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Context: Cognitive performance has been shown to be associated with musculoskeletal injury risk. Cognitive assessments are often administered in controlled environments despite sport settings challenging cognition in uncontrolled, less predictable environments. Cognitive assessments should be representative of sport demands; thus, integrating motor with cognitive assessments may be more clinically relevant. Accordingly, the purpose of this research was to investigate the relationship between tablet-based cognitive tests and choice reaction time during a hopping task. Design: Cross-sectional. Methods: A total of 20 healthy participants volunteered to participate. Participants completed 3 tablet-based cognitive assessments. Average raw response time and fully corrected scores were used for analysis. In addition, participants completed a choice reaction hopping task to capture neuromuscular–cognitive reaction time. Participants completed a forward hop over a hurdle, landing on a single limb. Light sensors were utilized for the choice reaction component to capture reaction time in seconds, cue them when to hop, and indicate the landing limb. The relationship between the tablet-based cognitive assessments and reaction time during a hopping task was examined with Pearson correlations (α = .05). Results: The choice reaction time from the hop task had a negligible correlation (r = −.20−.07) to the fully corrected tablet-based cognitive tests. The choice reaction time from the hop task had a negligible correlation (r = .02) to the average response time of the Pattern Comparison Processing Speed Test and a low correlation (r = .34−.36) to the Dimensional Change Card Sort Test and Flanker Inhibitory Control and Attention Test. Conclusions: This study determined that tablet-based cognitive assessments had trivial relationships to choice reaction time during a hopping task. This research has implications as clinicians aim to evaluate and analyze cognitive performance. Although reaction time was a critical component of all the assessments in this study, an individual’s performance on a tablet-based assessment does not indicate performance during a functional reaction time assessment.

This study examined the relationships between post-traumatic headache (PTH) and mental health symptoms after concussions to inform adolescent concussion management. Headache is the most common complaint following adolescent concussion. In this sample of 123 adolescents with concussion, there was a 5-fold increase in odds of clinically elevated anxiety, as well as increased mental health symptoms (anxiety, depression, anger, and disruptive behaviours), among adolescents with PTH relative to those without PTH. Adolescents with headache following concussions are vulnerable to worse mental health outcomes, particularly anxiety, and may benefit from routine monitoring of mental health symptoms for early detection and intervention.

A 53-year-old male with history of traumatic brain injury (TBI) presented with localized dissociative amnesia following a second head injury. While memory loss due to TBI is present in the literature, presentations of this type are very rare. Although fully independent in activities of daily living, this patient demonstrated severe deficits in visual memory and processing speed upon neurocognitive evaluation. Effort testing was unremarkable. Increased awareness and study of memory loss following TBI can contribute to enhanced understanding and improved care for patients experiencing these deficits. The authors present this unique case’s profile, clinical history, and discuss their findings.

Clinical neurotoxicology is an unrecognized neurologic subspecialty. Few neurology residency programs offer an organized education or training in the field. Nevertheless, neurotoxic exposures and subsequent injuries are common. This article provides a basic approach to clinical assessment and causal inference. It addresses the knowledge gap for clinical practice and provides a thematic structure to use interdisciplinary resources.

Several different types of exposure have the potential to produce olfactory and gustatory deficits related to neurotoxicity. Although the literature contains relatively few studies of such chemoreceptive dysfunction in the context of toxic exposure, this review explores the strength of such published associations. Several studies collectively demonstrated moderately strong evidence for an association between manganese dust exposure and olfactory deficits. Evidence of associations between individual chemicals, therapeutics, and composites, such as World Trade Center debris, and olfactory and gustatory deficits remains limited or mixed. Further need for controlled studies for clinical management, exposure limits, and policy development is identified.

