Objectives: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. Methods: Participants were children with traumatic brain injury (N=82; 8–13 years of age), arterial ischemic stroke (N=36; 6–16 years of age), and brain tumor (N=74; 9–18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children’s Version (TEA-Ch) subtests: Creature Counting, Walk-Don’t-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. Results: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. Conclusions: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529–538)

Objectives: This study examines the selective, sustained, and executive attention abilities of very preterm (VPT) born children in relation to concurrent structural magnetic resonance imaging (MRI) measures of regional gray matter development at age 12 years. Methods: A regional cohort of 110 VPT (≤32 weeks gestation) and 113 full term (FT) born children were assessed at corrected age 12 years on the Test of Everyday Attention-Children. They also had a structural MRI scan that was subsequently analyzed using voxel-based morphometry to quantify regional between-group differences in cerebral gray matter development, which were then related to attention measures using multivariate methods. Results: VPT children obtained similar selective (p=.85), but poorer sustained (p=.02) and executive attention (p=.01) scores than FT children. VPT children were also characterized by reduced gray matter in the bilateral parietal, temporal, prefrontal and posterior cingulate cortices, bilateral thalami, and left hippocampus; and increased gray matter in the occipital and anterior cingulate cortices (family-wise error–corrected p<.05). Poorer sustained auditory attention was associated with increased gray matter in the anterior cingulate cortex (p=.04). Poor executive shifting attention was associated with reduced gray matter in the right superior temporal cortex (p=.04) and bilateral thalami (p=.05). Poorer executive divided attention was associated with reduced gray matter in the occipital (p=.001), posterior cingulate (p=.02), and left temporal (p=.01) cortices; and increased gray matter in the anterior cingulate cortex (p=.001). Conclusions: Disturbances in regional gray matter development appear to contribute, at least in part, to the poorer attentional performance of VPT children at school age. (JINS, 2017, 23, 539–550)

Objectives: Cognitive impairment is an important aspect of Parkinson’s disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Methods: Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson’s Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Results: Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor (“Weak-Overall”), average (“Typical-Overall”), and strong (“Strong-Overall”) cognition. The remaining classes demonstrated unique patterns of cognition, characterized by “Strong-Memory,” “Weak-Visuospatial,” and “Amnestic” profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer’s disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Conclusions: Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551–563)

Objectives: Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes. Methods: A total of 806 participants diagnosed by means of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on “robust” normal control performance (n=260). Calculated Z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Results: Statistical fit indices suggested a 3-class model was the optimal LPA solution. The three-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be apolipoprotein e4+ and have worse Alzheimer’s disease CSF biomarkers than LPA-derived normal subjects. Conclusions: Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent “false-positive” diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive. (JINS, 2017, 23, 564–576)

Objectives: Social cognitive deficits have been discussed to be endophenotypes for schizophrenia and other serious mental illnesses. The current study aimed to assess emotional intelligence (EI) in unaffected siblings of schizophrenia patients to investigate its potential role as endophenotype for schizophrenia. Methods: EI was measured in 56 schizophrenia patients, 57 unaffected siblings, and 127 healthy control subjects by using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). In addition, non-social cognition was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Linear mixed models with compound symmetric correlation structure were used for of the three groups with respect to EI and non-social cognition. Results: Schizophrenia patients showed significantly lower overall EI and performed significantly worse in three out of four MSCEIT branches compared to unaffected siblings and control subjects, whereas the two latter groups had comparable EI levels. Similar performance patterns (patients<unaffected siblings=control subjects) were found with respect to non-social cognition. Solely in the “Tower of London” test, siblings achieved significantly lower task scores compared to control subjects. Conclusions: Based on our results, EI as measured with the MSCEIT does not seem to represent a marker of risk for schizophrenia. Further investigations should concentrate on other EI measures to reassess this finding. (JINS, 2017, 23, 577–583)

