scholarly journals Contribution of diffusion, perfusion and functional MRI to the disconnection hypothesis in subcortical vascular cognitive impairment

2018 ◽  
Vol 3 (3) ◽  
pp. 131-139 ◽  
Author(s):  
Qing Ye ◽  
Feng Bai
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Functional Mri ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Vascular Cognitive Impairment ◽  
Brain Abnormalities ◽  
Disconnection Syndrome ◽  
Subcortical Regions ◽  
Cortical Regions

Vascular cognitive impairment (VCI) describes all forms of cognitive impairment caused by any type of cerebrovascular disease. Early identification of VCI is quite difficult due to the lack of both sensitive and specific biomarkers. Extensive damage to the white matter tracts, which connect the cortical and subcortical regions, has been shown in subcortical VCI (SVCI), the most common subtype of VCI that is caused by small vessel disease. Two specific MRI sequences, including diffusion tensor imaging (DTI) and functional MRI (fMRI), have emerged as useful tools for identifying subtle white matter changes and the intrinsic connectivity between distinct cortical regions. This review describes the advantages of these two modalities in SVCI research and the current DTI and fMRI findings on SVCI. Using DTI technique, a variety of studies found that white matter microstructural damages in the anterior and superior areas are more specific to SVCI. Similarly, functional brain abnormalities detected by fMRI have also been mainly shown in anterior brain areas in SVCI. The characteristic distribution of brain abnormalities in SVCI interrupts the prefrontal-subcortical loop that results in cognitive impairments in particular domains, which further confirms the ‘disconnection syndrome’ hypothesis. In addition, another MRI technique, arterial spin labelling (ASL), has been used to describe the disconnection patterns in a variety of conditions by measuring cerebral blood flow. The role of the ASL technique in SVCI research is also assessed. Finally, the review proposes the application of multimodality fusion in the investigation of SVCI pathogenesis.

scholarly journals The Contribution of White Matter Diffusion and Cortical Perfusion Pathology to Vascular Cognitive Impairment: A Multimode Imaging-Based Machine Learning Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Yao Wang ◽  
Peiwen Lu ◽  
Yafeng Zhan ◽  
Xiaowei Wu ◽  
Yage Qiu ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cognitive Impairment ◽  
White Matter ◽  
Neural Circuit ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Critical Role ◽  
Vascular Cognitive Impairment ◽  
Imaging Features ◽  
Leave One Out

Widespread impairments in white matter and cerebrovascular integrity have been consistently implicated in the pathophysiology of patients with small vessel disease (SVD). However, the neural circuit mechanisms that underlie the developing progress of clinical cognitive symptoms remain largely elusive. Here, we conducted cross-modal MRI scanning including diffusion tensor imaging and arterial spin labeling in a cohort of 113 patients with SVD, which included 74 patients with vascular mild cognitive impairment (vMCI) and 39 patients without vMCI symptoms, and hence developed multimode imaging-based machine learning models to identify markers that discriminated SVD subtypes. Diffusion and perfusion features, respectively, extracted from individual white matter and gray matter regions were used to train three sets of classifiers in a nested 10-fold fashion: diffusion-based, perfusion-based, and combined diffusion-perfusion-based classifiers. We found that the diffusion-perfusion combined classifier achieved the highest accuracy of 72.57% with leave-one-out cross-validation, with the diffusion features largely spanning the capsular lateral pathway of the cholinergic tracts, and the perfusion features mainly distributed in the frontal-subcortical-limbic areas. Furthermore, diffusion-based features within vMCI group were associated with performance on executive function tests. We demonstrated the superior accuracy of using diffusion-perfusion combined multimode imaging features for classifying vMCI subtype out of a cohort of patients with SVD. Disruption of white matter integrity might play a critical role in the progression of cognitive impairment in patients with SVD, while malregulation of coritcal perfusion needs further study.

scholarly journals Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e040466
Author(s):  
Aravind Ganesh ◽  
Philip Barber ◽  
Sandra E Black ◽  
Dale Corbett ◽  
Thalia S Field ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Vascular Cognitive Impairment ◽  
White Matter Injury ◽  
White Matter Hyperintensity ◽  
Limb Ischaemia ◽  
Ischaemic Brain

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

Changes in mild cognitive impairment and its subtypes as seen on diffusion tensor imaging

