Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients

2013 ◽  
Vol 19 (11) ◽  
pp. 1478-1484 ◽  
Author(s):  
Ralph HB Benedict ◽  
Hanneke E Hulst ◽  
Niels Bergsland ◽  
Menno M Schoonheim ◽  
Michael G Dwyer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Cognitive Processing ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Brain Magnetic Resonance Imaging ◽  
Cognitive Tests ◽  
Explained Variance ◽  
Multiple Sclerosis Patients

Background: Gray-matter (GM) atrophy is strongly predictive of cognitive impairment in multiple sclerosis (MS) patients. The thalamus is the region where the atrophy/cognition correlation is most robust. However, few studies have assessed diffusion tensor imaging (DTI) metrics within the thalamus. Objective: This study was designed to determine if thalamus white matter DTI predicts cognitive impairment after accounting for the effects of volume loss. Methods: We enrolled 75 MS patients and 18 healthy controls undergoing 3T brain magnetic resonance imaging (MRI). Thalamus volumes were calculated on 3D T1 images. Voxelwise analyses of DTI metrics were performed within the thalamic white matter tracts. Neuropsychological (NP) testing, acquired using consensus standard methods, contributed measures of memory, cognitive processing speed and executive function. Results: All cognitive tests were significantly predicted ( R2 =0.31, p<0.001) by thalamus volume after accounting for influence of demographics. Mean diffusivity was retained in regression models predicting all cognitive tests, adding from 7–13% of additional explained variance ( p<0.02) after accounting for thalamus volume. Conclusions: We confirm the significant role of thalamus atrophy in MS-associated cognitive disorder, and further report that subtle thalamus pathology as detected by DTI adds incremental explained variance in predicting cognitive impairment.

scholarly journals Diffusion Tensor Imaging Abnormalities in Cognitively Impaired Multiple Sclerosis Patients

2010 ◽  
Vol 37 (5) ◽  
pp. 608-614 ◽  
Author(s):  
Nadine Akbar ◽  
Nancy J. Lobaugh ◽  
Paul O'Connor ◽  
Linda Moradzadeh ◽  
Christopher J. M. Scott ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Neuropsychological Testing ◽  
Mean Diffusivity ◽  
Brain Parenchyma ◽  
Hyperintense Lesion ◽  
Normal Appearing White Matter ◽  
Multiple Sclerosis Patients

Background:Cognitive impairment can add to the burden of disease in patients with multiple sclerosis (MS). The aim of this study was to assess the relative importance of diffusion tensor imaging (DTI) indices derived from normal appearing white matter (NAWM) and grey matter (NAGM) in determining cognitive dysfunction in MS patients.Methods:Sixty two MS patients [51 female, mean age= 41 (sd=9.6) years, median expanded disability status scale (EDSS)=2.5] meeting modified McDonald criteria for MS underwent neuropsychological testing using the Neuropsychological Screening Battery for MS (NSBMS) and magnetic resonance imaging (MRI, 1.5T GE) that included DTI sequences. Total T1 hypointense and T2 hyperintense lesion volumes were obtained using semi-automated software. Lesion volumes were subtracted from whole-brain parenchyma to obtain measures of NAWM and NAGM. Fractional anisotropy (FA) of NAWM and mean diffusivity (MD) of NAGM were obtained.Results:Cognitive impairment was present in 11 patients (18%). These patients had higher EDSS scores, were less educated, and were more likely to have secondary progressive MS. They also had higher hypointense (p=0.001) and hyperintense (p=0.004) lesion volumes, greater NAWM atrophy (p=0.007), lower FA of total NAWM (p=0.003), and higher MD of total NAGM (p=0.015). Using a logistic regression analysis, and after controlling for demographic and disease-related differences between groups, FA of NAWM emerged as a significant predictor of cognitive impairment adding to the variance derived from lesion and atrophy data.Conclusion:This study underlies the important role of normal-appearing brain tissue in the pathogenesis of MS-related cognitive impairment.

