosomes: Beta=2.19, p=0.0013). Plasma total tau and Aβ42 also correlated with PSQI (Beta=0.64, p=0.028, and Beta=0.40, p=0.049 respectively), but phospho-tau did not correlate significantly after controlling for the variables noted above.

Conclusions

This is the first data correlating markers of neuronal injury with subjective sleep dysfunction in warfighters with TBI. PSQI predicts biomarker levels in a mild TBI population of warfighters, possibly implicating sleep as a pathophysiological mediator of the neurodegeneration associated with TBI. Cross sectional studies cannot prove directionality, and prospective trials will be required to further explore our proposed hypothesis and may guide targeted therapeutic development.

Authors/Disclosures
J. Kent Werner, Jr., MD, PhD (Uniformed Services University) PRESENTER	Dr. Werner has received personal compensation for serving as an employee of Cogentis Therapeutics. Dr. Werner has stock in Cogentis Therapeutics. Dr. Werner has received intellectual property interests from a discovery or technology relating to health care. Dr. Werner has received intellectual property interests from a discovery or technology relating to health care. Dr. Werner has received personal compensation in the range of $100,000-$499,999 for serving as a Neurologist with United States Navy. Dr. Werner has received personal compensation in the range of $50,000-$99,999 for serving as a CEO / CoFounder with Cogentis Therapeutics.
Pashtun-Poh Shahim, MD, PhD	Pashtun-Poh Shahim has nothing to disclose.
	No disclosure on file
	No disclosure on file
Kimbra L. Kenney, MD, FAAN	Dr. Kenney has nothing to disclose.