Neurobehavioral Evaluation Research Articles

Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents: A cross-sectional study

Background: Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse. Methods: As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH. Results: A two-fold increase of the sum of serum PBDE’s was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE’s on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests. Conclusions: This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.

Neurobehavioural evaluation of Lophira alata (Ochnaceae) stem bark extract in mice.

Stem bark and leaves of Lophira alata (Family: Ochnaceae) have been used traditionally for their anti-psychotic, anti-convulsant and anxiolytic properties. Since no existing data was found on the neurobehavioural properties, this study was carried out to evaluate some neurobehavioural properties of the aqueous extract of the stem bark of L. alata in animal models. The oral mean lethal dose (LD50) of the extract was estimated, and preliminary phytochemical screening was conducted. Lophira alata extract (200, 400 and 800 mg/kg, p.o.) was investigated for antidepressant effect using the forced swim and tail suspension tests, and the anxiolytic potential was assessed using the stair case and hole board tests. Pentylenetetrazole-induced convulsion test was used to investigate the anticonvulsant potential of the extract. The LD50 was estimated to be >5000 mg/kg. Oral administration of L. alata extract produced a significant (p<0.05) non-dose-dependent decrease in the period of immobility in both the forced swim and tail suspension tests. While a significant decrease (p<0.05) in episodes of grooming was recorded in the staircase test, the number of head dips was not significantly reduced (p>0.05) in the hole board test. In the pentylenetetrazole-induced convulsion, a non-dose-dependent increase in onset of tonic-clonic seizures and protection from death was recorded. The results obtained suggest that the aqueous stem bark extract of L. alata possesses neurobehavioural properties which may account for its use in ethnomedicine.

Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea.

Children and adults with obstructive sleep apnea syndrome (OSAS) exhibit neurobehavioral abnormalities, but few studies have evaluated the transitional stage of adolescence. Obesity is also associated with neurobehavioral abnormalities, and many patients with OSAS are obese. However, the confounding effect of obesity on neurobehavioral abnormalities in adolescents with OSAS has not been evaluated. We hypothesized that obese adolescents with OSAS would exhibit more neurobehavioral abnormalities than obese and lean adolescents without OSAS. Cross-sectional, case control. Sleep Center and community. Obese adolescents with OSAS compared to (1) nonsnoring, obese controls without OSAS, and (2) nonobese, nonsnoring controls. Neurobehavioral evaluation. Obese adolescents with OSAS had significantly worse executive function and attention compared to both obese (P < 0.001) and lean (P < 0.001) controls, and more depression (P = 0.004) and externalizing symptoms than lean controls (P = 0.008). A higher percentage of participants in the OSAS group scored in the clinically abnormal range on executive functioning, attention, sleepiness, and behavioral functioning than lean controls. Mediation analyses indicated that level of sleep apnea significantly mediated the effect of body mass on executive functioning, attention, and behavior. Obese adolescents with OSAS show impaired executive and behavioral function compared to obese and lean controls, and are more likely to score in the clinically abnormal range on measures of neurobehavioral functioning. These results are especially concerning given that the frontal lobe is still developing during this critical age period. We speculate that untreated OSAS during adolescence may lead to significant neurobehavioral deficits in adulthood.

A cross sectional study of the association between walnut consumption and cognitive function among adult US populations represented in NHANES.

To examine the association between walnut consumption and measures of cognitive function in the US population. Nationally representative cross sectional study using 24 hour dietary recalls of intakes to assess walnut and other nut consumption as compared to the group reporting no nut consumption. 1988-1994 and 1999-2002 rounds of the National Health and Nutrition Examination Survey (NHANES). Representative weighted sample of US adults 20 to 90 years of age. The Neurobehavioral Evaluation System 2 (NES2), consisting of simple reaction time (SRTT), symbol digit substitution (SDST), the single digit learning (SDLT), Story Recall (SRT) and digit-symbol substitution (DSST) tests. Adults 20-59 years old reporting walnut consumption of an average of 10.3 g/d required 16.4ms less time to respond on the SRTT, P=0.03, and 0.39s less for the SDST, P=0.01. SDLT scores were also significantly lower by 2.38s (P=0.05). Similar results were obtained when tertiles of walnut consumption were examined in trend analyses. Significantly better outcomes were noted in all cognitive test scores among those with higher walnut consumption (P < 0.01). Among adults 60 years and older, walnut consumers averaged 13.1 g/d, scored 7.1 percentile points higher, P=0.03 on the SRT and 7.3 percentile points higher on the DSST, P=0.05. Here also trend analyses indicate significant improvements in all cognitive test scores (P < 0.01) except for SRTT (P = 0.06) in the fully adjusted models. These significant, positive associations between walnut consumption and cognitive functions among all adults, regardless of age, gender or ethnicity suggest that daily walnut intake may be a simple beneficial dietary behavior.

