Impaired Neurocognitive Function Research Articles

Drugs of Abuse in HIV infection and neurotoxicity.

HIV is a neurotropic virus that enters the brain right after infection. In the brain, HIV replicates in macrophages, microglia and small number of astrocytes (4.7 ± 2.8% in vitro and 8.2 ± 3.9 in vivo) (Eugenin et al., 2011) causing inflammatory and neurotoxic host responses. Severe neurological disorders caused by HIV are collectively known as HIV-associated neurocognitive disorders (HAND). HAND is characterized by development of abnormal reduction of motor speed, concentration, and memory. HAND consists of several clinical forms ranging from asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND) to the most severe HIV-associated dementia (HAD) (McArthur and Brew, 2010). HIV-encephalitis (HIVE) is the main cause of HAND and the most common neurologic disorder of the brain in HIV-1 infection. HIV-1 exhibits extensive genetic variation worldwide and is categorized into three groups (M, O, and N) and genetically into nine different subtypes (A–K). Of these, clades B and C represent the majority (>86%) of circulating HIV-1 variants (Osmanov et al., 2002). While HIV-1 clade B is predominant in North America, Western Europe, and Australia; clade C is common in Southern and East Africa, India and Nepal (responsible for around half of all HIV infections). HIV-1 clade B has been reported to be more neuropathogenic than clade C (Atluri et al., 2013; Samikkannu et al., 2014). Before the worldwide use of highly antiretroviral therapy (HAART), approximately, 20–30% of individuals with advanced HIV-1 clade B infection showed symptoms of HAD (Gonzalez-Scarano and Martin-Garcia, 2005; Kaul et al., 2005). Although the prevalence of HAD has decreased intensely after the introduction of HAART, 40–50% of HIV positive patients still suffer from HAND (Sacktor et al., 2001; Sacktor, 2002; McArthur, 2004; Antinori et al., 2007; Ellis et al., 2007). In developed countries, about 30% of HIV-positive individuals are intravenous drug abusers, which place them in a higher risk for HAND (Miro et al., 2003; Beyrer et al., 2010). Cocaine and marijuana are the most common drugs of abuse among HIV patients, whereas opioids are abused only by a small number of patients (Kuo et al., 2004; Cook et al., 2007; Korthuis et al., 2008). Overall, several drugs of abuse such as tobacco, stimulants, cannabinoids, opioids and alcohol are found to be consumed among HIV infected individuals, having an effect on synaptic plasticity and development found in the brain (Hauser and Knapp, 2014). Figure ​Figure11 is showing different neurotoxic mechanisms of drugs of abuse in HIV infection which may lead to the impaired neurocognitive functions. Figure 1 Schematic representation of neurotoxic mechanisms of different illicit drugs of abuse in HIV infection. Nicotine and HIV Recently, in nicotine and HIV infected SK-N-MC cells, an up-regulation of HDAC2 was observed (Atluri et al., 2014). HDAC2 overexpression has been reported in depleted memory formation, synaptic plasticity and dendritic spine density (Guan et al., 2009). Nevertheless, use of nicotine in infected patients can have beneficial outcomes on neurological deficits that were HIV-1 induced (Cao et al., 2013). In nicotine injected HIV-1 transgenic rats brain regions, such as in the prefrontal cortex, Wnt/β-catenin signaling has shown improvement by restoring the down-regulation of Axin1, Wnt5a, Wnt7a and the up-regulation of Gnao1 (Cao et al., 2013). This signaling pathway plays an important role in the early development of the nervous system, in which a neuroprotective outcome in adults is established after the activation of this pathway (Nave and Trapp, 2008). These results are important since central demyelination and neurodegeneration have been observed in HIV-1 infected individuals. In the dorsal hippocampus, CREB signaling has also been restored, in which the decreased expression of calcium sensor proteins, Calm3 and Cabp1, was regulated to normal levels. This signaling pathway is significant in neuronal survival and long-term synaptic plasticity. In the dorsal striatum, nicotine has also shown to restore the function of the tricarboxylic acid (TCA) cycle and its related pathways, such as the down-regulation of Idh3B and up-regulation of Ndufs4 that came back to normal levels (Cao et al., 2013).

