White matter network damage mediates association between cerebrovascular disease and cognition

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.

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Nicotine Effects on White Matter Microstructure in Young Adults

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acy101 ◽

2019 ◽

Vol 35 (1) ◽

pp. 10-21 ◽

Cited By ~ 2

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.

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Distinctive Patterns of Tau Accumulation and White-Matter Degeneration on Domain-Specific Neuropsychiatric Test Scores

Proceedings of IMPRS ◽

10.18060/24617 ◽

2020 ◽

Vol 3 ◽

Author(s):

Zack Hall ◽

Billy Chien ◽

Shannon Risacher ◽

Andrew Saykin ◽

Yu-Chien Wu ◽

...

Keyword(s):

White Matter ◽

Verbal Memory ◽

Test Scores ◽

Visual Memory ◽

Visuospatial Ability ◽

Domain Specific ◽

Brain Functions ◽

White Matter Degeneration ◽

Tau Pet ◽

The Brain

Background: Diagnosis of AD is often started via cognitive tests such as the Mini Mental Status Exam (MMSE) or Montreal Cognitive Assessment (MOCA) with the diagnosis being finalized with autopsy. Currently, positron emission tomography (PET) tracers are used to visualize tau and beta amyloid accumulation in the brain. These imaging techniques demonstrate significant correlations with cognitive decline and have been used to aid in the diagnosis of AD. Particularly, tau accumulation has been shown to progress in a distinct pattern and has been linked to white matter degeneration. We hypothesized that tau accumulation and white matter degeneration in different brain regions have unique correlation patterns with domain-specific neuropsychiatric test scores. Methods: This study included 87 older adults (57 cognitively normal subjects and 27 mild cognitive impairment) from the Indiana Alzheimer’s Disease Center. All participants underwent tau-PET ([18F] Flortaucipir PET) and diffusion MRI (dMRI) exams. Tau accumulation was quantified with tau-PET SUVR. White-matter structural connectivity (SC), which probes the integrity of white-matter connections of the brain, was quantified by metrices extracted from dMRI using network analysis. Both tau accumulation and SC measurements were quantified in 84 cortical region of interests (ROIs) and were compared to their domain specific neuropsychiatric test scores with linear regression analysis. Results: The verbal memory, visual memory, and visuospatial ability all had unique region-specific correlations with white-matter degeneration and tau accumulation. Verbal memory was solely correlated with tau accumulation. Visual memory was related to both tau accumulation and white-matter SC. Finally, visuospatial ability was only correlated with white-matter SC. Potential Impact: This data reveals that although there is a tight interplay between tau accumulation and white-matter degeneration, they affect brain functions in different ways. Specifically, grey-matter tau accumulation is associated with overall memory loss and decrease in the white-matter connectivity affects the visual-related information processing.

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White Matter Connectivity Reflects Success in Musical Improvisation

10.1101/218024 ◽

2017 ◽

Cited By ~ 3

Author(s):

Tima Zeng ◽

Emily Przysinda ◽

Charles Pfeifer ◽

Cameron Arkin ◽

Psyche Loui

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Sound Perception ◽

Creative Behavior ◽

Domain Specific ◽

Statistical Measures ◽

Musical Improvisation ◽

White Matter Connectivity ◽

Expert Ratings ◽

Integrate Domain

AbstractCreativity is the ability to produce work that is novel, high in quality, and appropriate to an audience. One domain of creativity comes from musical improvisation, in which individuals spontaneously create novel auditory-motor sequences that are aesthetically rewarding. Here we test the hypothesis that individual differences in creative behavior are subserved by mesial and lateral differences in white matter connectivity. We compare jazz improvising musicians against classical (non-improvising) musicians and non-musician control subjects in musical performance and diffusion tensor imaging. Subjects improvised on short musical motifs and underwent DTI. Statistical measures of fluency and entropy for musical performances predicted expert ratings of creativity for each performance. Tract-Based Spatial Statistics (TBSS) showed higher Fractional Anisotropy (FA) in the cingulate cortex and corpus callosum in jazz musicians. FA in the cingulate also correlated with entropy. Probabilistic tractography from these mesial regions to lateral seed regions of the arcuate fasciculus, a pathway known to be involved in sound perception and production, showed mesial-to-lateral connectivity that correlated with improvisation training. Results suggest that white matter connectivity between lateral and mesial structures may integrate domain-general and domain-specific components of creativity.

