021 Poor sleep quality in traumatic brain injury patients is associated with elevated inflammatory biomarkers

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A10-A10
Author(s):  
Josephine Pucci ◽  
Sara Mithani ◽  
Jacqueline Leete ◽  
Chen Lai ◽  
Kimbra Kenney ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Protein Quantification ◽  
Model Systems ◽  
Inflammatory Biomarkers ◽  
Poor Sleep ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Cross Sectional

Abstract Introduction Mild traumatic brain injury (mTBI) and sleep disorders are independently associated with inflammation. Following mTBI, elevated levels of cytokines, such as interleukin-6 (IL-6), 10 (IL-10) and tumor necrosis factor alpha (TNFα), have been observed. These signals are also known to modulate sleep homeostasis. IL-6, IL-10 and TNFα concentrations are typically measured in plasma, but recent work has shown that their measurement in extracellular vesicles (EVs) may hold additional value, as they are shielded from degradation and may be more biologically relevant. We hypothesized that inflammatory biomarkers in chronic mTBI patients would be elevated in poor sleepers. Methods In a cross-sectional cohort of warfighters (n=137 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with EV and plasma IL-6, IL-10, TNFα. Protein quantification was performed with Simoa. Two-tailed tests were used with a type I error of p<0.05. Linear models controlled for age, sex, and body mass index. Results In the mTBI cohort, poor sleepers (PSQI>=10, a published military cutoff) had elevated IL-6 vs. good sleepers (mean [SD] pg/mL, EV: 0.47 [0.63] vs 1.01 [1.54], p=0.04, d=0.44; plasma: 5.00 [13.31] vs 6.88 [13.51], p=0.03, d=0.14). Poor sleepers with mTBI had less EV IL-10 (1.71 [8.18] vs 0.30 [0.54], p=0.017). Comparisons of plasma IL-10 were not significant. No differences in TNFα were observed in mTBI groups. In our model, PSQI was the strongest predictor of EV IL-6 (βstd=0.27, p=0.03) in mTBI patients, whereas only BMI predicted IL-6 in controls. EV IL-6, IL-10, and TNFα correlated with PSQI (R=0.21, p=0.019; R=0.21, p=0.014; R=0.22, p=0.013, respectively), but these relationships were not found with plasma. In controls, no correlations or differences in any biomarker were observed between groups. Conclusion Warfighters who report poor sleep had significantly elevated inflammatory biomarkers after chronic mTBI. Cytokine levels in EVs had greater effect sizes between groups compared to plasma levels suggesting EV measurements may have improved signal. Poor sleep and its association with inflammatory cytokines after mTBI may have therapeutic implications. Support (if any) DoD: Contract W91YTZ-13-C-0015/ HT0014-19-C-0004 with VHA Central Office VA TBI Model Systems Program of Research/DHA Contracting Office (CO-NCR) HT0014

scholarly journals 0416 Poor Sleep Quality Predicts Serum Markers of Neurodegeneration and Cognitive Deficits in Warriors with Mild Traumatic Brain Injury

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A159-A159
Author(s):  
K Werner ◽  
P Shahim ◽  
J Gill ◽  
R Nakase-Richardson ◽  
K Kenney
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Sleep Disorders ◽  
Cognitive Deficits ◽  
Neuronal Injury ◽  
Small Sample ◽  
Cross Sectional ◽  
Sleep Dysfunction ◽  
Obstructive Sleep