Neurocognitive Impairment in Major Depressive Disorder

Introduction Neurocognitive impairment has been widely reported in major depressive disorder. Patients with major depressive disorder are known to present cognitive deficits, namely in verbal and visual memory, verbal fluency, attention, working memory. Some studies related these deficits with antidepressants, although those were also described in medication-free patients. Other studies suggested that in some groups of patients there may be significant residual cognitive deficits despite an overall positive treatment response with remission of depressive episodes. Objectives/Aims The authors aim to contextualize cognitive deficits in patients with major depressive disorder and treatment options that could preserve/improve the cognitive functions. Methods Scientific literature search and review on the PubMed database with the keywords: 'major depressive disorder', 'cognition', 'neurocognitive impairment', 'memory', 'executive function', 'attention'. Results Given the perception of impaired neurocognitive functioning in patients with major depressive disorder even in the remission phases, there has been an increased interest in attempting to treat those deficits during the last decade. Studies suggest that different types of deficits are found in patients medicated with different types of antidepressants and medication-free patients. Some new treatment approaches have been used such as cognitive remediation therapy which is more frequently used in schizophrenia. Recent studies suggest that cognitive enhancing treatments could be an approach which should be further investigated. Conclusions Currently, the mechanisms underlying neurocognitive deficits in patients with major depressive disorder are not fully understood. Since these symptoms have a major impact on patients' lives this issue will remain an area of ??interest in the near future.

Volume of White Matter Hyperintensities Predicts Neurocognitive Functioning in Children with Sickle Cell Disease

IntroductionApproximately 40% of children with a severe form of sickle cell disease (SCD) will develop cerebral white matter hyperintensities (WMHs), visible on magnetic resonance imaging (MRI). This may be associated with impaired neurocognitive functioning. It is unknown whether the volume of these WHMs is associated with the degree of neurocognitive dysfunction. Our objective was to investigate the association between volume of WMHs and neurocognitive functioning.MethodsWe prospectively included children with HbSS or HbS-beta(0)thalassemia aged 8-16 years. Exclusion criteria were prior stroke and chronic blood transfusion therapy. Volume of WMHs was calculated on MRI and patients were ranked by size of WMHs. Neurocognitive function was evaluated by testing intelligence (IQ, intelligence quotient), memory, visuo-motor functioning and executive functioning. Fatigue was measured using a validated questionnaire (Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, PedsQL Fatigue) in which lower scores indicate more symptoms of fatigue. For each neurocognitive outcome, univariate linear regression was used to identify which variables (age, sex and hemoglobin level) were confounders. The independent association of volume of WMHs on neurocognitive outcomes was analyzed by multivariate linear regression, adjusted for these confounders when appropriate. The explained variance (R2) refers to the independently explained variance of volume of WMHs on the neurocognitive outcome and the presented p-value corresponds to the unique contribution of volume of WMHs on the outcome, both adjusted for confounders when appropriate.ResultsWe included 38 children; mean age was 12.5 ± 2.7 years, WMHs were present in 50%. Mean full-scale, verbal IQ, performal IQ and Processing Speed Index were all between 85 and 90; this is significantly lower compared to the mean norm scores of 100. Our patients had significantly more symptoms of fatigue compared to Dutch reference values. A higher volume of WMHs was significantly associated with lower scores on full-scale IQ, verbal IQ and Processing Speed Index (see table). In addition, higher volume of WMHs was associated with higher scores of total and cognitive fatigue. Standardized beta coefficients ranged from -0.350 to -0.461, indicating a substantial negative effect of an increasing volume of WMHs on neurocognitive outcome. The volume of WMHs could explain between 12.1% and 21.2% of the variance of these outcomes.ConclusionOur findings suggest that the volume of WMHs is an independent predictor of full-scale IQ, verbal IQ, Processing Speed Index and fatigue in children with SCD. As WMHs are mostly found in the frontal lobe, this could explain the association with processing speed, which is an executive function and thought to be located in the frontal lobe. The association between WMHs and measures of fatigue has not been investigated before. Our results suggest the PedsQL Fatigue could be a promising screening tool for larger studies as it is easy and quick to administer and has a high validity. We suggest that future studies should consider taking the total volume of WMHs into account as an independent predictor of neurocognitive outcome, instead of only the presence or absence of WMHs. Taking the volume of WMHs into account is an important approach for individualized diagnostic and treatment strategies that could be further explored in a clinical setting.TablePrediction model of neurocognitive outcome by volume of white matter hyperintensitiesßR2pFull-scale IQ-0.3820.1460.018Verbal IQ-0.4600.2120.004Performal IQ-0.1700.0290.314Processing Speed Index-0.4610.2120.005PedsQL Fatigue, Total Score-0.3500.1210.025PedsQL Fatigue, General Fatigue-0.2890.0830.071PedsQL Fatigue, Cognitive Fatigue-0.3520.1230.026IQ, Intelligence Quotient; PedsQL Fatigue, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale. DisclosuresNo relevant conflicts of interest to declare.