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

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. e2244-e2255 ◽  
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.

In vivo gradients of thalamic damage in paediatric multiple sclerosis: a window into pathology

Brain ◽  
2020 ◽  
Author(s):  
Ermelinda De Meo ◽  
Loredana Storelli ◽  
Lucia Moiola ◽  
Angelo Ghezzi ◽  
Pierangelo Veggiotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Fractional Anisotropy ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Healthy Controls ◽  
Paediatric Multiple Sclerosis ◽  
Multiple Sclerosis Patients

Abstract The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics—including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio—in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183–0.369; P range = 0.010–0.046), while we found significant mean diffusivity (f2 range = 0.101–0.369; P range = 0.018–0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = −0.27–0.34; P range = 0.004–0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24–0.27; P range = 0.006–0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.

Deep microbleeds and periventricular white matter disintegrity are independent predictors of attention/executive dysfunction in non-dementia patients with small vessel disease

2016 ◽  
Vol 29 (5) ◽  
pp. 793-803 ◽  
Author(s):  
Wen-wei Cao ◽  
Yao Wang ◽  
Quan Dong ◽  
Xue Chen ◽  
Yan-sheng Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Early Stage ◽  
Mean Diffusivity ◽  
Executive Dysfunction ◽  
Small Vessel ◽  
Periventricular White Matter ◽  
Vessel Disease

ABSTRACTBackground:Cerebral small vessel disease (SVD) is the common cause of cognitive decline in the old population. MRI can be used to clarify its mechanisms. However, the surrogate markers of MRI for early cognitive impairment in SVD remain uncertain to date. We investigated the cognitive impacts of cerebral microbleeds (CMBs), diffusion tensor imaging (DTI), and brain volumetric measurements in a cohort of post-stroke non-dementia SVD patients.Methods:Fifty five non-dementia SVD patients were consecutively recruited and categorized into two groups as no cognitive impairment (NCI) (n = 23) or vascular mild cognitive impairment (VaMCI) (n = 32). Detailed neuropsychological assessment and multimodal MRI were completed.Results:The two groups differed significantly on Z scores of all cognitive domains (all p < 0.01) except for the language. There were more patients with hypertension (p = 0.038) or depression (p = 0.019) in the VaMCI than those in the NCI group. Multiple regression analysis of cognition showed periventricular mean diffusivity (MD) (β = −0.457, p < 0.01) and deep CMBs numbers (β = −0.352, p < 0.01) as the predictors of attention/executive function, which explained 45.2% of the total variance. Periventricular MD was the independent predictor for either memory (β = −0.314, p < 0.05) or visuo-spatial function (β = −0.375, p < 0.01); however, only small proportion of variance could be accounted for (9.8% and 12.4%, respectively). Language was not found to be correlated with any of the MRI parameters. No correlation was found between brain atrophic indices and any of the cognitive measures.Conclusion:Arteriosclerotic CMBs and periventricular white matter disintegrity seem to be independent MRI surrogated markers in the early stage of cognitive impairment in SVD.

T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis

2010 ◽  
Vol 16 (10) ◽  
pp. 1203-1212 ◽  
Author(s):  
Francesca Bagnato ◽  
Zeena Salman ◽  
Robert Kane ◽  
Sungyoung Auh ◽  
Fredric K Cantor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Statistical Significance ◽  
Verbal Learning ◽  
Lesion Volume ◽  
Cognitive Disability ◽  
3.0 Tesla ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: Neocortical lesions (NLs) largely contribute to the pathology of multiple sclerosis (MS), although their relevance in patients’ disability remains unknown. Objective: To assess the incidence of T1 hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment. Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm3 three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T1- and T2-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated. Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed. Conclusions: Although T 1 hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease.

scholarly journals Disrupted white matter integrity is associated with cognitive deficits in patients with amnestic mild cognitive impairment: An atlas-based study

