Research advance in changes of brain white matter in cerebral small vessel disease with cognitive impairment / 中华行为医学与脑科学杂志

With the progress of population aging, cerebral small vessel disease is increasingly becoming a common and frequent disease threatening human health, which is a common reason leaing to cognitive function decline.The changes of white matter, especially white matter hyperintensities, are the most common and typical imaging marker of small cerebral vascular disease.In recent years, a number of studies has found that white matter hyperintensities are associated with cognitive decline.These studies mainly focused on the relationship between white matter hyperintensities and cognitive frailty, and the correlation between the size, location and dynamic evolution of white matter hyperintensities and cognitive impairment of small cerebral vascular disease.Functional magnetic resonance imaging studies also revealed that patients with cognitive impairment of cerebral small vessel disease had abnormal white matter changes and structural network connectivity.Structural network can be used for quantitative analysis because of its good stability.Diffusion tensor imaging and quantitative measurement of multi-dimensional structural network were used qualitatively.It was found that the structural network integrity was damaged, the network connection efficiency was reduced, and the connection was interrupted within the white matter hyperintensity.Big data and artificial intelligence research can make early prediction of white matter hyperintensity and structural networks in patients with cerebral small vessel disease with cognitive impairment.These studies provide a reliable basis for the discovery of abnormal microstructure and network changes in the early stage of white matter hyperintensities in cerebral small vessel disease with cognitive impairment.The paper reviews the research progress of white matter hyperintensity and brain structural network in patients with cognitive impairment of cerebral small vessel disease in recent years, and in order to improve the early diagnosis of the disease and promote the early prevention and treatment.

Study on relationship between venous system and white matter hyperintensitiy in cerebral small vessel disease / 中国综合临床

White matter hyperintensity (WMH) is one of the major imaging markers of cerebral small vascular disease, which is prevalent in the elderly. At present, the pathogenesis of WMH is not clear, most of the previous studies focused on the arterial system, but the role of the venous system in WMH is attracting more and more attention. Small venous collagen hyperplasia, downstream intracranial venous dilatation and internal jugular venous reflux may be involved in the formation and development of white matter hyperintensity.

Relationship between cerebral small vessel disease and thyroid hormones in the elderly / 中华老年医学杂志

Objective:To investigate the relationship between cerebral small vessel disease and thyroid hormones in the elderly.Methods:A total of 314 subjects aged ≥60 years with records of head magnetic resonance image(MRI), serum thyroid function tests and physical examinations collected in the Department of Health Care Neurology of Beijing Hospital from May 2019 to November 2020 were consecutively included for this cross-sectional study.Participants were assigned into the cerebral small vessel disease group if their head MRI presentations met the following standards: the Fazekas score ≥3 points; the Fazekas score ≥2 points, with 1 cavity; new subcortical infarcts; or cerebral microhemorrhage.Differences in thyroid function were compared between the cerebrovascular disease group(n=129)and the group without cerebrovascular disease(control group, n=185).Results:A total of 314 subjects were enrolled, of whom 129 met the head MRI standards for cerebrovascular disease, and 185 who did not meet the standards entered the control group.Comparison of thyroid function found a statistically significant difference in FT3( t=3.270, P=0.001)between the two groups.As for the association of a specific type of cerebral small vessel disease with thyroid function, there was a statistically significant difference in the FT3 level between the lacunar infarction group and the non-lacunar infarction group( t=3.106, P=0.002)and between the cerebral microhemorrhage group and the non-cerebral microhemorrhage group( t=2.125, P=0.034). Groups with different Fazekas scores in white matter hyperintensity showed statistically significant differences in rT3( F=3.092, P=0.027), FT3( F=5.427, P=0.001)and FT4( F=2.646, P=0.049). After correction for hyperlipidemia, rT3 and FT4, it was found that age( OR=1.044, 95% CI: 1.022-1.067, P=0.000), hypertension( OR=0.533, 95% CI: 0.294-0.963, P=0.037)and FT3( OR=0.276, 95% CI: 0.159-0.478, P=0.000)were related to cerebral small vessel disease. Conclusions:FT3 levels at the lower end of the normal range are associated with cerebral small vessel disease in the elderly.