Whole-scale neurobehavioral assessments of photothrombotic ischemia in freely moving mice.

Neurobehavioral assessments have been considered as an essential component of preclinical research in ischemic stroke. However, real-time neurobehavioral evaluation is seldom applied during ischemia induction as it is usually accompanied with anesthesia. We induced photothrombosis in freely moving mice after one-week recovery from cannula implantation surgeries. After rose bengal (RB) injection (100 mg/kg, i.p.), photothrombosis was induced in freely moving mice by 473 nm laser irradiation through the cannulas implanted into unilateral primary motor cortex beforehand. Mice received nimodipine (15 mg/kg, i.p.), a widely used anti-ischemic agent, or vehicle before irradiation. Motor coordination and equilibrium were evaluated by rotarod and rung walk tests throughout the whole process of ischemia. Endurance capacity was assessed by treadmill at 1 day and 7 days after irradiation. Mice were decapitated at different time points post irradiation for TTC (2,3,5-triphenyltetrazolium chloride) staining. Consistent with the results of TTC staining, motor deficits firstly occurred at 15-min post irradiation and aggravated 1-day later, while the capacity improved 3-days later and partially recovered 7-days post irradiation. And, the recovery process was accelerated by nimodipine application. This method established a precise linkage between focal brain ischemia development and neurobehavioral deficits throughout a full scale of photothrombosis, which avoided the confounding factors of anesthetics and surgeries on neurobehavioral assessments, as infarct was induced in freely moving mice. This method with high temporal and spatial resolution will be an optimal model for neurobehavioral evaluation in preclinical anti-ischemic drug screening.

Effect of Resveratrol as Caloric Restriction Mimetic and Environmental Enrichment on Neurobehavioural Responses in Young Healthy Mice

Caloric restriction and environmental enrichment have been separately reported to possess health benefits such as improvement in motor and cognitive functions. Resveratrol, a natural polyphenolic compound, has been reported to be caloric restriction mimetic. This study therefore aims to investigate the potential benefit of the combination of resveratrol as CR and EE on learning and memory, motor coordination, and motor endurance in young healthy mice. Fifty mice of both sexes were randomly divided into five groups of 10 animals each: group I animals received carboxymethylcellulose (CMC) orally per kg/day (control), group II animals were maintained on every other day feeding, group III animals received resveratrol 50 mg/kg, suspended in 10 g/L of (CMC) orally per kg/day, group IV animals received CMC and were kept in an enriched environment, and group V animals received resveratrol 50 mg/kg and were kept in EE. The treatment lasted for four weeks. On days 26, 27, and 28 of the study period, the animals were subjected to neurobehavioural evaluation. The results obtained showed that there was no significant change (P&gt;0.05) in neurobehavioural responses in all the groups when compared to the control which indicates that 50 mg/kg of resveratrol administration and EE have no significant effects on neurobehavioural responses in young healthy mice over a period of four weeks.

Health-related quality of life within the first 5 years following military-related concurrent mild traumatic brain injury and polytrauma.

