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

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  

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.

2019 ◽  
Author(s):  
Nicolas Nicastro ◽  
Patricia Vazquez Rodriguez ◽  
Maura Malpetti ◽  
William Richard Bevan-Jones ◽  
P. Simon Jones ◽  
...  

ABSTRACTIntroductionProgressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.MethodsTwenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18F-AV1451 imaging measures were correlated with clinical impairment.ResultsWidespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).ConclusionThis cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.


Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S4.2-S5
Author(s):  
James Houston ◽  
Frank Skidmore ◽  
William Monroe ◽  
Jon Amburgy ◽  
Mitchell Self

ObjectiveTo compare preseason and post-concussive MRI in a cohort of collegiate football players utilizing Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) post processing.BackgroundAcute post-concussive symptoms can vary in clinical characteristics and severity. However, vestibular and ocular dysfunction in particular, has been associated with poor clinical outcomes. The vestibular system comprises a complex network of projections from peripheral vestibular organs to thalamic relay systems and numerous cortical regions. The visual/oculomotor system is also complex, involving brainstem, subcortical-cortical and thalamo-cortical connections. Oculomotor deficits are thought to involve the midbrain and the visual and parietal association cortices, both of which have thalamic projections.Design/MethodsWe gathered pre-season MR diffusion weighted imaging on a cohort of 30 collegiate football players. We performed repeat imaging within 36 hours of any diagnosed concussion in the same subject cohort. DTI metrics: mean diffusivity (MD), axial diffusivity (AD), fractional anisotropy (FA), and radial diffusivity (RD) along with NODDI metric: orientation dispersion index (ODI), were analyzed for statistical comparisons between groups.Results4 subjects with pre-season MRI underwent repeat MRI within 36 hours of concussive injury. A paired t-test between these two groups using DTI and NODDI metrics showed significant (p < 0.05) decreases in: AD and MD in the left posterior thalamic radiations, FA in the column and body of the fornix, and MD in the right anterior corona radiata and superior fronto-occipital fasciculus, and a significant decrease in ODI in the anterior thalamus.ConclusionsDisruptions in the thalamus and its white matter projections may play a role in the vestibular/ocular dysfunction associated with acute concussive injury. While our numbers are small, the findings suggest that DTI and NODDI processing techniques have the capability to locate and measure grey and white matter injury patterns after concussive injury.


2021 ◽  
Vol 13 ◽  
Author(s):  
Stephanie Matijevic ◽  
Lee Ryan

Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54–92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.


Neurology ◽  
2019 ◽  
Vol 92 (19) ◽  
pp. e2221-e2231 ◽  
Author(s):  
Pauline Maillard ◽  
Evan Fletcher ◽  
Baljeet Singh ◽  
Oliver Martinez ◽  
David K. Johnson ◽  
...  

ObjectiveTo determine whether free water (FW) content, initially developed to correct metrics derived from diffusion tensor imaging and recently found to be strongly associated with vascular risk factors, may constitute a sensitive biomarker of white matter (WM) microstructural differences associated with cognitive performance but remains unknown.MethodsFive hundred thirty-six cognitively diverse individuals, aged 77 ± 8 years, received yearly comprehensive clinical evaluations and a baseline MRI examination of whom 224 underwent follow-up MRI. WM microstructural measures, including FW, fractional anisotropy, and mean diffusivity corrected for FW and WM hyperintensity burden were computed within WM voxels of each individual. Baseline and change in MRI metrics were then used as independent variables to explain baseline and change in episodic memory (EM), executive function (EF), and Clinical Dementia Rating (CDR) scores using linear, logistic, and Cox proportional-hazards regressions.ResultsHigher baseline FW and WM hyperintensity were associated with lower baseline EM and EF, higher baseline CDR, accelerated EF and EM decline, and higher probability to transition to a more severe CDR stage (p values <0.01). Annual change in FW was also found to be associated with concomitant change in cognitive and functional performance (p values <0.01).ConclusionsThis study finds cross-sectional and longitudinal associations between FW content and trajectory of cognitive and functional performance in a large sample of cognitively diverse individuals. It supports the need to investigate the pathophysiologic process that manifests increased FW, potentially leading to more severe WM territory injury and promoting cognitive and functional decline.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S249-S250
Author(s):  
Seda Arslan ◽  
Tuba Şahin ◽  
Didenur Şahin ◽  
Timothea Toulopoulou

