scholarly journals Role of White Matter Hyperintensities and Related Risk Factors in Vascular Cognitive Impairment: A Review

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1102
Author(s):  
Yiyi Chen ◽  
Xing Wang ◽  
Ling Guan ◽  
Yilong Wang
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Treatment Strategies ◽  
Vascular Cognitive Impairment ◽  
Older Individuals ◽  
The Status ◽  
Vascular Origin ◽  
Detection And Diagnosis

White matter hyperintensities (WMHs) of presumed vascular origin are one of the imaging markers of cerebral small-vessel disease, which is prevalent in older individuals and closely associated with the occurrence and development of cognitive impairment. The heterogeneous nature of the imaging manifestations of WMHs creates difficulties for early detection and diagnosis of vascular cognitive impairment (VCI) associated with WMHs. Because the underlying pathological processes and biomarkers of WMHs and their development in cognitive impairment remain uncertain, progress in prevention and treatment is lagging. For this reason, this paper reviews the status of research on the features of WMHs related to VCI, as well as mediators associated with both WMHs and VCI, and summarizes potential treatment strategies for the prevention and intervention in WMHs associated with VCI.

Abstract TP442: Periventricular Not Deep White Matter Hyperintensities Are Associated With Vascular Cognitive Impairment

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yan Chen ◽  
Renyuan Liu ◽  
Shuwei Qiu ◽  
Yun Xu
Keyword(s):  
Regression Analysis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Linear Regression ◽  
Cognitive Performance ◽  
White Matter Hyperintensities ◽  
Rating Scale ◽  
Linear Regression Analysis ◽  
Vascular Cognitive Impairment ◽  
Cerebral White Matter

Introduction: Cerebral White matter hyperintensities(WMH) are frequent findings on MRI scan. They are well known to correlate with vascular cognitive impairment(VCI). However, controversies still remain about the relationship between WMH locations and cognitive function across studies. Hypothesis: Periventricular WMHs(PWH) rather than deep WMHs(DWH) are associated with cognitive decline in VCI. Methods: Fifty-nine subjects with WMHs on MRI were divided into three groups, normal control(NC), mild cognitive impairment(MCI) and vascular dementia(VaD), according to clinical manifestation and neuropsychological performance. WMH volumes were evaluated by Fazekas rating scale and segmental volumetric. Correlations between cognitive performance and WMH volumes were determined in virtue of Spearman correlation analysis. Receiver operator characteristic (ROC) curves were generated to define the classification cut-off value of WMH volumes for distinguishing VCI versus normal controls. Multiple linear regression analysis was used to predict cognitive performance with WMH volumes and locations after adjusting for sex ,age and education level. Results: Cognitive capacities were gradually declined from NC through MCI to VaD patients while WMH volumes and Fazekas scores altered oppositely. Both PWH and DWH volumes and Fazekas scores were correlated with cognitive performance, and moreover, WMH volumes were correlated with Fazekas scores. ROC analysis showed a cut-off value of PWH rather than DWH to distinguish VCI from NC(AUC=0.745 and 0.635, p =0.001 and 0.076, respectively). Linear regression analysis demonstrated that only PWH volumes were associated with cognitive performance( p < 0.001). Conclusion: Our study demonstrate that PWHs are independent predictors for vascular contribution in white matter lesions and suggest clinicians that PWH should be emphasized on evaluating vascular cognitive impairment related with white matter load.

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.

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.

scholarly journals Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment

2015 ◽  
Vol 221 (4) ◽  
pp. 2135-2146 ◽  
Author(s):  
Zoe Arvanitakis ◽  
Debra A. Fleischman ◽  
Konstantinos Arfanakis ◽  
Sue E. Leurgans ◽  
Lisa L. Barnes ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Gray Matter ◽  
White Matter Hyperintensities ◽  
Gray Matter Volume ◽  
Older Individuals ◽  
Matter Volume

scholarly journals Heterogeneity of White Matter Hyperintensities in Cognitively Impaired Patients With Cerebral Small Vessel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Wang ◽  
Aoming Jin ◽  
Ying Fu ◽  
Zaiqiang Zhang ◽  
Shaowu Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Cognitively Impaired ◽  
Imaging Features ◽  
Vessel Disease

