Wide Range Assessment Of Memory Research Articles

Detecting High-Dose Methotrexate-Induced Brain Changes in Pediatric and Young Adult Cancer Survivors Using [18F]FDG PET/MRI: A Pilot Study.

Significant improvements in treatments for children with cancer have resulted in a growing population of childhood cancer survivors who may face long-term adverse outcomes. Here, we aimed to diagnose high-dose methotrexate-induced brain injury on [18F]FDG PET/MRI and correlate the results with cognitive impairment identified by neurocognitive testing in pediatric cancer survivors. Methods: In this prospective, single-center pilot study, 10 children and young adults with sarcoma (n = 5), lymphoma (n = 4), or leukemia (n = 1) underwent dedicated brain [18F]FDG PET/MRI and a 2-h expert neuropsychologic evaluation on the same day, including the Wechsler Abbreviated Scale of Intelligence, second edition, for intellectual functioning; Delis-Kaplan Executive Function System (DKEFS) for executive functioning; and Wide Range Assessment of Memory and Learning, second edition (WRAML), for verbal and visual memory. Using PMOD software, we measured the SUVmean, cortical thickness, mean cerebral blood flow (CBFmean), and mean apparent diffusion coefficient of 3 different cortical regions (prefrontal cortex, cingulate gyrus, and hippocampus) that are routinely involved during the above-specified neurocognitive testing. Standardized scores of different measures were converted to z scores. Pairs of multivariable regression models (one for z scores < 0 and one for z scores > 0) were fitted for each brain region, imaging measure, and test score. Heteroscedasticity regression models were used to account for heterogeneity in variances between brain regions and to adjust for clustering within patients. Results: The regression analysis showed a significant correlation between the SUVmean of the prefrontal cortex and cingulum and DKEFS-sequential tracking (DKEFS-TM4) z scores (P = 0.003 and P = 0.012, respectively). The SUVmean of the hippocampus did not correlate with DKEFS-TM4 z scores (P = 0.111). The SUVmean for any evaluated brain regions did not correlate significantly with WRAML-visual memory (WRAML-VIS) z scores. CBFmean showed a positive correlation with SUVmean (r = 0.56, P = 0.01). The CBFmean of the cingulum, hippocampus, and prefrontal cortex correlated significantly with DKEFS-TM4 (all P < 0.001). In addition, the hippocampal CBFmean correlated significantly with negative WRAML-VIS z scores (P = 0.003). Conclusion: High-dose methotrexate-induced brain injury can manifest as a reduction in glucose metabolism and blood flow in specific brain areas, which can be detected with [18F]FDG PET/MRI. The SUVmean and CBFmean of the prefrontal cortex and cingulum can serve as quantitative measures for detecting executive functioning problems. Hippocampal CBFmean could also be useful for monitoring memory problems.

Prenatal ambient air pollutant mixture exposure and neurodevelopment in urban children in the Northeastern United States

BackgroundStudies of prenatal air pollution (AP) exposure on child neurodevelopment have mostly focused on a single pollutant. We leveraged daily exposure data and implemented novel data-driven statistical approaches to assess effects of prenatal exposure to a mixture of seven air pollutants on cognitive functioning in school-age children from an urban pregnancy cohort. MethodsAnalyses included 236 children born at ≥37 weeks gestation. Maternal prenatal daily exposure levels for nitrogen dioxide (NO2), ozone (O3), and constituents of fine particles [elemental carbon (EC), organic carbon (OC), nitrate (NO3−), sulfate (SO42−), ammonium (NH4+)] were estimated based on residential addresses using validated satellite-based hybrid models or global 3-D chemical-transport models. Children completed Wide Range Assessment of Memory and Learning (WRAML-2) and Conners’ Continuous Performance Test (CPT-II) at 6.5 ± 0.9 years of age. Time-weighted levels for mixture pollutants were estimated using Bayesian Kernel Machine Regression Distributed Lag Models (BKMR-DLMs), with which we also explored the interactions in the exposure-response functions among pollutants. Resulting time-weighted exposure levels were used in Weighted Quantile Sum (WQS) regressions to examine AP mixture effects on outcomes, adjusted for maternal age, education, child sex, and prenatal temperature. ResultsMothers were primarily ethnic minorities (81% Hispanic and/or black) reporting ≤12 years of education (68%). Prenatal AP mixture (per unit increase in WQS estimated AP index) was associated with decreased WRAML-2 general memory (GM; β = −0.64, 95%CI = −1.40, 0.00) and memory-related attention/concentration (AC; β = −1.03, 95%CI = −1.78, −0.27) indices, indicating poorer memory functioning, as well as increased CPT-II omission errors (OE; β = 1.55, 95%CI = 0.34, 2.77), indicating increased attention problems. When stratified by sex, association with AC index was significant among girls, while association with OE was significant among boys. Traffic-related pollutants (NO2, OC, EC) and SO42− were major contributors to these associations. There was no significant evidence of interactions among mixture components. ConclusionsPrenatal exposure to an AP mixture was associated with child neurocognitive outcomes in a sex- and domain-specific manner.

