Cognitive reserve and brain volumes in pediatric acute lymphoblastic leukemia

Department of Psychiatry and Behavioral Sciences, Neuropsychology and Neurorehabilitation Laboratory, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Brain Imaging and Behavior (Impact Factor: 4.6). 12/2010; 4(3-4):256-69. DOI: 10.1007/s11682-010-9104-1
Source: PubMed


Acute lymphoblastic leukemia (ALL) is associated with long-term, progressive cognitive deficits and white matter injury. We measured global and regional white and gray matter as well as cognitive function and examined relationships between these variables and cognitive reserve, as indicated by maternal education level, in 28 young survivors of ALL and 31 healthy controls. Results indicated significantly reduced white matter volumes and cognitive testing scores in the ALL group compared to controls. Maternal education was inversely related to both global and regional white matter and directly related to gray matter in ALL and was directly related to both gray and white matter in controls, consistent with the cognitive reserve hypothesis. Cognitive performance was associated with different brain regions in ALL compared to controls. Maternal education was significantly positively correlated with working and verbal memory in ALL as well as processing speed and verbal memory in controls, improving models of cognitive outcome over medical and/or demographic predictors. Our findings suggest that cognitive reserve may be an important factor in brain injury and cognitive outcome in ALL. Additionally, children with ALL may experience some neural reorganization related to cognitive outcome.

Download full-text


Available from: Shelli R Kesler, Oct 06, 2015
30 Reads
  • Source
    • "The fact that survivors demonstrated increased BOLD signal in the left DACC throughout the n-back task may indicate this so-called compensatory activation, in which survivors required an increase in resources to this region in order to manage the increase in cognitive load. This is consistent with literature documenting structural reorganization in prefrontal regions in pediatric leukemia (Kesler, Tanaka, & Koovakkattu, 2010). However, survivors of ALL were able to successfully and accurately complete the n-back task during fMRI, whereas survivors of pediatric brain tumors performed significantly less accurately than controls. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Research on the long-term sequelae of treatment for pediatric brain tumors has identified significant neurocognitive deficits experienced by many survivors. Despite indications of deficits based on cognitive assessment, the identification of specific neurobiological mechanisms of these deficits using neuroimaging techniques has yet to be considered. Method: This study used norm-referenced standardized assessment and functional MRI (fMRI) to examine attention and executive functioning deficits of survivors of pediatric brain tumors, as compared with healthy children. Results: Survivors of pediatric brain tumors performed more poorly than healthy children on measures of overall cognitive ability, attention, and executive function during testing, as well as on a working memory task during fMRI. Survivors showed lower blood-oxygen level dependent (BOLD) signal in bilateral frontal regions associated with sustained attention (BA6/8) and greater BOLD signal in left cingulate regions associated with complex problem-solving and performance monitoring (BA32) during working memory task completion. Both group and brain activation accounted for significant variance in neurocognitive functioning. Conclusions: Survivors of pediatric brain tumor and healthy children differed in brain activation during completion of a working memory task, and brain activation was associated with deficits noted in testing. These findings may improve understanding of mechanisms of cognitive deficits and avenues for intervention for children with brain tumors.
    Neuropsychology 04/2014; 28(5). DOI:10.1037/neu0000077 · 3.27 Impact Factor
  • Source
    • "These candidate mechanisms might have diffuse effects on brain structure. Second, structural neuroimaging studies, including our own [34] have shown diffuse changes in white matter and gray matter structure associated with ALL [35]–[38]. Third, meta-analyses of neuropsychological studies on ALL survivors have indicated decline in a wide range of cognitive functions including executive functioning, processing speed and memory [39], [40] (see [41], [42] for a review). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, graph theoretical analyses of neuroimaging data have increased our understanding of the organization of large-scale structural and functional brain networks. However, tools for pipeline application of graph theory for analyzing topology of brain networks is still lacking. In this report, we describe the development of a graph-analysis toolbox (GAT) that facilitates analysis and comparison of structural and functional network brain networks. GAT provides a graphical user interface (GUI) that facilitates construction and analysis of brain networks, comparison of regional and global topological properties between networks, analysis of network hub and modules, and analysis of resilience of the networks to random failure and targeted attacks. Area under a curve (AUC) and functional data analyses (FDA), in conjunction with permutation testing, is employed for testing the differences in network topologies; analyses that are less sensitive to the thresholding process. We demonstrated the capabilities of GAT by investigating the differences in the organization of regional gray-matter correlation networks in survivors of acute lymphoblastic leukemia (ALL) and healthy matched Controls (CON). The results revealed an alteration in small-world characteristics of the brain networks in the ALL survivors; an observation that confirm our hypothesis suggesting widespread neurobiological injury in ALL survivors. Along with demonstration of the capabilities of the GAT, this is the first report of altered large-scale structural brain networks in ALL survivors.
    PLoS ONE 07/2012; 7(7):e40709. DOI:10.1371/journal.pone.0040709 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Purpose: The aim of the study was to estimate the prevalence of allergic diseases and symptoms in children of the Ternopil Region (Ukraine) and to explore their familial and environmental correlates. Material and methods: A cross-sectional study based on parental answers to a respiratory questionnaire based on ISAAC that included 4871 urban and rural children aged 6-14 years. Association of physician-made diagnoses and symptoms with environmental factors was examined by means of multivariate logistic regression. Results: Increased risk of asthma (1.7%) was associated with urban residence (OR=1.8; p=0.04) and high parental education (OR=1.8; p= 0.02); spastic bronchitis (6.2%) with parental allergy (OR=1.3; p= 0.03); atopic eczema (6.2%) with younger age (OR=1.3; p=0.03), high parental education (OR=1.3; p=0.03), parental allergy (OR=1.4; p=0.02), tobacco smoke at home (OR=0.7; p=0.01) and household density (OR=0.6; p=0.001); diagnosis of unspecified allergic sensitization (11.8%) was related to high parental education (OR=1.2; p=0.03), parental employment (OR=0.8; p=0.02) and pets at home (OR=1.2; p=0.06). Symptoms of chest wheezing (11.5%) were related to tobacco smoke at home (OR=0.8; p=0.06). Attacks of dyspnea (7.3%) were related to parental allergy (OR=1.4; p=0.007), and type of heating (OR=1.7; p=0.04). Hay fever symptoms (5.7%) were related to younger age (OR=1.3; p=0,01) and urban residence (OR=2.0; p<0.0001). Conclusions: Except for asthma the prevalence of allergic diseases and symptoms as well as their correlates in children of Ternopil are similar to other estimates obtained in Eastern Europe. Low prevalence of asthma and relatively frequent occurrence of spastic bronchitis may suggest substantial underdiagnosis of childhood asthma.
    Advances in Medical Sciences 10/2012; DOI:10.2478/v10039-012-0035-5 · 1.11 Impact Factor
Show more