OBJECTIVE There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN. METHODS Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. Images were analyzed by a board-certified neuroradiologist blinded to pretrial diagnosis and treatment status. Secondary outcomes included changes in headache, steroid use, and functional status and absence of neurocognitive sequelae. Comparisons were analyzed using the Fisher exact test, Mann-Whitney U-test, linear mixed models, Wilcoxon signed-rank test, and repeated-measures 1-way ANOVA. RESULTS Ten adults (mean ± SD [range] age 35 ± 15 [22–62] years) participated in this study. No patients died or exhibited serious adverse effects of systemic bevacizumab. At 3 months, 80% (95% CI 44%–98%) and 90% (95% CI 56%–100%) of patients demonstrated > 25% decrease in RN and vasogenic edema volume, respectively. At 12 months, RN volume decreased by 74% (median [range] 76% [53%–96%], p = 0.012), edema volume decreased by 50% (median [range] 70% [−11% to 83%], p = 0.086), and headache decreased by 84% (median [range] 92% [58%–100%], p = 0.022) among the 8 patients without RN recurrence. Only 1 (10%) patient was steroid dependent at the end of the trial. Scores on 12 of 16 (75%) neurocognitive indices increased, thereby supporting a pattern of cerebral white matter recovery. Two (20%) patients exhibited RN recurrence that required further treatment at 10 and 11 months, respectively, after bevacizumab infusion. CONCLUSIONS For the first time, to the authors’ knowledge, the authors demonstrated that a single low-dose targeted bevacizumab infusion resulted in durable clinical and imaging improvements in 80% of patients at 12 months after treatment without adverse events attributed to bevacizumab alone. These findings highlight that targeted bevacizumab may be an efficient one-time treatment for adults with brain RN. Further confirmation with a randomized controlled trial is needed to compare the intra-arterial approach with the conventional multicycle intravenous regimen. Clinical trial registration no.: NCT02819479 (ClinicalTrials.gov)

βeta-hydroxybutyrate (BHB) is a ketone body produced by the liver in a process known as ketosis, as an alternative fuel source during fasting or carbohydrate caloric restriction, and is readily used as fuel throughout the body, including in the brain. While glucose is the brain’s principal energy source, when limited, ketones derived from fats become the major energy substrate. Exogenous BHB is safe to administer orally and can enhance energy and physical performance. While the literature suggests cognitive and/or behavioural performance improvement in animal models following elevation in ketones, and in clinical human samples such as those with Mild Cognitive Impairment, Alzheimer’s disease, epilepsy, and severe traumatic brain injury, the literature investigating the neurocognitive effects of exogenous administration of ketones in nonclinical, healthy samples remains limited. For this proof of concept, we present twelve subjects who underwent exogenous administration of 11.7 g of BHB. After ingestion, participants performed significantly better in attentional accuracy compared to pre-intervention scores (p < 0.05; d = 0.65), demonstrating that exogenous administration of BHB may have positive effects on the attentional accuracy domain of neurocognition in neurotypical adults. Further analysis and its clinical implications are discussed.

Over the past several decades, there has been much interest regarding the effects of video game play. Research has evaluated the behavioral, cognitive, and psychological effects of video game play, and found individuals who play games using complex and dynamic game settings and require focused attention with quick responses, such as action video games, demonstrate improved cognitive performance. Action video game training has also yielded rehabilitation efficacy for a myriad of patients, such as stroke patients and individuals with vestibular and balance deficits. Recently, new technology platforms have been developed such as mixed reality (MR); however, little to no research has been conducted examining the effects of advanced technology platforms. The purpose of the current study was to explore whether MR game training improved visuo-motor reaction time and balance performances. Fourteen participants (11 male; 18–50 years of age) underwent baseline and post-intervention assessments, and then complete 8 h of MR action game training. Visuo-motor reaction times were obtained via computerized Automated Neurocognitive Assessment Metric testing and balance measures were obtained via Sensory Organizational Testing. Baseline and post-intervention comparisons were analyzed using Wilcoxon signed-rank tests. Baseline and post-intervention visuo-motor reaction time and balance comparisons revealed that MR game training yielded significant reaction time improvements (p

Objectives Poorer neurocognitive performance may increase lower extremity injury risk due to alterations in biomechanics. However, it is unclear if poorer neurocognitive function may be associated with altered dynamic postural stability. Therefore, the purpose of this study was to investigate the relationship between neurocognitive performance and dynamic postural stability in healthy collegiate athletes. Design Cross-sectional cohort. Methods Forty-five Division-I collegiate athletes (21 males, 24 females; age: 19.69 ± 1.50) completed neurocognitive assessments from the NIH Toolbox® (NIHTB). Three groups were established from the NIHTB composite score: high performers (HP), moderate performers (MP), and low performers (LP). Additionally, participants completed a dynamic hop-to-stabilization task. Accelerometer and gyroscopic data were recorded during landing through an inertial measurement unit (IMU) on the participant's low back. The root mean squared (RMS) of the accelerometer and gyroscope was calculated for the orthogonal planes and the resultant vector. Group differences for demographic variables, NIHTB composite scores, and IMU based measures were analyzed with one-way ANOVAs with Bonferroni post hoc analyses were performed. Cohen's d effect sizes were also calculated. Results Post hoc tests determined the LP group had higher vertical acceleration RMS values (p = 0.013, d = −0.85) and lower anteroposterior acceleration RMS values (p = 0.005, d = 0.95) compared to the HP group. Conclusions Neurocognitive performance may influence dynamic postural stability strategies in athletes. Higher neurocognitive performers may use different approaches to perform difficult postural tasks by adopting strategies associated with lower vertical and higher anteroposterior acceleration compared to lower neurocognitive performers.