Association of Potentially Damaging De Novo Gene Variants With Neurologic Outcomes in Congenital Heart Disease

Neurodevelopmental disabilities are commonly associated with congenital heart disease (CHD), but medical and sociodemographic factors explain only one-third of the variance in outcomes. To examine whether potentially damaging de novo variants (dDNVs) in genes not previously linked to neurodevelopmental disability are associated with neurologic outcomes in CHD and, post hoc, whether some dDNVs or rare putative loss-of-function variants (pLOFs) in specific gene categories are associated with outcomes. This cross-sectional study was conducted from September 2017 to June 2020 in 8 US centers. Inclusion criteria were CHD, age 8 years or older, and available exome sequencing data. Individuals with pathogenic gene variants in known CHD- or neurodevelopment-related genes were excluded. Cases and controls were frequency-matched for CHD class, age group, and sex. Heterozygous for (cases) or lacking (controls) dDNVs in genes not previously associated with neurodevelopmental disability. Participants were separately stratified as heterozygous or not heterozygous for dDNVs and/or pLOFs in 4 gene categories: chromatin modifying, constrained, high level of brain expression, and neurodevelopmental risk. Main outcomes were neurodevelopmental assessments of academic achievement, intelligence, fine motor skills, executive function, attention, memory, social cognition, language, adaptive functioning, and anxiety and depression, as well as 7 structural, diffusion, and functional brain magnetic resonance imaging metrics. The study cohort included 221 participants in the post hoc analysis and 219 in the case-control analysis (109 cases [49.8%] and 110 controls [50.2%]). Of those 219 participants (median age, 15.0 years [IQR, 10.0-21.2 years]), 120 (54.8%) were male. Cases and controls had similar primary outcomes (reading composite, spelling, and math computation on the Wide Range Achievement Test, Fourth Edition) and secondary outcomes. dDNVs and/or pLOFs in chromatin-modifying genes were associated with lower mean (SD) verbal comprehension index scores (91.4 [20.4] vs 103.4 [17.8]; P = .01), Social Responsiveness Scale, Second Edition, scores (57.3 [17.2] vs 49.4 [11.2]; P = .03), and Wechsler Adult Intelligence Scale, Fourth Edition, working memory scores (73.8 [16.4] vs 97.2 [15.7]; P = .03), as well as higher likelihood of autism spectrum disorder (28.6% vs 5.2%; P = .01). dDNVs and/or pLOFs in constrained genes were associated with lower mean (SD) scores on the Wide Range Assessment of Memory and Learning, Second Edition (immediate story memory: 9.7 [3.7] vs 10.7 [3.0]; P = .03; immediate picture memory: 7.8 [3.1] vs 9.0 [2.9]; P = .008). Adults with dDNVs and/or pLOFs in genes with a high level of brain expression had greater Conners adult attention-deficit hyperactivity disorder rating scale scores (mean [SD], 55.5 [15.4] vs 46.6 [12.3]; P = .007). The study findings suggest neurodevelopmental outcomes are not associated with dDNVs as a group but may be worse in individuals with dDNVs and/or pLOFs in some gene sets, such as chromatin-modifying genes. Future studies should confirm the importance of specific gene variants to brain function and structure.

Preliminary Evidence of Memory Dysfunction in Youth with Moderate-Severe Versus Complicated Mild Traumatic Brain Injury and Matched Controls Using the Wide Range Assessment of Memory and Learning, Third Edition (WRAML3)

Preliminary Evidence of Memory Dysfunction in Youth with Moderate-Severe Versus Complicated Mild Traumatic Brain Injury and Matched Controls Using the Wide Range Assessment of Memory and Learning, Third Edition (WRAML3)

Abstract 10514: Compromised Cerebral Artery Integrity is Associated With Brain Tissue Injury and Cognition Deficits in Adolescents With Complex Congenital Heart Disease