Abstract Introduction Increasing evidence links neurodegeneration to traumatic brain injury (TBI), and a separate body of literature links neurodegeneration to sleep dysfunction, implicating increased toxin production and decreased glymphatic clearance. Sleep disorders affect 50% of TBI patients, yet the sleep-neurodegeneration connection in these patients remains unexplored. We hypothesized that warfighters with TBI and sleep dysfunction would have increased neuronal injury, revealing potential mechanistic underpinnings for TBI outcomes. We measured plasma biomarkers, cognitive function and sleep surveys for correlation analysis. Methods In a retrospective cross-sectional study of warfighters (n=113 chronic mild TBI patients), the Pittsburgh sleep quality index (PSQI) was compared with amyloid β42 (Aβ42), neurofilament light (NFL), tau, and phospho-tau (threonine 181) isolated from plasma and exosomes. Executive function was tested with the categorical fluency test. Exosomes were precipitated from plasma. Proteins were measured with the Single Molecule Array (Quanterix). Linear models were adjusted for age, ApoE, and number of TBIs. Results Poor sleepers with TBI (PSQI>8) had elevated NFL compared to good sleepers in plasma (p=0.007) and exosomes (p=0.00017), and PSQI directly correlated with NFL (plasma: Beta=0.23, p=0.0079; exosomes: Beta=2.19, p=0.0013) stronger than any other marker of neurodegeneration. Poor sleepers also showed higher obstructive sleep apnea (OSA) risk compared to good sleepers by STOP-BANG scores (3.6, SD=1.6 vs 2.8, SD=1.74; p=0.0014) as well as decreased categorical fluency (20.7, SD=4.1) (18.3, SD=4.6, p=.0067). Plasma tau and Aβ42 also correlated with PSQI (Beta=0.64, p=0.028, and Beta=0.40, p=0.049 respectively). Conclusion This is the first reported data correlating markers of neuronal injury and cognitive deficits with sleep complaints and OSA risk in patients with TBI - possibly identifying treatable pathophysiological mediators of TBI neurodegeneration. Limitations include a small sample size, lack of objective sleep measures, and inability to establish directionality due to cross-sectional design. Prospective trials will be required to further explore our proposed hypothesis. If confirmed, these findings would call for targeting sleep disorders in the TBI population to mitigate risk of neurodegeneration. Support This work was supported by grant funding from: Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095 and Department of Veterans Affairs CENC Award I01 CX001135.

scholarly journals Comprehensive insomnia assessment following mild traumatic brain injury

2021 ◽  
Author(s):  
Dora M. Zalai
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Sleep Disorders ◽  
Mild Traumatic Brain Injury ◽  
Primary Insomnia ◽  
Chronic Insomnia ◽  
Poor Sleep ◽  
Wake Time ◽  
Insomnia Symptoms

Background and Rationale: Insomnia symptoms following mild traumatic brain injury (mTBI) predict poor TBI outcomes. Insomnia symptoms may be caused by sleep disorders that can be effectively treated, which in turn, may improve mTBI outcomes. Previous studies have focused on insomnia symptom assessment in mTBI or evaluated samples with all TBI severities. To effectively manage insomnia following mTBI, it is important to understand which sleep disorders contribute to insomnia symptoms in this clinical group. Furthermore, it is important to extend research on primary insomnia to determine which variables are related to the perception of poor sleep among individuals who report new onset/worsening insomnia symptoms following mTBI. Objectives: (1) determine the prevalence of sleep disorders that contribute to chronic insomnia symptoms in patients with mTBI and (2) determine which objectively measured electroencephalographic and subjective variables are associated with subjective wake time and the perception of poor sleep among patients with chronic insomnia symptoms following mTBI. Methods: Individuals with chronic insomnia symptoms following mTBI (N = 50; age 17-65; 64% females; 3 - 24 months post mTBI) participated in a multi-method sleep and circadian assessment. Sleep disorders were diagnosed according to ICSD-3 criteria. Results: Insomnia disorder was the most common diagnosis (62%), followed by obstructive sleep apnea (OSA) -44%; circadian rhythm sleep-wake disorders (CRSWD) - 26% and periodic limb movement disorder (PLMD) - 8%. The overestimation of wake time was similar to what has been described in primary insomnia. In contrast to the REM instability hypothesis of primary insomnia, REM sleep duration was not related to subjective wake time. Both low sleep quality and feeling unrested in the morning had the strongest relationship to subjective wake time. Feeling unrested was also associated with anxiety. Conclusions: OSA and CRSWD frequently occur among patients whose main presenting sleep symptom is chronic insomnia following a mTBI. Accordingly, objective sleep and circadian assessment should be part of chronic insomnia evaluation following a mTBI. The results imply that interventions reducing subjective wake time and anxiety could improve subjective sleep quality; however, these interventions should be mplemented in conjunction with the treatment for OSA, CRSWD and PLMD.

scholarly journals Comprehensive insomnia assessment following mild traumatic brain injury

2021 ◽  
Author(s):  
Dora M. Zalai
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Sleep Disorders ◽  
Mild Traumatic Brain Injury ◽  
Primary Insomnia ◽  
Chronic Insomnia ◽  
Poor Sleep ◽  
Wake Time ◽  
Insomnia Symptoms

