Severe Neurocognitive Deficits Research Articles

The Effect of Methylphenidate on Cognition in Patients with Comorbid Attention Deficit/Hyperactivity Disorder and Amphetamine Use Disorder: An Exploratory Single-Blinded within-Subject Study

Introduction: Attention deficit/hyperactivity disorder (ADHD) with co-occurring substance use disorder (SUD) is associated with poor treatment outcomes. Two randomized controlled trials, utilizing robust doses of stimulants, demonstrated a significant effect on treatment outcomes in patients with ADHD/SUD. This study aimed to investigate differences in executive functioning and explore the dose-dependent effect of OROS-methylphenidate (MPH) in patients with comorbid ADHD and amphetamine use disorder (ADHD+AMPH) and patients with ADHD only. Methods: Three groups (ADHD+AMPH, ADHD only, and healthy controls) were assessed repeatedly with a neuropsychological test battery. An exploratory within-subject single-blinded design was employed where the ADHD only group received a maximum dose of 72 mg OROS-MPH, the ADHD+AMPH group a maximum dose of 180 mg, whereas the healthy subjects did not receive any study medication. Both ADHD groups received the same dose titration up to 72 mg OROS-MPH. Results: The ADHD+AMPH group demonstrated a significantly poorer motor inhibition and spatial working memory and reported more severe ADHD symptoms compared to the ADHD only group. 180 mg OROS-MPH was associated with a significant improvement in executive functioning in the dual diagnosis group. However, the exploratory study design and recruitment issues do not allow for any conclusion to be drawn regarding the effect of 180 mg OROS-MPH. Conclusion: Patients with ADHD+AMPH present with more severe neurocognitive deficits compared to ADHD only. The effect of 180 mg OROS-MPH on cognition in patients with ADHD+AMPH was inconclusive. Future studies should consider recruitment issues and high drop-out rates in this study population.

Baseline neurocognitive dysfunction is ubiquitous in intrinsic brain tumors– results from a large Indian cohort of patients and analysis of factors associated with domain-specific dysfunction

BackgroundNeurocognitive function (NCF) before surgery is an important marker of baseline performance in patients with brain tumors. Increasingly, neurocognitive deficits (NCD) have been demonstrated in a high proportion of patients. Selection bias (patient, tumor, and surgical procedure related) may influence the prevalence and type of domains involved in patients with gliomas. MethodsWe evaluated baseline NCF in a consecutive cohort of intra-axial tumors in Indian patients (n = 142). A comprehensive battery evaluating five domains – attention & executive function (EF), memory, language, visuospatial function and visuomotor abilities was used. Deficits were categorized as severe and mild-moderate. Factors associated with severe NCD were evaluated. ResultsSevere NCD was present in 90% of the patients, 70% of them having affection of at least 2 domains. Attention-EF, memory and visuomotor speed were most affected. 132 underwent surgery (69 awake, 63 under general anesthesia - GA). The awake cohort had younger patients with lower grade gliomas and more left sided tumors. Multi-domain dysfunction was seen almost equally in awake/GA groups as well as left/right sided tumors. On multivariate analysis, older age, lower educational status and larger tumor volume adversely affected NCF in many of the domains. Only language dysfunction was location specific (temporal lobe tumors) though not laterality (left/right) specific. ConclusionsNCD were seen in a large majority of cases before surgery, including those undergoing awake surgery. Language may be affected even in tumors in the non-dominant hemisphere. Attention-EF and memory are most affected and need to be factored in while assessing patient performance intraoperatively during awake surgery as well as tailoring rehabilitative measures subsequently.

