Risks of Young Age for Selected Neurocognitive Deficits in Medulloblastoma Are Associated With White Matter Loss

2001 ◽  
Vol 19 (2) ◽  
pp. 472-479 ◽  
Author(s):  
Raymond K. Mulhern ◽  
Shawna L. Palmer ◽  
Wilburn E. Reddick ◽  
John O. Glass ◽  
Larry E. Kun ◽  
...  
Keyword(s):  
White Matter ◽  
Sustained Attention ◽  
Verbal Memory ◽  
Young Age ◽  
Factual Knowledge ◽  
Test Results ◽  
Neurocognitive Deficits ◽  
Neurocognitive Performance ◽  
Neurocognitive Tests ◽  
Neurocognitive Test

PURPOSE: To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma. PATIENTS AND METHODS: Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM. RESULTS: Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory. CONCLUSION: The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT.

scholarly journals Nicotine Effects on White Matter Microstructure in Young Adults

2019 ◽  
Vol 35 (1) ◽  
pp. 10-21 ◽  
Author(s):  
Megan M Kangiser ◽  
Alicia M Thomas ◽  
Christine M Kaiver ◽  
Krista M Lisdahl
Keyword(s):  
Working Memory ◽  
Young Adults ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Sustained Attention ◽  
Verbal Memory ◽  
Diffusion Tensor ◽  
Memory Performance ◽  
Mean Diffusivity ◽  
White Matter Microstructure

Abstract Objective Nicotine use is widely prevalent among youth, and is associated with white matter microstructural changes as measured by diffusion tensor imaging (DTI). In adults, nicotine use is generally associated with lower fractional anisotropy (FA), but in adolescents/young adults (≤30 years), microstructure appears healthier, indicated by higher FA. This cross-sectional study examined associations between nicotine use and white matter microstructure using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in young adults. Methods Fifty-three participants (18 nicotine users [10 female]/35 controls [17 female]) ages 18–25 underwent MRI scan, neuropsychological battery, toxicology screening, and drug use interview. Nicotine group associations with FA and MD were examined in various white matter tracts. In significant tracts, AD and RD were measured. Exploratory correlations were conducted between significant tracts and verbal memory and sustained attention/working memory performance. Results Nicotine users exhibited significantly lower FA than controls in the left anterior thalamic radiation, left inferior longitudinal fasciculus, left superior longitudinal fasciculus—temporal, and left uncinate fasciculus. In these tracts, AD and RD did not differ, nor did MD differ in any tract. White matter quality was positively correlated with sustained attention/working memory performance. Conclusions Cigarette smoking may disrupt white matter microstructure. These results are consistent with adult studies, but inconsistent with adolescent/young adult studies, likely due to methodological and sample age differences. Further studies should examine longitudinal effects of nicotine use on white matter microstructure in a larger sample.

scholarly journals Tau Deposition and Structural Connectivity Demonstrate Differential Association Patterns with Neurocognitive Tests

2021 ◽  
Author(s):  
Zack Hall ◽  
Billy Chien ◽  
Yi Zhao ◽  
Shannon L. Risacher ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
White Matter ◽  
Interaction Analysis ◽  
Memory Function ◽  
Structural Connectivity ◽  
Neurocognitive Performance ◽  
Association Patterns ◽  
Neurocognitive Tests ◽  
White Matter Connectivity ◽  
Network Metrics

Abstract Tau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer’s Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. The current study aims to investigate how tau deposition and structural connectivity are associated with memory function in prodromal AD. In this study, tau accumulation and structural connectivity data from 83 individuals (57 cognitively normal participants and 26 participants with mild cognitive impairment) were associated with neurocognitive test scores. Statistical analyses were performed in 70 cortical/subcortical brain regions to determine: 1. the level of association between tau and network metrics extracted from structural connectivity and 2. the association patterns of brain memory function with tau accumulation and network metrics. The results showed that tau accumulation and network metrics were correlated in early tau deposition regions. Furthermore, tau accumulation was associated with worse performance in almost all neurocognitive tests performance evaluated in the study. In comparison, decreased network connectivity was associated with declines in the delayed memory recall in Craft Stories and Benson Figure Copy. Interaction analysis indicates that tau deposition and dysconnectivity have a synergistic effect on the delayed Benson Figure Recall. Overall, our findings indicate that both tau deposition and structural dysconnectivity are associated with neurocognitive dysfunction. They also suggest that tau-PET may have better sensitivity to neurocognitive performance than diffusion MRI-derived measures of white-matter connectivity

scholarly journals Tau deposition and structural connectivity demonstrate differential association patterns with neurocognitive tests

2021 ◽  
Author(s):  
Zack Hall ◽  
Billy Chien ◽  
Yi Zhao ◽  
Shannon L. Risacher ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
White Matter ◽  
Interaction Analysis ◽  
Memory Function ◽  
Structural Connectivity ◽  
Neurocognitive Performance ◽  
Association Patterns ◽  
Neurocognitive Tests ◽  
White Matter Connectivity ◽  
Network Metrics