Background and Rationale: Insomnia symptoms following mild traumatic brain injury (mTBI) predict poor TBI outcomes. Insomnia symptoms may be caused by sleep disorders that can be effectively treated, which in turn, may improve mTBI outcomes. Previous studies have focused on insomnia symptom assessment in mTBI or evaluated samples with all TBI severities. To effectively manage insomnia following mTBI, it is important to understand which sleep disorders contribute to insomnia symptoms in this clinical group. Furthermore, it is important to extend research on primary insomnia to determine which variables are related to the perception of poor sleep among individuals who report new onset/worsening insomnia symptoms following mTBI. Objectives: (1) determine the prevalence of sleep disorders that contribute to chronic insomnia symptoms in patients with mTBI and (2) determine which objectively measured electroencephalographic and subjective variables are associated with subjective wake time and the perception of poor sleep among patients with chronic insomnia symptoms following mTBI. Methods: Individuals with chronic insomnia symptoms following mTBI (N = 50; age 17-65; 64% females; 3 - 24 months post mTBI) participated in a multi-method sleep and circadian assessment. Sleep disorders were diagnosed according to ICSD-3 criteria. Results: Insomnia disorder was the most common diagnosis (62%), followed by obstructive sleep apnea (OSA) -44%; circadian rhythm sleep-wake disorders (CRSWD) - 26% and periodic limb movement disorder (PLMD) - 8%. The overestimation of wake time was similar to what has been described in primary insomnia. In contrast to the REM instability hypothesis of primary insomnia, REM sleep duration was not related to subjective wake time. Both low sleep quality and feeling unrested in the morning had the strongest relationship to subjective wake time. Feeling unrested was also associated with anxiety. Conclusions: OSA and CRSWD frequently occur among patients whose main presenting sleep symptom is chronic insomnia following a mTBI. Accordingly, objective sleep and circadian assessment should be part of chronic insomnia evaluation following a mTBI. The results imply that interventions reducing subjective wake time and anxiety could improve subjective sleep quality; however, these interventions should be mplemented in conjunction with the treatment for OSA, CRSWD and PLMD.

scholarly journals Screening for Poor Self-Reported Sleep Quality at 12 Weeks in Post-Mild Traumatic Brain Injury Patients Using the HF–Age–Gender (HAG) Index

2021 ◽  
Vol 11 (11) ◽  
pp. 1369
Author(s):  
Hon-Ping Ma ◽  
Ju-Chi Ou ◽  
Kai-Yun Chen ◽  
Kuo-Hsing Liao ◽  
Shuo-Jhen Kang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Mild Traumatic Brain Injury ◽  
Poor Sleep ◽  
Poor Sleep Quality ◽  
Non Invasive ◽  
Patient Will ◽  
Improve Sleep Quality

To identify a screening tool for poor self-reported sleep quality at 12 weeks according to non-invasive measurements and patients’ characteristics in the first week after mild traumatic brain injury (mTBI), data from 473 mTBI participants were collected and follow-ups were performed at 12 weeks. Patients with previous poor self-reported sleep quality prior to the injury were excluded. Patients were then divided into two groups at 12 weeks according to the Pittsburgh Sleep Quality Index based on whether or not they experienced poor sleep quality. The analysis was performed on personal profiles and heart rate variability (HRV) for 1 week. After analyzing the non-invasive measurements and characteristics of mTBI patients who did not complain of poor sleep quality, several factors were found to be relevant to the delayed onset of poor sleep quality, including age, gender, and HRV measurements. The HRV–age–gender (HAG) index was proposed and found to have 100% sensitivity (cut-off, 7; specificity, 0.537) to predicting whether the patient will experience poor sleep quality after mTBI at the 12-week follow-up. The HAG index helps us to identify patients with mTBI who have no sleep quality complaints but are prone to developing poor self-reported sleep quality. Additional interventions to improve sleep quality would be important for these particular patients in the future.

Poor Sleep Quality and Changes in Objectively Recorded Sleep After Traumatic Brain Injury: A Preliminary Study

2008 ◽  
Vol 89 (5) ◽  
pp. 843-850 ◽  
Author(s):  
Diane L. Parcell ◽  
Jennie L. Ponsford ◽  
Jennifer R. Redman ◽  
Shantha M. Rajaratnam
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Poor Sleep ◽  
Poor Sleep Quality ◽  
Preliminary Study

scholarly journals 0046 Diffusion Tensor Imaging Evidence of Hypothalamic Injury in Traumatic Brain Injury Warfighters with Sleep Dysfunction

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A19-A19
Author(s):  
K Werner ◽  
B Gerstenslager ◽  
P Yeh ◽  
R Srikanchana ◽  
K Kenney ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Linear Models ◽  
Diffusion Tensor ◽  
Small Sample Size ◽  
Small Sample ◽  
Poor Sleep ◽  
Sleep Dysfunction ◽  
California Institute Of Technology