This study examined health-related quality of life within the first 5 years following concurrent mild traumatic brain injury (MTBI) and polytrauma. Participants were 167 U.S. service members who had sustained a MTBI who had completed a brief neurobehavioral evaluation within 3 months postinjury and at least one telephone follow-up interview at 6 (n = 46), 12 (n = 89), 24 (n = 54), 36 (n = 42), 48 (n = 30) or 60 months (n = 25) postinjury. Within the first 5 years postinjury, service members reported ongoing headaches (67.4% to 92.0%), bodily pain (66.7% to 88.9%), medication use (71.7% to 92.0%), mental health treatment (28.3% to 60.0%), and the need for help with daily activities (18.5% to 40.0%). Problematic alcohol consumption was common within the first 24 months postinjury (23.9% to 29.2%). Many service members were working for pay (36.0% to 70.8%) though many reported a decline in work quality (16.0% to 30.4%). Despite ongoing symptom reporting, many service members reported that their medications were effective (43.3% to 80.0%), good/excellent health status (68.0% to 80.0%), and life satisfaction (79.6% to 90.5%). A minority reported suicidal or homicidal ideation (5.6% to 14.8%). Recovery from MTBI in a military setting is complex and multifaceted. Continued support and care for all service members who sustain a combat-related MTBI with polytrauma is recommended, regardless of the presence or absence of symptom reporting within the first few months postinjury.

Neonatal neuropsychology: Emerging relations of neonatal sensory–motor responses to white matter integrity

The neonatal period is considered to be essential for neurodevelopment and wellbeing throughout the life span, yet little is known about brain–behavior relationships in the neonatal period. The aim of this study was to evaluate the association between neonatal sensory–motor regulation and white-matter (WM) integrity of major fiber tracts in the neonatal period. We hypothesized that WM integrity of sensory–motor systems would predict neurobehavioral maturation during the first month of life.Forty-nine premature neonates underwent magnetic-resonance-imaging at term. Diffusion-tensor-imaging analysis was performed in major WM tracts along with repeated neonatal neurobehavioral evaluations assessing sensory reactivity and motor regulation.Difficulties in one or more behavioral sub-category, mostly in auditory and visual attention, hypotonicity and jitteriness, were documented in 78.3% infants at term. Sixty-six percent of infants experienced difficulties, mostly in auditory attention, head–neck control, hypotonicity and motor asymmetry, at 44 weeks.Attention difficulties were associated with reduced integrity of cerebral and superior cerebellar peduncles; while tonicity was associated with reduced integrity of the corpus-callosum and inferior–posterior tracts. Overall, results showed that early maturing tracts were related with the degree of typicality of sensory reactivity status while late maturing tracts were related with the degree of typicality of tonic regulation. WM integrity and maturation factors explained 40.2% of the variance in neurobehavior at 44 weeks.This study suggests that in preterm neonates, deviant sensory–motor reactivity can be detected very early in development in manners that are related to lower integrity/maturational level of early and late maturing fiber tracts.

Neurobehavioral and thyroid evaluations of rats developmentally exposed to tris(1,3-dichloro-2-propyl)phosphate (TDCPP)

Neurobehavioral and thyroid evaluations of rats developmentally exposed to tris(1,3-dichloro-2-propyl)phosphate (TDCPP)

Neurobehavioral evaluation of adolescent male rats following repeated exposure to chlorpyrifos

Chlorpyrifos (CPF), a highly effective organophosphate pesticide (OP), is extensively used worldwide. However, its agricultural use was extensively reduced in 2001. Several studies have suggested an association between mood disorders and CPF exposure in humans, especially in children, a subgroup that is highly susceptible to xenobiotics. We investigated the hypothesis that repeated CPF exposure in animals would elicit depressive-like behavioral alterations that reflected depression-related symptoms. Adolescent male rats were subcutaneously injected with either olive oil or 2.5, 5, 10, or 20mg/kg CPF from postnatal day 27 to 36, then were followed by a series of neurobehavioral evaluation. Our studies revealed depressive-like alterations that were manifested by increased despair behavior in the forced swimming test, increased escape failure in the learned helplessness test, and altered approach-avoidance conflict in the novelty-suppressed feeding test. There was no effect on locomotor activity in the open-field activity test. This study indicates that repeated exposure to CPF elicits depressive-like behavioral alterations in adolescent male rats.