Neurocognitive Function After (Chemo)-Radiotherapy for Head and Neck Cancer

Radical radiotherapy has a pivotal role in the treatment of head and neck cancer (HNC) and cures a significant proportion of patients while simultaneously sparing critical normal organs. Some patients treated with radical radiotherapy for HNC receive significant radiation doses to large volumes of brain tissue. In fact, intensity-modulated radiotherapy techniques for HNC have been associated with a net increase in irradiated brain volumes. The increasing use of chemoradiotherapy for HNC has additionally exposed this patient population to potential neurotoxicity due to cytotoxic drugs. Patients with HNC may be particularly at risk for adverse late brain effects after (chemo)-radiotherapy, such as impaired neurocognitive function (NCF), as risk factors for the development of HNC, such as smoking, excess alcohol consumption and poor diet, are also associated with impaired NCF. The relatively good survival rates with modern treatment for HNC, and exposure to multiple potentially neurotoxic factors, means that it is important to understand the impact of (chemo)-radiotherapy for HNC on NCF, and to consider what measures can be taken to minimise treatment-related neurotoxicity. Here, we review evidence relating to the late neurotoxicity of radical (chemo)-radiotherapy for HNC, with a focus on studies of NCF in this patient population.

Association between schizophrenia symptoms and neurocognition on mobility in older adults with schizophrenia

Objectives: Older persons with schizophrenia develop problems associated with aging, such as poor mobility, at more rapid rates than people without serious mental illness. Decrements in mobility contribute to poor health outcomes. Impaired neurocognitive function and psychiatric symptoms are central aspects of schizophrenia. The purpose of this study was to determine the association between neurocognitive impairment and schizophrenia symptoms to mobility in older adults with schizophrenia.Methods: A cross-sectional study with 46 older adults with schizophrenia. Participants were assessed on neurocognitive function (MATRICS Consensus Cognitive Battery), psychiatric symptoms (Positive and Negative Syndrome Scale or PANSS), and mobility (Timed Get Up and Go or TGUG test). Pearson's bivariate correlations (two-tailed) and a simultaneous regression model were used.Results: Lower severity of negative symptoms and faster speed of processing tests were associated with faster TGUG time in bivariate correlations and multivariate regression analyses (p < .05).Conclusion: Our data suggest that lower negative symptoms and faster speed of processing positively impact mobility in older patients with schizophrenia. Mobility interventions for this population need to target neurocognitive impairment and schizophrenia symptoms for optimal results.

Factors affecting functional outcomes in long-term survivors of intracranial germinomas: a 20-year experience in a single institution

Radiation monotherapy-prophylactic craniospinal or whole-brain irradiation paired with a radiation boost to the primary tumor-is the standard treatment for intracranial germinomas at the authors' institution. The authors assessed long-term outcomes of patients with germinoma who underwent therapy and identified factors affecting them. The authors retrospectively analyzed data obtained in 46 patients (35 males and 11 females, age 5-43 years at diagnosis) who had been treated for intracranial germinomas between 1990 and 2009 at the authors' institution. Thirty patients had germinomas in localized regions and 16 in multiple regions. Thirty-eight patients (83%) underwent radiotherapy alone (craniospinal irradiation in 32 and whole-brain irradiation in 6). Seven patients underwent radiochemotherapy and 1 underwent chemotherapy alone. The mean radiation doses for the whole brain, spine, and primary tumor site were 26.9, 26.6, and 49.8 Gy, respectively. The median follow-up period was 125 months. The 10-year overall and recurrence-free survival rates were 93.3% and 89.3%, respectively. None of the 38 patients who received radiation monotherapy developed a recurrent lesion, whereas 1 of 7 who underwent radiochemotherapy and the 1 patient who underwent chemotherapy had a recurrent lesion. Of the entire population, 26 patients required hormone replacement therapy, 2 had short stature, and 1 developed a radiation-induced meningioma. Seventeen of the 25 childhood- or adolescent-onset patients were 19 years or older at the latest follow-up visit, 15 of whom graduated from senior high school, and only 2 of whom graduated from college. Of 34 patients who were 19 years or older at the latest visit, 4 were students, 18 worked independently, 4 worked in sheltered workplaces, and 8 were unemployed. Of the 34 patients, 4 got married after the initial treatment, 3 of whom had children. There were 8 patients (17%) with low postoperative Karnofsky Performance Scale (KPS) scores that were significantly associated with impaired neurocognitive functions, severe surgical complications, and neurological impairments. In 10 of the 46 patients, KPS scores at the latest visit were lower than their postoperative KPS scores. These decreases in KPS scores were significantly correlated with a delayed decline in neurocognitive functions in childhood-onset patients and a postoperative impairment of neurocognitive functions in patients with adolescent- or adult-onset germinoma. No tumor recurrence occurred in germinoma patients treated with the authors' radiation monotherapy, which appears to be effective enough to cure the tumor. Brain damage caused by tumors themselves and surgical complications were found to adversely affect functional outcomes in patients regardless of their age. Although radiotherapy rarely caused late adverse effects in patients with adolescent- or adult-onset, in some childhood-onset lesions, the radiation seems to carry the risk of neurocognitive dysfunctions, which are attributable to late adverse effects. Accordingly, treatments for germinoma patients should be selected according to a patient's age and the extent of the tumor and with particular care to avoid surgical complications.