Neurocognitive function and mortality in patients with schizophrenia spectrum disorders

Individuals with schizophrenia spectrum disorders (SSD) have significantly lower life-expectancy than healthy people. Previously, we have identified baseline neurocognitive function in general and verbal memory and executive function in particular as related to mortality nearly two decades later. In this study, we aim to replicate these findings with a larger and age-matched sample. The patient group consisted of 252 individuals, 44 of whom were deceased and 206 alive. Neurocognition was assessed with a comprehensive battery. Results showed that the deceased group, compared to the living group, had significantly more severe neurocognitive deficits across nearly all domains. There were no differences in sex, remission status, psychosis symptoms, or function level between the groups. Immediate verbal memory and executive function were the strongest predictors of survival status. These results were nearly identical to our previous studies, and we conclude that baseline neurocognitive function is an important predictor for mortality in SSD. Clinicians should be mindful of this relationship in patients with significant cognitive deficits.

Prevalence of neuropsychiatric disorders in internally displaced persons with dementia during wartime in Ukraine

IntroductionDuring the second wave of Russia-Ukraine war, around 8 million were internally displaced. Negative mental health impact of the war cannot be underestimate. Among internally displaced persons (IDPs), particularly vulnerable category is people with neurocognitive deficits. Stress associated with displacement may cause a change not only in cognitive functions, but also affect the onset or evaluation of behavioral and psychological symptoms.Objectivesto study the prevalence of neuropsychiatric disorders in hospitalized patients with dementia, who were internally displaced and to compare with general population frequency.Methods64 IDPs with dementia (moderate and severe neurocognitive deficits) who were examined during March-September 2022. Cases of newly arrived persons were taken into account, after 1 to 30 days had passed since their relocation. The diagnosis was verified based on the ICD-10 criteria (F00-F01). The degree of neurocognitive deficit was determined using the MMSE and MoCA tests. Affective pathology was studied using the HAM-D, HAM-A, PHQ-9, AES scales. Psychotic symptoms and behavioral disorders were studied based on clinical examination and medical records. The study was conducted in Lviv Regional Psychiatric Hospital.Resultsamong the examined patients, 60 (94% of all examined) had neuropsychiatric disorders. Among this sample, neuropsychiatric symptoms (an isolated symptom or a combination of two or more symptoms) occurred with the following frequency: apathy 16 (26.7%), anxiety49 (81.7%), depressive symptoms 32 (53.3%), agitation and aggression 41 (68.3%), hallucinatory symptoms 8 (13.3%), delusional disorders 34 (56.7%), wandering and disorientation 18 (30%), refusal of food and medicine 12 (20%)Image:ConclusionsIn this study the frequency of occurrence of certain neuropsychiatric syndromes among IDPs with dementia differed from the studied average frequency of occurrence of the same symptomatology among the general population. In particular, anxiety symptoms among IDPs with dementia occurred 42% more often than on average among patients with dementia in the general population (with a frequency of 81% vs 39%), agitation and aggression - 28% more often (68% vs 40%), and delusions - 16% more often (57% vs 31%). At the same time, symptoms such as apathy (by 19%) and refusal to eat (by 14%) were observed less often among IDPs with dementia than among dementia patients from the general populationDisclosure of InterestNone Declared

Reward network dysfunction is associated with cognitive impairment after stroke

Stroke survivors not only suffer from severe motor, speech and neurocognitive deficits, but in many cases also from a “lack of pleasure” and a reduced motivational level. Especially apathy and anhedonic symptoms can be linked to a dysfunction of the reward system. Rewards are considered as important co-factor for learning, so the question arises as to why and how this affects the rehabilitation of stroke patients.We investigated reward behaviour, learning ability and brain network connectivity in acute (3-7d) mild to moderate stroke patients (n = 28) and age-matched healthy controls (n = 26). Reward system activity was assessed using the Monetary Incentive Delay task (MID) during magnetoencephalography (MEG). Coherence analyses were used to demonstrate reward effects on brain functional network connectivity.The MID-task showed that stroke survivors had lower reward sensitivity and required greater monetary incentives to improve performance and showed deficits in learning improvement. MEG-analyses showed a reduced network connectivity in frontal and temporoparietal regions. All three effects (reduced reward sensitivity, reduced learning ability and altered cerebral connectivity) were found to be closely related and differed strongly from the healthy group.Our results reinforce the notion that acute stroke induces reward network dysfunction, leading to functional impairment of behavioural systems. These findings are representative of a general pattern in mild strokes and are independent of the specific lesion localisation. For stroke rehabilitation, these results represent an important point to identify the reduced learning capacity after stroke and to implement individualised recovery exercises accordingly.