Objective Evaluate neurocognitive change after single low-dose targeted intra-arterial (IA) bevacizumab in patients with brain radiation necrosis. Methods Phase II, single-arm, prospective trial. 10 adults underwent targeted 2.5 mg/kg IA bevacizumab. Neurocognitive indices (Neuropsychological Assessment Battery® and Wechsler Test of Adult Reading) were measured at baseline and 12-months to document performance in 5 domains: Attention, Language, Learning and Memory, Visuospatial, and Executive Function. Clinical indices also quantified. Data (mean ± SD, 95% confidence interval [CI], Cohen’s d) were analyzed using paired t tests. Null hypothesis rejected for p Results At baseline, Numbers-&-Letters Speed T-score (38.2 ± 10.7) indicated decreased processing speed consistent with sub-cortical pattern of illness. All other baseline neurocognitive indices were within normalized means (image). 12-months post-treatment, Numbers-&-Letters Errors T-score increased by 6.0 ± 4.9 [95%CI 1.9,10.1] (t = 3.464, d = 1.225, p = 0.010). List-Learning List-Long-Delayed-Recall T-score increased by 9.0 ± 5.6 [95% CI 4.3,13.7] (t = 4.520, d = 1.598, p = 0.003) and Design-Construction T-score increased by 3.5 ± 4.1 [95%CI 0.04,7.0] (t = 2.391, d = 0.845, p = 0.048). Volume of radiation necrosis decreased by 74.4 ± 14.7% (t = −3.308, d = 1.169, p = 0.013). Headache decreased by 84.4 ± 18.2% (t = −3.495, d = 1.236, p = 0.010). 0/10 died or exhibited AEs attributed to bevacizumab. 2/10 patients experienced radiation necrosis recurrence at months 10 and 11, respectively. Conclusions Single low-dose intra-arterial targeted bevacizumab led to durable neuropsychological performance increase in memory retrieval and visuospatial ability consistent with improvement in sub-cortical function. To our knowledge this is the first prospective report of this novel approach in adults. Clinical improvements mirrored neuropsychologic improvements. Randomized trials are needed comparing targeted low-dose IA bevacizumab to multi-cycle IV bevacizumab at higher doses to determine which is best alternative in brain radiation necrosis.

Clinical neurotoxicology is an unrecognized neurologic subspecialty. Few neurology residency programs offer an organized education or training in the field. Nevertheless, neurotoxic exposures and subsequent injuries are common. This article provides a basic approach to clinical assessment and causal inference. It addresses the knowledge gap for clinical practice and provides a thematic structure to use interdisciplinary resources.

The encoding of odors is believed to begin as a combinatorial code consisting of distinct patterns of responses from odorant receptors (ORs), trace-amine associated receptors (TAARs), or both. To determine how specific response patterns arise requires detecting patterns in vivo and understanding how the components of an odor, which are nearly always mixtures of odorants, give rise to parts of the pattern. Cigarette smoke, a common and clinically relevant odor consisting of >400 odorants, evokes responses from 144 ORs and 3 TAARs in freely behaving male and female mice, the first example of in vivo responses of both ORs and TAARs to an odor. As expected, a simplified artificial mimic of cigarette smoke odor tested at low concentration to identify highly sensitive receptors evokes responses from four ORs, all also responsive to cigarette smoke. Human subjects of either sex identify 1-pentanethiol as the odorant most critical for perception of the artificial mimic; and in mice the OR response patterns to these two odors are significantly similar. Fifty-eight ORs respond to the headspace above 25% 1-pentanethiol, including 9 ORs responsive to cigarette smoke. The response patterns to both cigarette smoke and 1-pentanethiol have strongly responsive ORs spread widely across OR sequence diversity, consistent with most other combinatorial codes previously measured in vivo. The encoding of cigarette smoke is accomplished by a broad receptor response pattern, and 1-pentanethiol is responsible for a small subset of the responsive ORs in this combinatorial code. SIGNIFICANCE STATEMENT Complex odors are usually perceived as distinct odor objects. Cigarette smoke is the first complex odor whose in vivo receptor response pattern has been measured. It is also the first pattern shown to include responses from both odorant receptors and trace-amine associated receptors, confirming that the encoding of complex odors can be enriched by signals coming through both families of receptors. Measures of human perception and mouse receptor physiology agree that 1-pentanethiol is a critical component of a simplified odorant mixture designed to mimic cigarette smoke odor. Its receptor response pattern helps to link those of the artificial mimic and real cigarette smoke, consistent with expectations about perceptual similarity arising from shared elements in receptor response patterns.