Attention networks in pediatric brain tumor survivors

INTRODUCTION Pediatric brain tumor survivors (PBTS) are at increased risk of impaired neurocognitive functioning. Attention plays an important role in acquiring new knowledge and skills. Posner and Peterson (1990) distinguish three independent attention networks in the brain that enable alerting, orienting, and executive attention. We aim to investigate the functioning of these networks in PBTS.

Perinatal risk factors for neurocognitive impairments in preschool children born very preterm.

This study aimed to compare a broad array of neurocognitive functions (processing speed, aspects of attention, executive functioning, visual-motor coordination, and both face and emotion recognition) in very preterm and term-born children and to identify perinatal risk factors for neurocognitive dysfunctions. Children who were born very preterm (n=102; 46 males, 56 females), defined as a gestational age of less than 30 weeks and/or birthweight under 1000 g, and a comparison group of term-born children (n=95; 40 males, 55 females) were assessed at age 5 with the Wechsler Preschool and Primary Scale of Intelligence, Stop Signal Task, several tasks of the Amsterdam Neuropsychological Tasks, and a Digit Span task. When sociodemographic characteristics were taken into account, very preterm children scored worse than term-born children on all neurocognitive functions, except on tasks measuring inhibition and sustained attention, for which results were inconclusive. Effect sizes for group effects were small to medium (r(2) varying between 0.02 and 0.07). Principal component isolated four factors: visual-motor coordination, face/emotion recognition, reaction time/attention, and accuracy/attention. When sociodemographic and child characteristics at birth were accounted for, bronchopulmonary dysplasia was significantly negatively associated with all four components and also with working memory. Very preterm children are at risk for problems on a broad array of neurocognitive functions. Bronchopulmonary dysplasia is an independent risk factor for impaired neurocognitive functioning.

Impaired neurocognitive function among HIV‐infected Thais on stable antiretroviral therapy for more than 7 years

BackgroundThere are limited data on HIV‐associated neurocognitive disorders (HANDs) from resource‐constraint region and few studies have firm documentation of duration of treatment and suppression of plasma virus. This study aimed to estimate the prevalence of HIV‐related cognitive deterioration among HIV‐infected patients who were on stable ART and to describe the pattern of neurocognitive impairment (NCI), daily life disturbance and associated factors.MethodsThis was a cross‐sectional evaluation of cognition in a sample of HIV adults at HIV‐NAT, the Thai Red Cross AIDS Research Centre with data captured over a 6‐month period. The Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS) and Activities of Daily Living Questionnaire (ADLQ) scale were administered. NCI was defined as a score of ≤10 on the IHDS or &lt;26 on the MoCA. The HIV‐NAT Cohort Database was explored to retrieve sociodemographic data and clinical factors.ResultsAmong the 162 patients evaluated, the mean (±SD) age was 42.8 (±7.3) years and 56.8% were male. HBV and HCV co‐infection frequencies were 11.7% and 7.4%, respectively. The mean (±SD) duration of ART was 9.03 (±3.12) years. Of all, 59.3% were concurrently on protease inhibitor (PI) based regimens. 97.5% had virologic success with HIV‐RNA load of less 200 copies/mL. The prevalence of NCI was 68.5% by MoCA and 75.8% by IHDS. Tests on visuospatial cognition, language and abstraction were most commonly poor scores (81.5%, 89.5% and 74.1%, respectively). Among these, 54.9% and 61.3%, respectively, were asymptomatic without overt daily functioning interference. Daily self‐care and household care were the most commonly endorsed daily activity defects (16.7% and 12.3%, respectively). Remaining as a couple (p=0.001), duration of education &lt;12 years (p&lt;0.001) and heterosexual risk (p=0.001) were associated with NCI. The MoCA and IHDS scales correlated to each other (r2=0.177, p=0.024). Logistic regression demonstrated fewer years of education and remaining as a couple were associated with impaired MoCA scale (P=0.001 and 0.008, respectively).ConclusionImpaired cognitive function is commonly detected among HIV‐infected Thais on stable ART for over 7 years. The frequency of NCI is higher than that reported in other settings. However the performance characteristics of our screens have not been firmly established in this setting and the cut‐off levels used may over‐estimate NCI.