Introduction: Adolescents with complex congenital heart disease (CCHD) show brain tissue injury in regions associated with cognitive deficits. Alteration in cerebral artery integrity (CAI), as measured by arterial transit time (ATT), may lead to perfusion deficits, and be a potential cause of brain injury in CCHD. To date, there are no reports of CAI in CCHD or associations between CAI, brain tissue integrity, and cognition in CCHD. Methods: 70 subjects (37 CCHD / 33 controls), 14-18 years of age, undergone surgical palliation (CCHD), and no contraindications for a magnetic resonance imaging (MRI) and healthy controls (age- and sex-matched) participated. Participants completed cognitive testing (Montreal Assessment of Cognition [MoCA] and the Wide Range Assessment of Memory and Learning [General Memory Index, GMI]) and brain MRI using 3.0 Tesla scanner. ATT values (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures), and regional brain mean diffusivity [MD] (measure of tissue integrity) were computed in whole brain. Descriptive, partial correlations, and ANCOVA analyses used (covariates, age and sex). Results: Mean MoCA [23.1 ± 4.1 vs. 28.1 ± 2.3; p &lt;.001] and GMI scores [86.8 ± 15.4 vs. 110.3 ± 14.5; p&lt;.001] show significant cognitive deficits in CCHD compared to controls. ATT was significantly increased in CCHD vs controls (mean ± SD, sec, 1.3±0.13 vs 1.22±0.13, p=0.02), respectively, indicating compromised CAI. Partial correlations between ATT, MD values, and cognition (covariates, age and sex, p&lt; 0.005) showed significant associations in various areas including the hippocampus, prefrontal cortices, cerebellum, frontal white matter, anterior and posterior cingulate, frontal cortex, temporal cortices, and midbrain. Conclusion: Adolescents with CCHD have prolonged ATTs compared to controls indicative of compromised CAI and altered cerebral perfusion. CAI is significantly associated with alterations in regional brain tissue integrity and cognitive impairment. Further evaluation is needed to test interventions to increase cerebral perfusion and to protect neural tissue.

Early Childhood Lutein and Zeaxanthin Intake Is Positively Associated with Early Childhood Receptive Vocabulary and Mid-Childhood Executive Function But No Other Cognitive or Behavioral Outcomes in Project Viva

Lutein and zeaxanthin are carotenoids associated with better cognition in older adults. Recent evidence suggests that their dietary intake may also have cognitive implications in childhood. The aim was to examine associations of early childhood lutein and zeaxanthin (L/Z) intake with cognition in early and mid-childhood. Among 1378 children in Project Viva, a prospective cohort, mothers reported their child's dietary intake in early childhood (median: 3.2 y) using a food-frequency questionnaire. Child cognition and behavior were assessed at the same time point using the Peabody Picture Vocabulary Test (PPVT-III) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) and at mid-childhood (median: 7.7 y) using the Kaufman Brief Intelligence Test, the WRAVMA drawing subtest, the Wide Range Assessment of Memory and Learning, the Behavior Rating Inventory of Executive Function (BRIEF), and the Strengths and Difficulties Questionnaire. Children consumed a daily mean (SD) of 1.0 (0.4) mg L/Z in early childhood. Children in the third-quartile category of L/Z intake had a mean PPVT-III score 2.40 (95% CI: 0.27, 4.53) points higher than children in the lowest quartile category in early childhood, suggesting better receptive vocabulary. Children in the highest quartile category of L/Z intake had a parent-reported mean BRIEF Global Executive Composite score 1.65 (95% CI: -3.27, -0.03) points lower than children in the lowest quartile category in mid-childhood, indicating better executive function. We did not observe associations between L/Z intake and any of the other cognitive or behavioral outcomes assessed. The overall findings do not provide strong evidence of an association between child L/Z intake and cognition and behavior. However, the positive associations found between early childhood L/Z intake and early childhood receptive vocabulary and mid-childhood executive function, in addition to previous evidence of neurodevelopmental benefit of L/Z intake, suggest that this relation deserves further investigation.

The association of prenatal manganese exposure with problem-solving skills and its mediation by the building blocks of executive function