2016 ◽  
Vol 4 ◽  
pp. 205031211664881 ◽  
Author(s):  
Duan Liu ◽  
Zan Wang ◽  
Hao Shu ◽  
Zhijun Zhang
Keyword(s):  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Amnestic Mild Cognitive Impairment ◽  
Uncinate Fasciculus ◽  
Radial Diffusivity ◽  
Mild Cognitive Impairment Group

Objective: This study investigated white matter integrity in patients with amnestic mild cognitive impairment by diffusion tensor imaging. Methods: A total of 83 patients with amnestic mild cognitive impairment and 85 elderly healthy controls underwent neuropsychological testing and a diffusion tensor imaging scan. Whole-brain white matter data were parcellated into 50 regions based on the anatomical ICBM-DTI-81 atlas, and regional diffusion metrics consisting of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated for each region. Diffusion tensor imaging indices were compared between groups, and it was determined that between-group differences were significantly correlated with neurocognitive performance. Results: Relative to the healthy controls group, the amnestic mild cognitive impairment group exhibited poorer cognitive performance in all neuropsychological tests except the complex figure test ( p = 0.083) and showed decreased mean fractional anisotropy in the fornix, increased mean diffusivity in the fornix and bilateral uncinate fasciculus, elevated axial diffusivity in the fornix and genu of corpus callosum, and elevated radial diffusivity in the fornix and bilateral uncinate fasciculus ( p < 0.05). Behaviorally, integrity of the bilateral uncinate fasciculus was correlated positively with episodic memory function, while left uncinate fasciculus integrity was positively associated with language function in the amnestic mild cognitive impairment group ( p < 0.05). Conclusion: White matter abnormalities in neural pathways associated with memory were correlated with neurocognitive deficiencies in amnestic mild cognitive impairment. Given that amnestic mild cognitive impairment is putatively a prodromal syndrome for Alzheimer’s disease, this study furthers our understanding of the white matter changes associated with Alzheimer’s disease pathogenesis in the predementia stage.

scholarly journals White matter and neurocognitive changes in adults with chronic traumatic brain injury

2009 ◽  
Vol 15 (1) ◽  
pp. 130-136 ◽  
Author(s):  
MARY R.T. KENNEDY ◽  
JEFFREY R. WOZNIAK ◽  
RYAN L. MUETZEL ◽  
BRYON A. MUELLER ◽  
HSIN-HUEI CHIOU ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Analysis Of Covariance ◽  
Severely Injured ◽  
Motor Speed ◽  
Time Since Injury

AbstractDiffusion tensor imaging was used to investigate white matter (WM) integrity in adults with traumatic brain injury (TBI) and healthy adults as controls. Adults with TBI had sustained severe vehicular injuries on the average of 7 years earlier. A multivariate analysis of covariance with verbal IQ as the covariate revealed that adults with TBI had lower fractional anisotropy and higher mean diffusivity than controls, specifically in the three regions of interest (ROIs), the centrum semiovale (CS), the superior frontal (SPF), and the inferior frontal (INF). Adults with TBI averaged in the normal range in motor speed and two of three executive functions and were below average in delayed verbal recall and inhibition, whereas controls were above average. Time since injury, but not age, was associated with WM changes in the SPF ROI, whereas age, but not time since injury, was associated with WM changes in the INF ROI, suggesting that the effects of WM on time since injury may interact with age. To understand the utility of WM changes in chronic recovery, larger sample sizes are needed to investigate associations between cognition and WM integrity of severely injured individuals who have substantial cognitive impairment compared to severely injured individuals with little cognitive impairment. (JINS, 2009, 15, 130–136.)

scholarly journals Cortical axonal loss is associated with both gray matter demyelination and white matter tract pathology in progressive multiple sclerosis: Evidence from a combined MRI-histopathology study