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Cognitive phenotypes in temporal lobe epilepsy are associated with distinct patterns of white matter network abnormalities

Neurology ◽

10.1212/wnl.0000000000007370 ◽

2019 ◽

Vol 92 (17) ◽

pp. e1957-e1968 ◽

Cited By ~ 12

Author(s):

Anny Reyes ◽

Erik Kaestner ◽

Naeim Bahrami ◽

Akshara Balachandra ◽

Manu Hegde ◽

...

Keyword(s):

White Matter ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Network Structure ◽

Verbal Memory ◽

Language Impairment ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Language Impaired ◽

Impaired Group

ObjectiveTo identify distinct cognitive phenotypes in temporal lobe epilepsy (TLE) and evaluate patterns of white matter (WM) network alterations associated with each phenotype.MethodsSeventy patients with TLE were characterized into 4 distinct cognitive phenotypes based on patterns of impairment in language and verbal memory measures (language and memory impaired, memory impaired only, language impaired only, no impairment). Diffusion tensor imaging was obtained in all patients and in 46 healthy controls (HC). Fractional anisotropy (FA) and mean diffusivity (MD) of the WM directly beneath neocortex (i.e., superficial WM [SWM]) and of deep WM tracts associated with memory and language were calculated for each phenotype. Regional and network-based SWM analyses were performed across phenotypes.ResultsThe language and memory impaired group and the memory impaired group showed distinct patterns of microstructural abnormalities in SWM relative to HC. In addition, the language and memory impaired group showed widespread alterations in WM tracts and altered global SWM network topology. Patients with isolated language impairment exhibited poor network structure within perisylvian cortex, despite relatively intact global SWM network structure, whereas patients with no impairment appeared similar to HC across all measures.ConclusionsThese findings demonstrate a differential pattern of WM microstructural abnormalities across distinct cognitive phenotypes in TLE that can be appreciated at both the regional and network levels. These findings not only help to unravel the underlying neurobiology associated with cognitive impairment in TLE, but they could also aid in establishing cognitive taxonomies or in the prediction of cognitive course in TLE.

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Superficial white matter damage in anti-NMDA receptor encephalitis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-316822 ◽

2017 ◽

Vol 89 (5) ◽

pp. 518-525 ◽

Cited By ~ 12

Author(s):

Owen Robert Phillips ◽

Shantanu H Joshi ◽

Katherine L Narr ◽

David W Shattuck ◽

Manpreet Singh ◽

...

Keyword(s):

White Matter ◽

Verbal Memory ◽

Diffusion Tensor ◽

Brain Mri ◽

Strong Association ◽

Mean Diffusivity ◽

Cognitive Testing ◽

Healthy Controls ◽

White Matter Damage ◽

Nmdar Encephalitis

BackgroundClinical brain MRI is normal in the majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter.MethodsForty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity.ResultsNon-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients.ConclusionsAnti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.

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Distinct white matter alterations following severe stroke

Neurology ◽

10.1212/wnl.0000000000003843 ◽

2017 ◽

Vol 88 (16) ◽

pp. 1546-1555 ◽

Cited By ~ 19

Author(s):

Roza M. Umarova ◽

Lena Beume ◽

Marco Reisert ◽

Christoph P. Kaller ◽

Stefan Klöppel ◽

...