Abstract Background Psychotic disorders are characterized by neurobiological deviations, including in the macro and microstructure of white matter. White matter alterations are also seen in psychosis-proneness and in individuals who have a high risk of psychosis. For example, studies have indicated decreases in white matter integrity in the genu/forceps minor of corpus callosum (CC) in the latter populations. Anterior corona radiata (ACR) is one crucial white-matter tract connecting the anterior cingulate cortex to the striatum. Indeed, reductions in the white matter structure of anterior genu of CC significantly predict the transition from ultra-high risk to psychosis. However, there is a gap in the literature related to observing the psychosis-proneness by applying both micro and macrostructural brain analyses, and most of the microstructural white matter studies in psychosis focus on fractional anisotropy (FA) and not include mean diffusivity (MD). Thus, the current study aims to assess whether white matter deviations in CG, ACR, and CC, are associated with psychosis proneness by combining both tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM) analyses in a sample of participants with psychosis proneness (PP) and without psychosis proneness (NPP). Methods The study included 53 participants (29 PP vs. 24 NPP) whose ages were between 17 and 24 years. Participants were split into two groups based on their scores on Structured Interview for Schizotypy assessment, a well-validated instrument of psychosis proneness. White matter integrity was analyzed via diffusion tensor imaging (DTI) and white matter volume (WMV) via VBM. Two sample t-test was used in GLM for both DTI and VBM analyses. FA, MD, and VMV were compared between two groups to observe micro and macro white matter structure alterations in the region of interest. Results DTI analysis revealed decreased FA values in the right ACR and right genu of the CC in the psychosis-proneness group (F(1,52)= 7.37, p= 0.009). Moreover, VBM showed a significant WMV decreases in the right CG, Brodmann areas 8, 9, and 32 in the PP group (F(1,52)= 50.85, uncorrected p&lt;0.01). However, MD did not differ between the two groups (F(1,51)= 3.65, p=0.06) Discussion These findings suggest that PP associated with decreased white matter integrity in ACR, genu of CC, and also reduced white matter volumes in the right CG, Brodmann areas 8, 9, and 32. Significant FA decreases might result from alterations in radial or axial diffusivity since we did not observe significant MD differences between two groups. The current findings suggested that participants with PP had both macro and micro white matter structure disruptions, mostly in frontal parts of the right cerebrum, compared to no PP group.


NeuroImage ◽  
2019 ◽  
Vol 186 ◽  
pp. 577-585 ◽  
Author(s):  
Atef Badji ◽  
Adrián Noriega de la Colina ◽  
Agah Karakuzu ◽  
Tanguy Duval ◽  
Laurence Desjardins-Crépeau ◽  
...  

2021 ◽  
Author(s):  
Yiming Xiao ◽  
Terry M. Peters ◽  
Ali R. Khan

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by a range of motor and non-motor symptoms, often with the motor dysfunction initiated unilaterally. Knowledge regarding disease-related alterations in white matter pathways can effectively help improve the understanding of the disease and propose targeted treatment strategies. Microstructural imaging techniques, including diffusion tensor imaging (DTI), allows inspection of white matter integrity to study the pathogenesis of various neurological conditions. Previous voxel-based analyses with DTI measures, such as fractional anisotropy and mean diffusivity have uncovered changes in brain regions that are associated with PD, but the conclusions were inconsistent, partially due to small patient cohorts and the lack of consideration for clinical laterality onset, particularly in early PD. Fixel-based analysis (FBA) is a recent framework that offers tract-specific insights regarding white matter health, but very few FBA studies on PD exist. We present a study that reveals strengthened and weakened white matter integrity that is subject to symptom laterality in a large drug-naïve de novo PD cohort using complementary DTI and FBA measures. The findings suggest that the disease gives rise to both functional degeneration and the creation of compensatory networks in the early stage.


2017 ◽  
Vol 31 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Maria M D’Souza ◽  
SP Gorthi ◽  
Kunal Vadwala ◽  
Richa Trivedi ◽  
C Vijayakumar ◽  
...  

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.


2020 ◽  
Vol 35 (1) ◽  
pp. 44-57
Author(s):  
Yi Zhao ◽  
Bronte Ficek ◽  
Kimberly Webster ◽  
Constantine Frangakis ◽  
Brian Caffo ◽  
...  

Background Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA. Objective We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA. Methods Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming. Results Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items. Conclusions White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1280-1280 ◽  
Author(s):  
M. Kyriakopoulos ◽  
L. Samartzis ◽  
D. Dima ◽  
D. Hayes ◽  
R. Corrigall ◽  
...  

IntroductionWhite matter (WM) abnormalities are considered integral to the pathophysiology of Schizophrenia (SZ) and Bipolar Disorder (BD), but there is ongoing uncertainty about the contribution of medication to these findings.ObjectivesDiffusion Tensor Imaging (DTI) is a neuroimaging technique that provides quantitative indices of the structural and orientational characteristics of WM. These indices include mean diffusivity (MD), which is a directionally averaged measure of the apparent diffusion coefficient, and fractional anisotropy (FA), which summarizes the orientational dependence of diffusivity. We wanted to determine if these indices are affected by antipsychotic medication.AimsOur aim was to examine the available literature in order to differentiate antipsychotic effects from disorder-specific WM abnormalities on DTI measures.MethodsWe conducted a systematic qualitative review of the DTI literature in Bipolar Disorder (BD) and Schizophrenia (SZ), between 1998 and 2010 and included only studies where the relationship between DTI measures and antipsychotic medication was explicitly examined and reported.ResultsWe identified 40 studies in SZ and 8 in BD. All studies were cross-sectional and involved relatively small patient samples. 32 studies (80%) did not find any relationship between antipsychotic medication (dose, cumulative exposure) and FA or MD.ConclusionsCurrent evidence does not indicate a major impact of antipsychotic treatment on DTI indices of WM integrity. However, the lack of longitudinal, within-subject designs is a major gap in the current literature.


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