Familial Danish dementia (FDD) is a rare, autosomal dominant neurodegenerative disorder characterized by progressive hearing loss, cataracts, progressive ataxia, and dementia. While multiple pathophysiological studies exist in the literature, clinical case presentations are currently limited. We present a case of young-onset dementia in a 47-year-old patient with Danish heritage who was subsequently diagnosed FDD through genetic testing. Cognitive impairment was his initial symptom, followed by Parkinsonian symptoms, and mood disturbances. The patient experienced rapid decline over only 19 months. Increased awareness and understanding of familial forms of dementia (i.e., FDD) can contribute to an enhanced provision of care for patients with such conditions.

Sports concussions are recognized as significant injuries among young athletes. Research demonstrates that return-to-play prior to becoming asymptomatic has significant repercussions including sustained cognitive deficits. Many programs have begun to use computerized testing rather than traditional neuropsychological tests to (a) determine baseline performance, (b) track symptoms, and (c) measure symptoms following concussion. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is one such tool. The current study examined ImPACT's convergent and discriminant validity by comparing scores from sports-related concussion athletes (SRC) to those from nonconcussed controls (CTL). SRC included 29 athletes, ages 12-16, referred for neuropsychological assessment following sports-related concussions. CTL included 25 healthy athletes, ages 12-16, who were concussion-free in the past year. Overall, results showed general support for ImPACT, when used to screen cognition. In fact, all ImPACT domains successfully differentiated between SRC and CTL athletes. Evidence supporting appropriate convergent validity was best for the Visual Memory domain. Further, ImPACT domains demonstrated variable discriminant validity. Overall examination of validity demonstrated that ImPACT has some weaknesses but may have utility in detecting postconcussion cognitive impairment.

Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune disorder tightly conceptualized only as recently as the mid-2000s. It presents itself in a combination of psychiatric, neurological, and autonomic features. We observe a unique case with probable earlier episode (prior to the mid-2000s conceptualization of the disease) and a later relapse, accompanying a comprehensive neuropsychological profile tracked after the relapse and subsequent improvement. Neurocognitive findings revealed residual frontal deficits with mood changes even in the state after plasmapheresis. This case is the first to describe posttreatment cognition in anti-NMDAR encephalitis after probable serial autoimmune episodes.

Purpose There is a national shortage of physicians in brain related specialties (neurology, neurosurgery and psychiatry), with fewer students training in these specialties. This study explored socio-economic and experiential factors that determined medical trainees' interest in brain related specialties. Method Medical students and house-staff at a state university medical school completed a 46-item questionnaire sent as an anonymous email survey. Results Survey response rate was 22% ( n = 258). Eighty-eight (34.1%) trainees were interested in brain related specialties. Prior neuroscience experience (29.6%) and effective medical school neuroscience courses (23.9%) were identified as important by those interested in brain related specialties, while “neurophobia” was reported by 30% of those not interested. Multivariate regression model showed that effective college neuroscience course increased the likelihood for interest in brain related specialties (OR = 2.28, 95% CI 1.22, 4.28). Factors which decreased the likelihood included parent's possessing professional degree (OR = 0.37, 95% CI 0.17, 0.80), personal annual income > $50,000 (OR = 0.40, 0.18, 0.87) and current debt level ≥ $100,000 (OR = 0.33, 0.17, 0.64). The proportion of trainees interested in brain related specialties decreased from 51.7% (1st year medical students) to 27% (4th year students) and 25.3% among house-staff (χ 2 test of trend p = 0.001). Conclusions Socioeconomic (current personal debt and annual income) and experiential factors (college neuroscience course) influence a medical trainee's interest in brain related specialties. Career guidance and improved, better and early exposure to neurosciences may help mitigate trend for decreased interest in brain related specialties.

As an established risk factor for cardiovascular disease and stroke, hypertension risks are often thought to be more prevalent in Appalachian mountain ranges when compared with other neighboring counterpart regions. This study evaluated blood pressure (BP) readings among 2358 Kentucky residents attending community stroke risk screening events held in 15 counties, including nine Appalachian counties (n=1134) and six non‐Appalachian counties (n=1224). With high BP being operationally defined as ≥140/90 mm Hg, 41.5% of Appalachian county residents had elevated BP compared with 42.6% among those from non‐Appalachian counties. Although the counties with the highest rates of elevated BP did tend to reside in the Appalachian region, there was no significant difference between rates of elevated BP in Appalachia vs non‐Appalachian counties. This dataset is proposed as a pilot project to encourage further pursuit of a larger controlled project.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a commonly administered test used to identify cognitive impairment in geriatric patients. To date, no published studies have examined the relationship between depressive symptoms and performance on the RBANS in older adults. Using a clinical sample of 45 older adults, we found a significant negative correlation between depression scores (measured by Geriatric Depression Scale-15) and RBANS Immediate Memory Index. Further examination showed that the List Learning subtest was associated with depression, but Story Memory was not. All other RBANS indices and related subtests were not associated with depression scores. Clinical implications are discussed.