2012 ◽  
Vol 24 (9) ◽  
pp. 1483-1493 ◽  
Author(s):  
Senthil Thillainadesan ◽  
Wei Wen ◽  
Lin Zhuang ◽  
John Crawford ◽  
Nicole Kochan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Multiple Testing ◽  
Diffusion Tensor ◽  
Internal Capsule ◽  
Anterior Cingulate ◽  
Corona Radiata ◽  
Amnestic Mci ◽  
Subcortical Regions ◽  
The Right

ABSTRACTBackground: Previous studies using diffusion tensor imaging (DTI) have observed microstructural abnormalities in white matter regions in both Alzheimer's disease and mild cognitive impairment (MCI). The aim of this work was to examine the abnormalities in white matter and subcortical regions of MCI and its subtypes in a large, community-dwelling older aged cohortMethods: A community-based sample of 396 individuals without dementia underwent medical assessment, neuropsychiatric testing, and neuroimaging. Of these, 158 subjects were classified as MCI and 238 as cognitively normal (controls) based on international MCI consensus criteria. Regional fractional anisotropy (FA) and mean diffusivity (MD) measures were calculated from the DTI and compared between groups. The false discovery rate correction was applied for multiple testing.Results: Subjects with MCI did not have significant differences in FA compared with controls after correction for multiple testing, but had increased MD in the right putamen, right anterior limb of the internal capsule, genu and splenium of the corpus callosum, right posterior cingulate gyrus, left superior frontal gyrus, and right and left corona radiata. When compared with controls, changes in left anterior cingulate, left superior frontal gyrus, and right corona radiata were associated with amnestic MCI (aMCI), whereas changes in the right putamen, right anterior limb of the internal capsule, and the right corona radiata were associated with non-amnestic MCI (naMCI). On logistic regression, the FA values in the left superior gyrus and MD values in the anterior cingulate distinguished aMCI from naMCI.Conclusions: MCI is associated with changes in white matter and subcortical regions as seen on DTI. Changes in some anterior brain regions distinguish aMCI from naMCI.

scholarly journals Microstructural Predictors of Cognitive Impairment in Cerebral Small Vessel Disease and the Conditions of Their Formation

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 720
Author(s):  
Larisa A. Dobrynina ◽  
Zukhra Sh. Gadzhieva ◽  
Kamila V. Shamtieva ◽  
Elena I. Kremneva ◽  
Bulat M. Akhmetzyanov ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Venous Blood Flow ◽  
Csf Flow ◽  
Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.

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.

scholarly journals Evaluation of Cerebral Blood Flow Measured by 3D PCASL as Biomarker of Vascular Cognitive Impairment and Dementia (VCID) in a Cohort of Elderly Latinx Subjects at Risk of Small Vessel Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Kay Jann ◽  
Xingfeng Shao ◽  
Samantha J. Ma ◽  
Steven Y. Cen ◽  
Lina D’Orazio ◽  
...  
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Small Vessel Disease ◽  
Vascular Cognitive Impairment ◽  
Small Vessel ◽  
Vessel Disease ◽  
Brain White Matter

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer’s disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77–0.85, wsCV 3–9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD.

scholarly journals Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia

2017 ◽  
Vol 131 (19) ◽  
pp. 2451-2468 ◽  
Author(s):  
Jessica Duncombe ◽  
Akihiro Kitamura ◽  
Yoshiki Hase ◽  
Masafumi Ihara ◽  
Raj N. Kalaria ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Vascular Cognitive Impairment ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Pathophysiological Mechanism ◽  
Rodent Models ◽  
Recent Refinement

Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments.

Abstract TMP97: Demyelination, Cognition and Imaging in a Translational Model of Rat Vascular Cognitive Impairment

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Manan Nath ◽  
Mark E Wagshul ◽  
Janina Ferbinteanu ◽  
Daniel M Rosenbaum ◽  
Pradeep Selvan ◽  
...  
Keyword(s):  
Decision Making ◽  
Cognitive Impairment ◽  
White Matter ◽  
Fdg Pet ◽  
Small Vessel Disease ◽  
Declarative Memory ◽  
Vascular Cognitive Impairment ◽  
Bilateral Carotid ◽  
Place Avoidance ◽  
Behavioral Assays