Differential expression of circular RNA in patients with white matter hyperintensity and cognitive impairment / 中南大学学报(医学版)

OBJECTIVES@#White matter hyperintensity (WMH) is an important factor leading to cognitive impairment, and the mechanism has not been clarified. In recent years, studies have found that circular RNA (circRNA) has differential expression in cerebrovascular diseases. This study aims to analyze the expression profile of circRNA in peripheral blood mononuclear cell (PBMC) of patients with WMH with cognitive impairment, to screen the differentially expressed circRNA, and to explore the possible role of circRNA in WMH with cognitive impairment.@*METHODS@#CircRNA microarray was used to detect the circRNA expression profile of PBMC in patients with WMH with cognitive impairment, and in patients with WMH without cognitive impairment as well as in normal controls (3 cases each, male to female ratio of 2꞉1). The differentially expressed circRNA in patients with WMH with cognitive impairment was screened. The screening criteria for differentially expressed circRNA was fold change (FC) ≥2.0 (|log@*RESULTS@#Compared with the control group, there were 5 significantly up-regulated circRNA and 3 down-regulated circRNA in the WMH with cognitive impairment group; 8 circRNA were significantly up-regulated and 2 were down-regulated in the WMH without cognitive impairment group. When compared with the WMH with cognitive impairment group, no co-differentially expressed circRNA was found in WMH without cognitive impairment group and control group. Compared with the control group, the expression of hsa_circ_0092222 was up-regulated and the expressions of hsa_circ_0000662 and hsa_circ_0083773 were down-regulated in the WMH with cognitive impairment group and the WMH without cognitive impairment group, and there was no significant difference between the 2 groups (all @*CONCLUSIONS@#The circRNA expression profile of patients with WMH is changed significantly. The differentially expressed circRNA may be the cause of WMH; Hsa_circ_0092222, hsa_circ_0000662, and hsa_circ_0083773 may regulate the expression of target genes by targeting adsorption of the target miRNA, leading to brain white matter damage through Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT3) signal pathway and Wnt signal pathway.There is no significant difference in circRNA expression profile between WMH with or without cognitive impairment. Cognitive impairment in patients with WMH may have other reasons.

White matter hyperintensities and carotid intima media thikness In migraine without aura patients

@#Background: Migraine is associated with atherosclerosis and white matter hyperintensities. This study aims to evaluate the relationship between white matter hyperintensities and carotid intima-media thickness in patients who have migraines without auras. Methods: The study enrolled 105 patients; of these, 43 patients had migraine without white matter hyperintensity (WMH) and 32 had migraine with WMH. There were also 30 healthy control subjects. The patients were divided into two groups according to whether or not they had WMHs on their brain magnetic resonance imaging (MRI). All subjects, including the control group, underwent brain MRI and carotid ultrasonographic examination to evaluate WMH and carotid intima-media thickness (CIMT), respectively. Results: The groups did not differ with regard to demographics and clinical findings. The CIMT was significantly greater in patients who had migraine without WMH than in the control group (p < 0.001) and in those who had migraine with WMH than in those who had migraine without WMH (p = 0.004) Conclusion: CIMT values were higher in migraine patients with WMH than in migraine patients without WMH. Migraine patients with WMH may be at a greater risk of developing future vascular events.

Association between Cognitive Function, Behavioral and Psychological Symptoms of Dementia and White Matter Hyperintensities in Patients with Alzheimer's Disease and Mild Cognitive Impairment / 정신신체의학

OBJECTIVES: The aim of this study is to investigate correlation between degree of white matter hyperintensities (WMH) and neurocognitive function along with behavioral and psychological symptoms of dementia (BPSD) in Korean patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: Participants were 115 elderly subjects diagnosed with Alzheimer's disease or mild cognitive impairment in this retrospective study. WMH in brain MRI were rated with standardized visual rating scales (Fazekas scales) and the subjects were divided into two groups according to Fazekas scale. Cognitive function was evaluated with Korean version of the consortium to establish a registry for Alzheimer's Disease (CERAD-K), and BPSD was evaluated with Korean neuropsychiatric inventory (K-NPI). Independent t-test was performed to analyze the relationship between the degree of WMH and neurocognitive functions & BPSD. RESULTS: Especially, the group with high severity of WMH showed significantly lower language fluency (p < 0.05). In addition, the group with high severity of WMH showed significantly higher score in K-NPI. CONCLUSIONS: There was a significant association between WMH and neurocognitive test related with executive function. Moreover, WMH seems to affect BPSD severity. Evaluation of WMH would provide useful information in clinical settings.