BackgroundProblem-solving skills build upon three core executive functions: inhibition, working memory, and cognitive flexibility. There is evidence of adverse associations of prenatal exposure to manganese (Mn) with core executive functions, but less is known about Mn associations with problem-solving or potential mediators of this association. ObjectivesThis study aimed to investigate the association of prenatal Mn exposure with problem-solving and to identify potential neuropsychological mechanisms through which this association may be mediated. MethodsStudy participants were 410 adolescents from the New Bedford Cohort (NBC) who have undergone periodic evaluations since their birth (1993–1998) to mothers residing near a Massachusetts Superfund site. We investigated the association of cord blood Mn with problem-solving measured by the Delis-Kaplan Executive Function System (D-KEFS) Sorting and Tower subtests (scores scaled to a mean ± SD of 10 ± 3) using multivariable linear regression. Inhibition and cognitive flexibility were also measured by the D-KEFS; working memory was measured with the Wide Range Assessment of Memory and Learning, 2nd edition. Regression-based causal mediation analysis was used to assess the proportion of the Mn-problem-solving association mediated by inhibition, working memory, and cognitive flexibility individually and jointly. ResultsNBC adolescents (mean age 15.5 years) were socio-demographically diverse with 31 % in a low-income household at birth and had cord blood Mn concentrations similar to other general population samples. Mn was associated with Sorting but not Tower scores. Specifically, a doubling of cord blood Mn concentrations was associated with − 0.59 points lower (95 % CI: −1.16, −0.03) Sort Recognition score. In mediation analyses, there was suggestive evidence that inhibition, working memory, and cognitive flexibility combined mediated 30 % of the total effect of Mn on Sorting. When analyzed individually, working memory mediated a larger proportion (24 %) of the effect than inhibition or cognitive flexibility. DiscussionWe observed adverse associations of cord blood Mn with problem-solving among adolescents. There was suggestive evidence that the building blocks of executive function jointly, and working memory individually, were potentially important mediators of this association.

Prenatal exposure to chemical mixtures and working memory among adolescents

Working memory is the ability to keep information in one's mind and mentally manipulate it. Decrements in working memory play a key role in many behavioral and psychiatric disorders, therefore identifying modifiable environmental risk factors for such decrements is important for mitigating these disorders. There is some evidence that prenatal exposure to individual chemicals may adversely impact working memory among children, but few studies have explored the association of co-exposure to multiple chemicals with this outcome in adolescence, a time when working memory skills undergo substantial development. We investigated the association of organochlorines (DDE, HCB, PCBs) and metals (lead, manganese) measured in cord serum and cord blood, respectively, with working memory measured with the Wide Range Assessment of Memory and Learning, 2nd Edition among 373 adolescents living near a Superfund site in New Bedford, Massachusetts. We used Bayesian Kernel Machine Regression (BKMR) and linear regression analyses and assessed effect modification by sex and prenatal social disadvantage. In BKMR models, we observed an adverse joint association of the chemical mixture with Verbal, but not Symbolic, Working Memory. In co-exposure and covariate-adjusted linear regression models, a twofold increase in cord blood manganese was associated with lower working memory scaled scores, with a stronger association with Verbal Working Memory (difference = −0.75; 95% CI: −1.29, −0.20 points) compared to Symbolic Working Memory (difference = −0.44; 95% CI: −1.00, 0.12 points). There was little evidence of effect modification by sex and some evidence associating organochlorine pesticides with poorer working memory scores among those with greater prenatal social disadvantage. This study provided evidence of an adverse joint association of a chemical mixture with a verbal working memory task among adolescents, as well as an adverse association of prenatal manganese exposure with working memory.

Building blocks of executive function as mediators of the association of prenatal manganese exposure with problem-solving skills among adolescents

BACKGROUND AND AIM: Problem-solving skills build upon three core executive functions: inhibition, working memory, and cognitive flexibility. There is evidence of adverse associations of prenatal exposure to manganese (Mn) with core executive functions, but less is known about Mn associations with problem-solving. This study aimed to investigate the association of prenatal Mn exposure with problem-solving and to identify potential neuropsychological mechanisms through which this association may be mediated. METHODS: Study participants were 379 adolescents from the New Bedford Cohort (NBC) who have undergone periodic evaluations since their birth (1993-1998) to mothers residing near a Massachusetts Superfund site. We assessed the association of cord blood Mn with problem-solving measured by the Delis-Kaplan Executive Function System (D-KEFS) Sorting and Tower subtests [scores scaled to a mean (SD) of 10 (3)] using multivariable linear regression. Inhibition and cognitive flexibility were also measured with the D-KEFS; working memory was measured with the Wide Range Assessment of Memory and Learning, 2nd edition. Regression-based causal mediation was used to assess the proportion of the Mn-problem-solving association mediated by inhibition, working memory, and cognitive flexibility. RESULTS:NBC adolescents (age 13-17 years) were diverse with 29% non-white and 31% in a low-income household at birth. Their cord blood Mn concentrations were similar to other general population samples. Mn was associated with Sorting but not Tower scores. Specifically, a doubling of cord blood Mn concentrations was associated with a -0.66 points lower (95% CI: -1.26, -0.06) Sort Recognition score. In mediation analyses, inhibition, working memory, and cognitive flexibility combined mediated 44% of the total effect of Mn on Sort Recognition. When analyzed individually, working memory mediated a larger proportion (37%) of the effect than inhibition (14%) or cognitive flexibility (23%). CONCLUSIONS:We observed adverse associations of cord blood Mn with problem-solving among adolescents. Working memory was an important mediator of this association. KEYWORDS: Neurodevelopment outcomes, children's environmental health, environmental epidemiology, chemical exposures