Influence of clinical and therapeutic indicators on the severity of neurocognitive deficits in patients with schizophrenia

Aim. To assess the association of clinical and therapeutic parameters with the severity of the neurocognitive deficits in patients with schizophrenia. Materials and methods. We examined 118 patients with schizophrenia, aged 34 [29; 41] years, and with a disease duration of 10 [4; 16] years. 33 patients (28%) received conventional antipsychotic drugs (CAD), and 85 (72%) patients received atypical antipsychotic drugs (AAD). As concomitant therapy, 58 people (49.1%) took trihexyphenidyl, 60 people did not take it (50.9%). Assessment of cognitive functions was carried out for all patients using the Brief Assessment of Cognition in Schizophrenia (BACS), and clinical psychopathological symptomatology was evaluated using the Positive and Negative Syndrome Scale (PANSS). Statistical analysis of the data was performed using the Kruskal-Wallis test ANOVA with the multiple comparison procedure, the Pearson’s chi-squared test, and K-means cluster analysis. Results. Neurocognitive deficits formed three clusters of disturbances that differ in clinical severity: 1) mild, 2) moderate, 3) severe. According to the subscale of positive PANSS symptoms, patients with mild neurocognitive deficits had a lower average total score compared to patients with severe neurocognitive deficits ( p = 0.011), who, in turn, received significantly longer antipsychotic therapy compared with patients with moderate ( p = 0.014) and mild ( p = 0.01) neurocognitive deficits. Herewith, the duration of CAD treatment did not differ between clusters; consequently, the obtained results on antipsychotics as a whole were obtained due to AAD ( p = 0.005 and p = 0.001, respectively). Trihexyphenidyl did not affect the severity of neurocognitive deficits. Conclusion. The severity of positive symptoms of schizophrenia was lower in patients with mild neurocognitive deficits. The most pronounced neurocognitive deficits are observed in patients receiving AAD.

A-146 A Comparison of Neuropsychological Assessment Results and Self-Reported Cognitive Deficits in Traumatic Brain Injury Patients with Variable Neurocognitive Impairment Severity

Abstract Objective This study aimed to determine the relationship between symptom self-report accuracy and objective cognitive functioning in multiple cognitive domains for varying neurocognitive impairment (NCI) subsequent to Traumatic Brain Injury (TBI). Specifically, the discrepancy between self-report and objective findings among participants with mild, moderate, and severe NCI was examined within the cognitive domains of Attention, Executive Functioning, Learning/Memory, and Speech/Language. Method The sample included archival data consisting of neuropsychological scores and self-reported Ruff Neurobehavioral Inventory (RNBI) results of 135 adult TBI patients with mild, moderate, or severe NCI who received neuropsychological assessment at a private practice. Patients were grouped based on level of impairment using Halstead Impairment Index criteria. Results No main effect was found for Attention. Patients with severe NCI had greater discrepancies in Executive Functioning (p = 0.015), Learning/Memory (p = 0.015), and Speech/Language (p < 0.001) function, when compared to those with mild NCI. Additionally, patients with severe NCI demonstrated greater discrepancies in Speech/Language (p < 0.001) function when compared to those with moderate NCI. Conclusion These findings indicate as severity of neurocognitive impairment increases for TBI patients, self-reported cognitive symptomatology—specifically executive functioning, learning/memory, and speech/language—will become less accurate. Clinically, these findings suggest that when working with patients who have severe neurocognitive deficits subsequent to TBI, it is important to consider objective testing as self-reporting may not be accurate. Understanding patient’s genuine deficits will foster patient awareness and acceptance of TBI-related cognitive deficits with increased investment in treatment and improved neurorehabilitation outcomes.

Performance Validity Testing in Justice-Involved Adults with Fetal Alcohol Spectrum Disorder.