ObjectiveSimilar white matter hyperintensities (WMH) might have different impact on the cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study is to assess the possible factors related to the heterogeneity of WMH in cognitively impaired patients with CVSD.MethodsWe analyzed data from a cohort of patients with CVSD who were recruited consecutively from the Beijing Tiantan Hospital from 2015 to 2020. WMH, lacunes, enlarged perivascular space (ePVS), microbleeds and lacunar infarcts were rated on brain MRI. A score of &lt;26 on the Montreal Cognitive Assessment (MoCA) indicated cognitive impairment. A mismatch was defined as the severity of WMH not matching the severity of cognitive dysfunction. Type-1 mismatch was defined as a mild WMH (Fazekas score = 0-1) associated with cognitive impairment, and type-2 mismatch was defined as a severe WMH (Fazekas score = 5-6) associated with normal cognitive function. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced SWI on 3-Tesla MRI was used to image the penetrating arteries in basal ganglia to explore the underlying mechanism of this mismatch. Multivariable logistic regression was used to analyze the association between the imaging features and cognitive impairment.ResultsIn 156 patients, 118 (75.6%) had cognitive impairment and 37 (23.7%) showed mismatch. Twenty five (16.0%) had type-1 mismatch and 12 (7.7%) had type-2 mismatch. Regression analysis found that WMH, lacunes, microbleeds and total CSVD scores were associated with cognitive impairment and were independent of vascular risk factors. However, lacunes, microbleeds and total CSVD scores were related to the mismatch between WMH and cognitive impairment (p=0.006, 0.005 and 0.0001, respectively). Specially, age and ePVS in basal ganglia were related to type-1 mismatch (p=0.04 and 0.02, respectively); microbleeds and total CSVD scores were related to type-2 mismatch (p=0.01 and 0.03, respectively). Although the severity of WMH was similar, the injury scores of penetrating arteries were significantly different between those with and without cognitive impairment (p=0.04).ConclusionsHeterogeneity of WMH was present in cognitively impaired patients with CSVD. Conventional imaging features and injury of penetrating arteries may account for such heterogeneity, which can be a hallmark for early identification and prevention of cognitive impairment.

Abstract TP413: Compliance to Consistent Home Blood Pressure Monitoring Reduces the Risk of Vascular Cognitive Impairment in Stroke Patients

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Wenjun Deng ◽  
David McMullin ◽  
Lindsay Fisher ◽  
Richard Chou ◽  
Jared Jacobson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Blood Pressure Monitoring ◽  
Treatment Strategies ◽  
Home Monitoring ◽  
Vascular Cognitive Impairment ◽  
Home Blood Pressure ◽  
Stroke Patients ◽  
At Home

Background: Hypertension (HTN) is a well-recognized risk factor for vascular cognitive decline. Poorly controlled HTN is common in the outpatient setting, with multi-factorial components including a lack of consistent, continuous and accurate reporting of blood pressure (BP) to help clinicians to tailor therapy. In the current prospective study, we explore the association of stroke patients’ at-home BP self-monitoring compliance with clinical and imaging risk markers of developing cognitive impairment. Method: 146 consecutive stroke outpatients with diagnosed HTN were recruited per IRB protocol. All patients received BP education at their first clinical visit and were encouraged to monitor BP at home on a daily basis for two weeks three times during the course of the 5-year study. Compliance with BP monitoring was evaluated by completed BP log and questionnaire in follow-up visits at fixed intervals. At the end of the study, white matter disease (WMD) severity was estimated by Fazekas and Sheltens scores. Cognitive impairment was assessed using Montreal Cognitive Assessment (MoCA) scales. Result: Only 16.4% (n=24) patients had “good compliance,” monitoring their home BP regularly and consistently as instructed. The compliant group had better controlled systolic and diastolic BP (Figure A, p<0.05). As measured by Fazekas and Sheltens scales, patients compliant with BP monitoring had lower WMD burden (Figure B, p<0.05), and higher MoCA scores (Figure C, p=0.012) compared to noncompliant patients. Conclusion: Compliance with at-home BP monitoring is essential for better BP control in vascular cognitive impairment (VCI) patients post stroke. Consistent home BP monitoring resulted in decreased imaging-apparent small vessel disease and better long-term cognitive performance. Expanded study with a larger patient cohort is ongoing to account for other behavioral and psycho-social factors and to create improved home monitoring technology and treatment strategies.

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.

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