Small vessel disease and/or atherosclerosis produce microvascular and parenchymal inflammation in white matter and results in vascular cognitive impairment (VCI). We have performed bilateral carotid artery stenosis in hypertensive rats (SHR) to better understand disease pathology, targets for intervention and markers. Hypothesis: Complex cognitive deficits and diffuse fiber tract changes relevant to human VCI can be quantified and validated for future use. Methodology: We performed a series of behavioral assays to test declarative memory and executive functioning in stenosis compared to sham surgery SHR. Behavioral assays included T-maze decision making and alternation, novel object recognition (NOR) and active place avoidance (APA). MRI (DTI, DWI, Arterial Spin Labeling; ASL) and FDG-PET imaging was done in Corpus Callosum (CC). Histology-immunohistochemistry included measurements of microglia (Iba-1), astrocytes (GFAP) and Luxol fast blue (for myelin) in CC. Results: Stenosis resulted in consistent executive function decision making (T-maze) deficits (p<0.05) and impaired complex cognitive performance (APA). No significant differences occurred between sham and stenosis animals in NOR and T-maze alternation. DTI analysis indicated significant (p<0.05) changes in the CC of stenosis compared to sham SHR including: (1) decreased fractional anisotropy, (2) increased radial diffusivity, and (3) unchanged axial diffusivity. MRI ASL revealed significant (p<0.05) decreases in white matter perfusion. No significant changes were seen in FDG-PET. In summary, stenosis animals exhibited increased white matter glial cell inflammation related to demyelination and lost cognition. The inflammatory microglia phenotype was verified using TNFα plus Iba-1 double staining. CC changes were significantly (p<0.05) greater in the anterior, periventricular forebrain. Conclusion: We have successfully modeled the behavioral, imaging and histologic profile of human VCI in the rat. Currently pre/mature oligodendrocyte changes are being evaluated. This approach provides future opportunities to localize forebrain white matter changes using MR imaging parameters as markers for monitoring VCI demyelination/pathology and intervention.

Abstract 2749: Amyloid-beta (1-42) is Reduced in CSF in Vascular Cognitive Impairment

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Gary A Rosenberg ◽  
Jillian Prestopnik ◽  
Jeffrey Thompson ◽  
Charles Gasparovic ◽  
Branko N Huisa-Garate ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Vascular Disease ◽  
Small Vessel Disease ◽  
Executive Dysfunction ◽  
Vascular Cognitive Impairment ◽  
Small Vessel ◽  
Matrix Metalloproteinase 2 ◽  
Resonance Spectroscopy ◽  
Mri Findings

Introduction: Vascular cognitive impairment (VCI) and Alzheimer’s disease (AD) have a high degree of overlap in a number of large autopsy series. However, few studies have examined the overlap during life. VCI is a heterogeneous disorder due to large and small vessel vascular disease (SVD). Biomarkers of inflammation are present in the SVD, which is a progressive form of VCI that is characterized by MRI findings of lacunar strokes and white matter hyperintensities (WMHs), executive dysfunction, focal neurological findings, apathy, urinary problems and gait imbalance. Recently, we showed an association between a reduced matrix metalloproteinase-2 (MMP-2) CSF index and disruption of the blood-brain barrier (BBB) in SVD. We hypothesized that patients with both VCI and AD would show CSF and MRI biomarkers for both diseases. Patients and Methods: Patients (N=60) with VCI underwent neurological and neuropsychological testing. MRI was done with FLAIR, proton magnetic resonance spectroscopy (1H-MRS) to measure ischemia with N-acetylaspartate (NAA), and dynamic contrast-enhanced MRI (DCEMRI) to measure BBB transfer constants (K i ). CSF (N=37) was obtained by lumbar puncture for measurements of albumin index, MMP-2 and MMP-9 indexes, ABeta 1-42, total-tau (T-Tau) and hyperphosphorylated-tau (P-Tau). Results: BD patients had large WMHs, while large vessel (multi-infarct and single strategic stroke) patients had small WMHs. NAA was used as a biomarker of lesion size due to ischemic damage in the white matter. ROC plots showed that a NAA cut-point of 12 separated patients with large WMHs (low NAA) from small WMHs (p<0.0001). K i transfer constants above 0.0018 (ROC; p<0.0001) and MMP-2 below 0.0099 (ROC; p<0.0001) were considered abnormal. SVD patients had reduced ABeta 1-42 compared to control CSF. P-Tau was unaffected. Abnormal values for K i and MMP-2 index were present in both large and small vessel disease patients. Conclusions: Our results show that SVD patients have significantly reduced levels of ABeta 1-42 in CSF, suggesting impairment in amyloid metabolism associated with vascular disease. These findings conform to the autopsy findings and suggest that multimodal biomarkers may provide information during life about the presence of both AD and VCI.

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