Objective Identifying risk factors is important in adolescent sports concussions. This study aimed to explore the relationship between affective symptoms and physical symptoms in youth concussions. Design Athletes were split into two groups: self-reported emotional symptoms (irritability/aggression, anxiety, depression, apathy, and/or labile mood; EMO, n=22) and a control group without emotional symptoms (CON, n=15). Groups were examined for differences between post-concussive symptoms and peri-concussive factors. Setting Outpatient clinic. Participants 37 concussed adolescents age 12–17 with persisting concussion symptoms were assessed. Concussion diagnoses were indicated by traumatically induced alterations in mental status (with or without LOC), disruption in brain functioning (memory loss/neurological deficits), and other physiologic symptoms post-concussion. Those with baseline psychiatric history and/or special education were excluded. Assessment of risk factors Post-concussive symptom variable relationships were assessed. Outcome measures group differences were analysed using ANOVAs. Results No differences between positive LOC, positive amnesia, or post-concussive criteria existed, indicating likely comparable severity. While there were no group differences for number of concussions, headaches, or nausea, those in EMO were significantly more likely to endorse photo-sensitivity (p=0.003, F=10.155) and phono-sensitivity (p=0.007, F=8.108). Both anxiety and irritability/aggression were significantly (p Conclusions Results indicate that adolescents who self-report emotional difficulties following sports concussion are more likely to endorse some physical symptoms, particularly photo-sensitivity and phono-sensitivity. Those experiencing anxiety or irritability are also more likely to experience increased attentional difficulties. Competing interests None.

Posterior cortical atrophy (PCA), also known as the visual variant of Alzheimer’s Disease, is a rare neurodegenerative disorder that affects the visuospatial systems in its initial stages. Due to the rarity of this condition and the presence of relatively preserved memory during its early stages compared to other dementias, its accurate diagnosis can be delayed. When accompanied by a comorbid visual disorder, the diagnostic process becomes even more challenging. This study describes the disease course of a patient whose diagnosis of Fuchs’ Endothelial Corneal Dystrophy served to delay an additional diagnosis of PCA, illustrating the necessity of careful scrutiny of symptom presentation and especially its course.

Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

Among commercial and industrial chemicals, cosmetics, food additives, pesticides, and medicinal drugs, there are more than 50,000 substances distributed. Neurotoxic insults to the brain can manifest in many different ways, especially involving cognition. Given many possible differences in the pathophysiology of neurotoxic exposure and related cognitive sequelae, a systematic method of cognitive assessment is important for appropriate management of neurotoxic exposure. In the context of Neurotoxicology, this article briefly reviews the contemporary literature and the utility of cognitive assessment tools that are used in neuropsychology.

Cerebral fat embolism is an uncommon but serious complication of long-bone fracture. We report a young adult patient who sustained fat embolism after a femoral fracture. He developed stupor and coma within 24 hours from his injury. His acute recovery was characterized by marked frontal dysfunction. A comprehensive neuropsychological evaluation 4 months later revealed overall normal cognitive function, except for mild residual frontal dysfunction and weakness of verbal memory.

Correspondence: Brandon C Dennis Department of Neurology, University of Kentucky College of Medicine, 740 S Limestone St, Ste L-445, Lexington, KY 40536-0284, USA Tel +1 859 218 5051 Fax +1 859 323 3753 email brandoncdennis@uky.edu Abstract: The introduction of highly active antiretroviral therapy has had an enormous impact on the management of human immunodeficiency virus (HIV) infection and has led to an increase in survival and decrease in HIV-associated dementia. However, minor neurocognitive disturbances across various neurocognitive domains remain common in 50% or more of HIV patients according to recent estimates. Increased longevity has led to the investigation of several moderating and complicating factors, including vascular disease, neurotoxicity, aging, substance abuse, hepatitis C coinfection, and psychiatric illness. This article provides a review of the history of HIV-associated neurocognitive disorders (HAND), revised diagnostic terminology, factors moderating development of HAND, assessment techniques and neurocognitive profiles, current treatment and limitations, and future research directions.