Impaired Neurocognitive Functions Affect Social Learning Processes in Oppositional Defiant Disorder and Conduct Disorder: Implications for Interventions

In this review, a conceptualization of oppositional defiant (ODD) and conduct disorder (CD) is presented according to which social learning processes in these disorders are affected by neurocognitive dysfunctions. Neurobiological studies in ODD and CD suggest that the ability to make associations between behaviors and negative and positive consequences is compromised in children and adolescents with these disorders due to reduced sensitivity to punishment and to reward. As a result, both learning of appropriate behavior and learning to refrain from inappropriate behavior may be affected. Likewise, problem solving is impaired due to deficiencies in inhibition, attention, cognitive flexibility, and decision making. Consequently, children and adolescents with ODD and CD may have difficulty learning to optimize their behavior in changeable environments. This conceptualization of ODD and CD is relevant for the improvement of the effect of psychological treatments. Behavioral and cognitive-behavioral interventions that have been shown to be modestly effective in ODD and CD are based on social learning. Limited effectiveness of these interventions may be caused by difficulties in social learning in children and adolescents with ODD and CD. However, although these impairments have been observed at a group level, the deficits in reward processing, punishment processing, and cognitive control mentioned above may not be present to the same extent in each individual with ODD and CD. Therefore, the neurocognitive characteristics in children and adolescents with ODD and CD should be assessed individually. Thus, instead of delivering interventions in a standardized way, these programs may benefit from an individualized approach that depends on the weaknesses and strengths of the neurocognitive characteristics of the child and the adolescent.

Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth-)amphetamine, ecstasy and nicotine dependence, and excessive caffeine use, comparing stimulant abusers (SAs) to nondrug using healthy controls (HCs). Despite some inconsistencies, most studies indicated altered brain activation in prefrontal cortex (PFC) and insula in response to reward and punishment, and higher limbic and anterior cingulate cortex (ACC)/PFC activation during craving and attentional bias paradigms in SAs compared with HCs. Impulsivity in SAs was associated with lower ACC and presupplementary motor area activity compared with HCs, and related to both ventral (amygdala, ventrolateral PFC, insula) and dorsal (dorsolateral PFC, dorsal ACC, posterior parietal cortex) systems. Decision making in SAs was associated with low dorsolateral PFC activity and high orbitofrontal activity. Finally, executive function in SAs was associated with lower activation in frontotemporal regions and higher activation in premotor cortex compared with HCs. It is concluded that the lower activations compared with HCs are likely to reflect the neural substrate of impaired neurocognitive functions, whereas higher activations in SAs compared with HCs are likely to reflect compensatory cognitive control mechanisms to keep behavioral task performance to a similar level as in HCs. However, before final conclusions can be drawn, additional research is needed using neuroimaging in SAs and HCs using larger and more homogeneous samples as well as more comparable task paradigms, study designs, and statistical analyses.

Enhanced Lithium-Induced Brain Recovery Following Cranial Irradiation Is Not Impeded by Inflammation

Radiation-induced brain injury occurs in many patients receiving cranial radiation therapy, and these deleterious effects are most profound in younger patients. Impaired neurocognitive functions in both humans and rodents are associated with inflammation, demyelination, and neural stem cell dysfunction. Here we evaluated the utility of lithium and a synthetic retinoid receptor agonist in reducing damage in a model of brain-focused irradiation in juvenile mice. We found that lithium stimulated brain progenitor cell proliferation and differentiation following cranial irradiation while also preventing oligodendrocyte loss in the dentate gyrus of juvenile mice. In response to inflammation induced by radiation, which may have encumbered the optimal reparative action of lithium, we used the anti-inflammatory synthetic retinoid Am80 that is in clinical use in the treatment of acute promyelocytic leukemia. Although Am80 reduced the number of cyclooxygenase-2-positive microglial cells following radiation treatment, it did not enhance lithium-induced neurogenesis recovery, and this alone was not significantly different from the effect of lithium on this proinflammatory response. Similarly, lithium was superior to Am80 in supporting the restoration of new doublecortin-positive neurons following irradiation. These data suggest that lithium is superior in its restorative effects to blocking inflammation alone, at least in the case of Am80. Because lithium has been in routine clinical practice for 60 years, these preclinical studies indicate that this drug might be beneficial in reducing post-therapy late effects in patients receiving cranial radiotherapy and that blocking inflammation in this context may not be as advantageous as previously suggested.

