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 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.

scholarly journals Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

2017 ◽  
Vol 131 (12) ◽  
pp. 1361-1373 ◽  
Author(s):  
Iain D. Croall ◽  
Valerie Lohner ◽  
Barry Moynihan ◽  
Usman Khan ◽  
Ahamad Hassan ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Mean Diffusivity ◽  
Peak Height ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Single Centre ◽  
Vessel Disease ◽  
Multicentre Studies

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.

scholarly journals Diffusion tensor tractography in cerebral small vessel disease: correlation with cognitive function

2017 ◽  
Vol 31 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Maria M D’Souza ◽  
SP Gorthi ◽  
Kunal Vadwala ◽  
Richa Trivedi ◽  
C Vijayakumar ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Surrogate Marker ◽  
Mean Diffusivity ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Damage ◽  
Vessel Disease

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.

scholarly journals Multi-Dimensional Diffusion Tensor Imaging Biomarkers for Cognitive Decline From the Preclinical Stage: A Study of Post-stroke Small Vessel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Du ◽  
Hong Zhu ◽  
Ling Yu ◽  
Peiwen Lu ◽  
Yage Qiu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Mean Diffusivity ◽  
Cognitive Status ◽  
Preclinical Stage ◽  
Vessel Disease ◽  
Dimensional Diffusion

Objectives: We aim to investigate whether multi-dimensional diffusion tensor imaging (DTI) measures can sensitively identify different cognitive status of cerebral small vessel disease (CSVD) and to explore the underlying pattern of white matter disruption in CSVD.Methods: Two hundred and two participants were recruited, composed of 99 CSVD patients with mild cognitive impairment (VaMCI) and 60 with no cognitive impairment (NCI) and 43 healthy subjects as normal controls (NC). Full domain neuropsychological tests and diffusion-weighted imaging were performed on each subject. DTI metrics such as fractional anisotropy (FA), mean diffusivity (MD), the skeletonized mean diffusivity (PSMD), and structural brain network measures including network strength, global efficiency (EGlobal), and local efficiency (ELocal) were calculated. Region of interest (ROI) analysis of 42 white matter tracts was performed to examine the regional anatomical white matter disruption for each group.Results: Significant differences of multiple cognitive test scores across all cognitive domains especially processing and executive function existed among the three groups. DTI measures (FA, MD, and PSMD) showed significant group difference with the cognitive status changing. FA and EGlobal showed significant correlation with processing speed, executive function, and memory. ROI analysis found that white matter integrity impairment occurred from the preclinical stage of vascular cognitive impairment (VCI) due to CSVD. These lesions in the NCI group mainly involved some longitudinal fibers such as right superior longitudinal fasciculus (SLF-R), right superior fronto-occipital fasciculus (SFO-R), and right uncinate fasciculus (UNC-R), which might be more vulnerable to the cerebrovascular aging and disease process.Conclusions: DTI measures are sensitive neuroimaging markers in detecting the early cognitive impairment and able to differentiate the different cognitive status due to CSVD. Subtle changes of some vulnerable white matter tracts may be observed from the preclinical stage of VCI and have a local to general spreading pattern during the disease progression.

scholarly journals T2 relaxation time of the normal-appearing white matter is related to the cognitive status in cerebral small vessel disease

2020 ◽  
pp. 0271678X2097251
Author(s):  
Annemarie Brandhofe ◽  
Christoph Stratmann ◽  
Jan-Rüdiger Schüre ◽  
Ulrich Pilatus ◽  
Elke Hattingen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cognitive Status ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Imaging Biomarker ◽  
Vessel Disease ◽  
Normal Appearing White Matter

Previous diffusion tensor imaging (DTI) studies indicate that impaired microstructural integrity of the normal-appearing white matter (NAWM) is related to cognitive impairment in cerebral small vessel disease (SVD). This study aimed to investigate whether quantitative T2 relaxometry is a suitable imaging biomarker for the assessment of tissue changes related to cognitive abnormalities in patients with SVD. 39 patients and 18 age-matched healthy control subjects underwent 3 T magnetic resonance imaging (MRI) with T2-weighted multiple spin echo sequences for T2 relaxometry and DTI sequences, as well as comprehensive cognitive assessment. Averaged quantitative T2, fractional anisotropy (FA) and mean diffusivity (MD) were determined in the NAWM and related to cognitive parameters controlling for age, normalized brain volume, white matter hyperintensity volume and other conventional SVD markers. In SVD patients, quantitative T2 values were significantly increased compared to controls (p = 0.002) and significantly negatively correlated with the global cognitive performance (r= –0.410, p = 0.014) and executive function (r= –0.399, p = 0.016). DTI parameters did not correlate with cognitive function. T2 relaxometry of the NAWM seems to be sensitive to microstructural tissue damage associated with cognitive impairment in SVD and might be a promising imaging biomarker for evaluation of disease progression and possible effects of therapeutic interventions.