The Effect of Leukoaraiosis on the Severity and Course of Delirium / 정신신체의학

OBJECTIVES: The significance of leukoaraiosis on brain magnetic resonance imaging (MRI) is uncertain, but it is often seen with vascular risk factors or in the context of cognitive impairment. We aimed to investigate the effect of leukoaraiosis on the severity and course of delirium. METHODS: Periventricular hyperintensity and deep white matter hyperintensity on brain MRI were rated in 42 patients with delirium by semiquantative visual rating scale. Correlations between their grades and the scores of Korean version of Delirium Rating Scale-Revised-98 (K-DRS-R-98) were analyzed, and the interaction effects between the groups according to the levels of leukoaraiosis and two evaluation points were also analyzed. RESULTS: The grade of deep white matter hyperintensity in the occipital lobe was positively correlated with the scores on the total, severity items, cognitive items, and non-cognitive items of K-DRS-R-98. The cognitive items scores of K-DRS-R-98 in the low grade group of periventricular hyperintensity showed significantly steeper decrease than the high grade group. CONCLUSIONS: A difference in severity or recovery speed of delirium according to the level of leukoaraiosis may result from disruption in brain functional connectivity. Our results have a clinical implication in that the severity and course of delirium can be possibly predicted using the level of leukoaraiosis.

Association between Aortic Atheroma and Cerebral Small Vessel Disease in Patients with Ischemic Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke. METHODS: We included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated. RESULTS: AA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75). CONCLUSIONS: In this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients.

Prognostic Impact of Cerebral Small Vessel Disease on Stroke Outcome / 대한뇌졸중학회지

Cerebral small vessel disease (SVD), which includes white matter hyperintensities (WMHs), silent brain infarction (SBI), and cerebral microbleeds (CMBs), develops in a conjunction of cumulated injuries to cerebral microvascular beds, increased permeability of blood-brain barriers, and chronic oligemia. SVD is easily detected by routine neuroimaging modalities such as brain computed tomography or magnetic resonance imaging. Research has revealed that the presence of SVD markers may increase the risk of future vascular events as well as deteriorate functional recovery and neurocognitive trajectories after stroke, and such an association could also be applied to hemorrhagic stroke survivors. Currently, the specific mechanistic processes leading to the development and manifestation of SVD risk factors are unknown, and further studies with novel methodological tools are warranted. In this review, recent studies regarding the prognostic impact of WMHs, SBI, and CMBs on stroke survivors and briefly summarize the pathophysiological concepts underlying the manifestation of cerebral SVD.

White Matter Hyperintensity in Ischemic Stroke Patients: It May Regress Over Time / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are frequently observed on MRI in ischemic stroke patients as well as in normal elderly individuals. Besides the progression of WMH, the regression of WMH has been rarely reported. Thus, we aimed to investigate how WMH change over time in patients with ischemic stroke, particularly focusing on regression. METHODS: We enrolled ischemic stroke patients who underwent brain MRI more than twice with at least a 6 month time-interval. Based on T2-weighted or FLAIR MRI, WMH were visually assessed, followed by semiautomatic volume measurement. Progression or regression of WMH change was defined when 0.25 cc increase or decrease was observed and it was also combined with visible change. A statistical analysis was performed on the pattern of WMH change over time and factors associated with change. RESULTS: A total of 100 patients were enrolled. Their age (mean+/-SD) was 67.5+/-11.8 years and 63 were male. The imaging time-interval (mean) was 28.0 months. WMH progressed in 27, regressed in 9 and progressed in distinctive regions and regressed in others in 5 patients. A multiple logistic regression model showed that age (odds ratio[OR] 2.51, 90% confidence interval[CI] 1.056-5.958), male gender (OR 2.957, 95% CI 1.051-9.037), large vessel disease (OR 1.955, 95% CI 1.171-3.366), and renal dysfunction (OR 2.900, 90% CI 1.045-8.046) were associated with progression. Regarding regression, no significant factor was found in the multivariate analysis. CONCLUSIONS: In 21.5% of ischemic stroke patients, regression of WMH was observed. WMH progression was observed in a third of ischemic stroke patients.