The Effects of the Benzodiazepine, Temazepam, on Neurocognitive Functioning and Sleep Patterns in Methamphetamine-Dependent Participants

Objectives: Previous research has shown that methamphetamine users demonstrate poorer sleep quality and daytime sleepiness when compared to healthy controls. It is also well known that long-term methamphetamine use is associated with impaired neurocognitive function and, similarly, sleep deprivation is associated with decreased neurocognitive performance. Temazepam is a potent sedative and is effective for the treatment of insomnia. It was hypothesized that treatment of methamphetamine dependent volunteers with temazepam would improve sleep characteristics resulting in improved cognitive functioning. Methods: 18 subjects completed a seven-day inpatient study where they completed daily subjective assessments, such as the PSQI, ESS, and VAS. Temazepam or placebo was administered on the evenings of Nights 5 and 6. Sleepiness was objectively assessed using the MSLT on Days 5-7 and neurocognitive testing was performed on Day 5 (prior to drug administration) and on Day 7. Results: The findings of this study demonstrate that temazepam did not improve quality of sleep, did not decrease sleep onset latency, and did not improve in neurocognition in methamphetamine-dependent participants. Discussion: Since the chosen dose and duration of temazepam did not improve neurocognitive performance when compared to placebo, further research must be performed to better understand temazepam’s effects and potential utility in this population.

Impaired behavioral and neurocognitive function in preschool children with obstructive sleep apnea

We aimed to examine the hypothesis that behavioral and neurocognitive functions of preschool children with Obstructive Sleep Apnea Syndrome (OSAS) are impaired compared to healthy children, and improve after adenotonsillectomy (TA). A comprehensive assessment battery was used to assess cognitive and behavioral functions, and quality of life in children with OSAS compared to matched controls. 45 children (mean age 45.5 ± 9 months, 73% boys, BMI 15.7 ± 2) with OSAS were compared to 26 healthy children (mean age 48.6 ± 8 months, 46% boys, BMI 16.4 ± 2). Mean AHI in the OSAS group was 13.2 ± 10.7 (ranging from 1.2 to 57). Significantly impaired planning and fluency (executive function) were found in children with OSAS, as well as impaired attention and receptive vocabulary. Parents and teachers described the OSAS group as having significantly more behavior problems. Quality of life questionnaire in children with OSAS (mean 2.3, range 0.7-4.3) was significantly worse compared to controls (mean 0, range: 0-4), P < 0.004. One year following TA, 23 children with OSAS and 18 controls were re-evaluated. Significant improvement was documented in verbal and motor fluency, sustained attention, and vocabulary. After TA, fewer behavioral problems were seen. Preschool children with OSAS present significantly impaired executive functions, impaired attention and receptive vocabulary, and more behavior problems. One year after TA, the prominent improvements were in behavior and quality of life. These findings suggest that the impact of OSAS on behavioral and cognitive functions begins in early childhood.

Hypertension and Cerebral Vascular Reactivity in Childhood: Challenge and Opportunity