A number of commonly used performance validity tests (PVTs) may be prone to high failure rates when used for individuals with severe neurocognitive deficits. This study investigated the validity of 10 PVT scores in justice-involved adults with fetal alcohol spectrum disorder (FASD), a neurodevelopmental disability stemming from prenatal alcohol exposure and linked with severe neurocognitive deficits. The sample comprised 80 justice-involved adults (ages 19-40) including 25 with confirmed or possible FASD and 55 where FASD was ruled out. Ten PVT scores were calculated, derived from Word Memory Test, Genuine Memory Impairment Profile, Advanced Clinical Solutions (Word Choice), the Wechsler Adult Intelligence Scale - Fourth Edition (Reliable Digit Span and age-corrected scaled scores (ACSS) from Digit Span, Coding, Symbol Search, Coding - Symbol Search, Vocabulary - Digit Span), and the Wechsler Memory Scale - Fourth Edition (Logical Memory II Recognition). Participants with diagnosed/possible FASD were more likely to fail any single PVT, and failed a greater number of PVTs overall, compared to those without FASD. They were also more likely to fail based on Word Memory Test, Digit Span ACSS, Coding ACSS, Symbol Search ACSS, and Logical Memory II Recognition, compared to controls (35-76%). Across both groups, substantially more participants with IQ <70 failed two or more PVTs (90%), compared to those with an IQ ≥70 (44%). Results highlight the need for additional research examining the use of PVTs in justice-involved populations with FASD.

A longitudinal study of neurocognition and behavior in patients with Hurler-Scheie syndrome heterozygous for the L238Q mutation

Previous research has demonstrated the mutation, c.712T>A (p.L238Q) of the gene for α-L- iduronidase (IDUA) in patients with Hurler-Scheie syndrome is relatively severe when paired with a nonsense or deletion or splice-site mutation. This mutation was also found to be associated with psychiatric symptoms. This research presents longitudinal data and protein analysis to further investigate the severity and natural history of these unique patients. MethodsSix patients heterozygous for L238Q were compared to six patients with Hurler-Scheie without the L238Q mutations. Somatic burden of disease, IQ, memory, attention, adaptive functioning and behavioral measures were given yearly over 2 to 4 years from 2009 to 2014. The impact of L238Q on the IDUA enzyme was examined using 7 bioinformatics tools and a 3D structural analysis. ResultsSimilar to the cross sectional study, the L238Q patients had more severe abnormalities in IQ, attention, adaptive functioning, and behavioral functioning than the comparison group. There were no major differences between the two groups in change over time; IQ for both groups was stable with some behavioral areas showing improvement. Over time, both groups declined in visual spatial memory and, attention/visual processing. They also showed increased anxiety. Structural and bioinformatics analysis of the L238Q suggest that this mutation causes a significant reduction in the IDUA enzyme's potential catalytic activity, and this mutation may be more severe than other mutations contributing to the Hurler-Scheie syndrome phenotype, presumably causing the psychiatric disease. ConclusionL238Q patients demonstrate severe neurocognitive and neurobehavioral deficits but are relatively stable. Like the comparison group, decreasing visual spatial memory and attention and increasing anxiety suggest more intervention in life skills and emotional social supports are needed.

Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea

Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea

S65. Assessing the Developmental Taxonomy of Antisocial Behavior: Structural Neural Correlates of Life-Course Persistent vs. Adolescence-Limited Subtypes in a Longitudinal Birth Cohort

Conduct Disorder (CD) is characterized by persistent antisocial behavior, typically emerging before adulthood. Developmental Taxonomic Theory suggests that there are two etiological pathways of antisocial behavior: ‘life-course persistent’ (LCP), beginning in childhood and persisting into adulthood, and ‘adolescence-limited’ (AL), beginning in adolescence and limited to this developmental window. AL antisocial behavior is common and influenced by a normative gap between biological and social maturity, whereas the LCP subtype is less-common and exhibits more severe offending and neurocognitive deficits. Neuroimaging research into CD subtypes is limited. Structural and functional findings have been mixed; some studies have differentiated the LCP and AL groups, whilst others have not. Inconsistent findings could arise because these CD subtypes are inadequately defined in small cross-sectional samples.

