MMP9 rs17576 Is Simultaneously Correlated with Symptomatic Intracranial Atherosclerotic Stenosis and White Matter Hyperintensities in Chinese Population

2020 ◽  
pp. 1-8
Author(s):  
Xianjing Feng ◽  
Fang Yu ◽  
Xiaoqing Zhou ◽  
Zeyu Liu ◽  
Di Liao ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Macrovascular Disease ◽  
Genome Project ◽  
Allele Frequencies ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Intracranial Atherosclerotic Stenosis ◽  
Atherosclerotic Stenosis

<b><i>Purpose:</i></b> The aim of this study was screening for single nucleotide polymorphisms (SNPs) associated with white matter hyperintensities (WMHs) in symptomatic intracranial atherosclerotic stenosis (sICAS) patients and exploring a possible connection in the genetic background between macrovascular disease and small vessel disease. <b><i>Methods:</i></b> There were 400 sICAS patients enrolled in the study. Fazekas scores were applied to WMH classification. Healthy controls were referred to 1,000 Genome Project and GeneSky company who provided 1,007 Chinese healthy controls. Fast target sequencing technology was used to select the SNPs of 102 genes related to the pathogenesis of sICAS in the sICAS patients. <b><i>Results:</i></b> The allele frequencies of 88 SNPs were significantly different between the sICAS group and the healthy controls (<i>p</i> &#x3c; 0.05). The allele frequencies of 53 SNPs were significantly different between the sICAS patients with and without WMHs (<i>p</i> &#x3c; 0.05). Further analysis found that matrix metalloproteinase 9 (<i>MMP9</i>) rs17576 was simultaneously related to sICAS and WMHs. The frequency of the rs17576 A allele was significantly lower in sICAS patients when compared to the normal controls (<i>p</i> = 0.03, OR [95% CI] = 0.75 [0.625–0.91]). Also, the frequency of the rs17576 genotypes was significantly different under codominant (<i>p</i> = 0.009), dominant (<i>p</i> = 0.014), and recessive (<i>p</i>= 0.023) models. The frequency of the rs17576 A allele was significantly higher in sICAS with WMH patients, compared to those without WMHs (<i>p</i> = 0.022, OR [95% CI] = 1.54 [1.06–2.22]); the frequency of the rs17576 genotypes was significantly different under codominant (<i>p</i> = 0.019) and recessive (<i>p</i> = 0.032) models. Logistic regression analysis showed that age, hypertension, and <i>MMP9</i> rs17576 AA genotype were independent risk factors for sICAS with WMHs. <b><i>Conclusion:</i></b> <i>MMP9</i> rs17576 may be simultaneously associated with the risk of sICAS and WMHs.

Abstract TP135: White Matter Hyperintensities in Relation to Severity of Intracranial Atherosclerotic Stenosis

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jong-Ho Park ◽  
Dong-Sun Kim ◽  
Hyun Jeong Han
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Multivariable Analysis ◽  
Cerebral Hypoperfusion ◽  
Intracranial Atherosclerotic Stenosis ◽  
Atherosclerotic Stenosis ◽  
Increased Risk

Background & Objectives: White matter hyperintensities (WMH) is regarded as a small-vessel disease because the accompanying silent infarcts are predominantly lacunes and share the same pathological basis with WMH. Endothelial dysfunction is known to play a cardinal role in progression of WMH. Accordingly, atherosclerotic burden might be associated with the development of WMH. Because metabolic syndrome (MetS) is associated with an increased risk of WMH and with intracranial atherosclerotic stenosis (ICAS), we assessed the hypothesis that WMH might be related to ICAS in ischemic stroke patients. We compared a severity of WMH among the ICAS, extracranial (ECAS), and no cerebral atherosclerotic stenosis (NCAS) groups. Methods: We conducted a cross-sectional study in 605 Korean patients with acute ischemic stroke (mean age 67.7±12.8; 347 males), who underwent brain MRI/MRA. The severity of deep WMH (d-WMH, n=495) and periventricular WMH (pv-WMH, n=521) was rated separately. Irrespective of index stroke mechanisms, patients were classified into three groups: ICAS (n=294), extracranial (ECAS, n=63), and no cerebral atherosclerotic stenosis (NCAS, n=248). Stenosis groups and demographics, including the presence of MetS, were compared between patients with d-/pv-WMH and without. Results: The ICAS group showed a higher d-WMH / pv-WMH grade (1.61±0.85 / 1.64±0.80) than both the ECAS (1.29±0.87 / 1.21±0.77) and NCAS (1.15±0.92 / 1.21±0.82) groups ( P <0.001 for all). Patients with more severe ICAS were more likely to have higher grades of d-WMH and pv-WMH ( P <0.001 for all). Patients with higher grades of d-WMH and pv-WMH had a higher incidence of ICAS ( P <0.001 for all) but not of ECAS or NCAS. Patients with a greater number of MetS components were more likely to have higher grades of d-WMH and pv-PWMH ( P <0.001 for all). With a multivariable analysis, a dose-response relationship was observed between the presence of ICAS and the WMH: (1) for d-WMH, OR=3.25 (95% CI, 1.18-8.96) for 2 ICAS, OR=6.39 (1.84-22.14) for ≥3 ICAS, (2) for pv-WMH, OR=2.22 (95% CI, 1.25-3.95) for 2 ICAS, OR=3.40 (1.89-6.09) for ≥3 ICAS versus 1 ICAS. Conclusions: ICAS, rather than ECAS or NCAS is a predictor of d-/pv-WMH. ICAS burden might be the substrate for chronic cerebral hypoperfusion.