Effects of Balance and Gait Training on the Recovery of the Motor Function in an Animal Model of Parkinson’s Disease

[Purpose] This study was conducted to investigate the effect of balance and gait training on the recovery of the motor function in a Parkinson’s disease animal models. [Subjects and Methods] A total of 40 mice were randomly classified into four groups with 10 in each group: Group I-Normal; Group II-Parkinson’s disease and no training; Group III-Parkinson’s disease and balance training was performed; and Group IV-Parkinson’s disease and gait training. Parkinson’s disease was induced by administration of MPTP to animals in Groups II–IV. Groups III and IV did training once a day, five days a week, for four weeks. Neurobehavioral evaluation was performed through the pole and open-field tests. Immunological evaluation was performed via TH (tyrosine hydroxylase) protein expression, using western blot analysis. [Results] In the result of the pole test, Groups III and IV showed significantly greater motor function recovery than to Group II. The results of the open-field test also showed that Groups III and IV had significantly greater motor function recovery than to Group II, and Group IV showed significantly greater motor function recovery than to Group III. Using western blot analysis, we determined that the expression of TH protein in the corpus striatum was greatest in group I, followed by Groups III and IV, and that Group II had the lowest TH protein expression in the corpus striatum. [Conclusion] The results of this study showed that balance and gait training were effective at recovering the motor functions of a Parkinson’s disease animal models induced by MPTP, and that gait training was more effective than balance training.

Neurobehavioral evaluation of mouse newborns exposed prenatally to low-dose bisphenol A

There have been few neurobehavioral toxicology studies on newborn animals. Thus, we developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants, by means of determining the newborn's motor activity applying the tare function of an analytical balance. Motor activities including crawling, pivoting, righting or tremors of mouse newborns were evaluated. Tremors of newborns of dams exposed to bisphenol A at 2, 20 or 200 µg/kg/day on days 5 through 18 of gestation were significantly increased when evaluated on postnatal day 1, as well as those of newborns exposed prenatally to diethylstilbestrol at 0.5 µg/kg/day. We suggest that our developed testing method may provide a useful addition to neurobehavioral assessment in very young rodents exposed to environmental hormone mimics.

A 13-Week Dermal Repeat-Dose Neurotoxicity Study of Hydrodesulfurized Kerosene in Rats

A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.

EXAMINER Executive Function Battery and Neurologic Morbidity in Pediatric Sickle Cell Disease

Sickle cell disease (SCD) is blood disorder with a high risk for cerebral vascular morbidities that impact neurocognitive functioning. Specific cognitive abilities are known to be more sensitive to neurologic effects of SCD than IQ scores, yet there is little consensus about which measures to use to assess neurocognitive functioning. We evaluated the ability of the Executive Abilities: Methods and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) Battery to detect neurologic effects in SCD. Thirty-two youth with SCD and sixty demographically-matched comparison youth completed the EXAMINER Battery and selected tests from the Woodcock-Johnson Tests of Cognitive Ability, 3rd edition (WJ-III). Neurologic severity was examined via clinical history for morbidities and midsagittal corpus callosum (CC) area. Results indicated cognitive performance decreased with increasing neurologic morbidity across all cognitive measures; two of four EXAMINER factors were related to CC area. The association with clinical history and midsagittal CC area appeared at least as large for the Examiner Battery scores as for the WJ-III measures. The Examiner Battery showed sensitivity to neurologic history and white matter effects in SCD; this new measure compares favorably to established measures of disease-related neurocognitive effects, but would benefit from further development.

Executive Function in Children with Attention Deficit/Hyperactivity Disorder: The NIH EXAMINER Battery

Theories of attention deficit/hyperactivity disorder (ADHD) increasingly highlight the role of neuropsychological impairment in ADHD; however, a consistent and identifiable pattern of performance on tests is not well established. The National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) battery provides measures of common variance across multiple executive function tests within specific domains and was used to characterize which executive functions are most affected in children with ADHD. Thirty-two children (24 male), ages 8-15 years (M = 12.02; SD = 2.29), diagnosed with ADHD and no comorbid disorder completed the NIH EXAMINER battery. Sixty age and gender matched healthy controls were chosen from a database of participants enrolled in the NIH EXAMINER multi-site study. Children with ADHD performed worse on the working memory score compared with the controls. No differences were found on the cognitive control or fluency scores. For children with ADHD, poorer working memory performance predicted parent report of child learning problems. Cognitive control and fluency scores did not predict learning problems. In summary, working memory emerges as a primary impairment in children with ADHD who have no comorbid disorders. Furthermore, working memory weaknesses may underlie the academic problems often seen in children with ADHD.