2020 ◽  
pp. 135245852091897 ◽  
Author(s):  
Svenja Kiljan ◽  
Paolo Preziosa ◽  
Laura E Jonkman ◽  
Wilma DJ van de Berg ◽  
Jos Twisk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Axonal Density ◽  
Neuroaxonal Degeneration

Background: Neuroaxonal degeneration is one of the hallmarks of clinical deterioration in progressive multiple sclerosis (PMS). Objective: To elucidate the association between neuroaxonal degeneration and both local cortical and connected white matter (WM) tract pathology in PMS. Methods: Post-mortem in situ 3T magnetic resonance imaging (MRI) and cortical tissue blocks were collected from 16 PMS donors and 10 controls. Cortical neuroaxonal, myelin, and microglia densities were quantified histopathologically. From diffusion tensor MRI, fractional anisotropy, axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were quantified in normal-appearing white matter (NAWM) and white matter lesions (WML) of WM tracts connected to dissected cortical regions. Between-group differences and within-group associations were investigated through linear mixed models. Results: The PMS donors displayed significant axonal loss in both demyelinated and normal-appearing (NA) cortices ( p < 0.001 and p = 0.02) compared with controls. In PMS, cortical axonal density was associated with WML MD and AD ( p = 0.003; p = 0.02, respectively), and NAWM MD and AD ( p = 0.04; p = 0.049, respectively). NAWM AD and WML AD explained 12.6% and 22.6%, respectively, of axonal density variance in NA cortex. Additional axonal loss in demyelinated cortex was associated with cortical demyelination severity ( p = 0.002), explaining 34.4% of axonal loss variance. Conclusion: Reduced integrity of connected WM tracts and cortical demyelination both contribute to cortical axonal loss in PMS.

scholarly journals Corpus Callosum and Cingulum Tractography in Parkinson's Disease

2010 ◽  
Vol 37 (5) ◽  
pp. 595-600 ◽  
Author(s):  
Katie Wiltshire ◽  
Luis Concha ◽  
Myrlene Gee ◽  
Thomas Bouchard ◽  
Christian Beaulieu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Method ◽  
Motor Symptoms ◽  
Mri Scans

Background:In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.Objective:To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.Methods:Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.Results:Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.Conclusions:The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

scholarly journals Increased hippocampal-inferior temporal cortex white matter connectivity following donepezil treatment in patients with mild cognitive impairment: A diffusion tensor probabilistic tractography study

2021 ◽  
Author(s):  
Gwang-Won Kim ◽  
Kwangsung Park ◽  
Gwang-Woo Jeong
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Early Stage ◽  
Structural Connectivity ◽  
Temporal Cortex ◽  
Mean Diffusivity ◽  
Inferior Temporal Cortex ◽  
Probabilistic Tractography

Abstract The incidence of Alzheimer’s disease (AD) has been increasing each year; however, few methods are available to identify the effects of treatment for AD. Defective hippocampus has been associated with mild cognitive impairment (MCI), an early stage of AD. However, the effect of donepezil treatment on hippocampus-related networks is unknown. The purpose of this study was to evaluate the hippocampal white matter (WM) connectivity following donepezil treatment in patients with MCI using probabilistic tractography, and to further determine the WM integrity and changes in brain volume. Magnetic resonance imaging and diffusion tensor imaging (DTI) data of patients with MCI before and after 6-month donepezil treatment were acquired. Volumes and DTI scalars of 11 regions of interest comprising the frontal and temporal cortices and subcortical regions were measured. Seed-based structural connectivity analyses were focused on the hippocampus. Compared with healthy controls, patients with MCI showed significantly decreased hippocampal volume and WM connectivity with the superior frontal gyrus, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the amygdala (p < 0.05, Bonferroni-corrected). After six months of donepezil treatment, patients with MCI showed increased hippocampal-inferior temporal gyrus (ITG) WM connectivity (p < 0.05, Bonferroni-corrected), which was normalized to the healthy control. These findings will be useful in developing theories to describe the etiology of MCI and the therapeutic role of anticholinesterases.

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