Efficacy of Morning Shorter Wavelength Lighting in the Visible (Blue) Range and Broad-Spectrum or Blue-Enriched Bright White Light in Regulating Sleep, Mood, and Fatigue in Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI) profoundly affects sleep, mood, and fatigue, impeding daily functioning and recovery. This systematic review evaluates the efficacy of morning shorter wavelength lighting in the visible (blue) range and broad-spectrum or blue-enriched bright white light exposure in mitigating these challenges among TBI patients. Through electronic database searches up to May 2023, studies assessing sleep, circadian rhythm, sleepiness, mood, and fatigue outcomes in TBI patients exposed to morning shorter wavelength lighting in the visible (blue) range and broad-spectrum or blue-enriched bright white light were identified. Seven studies involving 309 participants met the inclusion criteria. Results indicated consistent advancement in sleep timing among individuals with mild TBI, alongside improvements in total sleep time, mood, and reduced sleepiness with both types of light exposure, particularly in mild TBI cases. Notably, two studies demonstrated alleviation of fatigue exclusively in severe TBI cases following light exposure. Despite promising findings, evidence remains limited, emphasizing the need for future research with standardized protocols to confirm the potential and optimize the benefits of light therapy for TBI recovery.

Traumatic Brain Injury and Early Onset Dementia in Post 9-11 Veterans.

OBJECTIVES: To assess traumatic brain injury (TBI)-related risks factors for early-onset dementia (EOD). BACKGROUND: Younger Post-9/11 Veterans may be at elevated risk for EOD due to high rates of TBI in early/mid adulthood. Few studies have explored the longitudinal relationship between traumatic brain injury (TBI) and the emergence of EOD subtypes. METHODS: This matched case-control study used data from the Veterans Health Administration (VHA) to identify Veterans with EOD. To address the low positive predictive value (PPV = 0.27) of dementia algorithms in VHA records, primary outcomes were Alzheimer's disease (AD) and frontotemporal dementia (FTD). Logistic regression identified conditions associated with dementia subtypes. RESULTS: The EOD cohort included Veterans with AD (n = 689) and FTD (n = 284). There were no significant demographic differences between the EOD cohort and their matched controls. After adjustment, EOD was significantly associated with history of TBI (OR: 3.05, 2.42-3.83), epilepsy (OR: 4.8, 3.3-6.97), other neurological conditions (OR: 2.0, 1.35-2.97), depression (OR: 1.35, 1.12-1.63) and cardiac disease (OR: 1.36, 1.1-1.67). CONCLUSION: Post-9/11 Veterans have higher odds of EOD following TBI. A sensitivity analysis across TBI severity confirmed this trend, indicating that the odds for both AD and FTD increased after more severe TBIs.

The Importance of Therapeutic Time Window in the Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability. Despite its importance in public health, there are presently no drugs to treat TBI. Many reasons underlie why drugs have failed clinical trials, one reason is that most drugs to treat TBI lose much of their efficacy before patients are first treated. This review discusses the importance of therapeutic time window; the time interval between TBI onset and the initiation of treatment. Therapeutic time window is complex, as brain injury is both acute and chronic, resulting in multiple drug targets that appear and disappear with differing kinetics. The speed and increasing complexity of TBI pathophysiology is a major reason why drugs lose efficacy as time to first dose increases. Recent Phase III clinical trials treated moderate to severe TBI patients within 4-8 h after injury, yet they turned away many potential patients who could not be treated within these time windows. Additionally, most head trauma is mild TBI. Unlike moderate to severe TBI, patients with mild TBI often delay treatment until their symptoms do not abate. Thus, drugs to treat moderate to severe TBI likely will need to retain high efficacy for up to 12 h after injury; drugs for mild TBI, however, will likely need even longer windows. Early pathological events following TBI progress with similar kinetics in humans and animal TBI models suggesting that preclinical testing of time windows assists the design of clinical trials. We reviewed preclinical studies of drugs first dosed later than 4 h after injury. This review showed that therapeutic time window can differ depending upon the animal TBI model and the outcome measure. We identify the few drugs (methamphetamine, melanocortin, minocycline plus N-acetylcysteine, and cycloserine) that demonstrated good therapeutic windows with multiple outcome measures. On the basis of their therapeutic window, these drugs appear to be excellent candidates for clinical trials. In addition to further testing of these drugs, we recommend that the assessment of therapeutic time window with multiple outcome measures becomes a standard component of preclinical drug testing.

Deficits in Visual System Functional Connectivity after Blast-Related Mild TBI are Associated with Injury Severity and Executive Dysfunction.

INTRODUCTION: Approximately, 275,000 American service members deployed to Iraq or Afghanistan have sustained a mild traumatic brain injury (mTBI), with 75% of these incidents involving an explosive blast. Visual processing problems and cognitive dysfunction are common complaints following blast-related mTBI. METHODS: In 127 veterans, we examined resting fMRI functional connectivity (FC) of four key nodes within the visual system: lateral geniculate nucleus (LGN), primary visual cortex (V1), lateral occipital gyrus (LO), and fusiform gyrus (FG). Regression analyses were performed (i) to obtain correlations between time-series from each seed and all voxels in the brain, and (ii) to identify brain regions in which FC variability was related to blast mTBI severity. Blast-related mTBI severity was quantified as the sum of the severity scores assigned to each of the three most significant blast-related injuries self-reported by subjects. Correlations between FC and performance on executive functioning tasks were performed across participants with available behavioral data (n = 94). RESULTS: Greater blast mTBI severity scores were associated with lower FC between: (A) LGN seed and (i) medial frontal gyrus, (ii) lingual gyrus, and (iii) right ventral anterior nucleus of thalamus; (B) V1 seed and precuneus; (C) LO seed and middle and superior frontal gyri; (D) FG seed and (i) superior and medial frontal gyrus, and (ii) left middle frontal gyrus. Finally, lower FC between visual network regions and frontal cortical regions predicted worse performance on the WAIS digit-symbol coding task. CONCLUSION: These are the first published results that directly illustrate the relationship between blast-related mTBI severity, visual pathway neural networks, and executive dysfunction - results that highlight the detrimental relationship between blast-related brain injury and the integration of visual sensory input and executive processes.