AbstractTau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer’s Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. The current study aims to investigate how tau deposition and structural connectivity are associated with memory function in prodromal AD. In this study, tau accumulation and structural connectivity data from 83 individuals (57 cognitively normal participants and 26 participants with mild cognitive impairment) were associated with neurocognitive test scores. Statistical analyses were performed in 70 cortical/subcortical brain regions to determine: 1. the level of association between tau and network metrics extracted from structural connectivity and 2. the association patterns of brain memory function with tau accumulation and network metrics. The results showed that tau accumulation and network metrics were correlated in early tau deposition regions. Furthermore, tau accumulation was associated with worse performance in almost all neurocognitive tests performance evaluated in the study. In comparison, decreased network connectivity was associated with declines in the delayed memory recall in Craft Stories and Benson Figure Copy. Interaction analysis indicates that tau deposition and dysconnectivity have a synergistic effect on the delayed Benson Figure Recall. Overall, our findings indicate that both tau deposition and structural dysconnectivity are associated with neurocognitive dysfunction. They also suggest that tau-PET may have better sensitivity to neurocognitive performance than diffusion MRI-derived measures of white-matter connectivity.

scholarly journals Relationship between ventricular size, white matter injury, and neurocognition in children with stable, treated hydrocephalus

2015 ◽  
Vol 16 (3) ◽  
pp. 267-274 ◽  
Author(s):  
Abhaya V. Kulkarni ◽  
Ruth Donnelly ◽  
Donald J. Mabbott ◽  
Elysa Widjaja
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Multiple Comparisons ◽  
Ventricular Volume ◽  
White Matter Injury ◽  
Ventricular Size ◽  
Neurocognitive Deficits ◽  
Asymptomatic Children ◽  
Neurocognitive Test ◽  
Hydrocephalus Treatment

OBJECT Larger-than-normal ventricles can persist in children following hydrocephalus treatment, even if they are asymptomatic and clinically well. This study aims to answer the following question: do large ventricles result in brain injuries that are detectable on diffusion tensor imaging (DTI) and/or in measurable neurocognitive deficits in children with stable, treated hydrocephalus that are not seen in children with small ventricles? METHODS For this prospective study, we recruited 23 children (age range 8–18 years) with hydrocephalus due to aqueductal stenosis or tectal glioma who were asymptomatic following hydrocephalus treatment that had been performed at least 2 years earlier. All patients underwent detailed DTI and a full battery of neuropsychological tests. Correlation analysis was performed to assess the relationship between DTI parameters, neurocognitive tests, and ventricular size. The false-discovery rate method was used to adjust for multiple comparisons. RESULTS The median age of these 23 children at the time of assessment was 15.0 years (interquartile range [IQR] 12.1–17.6 years), and the median age at the first hydrocephalus treatment was 5.8 years (IQR 2.2 months–12.8 years). At the time of assessment, 17 children had undergone endoscopic third ventriculostomy and 6 children had received a shunt. After adjusting for multiple comparisons, there were no significant correlations between any neurocognitive test and ventricular volume, any DTI parameter and ventricular volume, or any DTI parameter and neurocognitive test. CONCLUSIONS Our data do not show an association between large ventricular size and additional white matter injury or worse neurocognitive deficits in asymptomatic children with stable, treated hydrocephalus caused by a discrete blockage of the cerebral aqueduct. Further investigations using larger patient samples are needed to validate these results.

Neurocognitive Function Following Remission in Major Depressive Disorder: Potential Objective Marker of Response?

2007 ◽  
Vol 41 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Peter Gallagher ◽  
Lucy J. Robinson ◽  
John M. Gray ◽  
Allan H. Young ◽  
Richard J. Porter
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Verbal Memory ◽  
Neurocognitive Deficits ◽  
Short Term ◽  
Major Depressive ◽  
Neurocognitive Test ◽  
Disorder Potential ◽  
Objective Marker

Objective: Neurocognitive deficits have been widely reported in patients with mood disorders. However, relatively little is known of the short-term trajectory of neurocognitive improvement once treatment has been initiated. Method: A neurocognitive test battery was administered to unipolar depressed (major depressive disorder, MDD) patients (aged 18–65 years) who had been medication-free for at least 6 weeks, and to healthy controls. Patients were then treated according to clinical need, predominantly with standard pharmacotherapy, and all participants were followed up within 6 months. Results: Of the 25 MDD patients who returned at follow up, 11 were defined as remitted and 14 as not remitted. Significantly less baseline psychomotor dysfunction was observed in patients who remitted compared to those who did not (effect size, d =0.78, 95% confidence interval (CI) =0.07–1.44). Analysis of the change scores between assessments revealed a significantly greater improvement in verbal memory in patients who remitted compared to those who did not (d =0.73, 95%CI =0.03–1.39). Conclusions: This preliminary report suggests that there may be distinct temporal trajectories of neurocognitive improvement following remission in MDD. Aspects of neurocognitive functioning should be examined further as a means of providing a useful objective marker of treatment response.