Abstract Introduction While sleep disorders occur in 40–70% of chronic traumatic brain injury (TBI) patients, the pathophysiology remains unknown. Increasingly, DTI has been used to evaluate gray matter structures, but no prior studies have evaluated hypothalamic regions in TBI. We hypothesized that TBI patients with poor sleep quality by questionnaire and/or polysomnography (PSG) may have structural injury to hypothalamic sleep circuitry and that this may be detectable by diffusion magnetic resonance imaging (dMRI). We examined diffusion tensor parameters in warfighters using dMRI within the hypothalamus of poor sleepers and compared them to good sleepers. Methods A retrospective review of 92 warfighters with blast TBI and loss of consciousness included demographics, structural MRI, dMRI, PSG and Pittsburgh Sleep Quality Index (PSQI) questionnaire. Acquisition of diffusion-weighted and structural data was performed with three Tesla MRI. Using the California Institute of Technology probabilistic high-resolution in vivo atlas as a prior, the hypothalamic nuclei were segmented by applying diffeomorphic registration of T1- and T2-weighted structural images and mapped to dMRI space. Results TBI patients within the lowest quartile of hypothalamic fractional anisotropy (FA) measures demonstrated decreased total sleep time (320 +/- 52 minutes vs. 382 +/- 19, p=0.006) on PSG and had more sleep complaints on PSQI (p=0.029) compared to those with the highest quartile of FA measures. There was no difference in BMI, age or AHI among the quartiles. Radial, mean and axial diffusivity quartiles did not carry significant differences in TST or PSQI. Linear models did not show significant correlation between any imaging parameter and sleep quality measures. Conclusion Our results reveal microstructural differences in the hypothalami of military TBI patients that may be related to clinical sleep dysfunction. Biomarkers of sleep circuitry damage may further our understanding of sleep dysfunction after TBI. Lack of correlations in linear models may be a reflection of the small sample size or a complex interaction, and removal of outliers did not change our results. Larger longitudinal studies may help clarify the association between hypothalamic and brainstem circuitry structure after TBI and sleep dysfunction. Support This work was supported by a grant 130132 from USAMRMC.

scholarly journals Poor sleep correlates with biomarkers of neurodegeneration in mild traumatic brain injury patients: a CENC Study

SLEEP ◽  
2020 ◽  
Author(s):  
J Kent Werner ◽  
Pashtun Shahim ◽  
Josephine U Pucci ◽  
Lai Chen ◽  
Sorana Raiciulescu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Executive Function ◽  
Brain Injury ◽  
Cognitive Function ◽  
Sleep Quality ◽  
Mild Traumatic Brain Injury ◽  
Poor Sleep ◽  
Neurofilament Light ◽  
Therapeutic Implications ◽  
Obstructive Sleep

Abstract Study Objectives Sleep disorders affect over half of mild traumatic brain injury (mTBI) patients. Despite evidence linking sleep and neurodegeneration, longitudinal TBI-related dementia studies have not considered sleep. We hypothesized that poor sleepers with mTBI would have elevated markers of neurodegeneration and lower cognitive function compared to mTBI good sleepers and controls. Our objective was to compare biomarkers of neurodegeneration and cognitive function with sleep quality in warfighters with chronic mTBI. Methods In an observational warfighters cohort (n=138 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with plasma biomarkers of neurodegeneration and cognitive scores collected an average of 8 years after injury. Results In the mTBI cohort, poor sleepers (PSQI≥10, n = 86) had elevated plasma neurofilament light (NfL, x̅ = 11.86 vs. 7.91 pg/mL, p=0.0007, d=0.63) and lower executive function scores by the categorical fluency (x̅ = 18.0 vs 21.0, p=0.0005, d= -0.65) and stop-go tests (x̅ = 30.1 vs 31.1, p=0.024, d = -0.37). These findings were not observed in controls (n = 44). PSQI predicted NfL (Beta=0.22, p=0.00002) and tau (Beta=0.14, p=0.007), but not amyloid β42. Poor sleepers showed higher obstructive sleep apnea (OSA) risk by STOP-BANG scores (x̅ = 3.8 vs 2.7, p=0.0005), raising the possibility that the PSQI might be partly secondary to OSA. Conclusions Poor sleep is linked to neurodegeneration and select measures of executive function in mTBI patients. This supports implementation of validated sleep measures in longitudinal studies investigating pathobiological mechanisms of TBI related neurodegeneration, which could have therapeutic implications.

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