Altered Functional Connectivity Patterns of Parietal Subregions Contribute to Cognitive Dysfunction in Patients with White Matter Hyperintensities

2021 ◽  
pp. 1-11
Author(s):  
Qiang Wei ◽  
Shanshan Cao ◽  
Yang Ji ◽  
Jun Zhang ◽  
Chen Chen ◽  
...  
Keyword(s):  
White Matter ◽  
Functional Connectivity ◽  
White Matter Hyperintensities ◽  
Parietal Lobe ◽  
Small Vessel Disease ◽  
Anterior Cingulate ◽  
Healthy Controls ◽  
Cingulate Gyrus ◽  
Anterior Cingulate Gyrus ◽  
Resting State Functional Connectivity

Background: The white matter hyperintensities (WMHs) are considered as one of the core neuroimaging findings of cerebral small vessel disease and independently associated with cognitive deficit. The parietal lobe is a heterogeneous area containing many subregions and play an important role in the processes of neurocognition. Objective: To explore the relationship between parietal subregions alterations and cognitive impairments in WHMs. Methods: Resting-state functional connectivity (rs-FC) analyses of parietal subregions were performed in 104 right-handed WMHs patients divided into mild (n = 39), moderate (n = 37), and severe WMHs (n = 28) groups according to the Fazekas scale and 36 healthy controls. Parietal subregions were defined using tractographic Human Brainnetome Atlas and included five subregions for superior parietal lobe, six subregions for inferior parietal lobe (IPL), and three subregions for precuneus. All participants underwent a neuropsychological test battery to evaluate emotional and general cognitive functions. Results: Differences existed between the rs-FC strength of IPL_R_6_2 with the left anterior cingulate gyrus, IPL_R_6_3 with the right dorsolateral superior frontal gyrus, and the IPL_R_6_5 with the left anterior cingulate gyrus. The connectivity strength between IPL_R_6_3 and the left anterior cingulate gyrus were correlated with AVLT-immediate and AVLT-recognition test in WMHs. Conclusion: We explored the roles of parietal subregions in WMHs using rs-FC. The functional connectivity of parietal subregions with the cortex regions showed significant differences between the patients with WMHs and healthy controls which may be associated with cognitive deficits in WMHs.

Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

scholarly journals Sexual Assault and White Matter Hyperintensities Among Midlife Women

2021 ◽  
Author(s):  
Rebecca Thurston ◽  
Karen Jakubowski ◽  
Minjie Wu ◽  
Howard Aizenstein ◽  
Yuefang Chang ◽  
...  
Keyword(s):  
White Matter ◽  
Sexual Assault ◽  
Traumatic Stress ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Midlife Women ◽  
Traumatic Experiences ◽  
Linear Regression Models ◽  
Post Traumatic Stress ◽  
Post Traumatic

Abstract Background Traumatic experiences have been linked to poor mental and physical health. However, there has been little examination of their relationship to neuroimaging markers of cerebrovascular risk. White matter hyperintensities (WMHs) are markers of brain small vessel disease. WMHs can be detected decades before the onset of dementia and other disorders and can serve as early markers for these brain disorders. We tested whether traumatic experiences were associated with brain WMH volume among midlife women. Methods In the MsBrain study, 145 women (mean age = 59 years) without cardiovascular disease, stroke, or dementia were recruited. Women completed questionnaires [trauma checklist, depression, post-traumatic stress measures]; physical measures [body mass index (BMI), blood pressure (BP)]; phlebotomy; actigraphy sleep measurement, and 3 Tesla magnetic resonance brain imaging for WMHs. Cross-sectional associations between traumatic experiences and WMH volume were assessed in linear regression models. Covariates were age, race/ethnicity, education, BMI, BP, lipids, preeclampsia, sleep, and additionally depressive and post-traumatic stress disorder symptoms. Results 68% of women endorsed at least one of the traumas assessed. The most common trauma was sexual assault (23% of women). Women with trauma exposure had greater WMH volume than women without trauma [B(SE) = .24 (.09), p = .01, multivariable]. The single trauma most associated with WMH was sexual assault [B(SE) = .25 (.11), p = .02, multivariable]. Results persisted adjusting for depressive or post-traumatic stress symptoms. Conclusions A trauma history, particularly sexual assault, was associated with greater WMH volume controlling for covariates, including depressive and post-traumatic symptoms. Sexual assault may place women at risk for poor brain health.