HomeStrokeVol. 42, No. 7Hypertension and Cerebral Vascular Reactivity in Childhood: Challenge and Opportunity Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBHypertension and Cerebral Vascular Reactivity in Childhood: Challenge and Opportunity Rebecca Ichord, MD Rebecca IchordRebecca Ichord From the Department Neurology & Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA. Search for more papers by this author Originally published26 May 2011https://doi.org/10.1161/STROKEAHA.111.617803Stroke. 2011;42:1805–1806Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 See related article, pages 1834–1838The study of childhood origins of adult cardiovascular disease has grown dramatically in the past decade. Childhood-onset obesity, hypertension, and hyperlipidemia confer increased risk of cardiovascular morbidity and mortality in adulthood.1 The mechanisms for these relationships are incompletely understood. Even less is known about the extent to which end-organ injury referable to these risk factors actually begins during childhood. The study by Wong et al2 provides new insights concerning the early-life effects of hypertension on cerebrovascular physiology. The rapid increase in prevalence of cardiovascular risk factors such as obesity and hypertension among US children underscores the public health implications of their observations.Wong et al evaluated cerebrovascular reactivity to hypercapnia among children with essential hypertension compared with normotensive control subjects. They tested the hypothesis that hypertension is associated with impaired hypercapnic reactivity measured by increased cerebral blood flow velocity on transcranial Doppler. Hypertension was carefully measured and quantified using well-defined and standardized 24-hour ambulatory blood pressure monitoring methods. Cerebrovascular reactivity measures were likewise well-defined and carried out in a standardized manner. These transcranial Doppler data on cerebrovascular reactivity are interesting and novel in their own right, because there are few published studies reporting transcranial Doppler data, much less hypercapnic reactivity, in awake, neurologically well children. They found hypercapnic reactivity is decreased in hypertensive children compared with normotensive control subjects with a negative linear correlation between reactivity and both mean 24-hour diastolic blood pressure and diastolic load. The relatively small sample size precluded additional analyses of potential modifying factors such as sex, race, age, and the effect of treatment with antihypertensive drugs.Having confirmed that hypertension is associated with decreased cerebrovascular reactivity, as is seen in adults, a number of compelling questions beg to be further evaluated. The authors have raised the question, for example, as to whether impaired cerebrovascular reactivity with hypertension is associated with impaired neurocognitive function in children as is seen in adults. A few tantalizing clues already exist in a small number of published studies that support an association between hypertension and diminished neurocognitive function and academic attainment in children.3,4Much more study is needed, however, to reproduce these observations in larger populations to determine the longitudinal trends through different stages of childhood and beyond to adult life and, importantly, to establish what the causal relationships and mechanisms may be. For example, there are no published studies evaluating neuroimaging correlates of neurocognitive impairments in hypertensive children. The existence of potentially quantifiable and anatomically specific structural neuroimaging markers of cerebral injury from childhood hypertension may provide additional insights concerning mechanism as well as objective end points for interventions. Juonala et al5 reported age-dependent associations between cardiovascular risk factors and the findings of early atherosclerosis on vessel imaging in children and adolescents. It would be of great interest to evaluate the relative contribution of childhood hypertension compared with other cardiovascular risk factors such as obesity and hyperlipidemia on vessel wall markers of early atherosclerosis and to understand how this is related, if at all, to the development of disturbed cerebrovascular reactivity.Ultimately, a clearer understanding of the mechanisms and epidemiology of childhood precursors of cerebrovascular disease will be essential for designing interventions and subjecting these to clinical trial. The magnitude of the public health implications of these problems can hardly be overstated. Studies such as that of Dr Wong and colleagues are groundbreaking by demonstrating that understanding and effectively preventing chronic adult-onset cardiovascular and cerebrovascular disease may best begin in childhood. Moreover, the dividends of treating childhood precursors of adult disease may become evident in childhood by halting or reversing clinically significant end-organ injury even early in life.DisclosuresNone.FootnotesThe opinions in this editorial are not necessarily those of the editors or of the American Heart Association.Correspondence to Rebecca Ichord, MD, CTRB 10th Floor, Department of Neurology, Children's Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, PA 19104. E-mail [email protected]chop.edu

Evidence of impaired neurocognitive functioning in school‐age children awaiting cardiac surgery

Children with congenital heart disease (CHD) are at risk of developing neurocognitive problems. However, as these problems are usually identified after cardiac surgery, it is unclear whether they resulted from the surgery or whether they pre-existed and hence might be explained by complications and events associated with the heart disease itself. The purpose of this study was to examine whether neurocognitive deficits commonly reported after cardiac surgery are present before surgery. Forty-five children (22 males, 23 females; mean age 11 y 6 mo, SD 3 y 0 mo) with cyanotic and acyanotic heart diseases scheduled for elective cardiac surgery were compared with 41 healthy peers (17 males, 24 females; mean age 11 y 10 mo, SD 2 y 10 mo) for attention and processing speed, construction, motor speed, motor planning and fluency, and visual memory. Twenty-three children in the patient group were awaiting their first cardiac surgery and 22 were awaiting follow-up surgery. The patients showed manifest neurocognitive difficulties. Their performance was inferior to that of the healthy comparison group for motor planning (p=0.02) and visual memory (p=0.01). The same neurocognitive profile was found in the group of patients awaiting their first cardiac operation. School-age children with various forms of CHD are at risk of neurocognitive impairments before cardiac surgery.