scholarly journals Fixel-Based Analysis of White Matter Alterations in Early- Stage Cerebral Small Vessel Disease

2021 ◽  
Author(s):  
Marvin Petersen ◽  
Benedikt M. Frey ◽  
Carola Mayer ◽  
Simone Kühn ◽  
Jürgen Gallinat ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Early Stage ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Health Study ◽  
Vessel Disease ◽  
Early Stages

Abstract Cerebral small vessel disease (CSVD) is a common cause of morbidity and cognitive decline in the elderly population. However, characterizing the disease pathophysiology and its association with potential clinical sequelae in early stages is less well explored. We applied fixel-based analysis (FBA), a novel framework of investigating microstructural white matter integrity by diffusion-weighted imaging, to data of 921 participants of the Hamburg City Health Study, comprising middle-aged individuals with increased cerebrovascular risk in early stages of CSVD. In individuals in the highest quartile of white matter hyperintensity loads (n=232, median age 63 years; IQR 15.3 years), FBA detected significantly reduced axonal density and increased atrophy of transcallosal fiber tracts, the bilateral superior longitudinal fasciculus, and corticospinal tracts compared to participants in the lowest quartile of white matter hyperintensities (n=228, mean age 55 years; IQR 10 years). Analysis of all participants (N=921) demonstrated a significant association between reduced fiber density and worse executive functions operationalized by the Trail Making Test. Findings were confirmed by complementary analysis of diffusion tensor metrics.

scholarly journals Executive dysfunction and altered cerebrovascular activity in a rodent model of vascular cognitive impairment

2018 ◽  
Vol 45 (S1) ◽  
pp. S4-S5
Author(s):  
K.D. Langdon ◽  
C. Cordova ◽  
S. Granter-Button ◽  
J. Boyd ◽  
J. Peeling ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Executive Dysfunction ◽  
Vascular Cognitive Impairment ◽  
Cerebral Hypoperfusion ◽  
Small Vessel ◽  
Sprague Dawley ◽  
Middle Aged ◽  
Metabolic Disturbances ◽  
Vessel Disease

Most basic science research has focused on overt stroke caused by blockage of major blood vessels. Less attention has been paid to small vessel disease giving rise to covert stroke that often leads to vascular cognitive impairment (VCI). One reason for this may be the relative lack of relevant animal models. This talk will describe a model of VCI induced in middle-aged Sprague-Dawley rats exposed to a diet high in saturated fats, salt and refined sugar (HFSS). In Experiment 1, rats fed HFSS and subjected to a small mediodorsal (MD) thalamic stroke with or without concomitant cerebral hypoperfusion experienced significant executive dysfunction. In Experiment 2, dietary influences on functional, physiological and anatomical parameters were assessed. We found significant hypertension, blockage of brain microvessels (2-photon microscopy) and white matter atrophy in HFSS diet animals. As in Experiment 1, profound, specific set-shifting executive dysfunction was noted following both small MD infarcts (0.332 mm3) and the HFSS diet. In summary, these data describe a middle-aged animal model of VCI that includes clinically-relevant metabolic disturbances and small vessel disease and as such may be helpful in developing new cognitive therapies.

scholarly journals White Matter Microstructural Damage on Diffusion Tensor Imaging in Cerebral Small Vessel Disease

Stroke ◽  
2016 ◽  
Vol 47 (6) ◽  
pp. 1679-1684 ◽  
Author(s):  
Marco Pasi ◽  
Inge W.M. van Uden ◽  
Anil M. Tuladhar ◽  
Frank-Erik de Leeuw ◽  
Leonardo Pantoni
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Microstructural Damage

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 Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Fanny Quandt ◽  
Felix Fischer ◽  
Julian Schröder ◽  
Marlene Heinze ◽  
Iris Lettow ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Functional Connectivity ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
White Matter Lesion ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Lesion Load ◽  
Vessel Disease

Abstract Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

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