NIH EXAMINER: Conceptualization and Development of an Executive Function Battery

Executive functioning is widely targeted when human cognition is assessed, but there is little consensus on how it should be operationalized and measured. Recognizing the difficulties associated with establishing standard operational definitions of executive functioning, the National Institute of Neurological Disorders and Stroke entered into a contract with the University of California-San Francisco to develop psychometrically robust executive measurement tools that would be accepted by the neurology clinical trials and clinical research communities. This effort, entitled Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of tasks targeting working memory, inhibition, set shifting, fluency, insight, planning, social cognition and behavior. We describe battery conceptualization and development, data collection, scale construction based on item response theory, and lay the foundation for studying the battery's utility and validity for specific assessment and research goals.

Factors associated with feeding difficulties in the very preterm infant

To investigate early medical and family factors associated with later feeding risk in preterm infants. For this longitudinal study, 136 infants born ≤30weeks gestation were enrolled. Medical and social background factors were assessed at term equivalent age. Infants underwent magnetic resonance imaging, neurobehavioral evaluation and feeding assessment. Parent involvement in the neonatal intensive care unit was tracked, and maternal mental health was assessed at neonatal intensive care unit discharge. At age 2years, feeding outcome was assessed using the Eating Subscale of the Infant-Toddler Social Emotional Assessment (n=80). Associations between feeding problems at age 2 years and (i) early medical factors, (ii) neurobehavioral functioning and feeding at term equivalent age, (iii) cerebral structure and (iv) maternal mental health were investigated using regression. Eighteen (23%) children had feeding problems at age 2years. Feeding problems were associated with early hypotonia (p=0.03; β=0.29) and lower socio-economic status (p=0.046; β=-0.22). No associations were observed between early medical factors, early feeding performance, cerebral structure alterations or maternal well-being and feeding outcome. Early hypotonia may disrupt the development of oral-motor skills. Hypotonia and poor feeding also may share a common aetiology. Associations with lower socio-economic status highlight the potential influence of family background factors in feeding problems in the preterm infant.

395 Solvent-induced DNA methylation changes: A translational study

ObjectivesWorkers exposed to solvents are at risk for developing cancer and neurobehavioral diseases. Evidence is growing on the role of epigenetic alterations involved in the development of both diseases. In...

Therapy Development for Diffuse Axonal Injury

Diffuse axonal injury (DAI) remains a prominent feature of human traumatic brain injury (TBI) and a major player in its subsequent morbidity. The importance of this widespread axonal damage has been confirmed by multiple approaches including routine postmortem neuropathology as well as advanced imaging, which is now capable of detecting the signatures of traumatically induced axonal injury across a spectrum of traumatically brain-injured persons. Despite the increased interest in DAI and its overall implications for brain-injured patients, many questions remain about this component of TBI and its potential therapeutic targeting. To address these deficiencies and to identify future directions needed to fill critical gaps in our understanding of this component of TBI, the National Institute of Neurological Disorders and Stroke hosted a workshop in May 2011. This workshop sought to determine what is known regarding the pathogenesis of DAI in animal models of injury as well as in the human clinical setting. The workshop also addressed new tools to aid in the identification of this axonal injury while also identifying more rational therapeutic targets linked to DAI for continued preclinical investigation and, ultimately, clinical translation. This report encapsulates the oral and written components of this workshop addressing key features regarding the pathobiology of DAI, the biomechanics implicated in its initiating pathology, and those experimental animal modeling considerations that bear relevance to the biomechanical features of human TBI. Parallel considerations of alternate forms of DAI detection including, but not limited to, advanced neuroimaging, electrophysiological, biomarker, and neurobehavioral evaluations are included, together with recommendations for how these technologies can be better used and integrated for a more comprehensive appreciation of the pathobiology of DAI and its overall structural and functional implications. Lastly, the document closes with a thorough review of the targets linked to the pathogenesis of DAI, while also presenting a detailed report of those target-based therapies that have been used, to date, with a consideration of their overall implications for future preclinical discovery and subsequent translation to the clinic. Although all participants realize that various research gaps remained in our understanding and treatment of this complex component of TBI, this workshop refines these issues providing, for the first time, a comprehensive appreciation of what has been done and what critical needs remain unfulfilled.

Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders

This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.