Predictors of residency status in chronically institutionalized and community dwelling schizophrenia patients

BackgroundThis cross-sectional study contrasted chronically hospitalized schizophrenia (SZ) spectrum disorder inpatients to SZ community dwelling patients on measures of psychopathology, social competence, neuropsychological performance and real-world functioning in order to discern factors predictive of patients' residency status and to characterize the contrasting ends of the SZ outcome continuum. MethodSubjects included 26 chronic SZ patients hospitalized continuously on average for 12.8 years, and 26 SZ patients with a history of at least 18 months tenure in community placement. ResultsA series of multivariate analyses revealed both chronically hospitalized and community dwelling patients were similar in terms of their real world functioning abilities such as work skills, interpersonal skills, self-care skills and community engagement. Chronic SZ inpatients' manifested more severe functional competency and neurocognitive deficits relative to outpatients. Additionally, chronic inpatients were discriminated from community dwelling outpatients by their symptom severity and commitment of more socially undesirable/antisocial type behaviors. ConclusionsFactors associated with chronic institutionalization are, in part, related to commission of antisocial type behaviors, as well as poor social and neurocognitive competences, and total symptom severity rather than deficits in everyday functional abilities.

Distinguishing neurocognitive deficits in adult patients with NP-C from early onset Alzheimer\u2019s dementia

BackgroundNiemann-Pick disease type C (NP-C) is a rare, progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Neurocognitive deficits are common in NP-C, particularly in patients with the adolescent/adult-onset form. As a disease-specific therapy is available, it is important to distinguish clinically between the cognitive profiles in NP-C and primary dementia (e.g., early Alzheimer’s disease; eAD).MethodsIn a prospective observational study, we directly compared the neurocognitive profiles of patients with confirmed NP-C (n = 7) and eAD (n = 15). All patients underwent neurocognitive assessment using dementia screening tests (mini-mental status examination [MMSE] and frontal assessment battery [FAB]) and an extensive battery of tests assessing verbal memory, visuoconstructive abilities, visual memory, executive functions and verbal fluency.ResultsOverall cognitive impairment (MMSE) was significantly greater in eAD vs. NP-C (p = 0.010). The frequency of patients classified as cognitively ‘impaired’ was also significantly greater in eAD vs. NP-C (p = 0.025). Patients with NP-C showed relatively preserved verbal memory, but frequent impairment in visual memory, visuoconstruction, executive functions and in particular, verbal fluency. In the eAD group, a wider profile of more frequent and more severe neurocognitive deficits was seen, primarily featuring severe verbal and visual memory deficits along with major executive impairment. Delayed verbal memory recall was a particularly strong distinguishing factor between the two groups.ConclusionA combination of detailed yet easy-to-apply neurocognitive tests assessing verbal memory, executive functions and verbal fluency may help distinguish NP-C cases from those with primary dementia due to eAD.

Association between traumatic stress load, psychopathology, and cognition in the Philadelphia Neurodevelopmental Cohort.

Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample. The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8-21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009-2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered. Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p &lt; 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p &lt; 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition. Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.

The Effects of Electroconvulsive Therapy Augmentation of Antipsychotic Treatment on Cognitive Functions in Patients With Treatment-Resistant Schizophrenia.