scholarly journals Quantitative white matter loss explains risks of young age for neurocognitive deficits in medulloblastoma survivors

2000 ◽  
Vol 15 (8) ◽  
pp. 791-792 ◽  
Author(s):  
R. Mulhern ◽  
S. Palmer ◽  
W. Reddick ◽  
J. Glass ◽  
L. Kun ◽  
...  
Keyword(s):  
White Matter ◽  
Young Age ◽  
Neurocognitive Deficits

scholarly journals White matter network damage mediates association between cerebrovascular disease and cognition

2021 ◽  
pp. 0271678X2199098
Author(s):  
Saima Hilal ◽  
Siwei Liu ◽  
Tien Yin Wong ◽  
Henri Vrooman ◽  
Ching-Yu Cheng ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebrovascular Disease ◽  
Verbal Memory ◽  
Visual Memory ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Domain Specific ◽  
Epidemiology Of Dementia ◽  
Z Scores ◽  
White Matter Connectivity

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.

scholarly journals Laterality phenotypes in patients with schizophrenia, their siblings and controls: Associations with clinical and cognitive variables

2005 ◽  
Vol 187 (3) ◽  
pp. 221-228 ◽  
Author(s):  
Milan Dragovic ◽  
Geoff Hammond ◽  
Johanna C. Badcock ◽  
Assen Jablensky
Keyword(s):  
Clinical Severity ◽  
Hand Dominance ◽  
Cognitive Variables ◽  
Neurocognitive Deficits ◽  
Neurocognitive Performance ◽  
Course Of Illness ◽  
Complex Phenotypes ◽  
Novel Approach ◽  
Behavioural Asymmetries ◽  
Grade Of Membership

BackgroundVarious behavioural indices of brain lateralisation significantly intercorrelate, but current research in this area still focuses on single behavioural asymmetries, such as handedness.AimsTo describe a novel approach, which simultaneously integrates various laterality indices and delineates complex phenotypes.MethodGrade of membership analysis was used to describe latent, complex lateralisation phenotypes in patients with schizophrenia (n=157), their siblings (n=74) and controls (n=77). The indices used were asymmetries of eye, foot and hand; hand motor proficiency; and handedness of patient's first-degree relatives.ResultsThree distinct pure types of lateralisation (‘right’, ‘left’ and ‘mixed’) were evident in patients compared with two (‘right’ and ‘left’) in siblings and controls. The ‘mixed’ type in patients featured absence of eye and foot lateralisation and presence of familial sinistrality, despite a right-hand dominance for writing. Patients with schizophrenia expressing the ‘left’ phenotype had a more severe course of illness, significantly increased scores on two schizotypy factors and poorer neurocognitive performance. The pure types in the siblings were similar to those in healthy controls.ConclusionsThe findings suggest that a leftward reversal, rather than a reduction in lateralisation, is associated with clinical severity and neurocognitive deficits in patients with schizophrenia.

scholarly journals MRI substrates of sustained attention system and cognitive impairment in pediatric MS patients

Neurology ◽  
2017 ◽  
Vol 89 (12) ◽  
pp. 1265-1273 ◽  
Author(s):  
Ermelinda De Meo ◽  
Lucia Moiola ◽  
Angelo Ghezzi ◽  
Pierangelo Veggiotti ◽  
Ruggero Capra ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Sustained Attention ◽  
Structural Damage ◽  
Performance Test ◽  
Diffusion Tensor ◽  
Group Analysis ◽  
Anterior Cingulate ◽  
Attention Network ◽  
Attention System

Objective:To explore the structural and functional integrity of the sustained attention system in patients with pediatric multiple sclerosis (MS) and its effect on cognitive impairment.Methods:We enrolled 57 patients with pediatric MS and 14 age- and sex-matched healthy controls (HCs). Patients with >3 abnormal tests at neuropsychological evaluation were classified as cognitively impaired (CI). Sustained attention system activity was studied with fMRI during the Conners Continuous Performance Test (CCPT). Structural integrity of attention network connections was quantified with diffusion tensor (DT) MRI.Results:Within-group analysis showed similar patterns of recruitment of the attention network in HCs and patients with pediatric MS. Diffuse network DT MRI structural abnormalities were found in patients with MS. During CCPT, with increasing task demand, patients with pediatric MS showed increased activation of the left thalamus, anterior insula, and anterior cingulate cortex (ACC) and decreased recruitment of the right precuneus compared to HCs. Thirteen patients (23%) were classified as CI. Compared to cognitively preserved patients, CI patients with pediatric MS had decreased recruitment of several areas located mainly in parietal and occipital lobes and cerebellum and increased deactivation of the ACC, combined with more severe structural damage of white matter tracts connecting these regions.Conclusions:Our results suggest that the age-expected level of sustained attention system functional competence is achieved in patients with pediatric MS. Inefficient regulation of the functional interaction between different areas of this system, due to abnormal white matter integrity, may result in global cognitive impairment in these patients.

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