Abstract TP181: Serum Eiocosapentaenoic Acids Is Protective Against White Matter Lesions

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Daiki Takano ◽  
Takashi Yamazaki ◽  
Tetsuya Maeda ◽  
Yuichi Satoh ◽  
Yasuko Ikeda ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
White Matter Hyperintensity ◽  
Partial Regression Coefficient ◽  
The Relationship ◽  
Total Pufa ◽  
Periventricular Hyperintensity

[Introduction] White matter hyperintensities (WMH) are considered manifestation of arteriosclerotic small vessel disease and WMH burden increases risk of ischemic stroke and cognitive decline. There are only a few evidences concerning the relationship between polyunsaturated fatty acids (PUFA) and WMH. The present study was designed to elucidate the association between WMH and PUFA profile including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in patients with Alzheimer’s disease (AD). [Methods] The present study was based on 119 patients who were diagnosed as having a probable AD according to the NINCDS-ADRDA criteria. Their mean age was 78.3 years old. All subjects underwent neuropsychological evaluation including mini mental state exam (MMSE) and 1.5-Tesla MRI. Fasting blood samples were also collected for the PUFA measurements. We measured the ratio of serum EPA, DHA and AA concentration to the total PUFA concentration. The WMH were evaluated on T2-weight images and classified into periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The severity of WMH was graded 5 categories. We investigated the relationship between WMH and PUFA profiles. [Results] The EPA ratio correlated negatively with both PVH (rs=-0.2036, p=0.0264) and DWMH grade (rs=-0.3155, p=0.0005). It remained still significant after adjustment for age, sex, statins use, antithrombotics use, mean blood pressure and presence of hypertension (standardized partial regression coefficient(β)=-0.2516, p=0.0122 for PVH, β=-0.3598, p=0.0001 for DWMH). Neither DHA nor AA ratio correlated with DWMH or PVH grade. The EPA ratio but not DHA or AA ratio correlated positively with total MMSE score (rs=0.2310, p=0.0115). [Conclusions] Our data revealed that the serum EPA was protective against WMH as well as cognitive decline in AD patients. Pathophysiology underlying WMH is complex and the possible mechanisms involved in the pathogenesis of WMH encompass incomplete brain ischemia, increased permeability of blood-brain barrier, and inflammation responses. The relationship between serum EPA and WMH can be partly explained by those anti-ischemic and anti-arteriosclerotic effects of EPA.

scholarly journals Cognitive consequences of regression of cerebral small vessel disease

2018 ◽  
Vol 4 (1) ◽  
pp. 85-89 ◽  
Author(s):  
Esther MC van Leijsen ◽  
Mayra I Bergkamp ◽  
Ingeborg WM van Uden ◽  
Sjacky Cooijmans ◽  
Mohsen Ghafoorian ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Disease Markers ◽  
Total Brain

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.

scholarly journals Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease

Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1404-1410 ◽  
Author(s):  
Michelle P. Lin ◽  
Thomas G. Brott ◽  
David S. Liebeskind ◽  
James F. Meschia ◽  
Kevin Sam ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Large Vessel ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Poor Recruitment

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.

Adverse effects of pre-existing cerebral small vessel disease on cognitive improvement after carotid endarterectomy

2019 ◽  
Vol 15 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Jun Yoshida ◽  
Fumio Yamashita ◽  
Makoto Sasaki ◽  
Kunihiro Yoshioka ◽  
Shunrou Fujiwara ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
Carotid Endarterectomy ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cognitive Improvement ◽  
Vessel Disease

Background Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. Aims The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. Methods Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. Results Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74–3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01–0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. Conclusion Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.

Automated detection of white matter hyperintensities of all sizes in cerebral small vessel disease

2016 ◽  
Vol 43 (12) ◽  
pp. 6246-6258 ◽  
Author(s):  
Mohsen Ghafoorian ◽  
Nico Karssemeijer ◽  
Inge W. M. van Uden ◽  
Frank-Erik de Leeuw ◽  
Tom Heskes ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Automated Detection ◽  
Small Vessel ◽  
Vessel Disease
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