Treatment-resistant schizophrenia (TRS) continues to be a challenge in modern psychiatry. Most of these patients have severe neurocognitive deficits. Electroconvulsive therapy (ECT) has proved effective and safe in the treatment of TRS, but because of potential neurocognitive adverse effects, it is associated with many controversies. The aim of this prospective, open study was to evaluate the effects of ECT augmentation of antipsychotics on cognitive functions in patients with TRS. Overall, 31 inpatients with TRS were included, 16 men, with an average (SD) age of 34.1 (11.187) years. The evaluation of clinical symptoms and global impression, as well as verbal memory, visual memory, working memory, psychomotor speed, verbal fluency, and executive functioning, was conducted before and after the completion of ECT treatment. We ran a series of paired-samples t tests, and the Bonferroni adjustment for multiple comparisons reduced the significance level to P = 0.004. The neurocognitive domains that demonstrated statistically significant improvement were immediate and delayed verbal memory, and executive functioning, whereas statistical trend was observed for visual memory and psychomotor speed. None of the neurocognitive functions exhibited significant deterioration after the ECT treatment. Electroconvulsive therapy was effective in reducing general symptoms of schizophrenia, resulting in more than 30% decrease in the overall symptom severity measured by the Positive and Negative Syndrome Scale. Notwithstanding some limitations of this study, the combination of ECT and antipsychotics has improved several neurocognitive domains, without evidence of worsening of any cognitive functions.

Neurocognitive Deficits in Borderline Personality Disorder: Associations With Childhood Trauma and Dimensions of Personality Psychopathology.

The present study evaluates the severity of neurocognitive deficits and assesses their relations with self-reported childhood trauma and dimensions of personality psychopathology in 45 outpatients with borderline personality disorder (BPD) matched to 56 non-psychiatric controls. Participants completed a comprehensive battery of neurocognitive tests, a retrospective questionnaire on early life trauma and a dimensional measure of personality psychopathology. Patients with BPD primarily showed deficits in verbal comprehension, sustained visual attention, working memory and processing speed. Comorbid posttraumatic stress disorder (PTSD) and an elevated childhood history of physical trauma were each accompanied by more severe neurocognitive deficits. There were no statistically significant associations between neurocognitive function and dimensions of personality psychopathology. These results suggest that patients with BPD display deficits mainly in higher-order thinking abilities that may be exacerbated by PTSD and substantial early life trauma. Potential relationships between neurocognitive deficits and dimensions of personality psychopathology in BPD need further examination.

Subjective versus objective cognition: Evidence for poor metacognitive monitoring in schizophrenia

BackgroundPatients with schizophrenia display a number of cognitive biases, particularly a tendency to jump to conclusions, which are implicated in the pathogenesis of the disorder. The present study contrasted the degree of objective reasoning biases with subjective cognitive insight. We expected that patients with schizophrenia would display greater objective than subjective impairment suggestive of poor metacognitive awareness. MethodsPatients with schizophrenia (n=140) and healthy controls (n=60) underwent a test battery encompassing a cognitive bias paradigm (beads task) as well as neurocognitive tests (story recall, trail-making tests). In addition, they were administered the Beck Cognitive Insight Scale (BCIS), a subjective measure of (meta)cognitive awareness. ResultsCorroborating prior research on decision making, draws to decisions were significantly delayed in controls relative to patients, whereas the core jumping to conclusion parameter (i.e., decision after one or two pieces of information) bordered significance. Patients with schizophrenia showed a lowered decision threshold and impaired neurocognition relative to nonclinical controls. Despite poor cognitive performance and prior psychotic episodes, patients with schizophrenia showed similar scores on the self-confidence subscale of the BCIS and reported even higher levels of self-reflectiveness relative to healthy controls. DiscussionThe study demonstrates that patients with schizophrenia show severe cognitive biases and neurocognitive deficits but display only partial awareness herein. Raising cognitive insight in a non-insulting fashion and elevating patients' corrigibility as well as willingness to consider others' feedback and advice may help to narrow this gap and improve psychiatric symptomatology.

