Insufficient Sleep Following Pediatric Mild Traumatic Brain Injury Correlates With Neurocognitive Dysfunction

ObjectiveAnalyze the impact of sleep disturbance on neurocognitive function in children recovering from mild traumatic brain injury (mTBI).BackgroundSleep disturbance of any nature is reported in more than half of all mTBI patients. The pathophysiology of sleep disturbance following mTBI is associated with structural and functional disruptions of sleep circuitry and circadian rhythm. Specifically in the pediatric population, untreated sleep disturbance has been shown to delay mTBI recovery and compound other morbidities including neurocognitive dysfunction.Design/MethodsA retrospective chart review of 118 pediatric patients (mean age = 14.56 ± 2.03 years) recovering from mTBI was performed. Epworth Sleepiness Scale (SF-8) results were analyzed in relation to CNS Vital Signs (CNSVS) neurocognitive test outcomes. SF-8 is a subjective estimation of a patient's daytime sleepiness. CNSVS uses a multitude of domains to objectively evaluate the overall neurocognitive status of a patient. Pearson correlations were calculated using a type I error of p < 0.05 between variables.ResultsEpworth Sleepiness Scale (SF-8) results showed 28.82% of participants experienced excessive daytime sleepiness sufficient enough to recommend medical attention. Upon further analysis, there was a significant negative correlation between SF-8 and CNSVS neurocognitive test outcomes including complex attention (r = −0.37; p = 0.0004), cognitive flexibility (r = −0.24; p = 0.0151), executive function (r = −0.21; p = 0.0350), and simple attention (r = −0.36; p = 0.0003) scores. This means as SF-8 scores increased (participants defined as excessively sleepy), neurocognitive function scores in these domains decreased. There was not enough evidence to conclude a significant correlation between other CNSVS domains and SF-8 (all p > 0.05).ConclusionsOur findings support the concern of neurocognitive dysfunction among pediatric mTBI patients with sleep disturbance. Further analysis is needed to determine if mTBI is the primary source or an exacerbating factor of sleep disturbance within this population. Nonetheless, these findings suggest a need for thorough evaluation when treating sleep concerns, irrespective of a history of childhood mTBI.

Metabolic Syndrome and Neurocognitive Function among older Hispanics/Latinos with HIV

Neurocognitive impairment is prevalent among persons with HIV (PWH), particularly among Hispanics/Latinos/as/x (henceforth Hispanics). We examined disparities in HIV-associated neurocognitive function between older Hispanic and non-Hispanic White PWH, and the potential role of metabolic syndrome (MetS) in explaining these disparities. Participants included 116 community-dwelling PWH ages 50-75, who were enrolled in a cohort study in southern California (58 Hispanic [53% Spanish-speaking] and 58 age-comparable non-Hispanic White; Overall group: Age: M=57.9, SD=5.7; Education: M=13, SD=3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy [ART], 4% detectable plasma RNA). A global neurocognition score was derived from T-Scores on a comprehensive neurocognitive battery, with separate demographic adjustments for English and Spanish-speakers. MetS was ascertained via standard criteria that considered central obesity, elevated triglycerides, low high-density lipoprotein cholesterol, and elevated fasting glucose, as well as current medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV-disease characteristics. Hispanics had higher rates of MetS (56%) than non-Hispanic Whites (37%; p&lt;.05). A stepwise regression model on global neurocognition including ethnicity and covariates that differed between ethnic groups, selected only Hispanic ethnicity as a significant predictor (B=-3.82, SE=1.27, p&lt;.01). A comparable model also including MetS showed that both Hispanic ethnicity (B=-3.39, SE=1.31, p=.01) and MetS (B=-2.73, SE=1.31, p=.04), were significantly associated with worse global neurocognition. Findings indicate that MetS does not fully explain disparities in neurocognitive function between Hispanic and non-Hispanic White older PWH, but rather is an independent predictor of neurocognitive function along with Hispanic ethnicity.

Sexually Dimorphic Effects of a Western Diet on Brain Mitochondrial Bioenergetics and Neurocognitive Function

A Western diet (WD), high in sugars and saturated fats, impairs learning and memory function and contributes to weight gain. Mitochondria in the brain provide energy for neurocognitive function and may play a role in body weight regulation. We sought to determine whether a WD alters behavior and metabolic outcomes in male and female rodents through impacting hippocampal and hypothalamic mitochondrial bioenergetics. Results revealed a sexually dimorphic macronutrient preference, where males on the WD consumed a greater percentage of calories from fat/protein and females consumed a greater percentage of calories from a sugar-sweetened beverage. Both males and females on a WD gained body fat and showed impaired glucose tolerance when compared to same-sex controls. Males on a WD demonstrated impaired hippocampal functioning and an elevated tendency toward a high membrane potential in hippocampal mitochondria. Comprehensive bioenergetics analysis of WD effects in the hypothalamus revealed a tissue-specific adaption, where males on the WD oxidized more fat, and females oxidized more fat and carbohydrates at peak energy demand compared to same-sex controls. These results suggest that adult male rats show a susceptibility toward hippocampal dysfunction on a WD, and that hypothalamic mitochondrial bioenergetics are altered by WD in a sex-specific manner.

Return of the Righting Reflex Does Not Portend Recovery of Cognitive Function in Anesthetized Rats

As the number of individuals undergoing general anesthesia rises globally, it becomes increasingly important to understand how consciousness and cognition are restored after anesthesia. In rodents, levels of consciousness are traditionally captured by physiological responses such as the return of righting reflex (RORR). However, tracking the recovery of cognitive function is comparatively difficult. Here we use an operant conditioning task, the 5-choice serial reaction time task (5-CSRTT), to measure sustained attention, working memory, and inhibitory control in male and female rats as they recover from the effects of several different clinical anesthetics. In the 5-CSRTT, rats learn to attend to a five-windowed touchscreen for the presentation of a stimulus. Rats are rewarded with food pellets for selecting the correct window within the time limit. During each session we tracked both the proportion of correct (accuracy) and missed (omissions) responses over time. Cognitive recovery trajectories were assessed after isoflurane (2% for 1 h), sevoflurane (3% for 20 min), propofol (10 mg/kg I.V. bolus), ketamine (50 mg/kg I.V. infusion over 10 min), and dexmedetomidine (20 and 35 μg/kg I.V. infusions over 10 min) for up to 3 h following RORR. Rats were classified as having recovered accuracy performance when four of their last five responses were correct, and as having recovered low omission performance when they missed one or fewer of their last five trials. Following isoflurane, sevoflurane, and propofol anesthesia, the majority (63–88%) of rats recovered both accuracy and low omission performance within an hour of RORR. Following ketamine, accuracy performance recovers within 2 h in most (63%) rats, but low omission performance recovers in only a minority (32%) of rats within 3 h. Finally, following either high or low doses of dexmedetomidine, few rats (25–32%) recover accuracy performance, and even fewer (0–13%) recover low omission performance within 3 h. Regardless of the anesthetic, RORR latency is not correlated with 5-CSRTT performance, which suggests that recovery of neurocognitive function cannot be inferred from changes in levels of consciousness. These results demonstrate how operant conditioning tasks can be used to assess real-time recovery of neurocognitive function following different anesthetic regimens.