Maternal Intake of Lutein and Zeaxanthin during Pregnancy Is Positively Associated with Offspring Verbal Intelligence and Behavior Regulation in Mid-Childhood in the Project Viva Cohort

BackgroundLutein and zeaxanthin are carotenoids associated with better cognition at older age. To our knowledge, no previous study has evaluated their cognitive implications in the prenatal period, when the brain undergoes its most rapid development. ObjectiveThe objective of this study was to examine associations of maternal lutein and zeaxanthin (L/Z) intake during pregnancy with child cognition. DesignAmong 1580 mother-child pairs in Project Viva, a prospective cohort, we assessed maternal intake of L/Z during pregnancy using food frequency questionnaires and offspring cognition by the Visual Recognition Memory paradigm in infancy, the Peabody Picture Vocabulary Test and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) in early childhood, and the Kaufman Brief Intelligence Test (KBIT-II), the WRAVMA drawing subtest, and the Wide Range Assessment of Memory and Learning in mid-childhood. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Strengths and Difficulties Questionnaire. ResultsMothers consumed a daily mean (SD) of 2.6 (2.0) mg L/Z in the first and second trimesters of pregnancy. Mean mid-childhood KBIT-II verbal scores were higher with greater maternal L/Z intake [difference of Q4–Q1 means for first trimester: 2.67 (95% CI: 0.13, 5.20) and for second trimester: 3.55 (95% CI: 0.81, 6.28)], indicating better verbal intelligence. Secondary analyses on cognitive subtests showed that mean mid-childhood BRIEF Behavioral Regulation Index scores were lower with greater maternal L/Z intake [difference of Q4–Q1 means for first trimester: –1.63 (95% CI: –3.22, –0.04) and for second trimester: –1.89 (95% CI: –3.58, –0.21)], indicating better behavior regulation ability. ConclusionsHigher maternal L/Z intake during pregnancy was associated with better offspring verbal intelligence and behavior regulation ability in mid-childhood, suggesting a potential benefit during prenatal development. We did not find a benefit of higher maternal L/Z intake on other child cognitive or behavioral outcomes. Project Viva is registered at clinicaltrials.gov as NCT02820402.

Reduced hippocampal volumes and memory deficits in adolescents with single ventricle heart disease.

IntroductionAdolescents with single ventricle congenital heart disease (SVHD) show functional deficits, particularly in memory and mood regulation. Hippocampi are key brain structures that regulate mood and memory; however, their tissue integrity in SVHD is unclear. Our study aim is to evaluate hippocampal volumes and their associations with memory, anxiety, and mood scores in adolescents with SVHD compared to healthy controls.MethodsWe collected brain magnetic resonance imaging data from 25 SVHD (age 15.9 ± 1.2 years; 15 male) and 38 controls (16.0 ± 1.1 years; 19 male) and assessed memory (Wide Range Assessment of Memory and Learning 2, WRAML2), anxiety (Beck Anxiety Inventory, BAI), and mood (Patient Health Questionnaire 9, PHQ‐9) functions. Both left and right hippocampi were outlined and global volumes, as well as three‐dimensional surfaces were compared between groups using ANCOVA and associations with cognitive and behavioral scores with partial correlations (covariates: age and total brain volume).ResultsThe SVHD group showed significantly higher BAI (p = .001) and PHQ‐9 (p < .001) scores, indicating anxiety and depression symptoms and significantly reduced WRAML2 scores (p < .001), suggesting memory deficits compared with controls. SVHD group had significantly reduced right global hippocampal volumes (p = .036) compared with controls, but not the left (p = .114). Right hippocampal volume reductions were localized in the CA1, CA4, subiculum, and dentate gyrus. Positive correlations emerged between WRAML2 scores and left (r = 0.32, p = .01) and right (r = 0.28, p = .03) hippocampal volumes, but BAI and PHQ‐9 did not show significant correlations.ConclusionAdolescents with SVHD show reduced hippocampal volumes, localized in several sites (CA1, CA4, subiculum, and dentate gyrus), which are associated with memory deficits. The findings indicate the need to explore ways to improve memory to optimize academic achievement and ability for self‐care in the condition.

Maternal glucose tolerance in pregnancy and child cognitive and behavioural problems in early and mid-childhood.