Neurocognitive profile in psychotic versus nonpsychotic individuals with 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is associated with increased rates of psychotic disorders and cognitive deficits, but large scale studies are needed to elucidate their interaction. The objective of this two-center study was to identify the neurocognitive phenotype of individuals with 22q11DS and psychotic disorders. We hypothesized that psychotic 22q11DS individuals compared to nonpsychotic deleted individuals would have more severe neurocognitive deficits, especially in executive function and social cognition. These deficits would be present when compared to IQ- matched individuals with Williams Syndrome (WS).Three groups were ascertained from the Tel Aviv and Philadelphia centers: 22q11DS individuals with a psychotic disorder (n=31), nonpsychotic 22q11DS (n=86) and typically-developing controls (TD, n=828). In Tel Aviv a group of individuals with WS (n=18) matched in IQ to the 22q11DS psychotic group was also included. The Penn Computerized Neurocognitive Battery (CNB) was used to assess a wide-range of cognitive functions and all patients underwent structured psychiatric evaluations. 22q11DS individuals performed poorly on all CNB domains compared to TD. Participants with 22q11DS and psychosis, compared to nonpsychotic 22q11DS, had more severe deficits in global neurocognitive performance (GNP), executive function, social cognition and episodic memory domains. The primary deficits were also significant when comparing the Tel Aviv 22q11DS psychotic group to IQ-matched individuals with WS. In conclusion, 22q11DS individuals with a psychotic disorder have specific neurocognitive deficits that are reliably identified cross nationality using the CNB. These cognitive dysfunctions should be further studied as potential endophenotypes of psychosis in 22q11DS and as targets for intervention.

Neurocognitive and Academic Outcomes at Age 10 Years of Extremely Preterm Newborns.

Despite reductions in mortality and morbidity among children born extremely preterm, they remain at high risk of neurocognitive deficits, with up to 40% having significant cognitive deficits at school age. We assessed the rate of neurocognitive impairment in a contemporary US cohort of 873 children aged 10 years who were born <28 weeks' gestation. The families of 889 of 966 (92%) children enrolled from 2002 to 2004 at 14 sites in 5 states returned at age 10 years for a comprehensive assessment of IQ, language, attention, executive function, processing speed, visual perception, visual-motor function, and academic achievement. A total of 873 children were assessed with well-validated tests of cognitive and academic function. Distributions of test scores were consistently and markedly shifted below normative expectation, with one-third to two-thirds of children performing >1 SD below age expectation. The most extreme downward shifts were on measures of executive control and processing speed. Multivariate analyses, adjusted for socioeconomic status, growth restriction, and other potential confounders, revealed that the risk of poor outcome was highest at the lowest gestational age across all 18 measures. More than half of our extremely preterm cohort exhibited moderate or severe neurocognitive deficits at age 10 years, with the most extensive impairments found among those born at the lowest gestational age. Children born extremely preterm continue to be at significant risk of persistent impairments in neurocognitive function and academic achievement, underscoring the need for monitoring and remediating such outcomes beginning in early childhood.

Effect of Sensorineural Hearing Loss on Neurocognitive Functioning in Pediatric Brain Tumor Survivors.

Intensified therapy with platinum-based regimens for pediatric brain tumors has dramatically increased the number of pediatric brain tumor survivors (PBTS) but frequently causes permanent sensorineural hearing loss (SNHL). Although neurocognitive decline in PBTS is known to be associated with radiation therapy (RT), SNHL represents a potential additional contributor whose long-term impact has yet to be fully determined. The neurocognitive impact of significant SNHL (Chang scale ≥ 2b) in PBTS was assessed through a retrospective cohort study of audiograms and neurocognitive testing. Scores for neurocognitive domains and subtest task performance were analyzed to identify specific strengths and weakness for PBTS with SNHL. In a cohort of PBTS (n = 58) treated with platinum therapy, significant SNHL was identified in more than half (55%, n = 32/58), of which the majority required hearing aids (72%, 23/32). RT exposure was approximately evenly divided between those with and without SNHL. PBTS were 6.7 ± 0.6 and 11.3 ± 0.7 years old at diagnosis and neurocognitive testing, respectively. In multivariate analyses adjusted for RT dose, SNHL was independently associated with deficits in intelligence, executive function, and verbal reasoning skills. Subtests revealed PBTS with SNHL to have poor learning efficiency but intact memory and information acquisition. SNHL in PBTS increases the risk for severe therapy-related intellectual and neurocognitive deficits. Additional prospective investigation in malignant brain tumors is necessary to validate these findings through integration of audiology and neurocognitive assessments and to identify appropriate strategies for neurocognitive screening and rehabilitation specific to PBTS with and without SNHL.