MAP'ing CNS Development and Cognition: An ERKsome Process

The ERK MAP kinase signaling cascade plays critical roles in brain development, learning, memory, and cognition. It has recently been appreciated that mutation or deletion of elements within this signaling pathway leads to developmental syndromes in humans that are associated with impaired cognitive function and autism. Here, we review recent studies that provide insight into the biological roles of the ERKs in the brain that may underlie the cognitive deficits seen in these syndromes.

Advances in endophenotyping schizophrenia

The search for the genetic architecture of schizophrenia has employed multiple, often converging strategies. One such strategy entails the use of tracing the heritability and neurobiology of endophenotypes. Endophenotypes are quantifiable traits not visible to the eye, which are thought to reflect an intermediate place on the path from genes to disorder. Endophenotype abnormalities in domains such as neurophysiology or neurocognition occur in schizophrenia patients as well as their clinically "unaffected" relatives, and reflect polymorphisms in the DNA of schizophrenia spectrum subjects which create vulnerability to developing schizophrenia. By identifying the single nucleotide polymorphisms (SNPs) associated with endophenotypes in schizophrenia, psychiatric neuroscientists can select new strong inference based molecular targets for the treatment of schizophrenia.

Delayed cognitive, behavioral, and radiological changes related to canial irradiation for pediatric brain tumors

20023 Purpose: To evaluate the delayed adverse changes in neuro-cognitive functions as well as white matter damage in radiated survivors of pediatric brain tumors. Methods: Forty two children (22 males) with primary brain tumors who were only treated with cranial radiation, were recruited. 28 patients were treated for low risk medulloblastoma, 10 patients for low grade astrocytoma, 3 patients for low grade ependymoma, and 1 patient for craniopharyngioma. Their ages ranged from 3 to 18 years (mean 10.3±3.98 years).They were subjected, initially just before radiotherapy and at follow-up 1–2 year after completion of cranial radiation, to serial clinical and neuropsychological assessments including Wechseler Intelligence Scale for Children, Vineland social maturity test, Benton Visual Memory Test, and Revised Behavior Problem Checklist. Magnetic resonance scans were also performed to detect the presence of white matter damage before radiotherapy and at follow up. Results: Initially, after surgery and before radiation, intelligence test scores were below normal scores for age and this was of high statistical significance (Total IQ: t= -3.02, P= 0.006). Visual memory test showed evidence of organicity in all cases. Social maturity showed a statistically significant decline as well (t= -2.11, P= 0.04). Follow-up after radiotherapy showed further decline with high statistical significance (Total IQ t= 3.228, P=0.003; visual memory t= 4.08, P= 0.001); An attentional problem has emerged (t= -6.12, P= 0.00). Both radiation dose and volume of radiation showed negative and statistically significant correlation with IQ. Age at diagnosis correlated positively and significantly with IQ ( r= 0.601, P=0.001). Multiple linear regression showed impaired neurocognitive function which was correlated with the degree of white matter damage. (standardized B= -0.577, P= 0.001) and young age at diagnosis (standardized B= -0.427, P= 0.014). Conclusions: Cranial radiation in pediatric brain tumors is associated with a decline in multiple neurocognitive functions including total IQ, visual memory, and attention; which are related to the toxic effect of cranial radiation on white matter of the brain especially in young age of childhood with high dose and whole cranial radiation. No significant financial relationships to disclose.

A meta‐analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia

Impaired neurocognitive functioning is one increasingly recognized long-term consequence of childhood ALL treatment. However, research findings have been inconsistent regarding the domains affected and the degree to which they are compromised. A comprehensive meta-analytic review of the long-term neurocognitive effects of childhood ALL was conducted. Studies were included if they were published in English, reported original quantitative data on the post-treatment neurocognitive functioning of childhood ALL patients in first remission and control groups, and used neurocognitive measures with adequate psychometric properties and published normative data. Data from 28 empirical studies yielding 13 effect sizes across nine domains were extracted and analyzed. All effects were negative (g = -0.34 to -0.71), demonstrating that ALL survivors consistently experienced significant deficits in intellectual functioning, academic achievement, and specific neurocognitive abilities compared to control groups. The role of potential moderators, including treatment with cranial irradiation, age at time of diagnosis, and time since treatment ended, was examined. However, no effects emerged as clearly and consistently moderated by these variables. The results from this meta-analysis suggest that declines in both global and specific areas of areas of neurocognitive functioning occur as a result of contemporary ALL treatment. Such deficits have significant implications for survivors' academic achievement and overall quality of life. Neurocognitive assessment plays a critical role in determining what remedial or specialized instruction is needed in childhood ALL survivors and should be included as a standard part of long-term follow-up care.