Maternal abnormal glucose tolerance during pregnancy may adversely affect offspring cognition and behaviour, but few prospective studies investigated this association at multiple points throughout childhood. We hypothesised that maternal abnormal glucose tolerance is associated with child cognitive and behavioural outcomes in early and mid-childhood. We examined the associations of maternal abnormal glucose tolerance at 26-28weeks of pregnancy with offspring cognitive and behavioural scores in 1421 children in the Project Viva pre-birth cohort. In early (mean 3.3years) and mid-childhood (mean 7.9years), we measured child cognition using validated instruments, the Kaufman Brief Intelligence Test, Wide Range Assessment of Memory and Learning, and the Wide Range Assessment of Visual Motor Abilities (WRAVMA); we assessed parent- and teacher-rated behavioural outcomes with the Strengths and Difficulties Questionnaire and the Behavioural Rating Inventory of Executive Function. We used linear regression models adjusted for potential confounders (maternal race/ethnicity, pre-pregnancy BMI, intelligence, age, parity, smoking status, education, and household income at enrolment, in addition to child's sex and age at assessment). Of 1421 mothers, 69 (4.9%) had gestational diabetes mellitus, 43 (3.0%) impaired glucose tolerance, 122 (8.6%) isolated hyperglycaemia, and 1187 (83.5%) normal glucose tolerance. Offspring born to women with gestational diabetes mellitus had lower total WRAVMA scores (-3.09 points; 95% CI -6.12, -0.05) in early childhood compared with offspring of women with normal glucose tolerance. None of the abnormal glucose tolerance categories during pregnancy were associated with any of the cognitive outcomes (verbal, non-verbal, and visual motor scores) or behavioural measures in mid-childhood. Children born to mothers who had gestational diabetes mellitus had slightly lower scores on one cognitive test in early childhood. We found no evidence to support that maternal abnormal glucose tolerance was associated with cognitive or behavioural development in mid-childhood.

The association between neurocognition and sexual abuse within a children’s psychiatric inpatient program

Objective: The aim of this study was to understand the detrimental effects of sexual abuse on neuropsychological variables including child’s intelligence, executive functioning (EF), and learning/memory within a pediatric inpatient population. Method: This study examined the effect of sexual abuse on children’s intelligence, EF, and learning/memory by conducting a retrospective chart review for 144 children (aged 7-12) who completed a neuropsychological assessment during a psychiatric inpatient hospitalization. Of the 144 children, participants were matched two to one by gender and age, with one group (n = 52) categorized by reported sexual abuse and the other group (n = 92) categorized by no reported sexual abuse. The neuropsychological measures included the Wechsler Abbreviated Scale of Intelligence (WASI-I/II) or Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), Wide Range Assessment of Memory and Learning – Second Edition (WRAML-2): Story Memory Immediate/Delayed Recall and Delayed Recognition, Trail Making Test-B, Stroop Interference Test: Color-Word Condition, WRAML-2: Sentence Memory and Conners Continuous Performance Test-Second Edition. Results: Statistical analysis showed that participants with reported sexual abuse had significantly (p< .05) lower intelligence, EF, and learning/memory skills than those without reported sexual abuse. Only working memory and cognitive flexibility differences remained after controlling for clinical variables (e.g., PTSD, amount of total abuse types). Conclusions: These findings contributed to the limited research on the detrimental effects of sexual abuse in a pediatric inpatient population. They demonstrated a relationship between early sexual abuse and neuropsychological deficits, specifically executive function and IQ deficits.

Caudate nuclei volume alterations and cognition and mood dysfunctions in adolescents with single ventricle heart disease.

Adolescents with single ventricle heart disease (SVHD) exhibit mood and cognitive deficits, which may result from injury to the basal ganglia structures, including the caudate nuclei. However, the integrity of the caudate in SVHD adolescents is unclear. Our aim was to examine the global and regional caudate volumes, and evaluate the relationships between caudate volumes and cognitive and mood scores in SVHD and healthy adolescents. We acquired two high-resolution T1-weighted images from 23 SVHD and 37 controls using a 3.0-Tesla MRI scanner, as well as assessed mood (Patient Health Questionnaire-9 [PHQ-9]; Beck Anxiety Inventory [BAI]) and cognition (Montreal Cognitive Assessment [MoCA]; Wide Range Assessment of Memory and Learning-2; General Memory Index [GMI]) functions. Both left and right caudate nuclei were outlined, which were then used to calculate and compare volumes between groups using ANCOVA (covariates: age, gender, and head-size), as well as perform 3D surface morphometry. Partial correlations (covariates: age, gender, and head-size) were used to examine associations between caudate volumes, cognition, and mood scores in SVHD and controls. SVHD subjects showed significantly higher PHQ-9 and BAI scores, indicating more depressive and anxiety symptoms, as well as reduced GMI scores, suggesting impaired cognition, compared to controls. SVHD patients showed significantly reduced caudate volumes (left, 3,198.8±490.1 vs. 3,605.0±480.4mm3 , p<0.004; right, 3,162.1±475.4 vs. 3,504.8±465.9mm3 , p<0.011) over controls, and changes were localized in the rostral, mid-dorsolateral, and caudal areas. Significant negative correlations emerged between caudate volumes with PHQ-9 and BAI scores and positive correlations with GMI and MoCA scores in SVHD and controls. SVHD adolescents show significantly reduced caudate volumes, especially in sites that have projections to regulate mood and cognition, which may result from developmental and/or hypoxia-/ischemia-induced processes.