Objectives: Cognitive dysfunction is a key feature of major depressive (MDD) and bipolar (BD) disorders. However, rather than a single cognitive profile corresponding to each diagnostic categories, recent studies have identified significant intra- and cross-diagnostic variability in patterns of cognitive impairment. The goal of this study was to contribute to the literature on cognitive heterogeneity in mood disorders by identifying cognitive subprofiles in a population of patients with MDD, BD type I, BD type II, and healthy adults. Methods: Participants completed a neuropsychological battery; scores were converted into Z-scores using normative data and submitted to hierarchical cluster analysis. Results: Three distinct neuropsychological clusters were identified: (1) a large cluster containing mostly control participants, as well as some patients with BD and MDD, who performed at above-average levels on all neuropsychological domains; (2) a cluster containing some patients from all diagnostic groups, as well as healthy controls, who performed worse than cluster 1 on most tasks, and showed impairments in motor inhibition and verbal fluency; (3) a cluster containing mostly patients with mood disorders with severe impairments in verbal inhibition and cognitive flexibility. Conclusions: These findings revealed multiple cognitive profiles within diagnostic categories, as well as significant cross-diagnostic overlap, highlighting the importance of developing more specific treatment approaches which consider patients’ demographic and cognitive profiles in addition to their diagnosis. (JINS, 2017, 23, 584–593)

Objectives: Academic difficulties are common in children with epilepsy, although little is known about the effect of various seizure-related and cognitive variables. Given that persistent seizures may negatively impact academics, and that working memory is predictive of academic abilities, we examined the effects of recent seizures and working memory on word reading, spelling, and arithmetic in pediatric epilepsy. We hypothesized that persistent seizures would be associated with lower working memory ability, which would in turn result in poorer academic performance. Methods: Our sample consisted of 91 children with epilepsy being treated at the Hospital for Sick Children in Toronto, Canada, who underwent neuropsychological testing between 2002 and 2009 to help determine surgical candidacy. Four to 11 years later, follow-up testing was conducted on both surgical (n=61) and non-surgical (n=30) patients. Seizure status was defined by the presence or absence of seizures within the preceding 12 months. Results: 5000 bias-corrected bootstrap resamples with replacement were used to calculate the 95% confidence intervals (CIs) for the indirect effect of seizure status on academics through working memory, controlling for baseline academic functioning. Persistent seizures were associated with reduced working memory, which was in turn associated with lower reading (B=−4.64, 95% CI [−10.21, −1.30]), spelling (B=−7.09, 95% CI [−13.97, −2.56], and arithmetic scores (B=−8.04, 95% CI [−13.66, −3.58] at follow-up. Conclusions: For children with intractable epilepsy, working memory deficits present a significant barrier to the development of academic skills. Working memory interventions may be a helpful adjunct to academic remediation in this population to facilitate academic progress. (JINS, 2017, 23, 594–604)

Objectives: The Internet is a fundamental tool for completing many different instrumental activities of daily living (IADL), including shopping and banking. Persons with HIV−associated Neurocognitive Disorders (HAND) are at heightened risk for IADL problems, but the extent to which HAND interferes with the performance of Internet-based household IADLs is not known. Methods: Ninety-three individuals with HIV disease, 43 of whom were diagnosed with HAND, and 42 HIV− comparison participants completed Internet-based tests of shopping and banking. Participants used mock credentials to log in to an experimenter-controlled Web site and independently performed a series of typical online shopping (e.g., purchasing household goods) and banking (e.g., transferring funds between accounts) tasks. Results: Individuals with HAND were significantly more likely to fail the online shopping task than neurocognitively normal HIV+ and HIV− participants. HAND was also associated with poorer overall performance versus HIV+ normals on the online banking task. In the HAND group, Internet-based task scores were correlated with episodic memory, executive functions, motor skills, and numeracy. In the HIV+ sample as a whole, lower Internet-based task scores were uniquely associated with poorer performance-based functional capacity and self-reported declines in shopping and financial management in daily life, but not with global manifest functional status. Conclusions: Findings indicate that HAND is associated with difficulties in using the Internet to complete important household everyday functioning tasks. The development and validation of effective Internet training and compensatory strategies may help to improve the household management of persons with HAND. (JINS, 2017, 23, 605–615)