Keyword(s):

White Matter ◽

Network Architecture ◽

Large Scale ◽

Diffusion Tensor ◽

Neuropsychological Testing ◽

Mean Diffusivity ◽

Spatial Neglect ◽

Association Cortex ◽

Structural Reorganization ◽

Domain Specific

Objective:To distinguish white matter remodeling directly induced by stroke lesion from that evoked by remote network dysfunction, using spatial neglect as a model.Methods:We examined 24 visual neglect/extinction patients and 17 control patients combining comprehensive analyses of diffusion tensor metrics and global fiber tracking with neuropsychological testing in the acute (6.3 ± 0.5 days poststroke) and chronic (134 ± 7 days poststroke) stroke phases.Results:Compared to stroke controls, patients with spatial neglect/extinction displayed longitudinal white matter alterations with 2 defining signatures: (1) perilesional degenerative changes characterized by congruently reduced fractional anisotropy and increased radial diffusivity (RD), axial diffusivity, and mean diffusivity, all suggestive of direct axonal damage by lesion and therefore nonspecific for impaired attention network and (2) transneuronal changes characterized by an increased RD in contralesional frontoparietal and bilateral occipital connections, suggestive of primary periaxonal involvement; these changes were distinctly related to the degree of unrecovered neglect symptoms in chronic stroke, hence emerging as network-specific alterations.Conclusions:The present data show how stroke entails global alterations of lesion-spared network architecture over time. Sufficiently large lesions of widely interconnected association cortex induce distinct, large-scale structural reorganization in domain-specific network connections. Besides their relevance to unrecovered domain-specific symptoms, these effects might also explain mechanisms of domain-general deficits in stroke patients, pointing to potential targets for therapeutic intervention.

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Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

Journal of Alzheimer s Disease ◽

10.3233/jad-201424 ◽

2021 ◽

Vol 80 (2) ◽

pp. 567-576

Author(s):

Fei Han ◽

Fei-Fei Zhai ◽

Ming-Li Li ◽

Li-Xin Zhou ◽

Jun Ni ◽

...

Keyword(s):

Cognitive Function ◽

White Matter ◽

Arterial Stiffness ◽

Cognitive Decline ◽

Sex Education ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

White Matter Injury ◽

White Matter Integrity ◽

Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

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White Matter Integrity Predicts Delay Discounting Behavior in 9- to 23-Year-Olds: A Diffusion Tensor Imaging Study

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2009.21107 ◽

2009 ◽

Vol 21 (7) ◽

pp. 1406-1421 ◽

Cited By ~ 119

Author(s):

Elizabeth A. Olson ◽

Paul F. Collins ◽

Catalina J. Hooper ◽

Ryan Muetzel ◽

Kelvin O. Lim ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Delay Discounting ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Study ◽

Temporal Lobes ◽

Brain White Matter ◽

Independent Effects ◽

Age Range

Healthy participants (n = 79), ages 9–23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.

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White matter differences between essential tremor and Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006694 ◽

2018 ◽

Vol 92 (1) ◽

pp. e30-e39 ◽

Cited By ~ 5

Author(s):

Meher R. Juttukonda ◽

Giulia Franco ◽

Dario J. Englot ◽

Ya-Chen Lin ◽

Kalen J. Petersen ◽

...

Keyword(s):

White Matter ◽

Parkinson Disease ◽

Essential Tremor ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Superior Cerebellar Peduncle ◽

Radial Diffusivity ◽

Cerebellar Peduncles ◽

Cerebellar Peduncle

ObjectiveTo assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.MethodsSedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.ResultsFractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body (p < 0.01), sagittal stratum (p = 0.01), forceps major (p = 0.02), pontine crossing tract (p = 0.03), and retrolenticular internal capsule (p = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle (p < 0.01), middle cerebellar peduncle (p = 0.05), and inferior cerebellar peduncle (p = 0.05).ConclusionsRegionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.

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White matter abnormalities in the corpus callosum with cognitive impairment in Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006646 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2244-e2255 ◽

Cited By ~ 16

Author(s):

Ian O. Bledsoe ◽

Glenn T. Stebbins ◽

Doug Merkitch ◽

Jennifer G. Goldman

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Corpus Callosum ◽

Parkinson Disease ◽

Information Transfer ◽

Diffusion Tensor ◽

Anterior Segment ◽

Mean Diffusivity ◽

Cognitive Domain ◽

White Matter Abnormalities

ObjectiveTo evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).MethodsSeventy-five participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function) z scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain z scores and DTI metrics.ResultsParticipants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.ConclusionsMicrostructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal–cortical projections.

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