Increased Risk of Executive Function and Emotional Behavioral Problems Among Virologically Well-Controlled Perinatally HIV-Infected Adolescents in Thailand and Cambodia.

Large numbers of perinatally HIV-infected (PHIV) children are aging into adolescence. We examined cognitive and behavioral outcomes in a longitudinal cohort of Asian youth. We followed up 231 PHIV, 125 perinatally HIV-exposed, uninfected (HEU), and 138 HIV-unexposed, uninfected (HUU) adolescents (aged 10 years and older), matched by age/sex, in Thailand and Cambodia for 3 years. Executive function was assessed with Children's Color Trails Tests 1 and 2 (CCTT-1 and -2), the design fluency test, and the verbal fluency test. Working memory (Freedom from Distractibility Index) and processing speed index were assessed using WISC-III. Visual memory was assessed by design memory and design recognition subtests of the Wide Range Assessment of Memory and Learning (WRAML-2) and behavioral problems using the Child Behavior Checklist (CBCL). Generalized estimating equations examined adjusted odds ratios of cognitive impairment (Z-scores ≥2 SD below age-adjusted means of the HUU group) and CBCL T-scores in the borderline-clinical range (T-Scores ≥60) in PHIV and HEU versus HUU youth, adjusting for ethnicity, household income, and caregiver characteristics. The median age at enrollment was 13.8 years, with 58% women and 63% Thai participants. PHIV youth had >86% virological suppression and significantly higher impairment rates on CCTT-1 and -2 tests, design fluency test, verbal fluency tests, design memory, and CBCL internalizing and externalizing problems. Results were mostly similar between HEU and HUU groups, apart from higher impairment rates on CCTT-1 and internalizing problems in HEU. Asian adolescents with PHIV remain at risk of cognitive and mental health problems despite HIV treatment. Selective risks are observed among HEU youth.

Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure.

Background:Adolescents with single ventricle heart disease (SVHD), who have undergone the Fontan procedure, show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls.Methods:Brain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total-brain-volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV).Results:SVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls.Conclusion:Adolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory.

Neurodevelopmental and health-related quality-of-life outcomes in adolescence after surgery for congenital heart disease in infancy.

To assess outcomes in adolescence after surgery for congenital heart disease (CHD) in infancy. Domains analysed included cognition and executive function, social and emotional well-being, adaptive behaviour, academic achievement, and health-related quality of life (HRQoL). Twenty-one participants (10 males, 11 females) ranged in age from 14 to 17years (mean 15y 4.8mo, SD 8.4mo). Twenty had biventricular repairs. All were classified as New York Heart Association class I. Measures included: Wechsler Intelligence and Achievement scales; Wide Range Assessment of Memory and Learning, Second Edition; California Verbal Learning Test - Children's Version; Behaviour Rating Inventory of Executive Function; Conners, Third Edition; Adaptive Behavior Assessment System, Second Edition; Behavior Assessment System for Children, Second Edition; Rey-Osterrieth Complex Figure; and Pediatric Quality of Life Inventory. Outcomes were significantly lower (p≤0.01) than population norms for processing speed, mathematical achievement, attention, and visual-spatial ability. Participants reported more frequent learning problems but more positive family relations. HRQoL was significantly lower across most domains by self- and parent-proxy report. Individuals with CHD may experience difficulties across a range of domains. These findings emphasize the importance of comprehensive screening, early intervention, and long-term follow-up, as deficits may extend into young adulthood. Identified cognitive, learning, and attentional impairments in adolescents after congenital heart disease surgery in infancy. Combined self-report, caregiver report, and laboratory tasks in a comprehensive neurodevelopmental assessment protocol. Health-related quality of life was lower across most domains.

Associations of Prenatal and Postnatal Maternal Depressive Symptoms with Offspring Cognition and Behavior in Mid-Childhood: A Prospective Cohort Study.

Exposure to maternal depressive symptoms in the peri-pregnancy periods may be associated with poorer child development, but research is often limited to only maternal assessments of behavior and cognition. This study investigates the specific periods of prenatal and postnatal exposure to maternal depressive symptoms in association with child development using reports from teachers and mothers. This study is based on 1225 mother–child pairs from Project Viva, a prospective pre-birth cohort study. Mothers reported depressive symptoms on the Edinburgh Postpartum Depression Scale (EPDS) in mid-pregnancy as well as at 6 months and 12 months postpartum. Teachers and mothers reported child executive functions using the Behavioral Rating Inventory of Executive Function (BRIEF) and behavior using the Strengths and Difficulties Questionnaire (SDQ). Children completed the Kaufman Brief Intelligence Test (KBIT-2), the Wide Range Assessment of Visual Motor Abilities (WRAVMA), and the Visual Memory Index of the Wide Range Assessment of Memory and Learning (WRAML). We used multivariable linear regression models to examine associations of prenatal and postpartum depressive symptoms with outcomes. Many of the crude associations observed were attenuated after adjusting for demographic factors and maternal IQ, yet some remained significant. For example, high prenatal maternal depressive symptoms were associated with poorer scores on the BRIEF Behavior Regulation Index and some SDQ scales based on reports from teachers and mothers. High prenatal maternal depressive symptoms were associated with poorer behavioral development. Postpartum symptoms did not show strong associations with outcomes once we adjusted for the prenatal period.

Do Differences in Learning Performance Precede or Follow Initiation of Marijuana Use?

Studies examining cross-sectional associations between age at marijuana initiation and memory deficits yield mixed results. Because longitudinal data are sparse, controversy continues regarding whether these deficits reflect premorbid risk factors or sequelae of early marijuana initiation; here, we examine this question in a community sample followed since birth. Masked examiners administered four subtests of the Wide Range Assessment of Memory and Learning (WRAML/WRAML2) from childhood until young adulthood to 119 urban, predominantly African American participants. Multivariable generalized estimated equation models measured longitudinal trajectories of learning. Participants were grouped as never users (n = 26), later initiators (≥16 years old; n = 31), and earlier initiators of marijuana use (n = 62). Marijuana onset groups did not significantly differ on WRAML scaled scores or IQ in childhood, nor did they differ on WRAML scaled scores in adolescence. On most WRAML2 subtests, these groups did not significantly differ in young adulthood after taking into account sex and childhood IQ. However, on Story Memory, later initiators attained higher scaled scores in young adulthood, even after including additional covariates of anxiety, depression, postsecondary education, past-month marijuana use, and past-week high-risk drinking. They showed a significantly more positive trajectory than never users that was driven by within-group improvement after adolescence. Earlier initiators showed within-group decline in Story Memory after adolescence. Differences in learning following earlier initiation of marijuana use may not be solely attributable to premorbid deficits.

Memory in children with epilepsy: Utility of the WRAML-2 in generalized and focal epilepsy syndromes

The material-specific model for memory impairment predicts that verbal memory deficits are seen with left temporal seizures, and visual memory deficits are seen with right temporal seizures (Henkin et al., 2005). In pediatric epilepsy, seizure pathology has not always yielded the expected material-specific memory profiles. This study used the Wide Range Assessment of Memory and Learning—Second Edition (WRAML-2) to assess memory functioning among pediatric patients with epilepsy. The WRAML-2 was administered to 180 youth with epilepsy during their neuropsychological evaluations. Memory and recognition scores correlated significantly with epilepsy severity variables. There were no significant differences in verbal and visual memory and recognition index scores among patients with generalized epilepsy or among those with lateralized or localized electroencephalography (EEG) patterns and lesions on imaging. However, clinically meaningful verbal versus visual discrepancy scores were significantly related to lateralized abnormalities on EEG and magnetic resonance imaging (MRI) results. Most patients with right hemisphere pathology showed the expected material-specific visual memory deficits, while fewer than 15% of the left hemisphere cases showed the expected verbal memory deficits. Over one-third of those with identified left-sided pathology showed clinically significant deficits in visual memory. Findings are incongruent with the material-specific memory model and reflect the fact that early developmental neurological insults can lead to functional reorganization/crowding effects in children with left hemisphere epilepsy. On exploratory analyses, there were no significant differences in discrepancy scores among participants with left, right, and bilateral languages on Wada and functional MRI (fMRI). However, those with right and bilateral language dominance were more likely to show discrepancies that were incongruent with the material-specific model.