Subacute sclerosing panencephalitis resembling Rasmussen's encephalitis on magnetic resonance imaging

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressing but invariably fatal disease that is related to a prior measles virus infection and most commonly affects paediatric patients. Magnetic resonance (MR) imaging is the modality of choice for determining such changes in white matter. SSPE typically demonstrates bilateral but asymmetric periventricular and subcortical white matter involvement. We herein report a rare case of unilateral white matter involvement in a 13-year-old boy with SSPE that closely simulated Rasmussen's encephalitis. To the best of our knowledge, this is the first report of an atypical presentation on MR imaging in which SSPE was a rare cause of unilateral brain parenchymal involvement in a patient with intractable seizures.

Micro-vascular Diseases of White Matter

White matter hyperintensity (WMH) is commonly observed on the brain MRI of elderly subjects. It has been considered as an important biomarker for the micro-vascular damages of white matter of the brain. Aging, hypertension, diabetes mellitus, and hyperhomocysteinemia have been associated with WMH development. WMH is an important risk factor for the vascular dementia (VD), however it also considered as one of risk factors for conversion of mild cognitive impairment to dementia and progression of Alzheimer's disease (AD). WMH has impact on gait, bladder control, and fine motor coordination. It also has negative effects on memory retrieval, mental flexibility, mental processing speed, and executive function by disconnecting nerve fibers that convey signals for normal cognition. Control of vascular risk factors can delay progression of WMH and this may be beneficial for VD as well as AD with ischemic changes, especially in the early state of diseases. In this paper, we will review clinical significance of WMH and three important diseases, subcortical vascular dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral amyloid angiopathy that associated with cerebral micro-vascular damages.

Clinical Characteristics of Vascular Depression in Korean Elderly People / 신경정신의학

OBJECTIVES: This study was done in Korean elderly people in order to examine the relationship of white matter hyperintensity with clinical neuropsychological function and depression symptom severity. METHODS: A total of 148 subjects diagnosed first major depressive episode after age of 60 years were included. Brain magnetic resonance imaging scan was rated with the modified Fazekas White Matter Rating Scale by researcher blinded to clinical information. Cognitive function was evaluated with a comprehensive neurological battery and depression severity was assessed by Hamilton Depression Scale. Subjects were divided into vascular depression group and non vascular group according to the degree of white matter hyperintensity. Independent t-test was used to compare clinical difference between two groups and correlation analysis was used to identify whether white matter hyperintensity severity is correlated with neuropsychological function and depressive symptom. RESULTS: Vascular depression group was significantly poorer performance in verbal fluency, Boston naming test, Mini-Mental State Examination, trail making test B and stroop test (p<0.05). Furthermore, trail making test B and stroop test performance was correlated with white matter hyperintensity severity. However, Hamilton Depression Scale score was not significantly different between two groups. CONCLUSION: Several findings from our study suggest that white matter hyperintensity is associated with neuropsychological performance, especially executive function. Moreover, executive dysfunction might contribute to poor treatment outcome of vascular depression group.

The Association of Cognitive Dysfunction with White Matter Hyperintensity in Alzheimer's Disease and Mild Cognitive Impairment / 신경정신의학

OBJECTIVES : We investigated the relationship between periventricular and deep white matter hyperintensity and cognitive function in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS : T2-weighted MRI scans were performed in 41 subjects with AD 38 subjects with mild cognitive impairment and 38 control subjects. Periventricular and deep white matter hyperintensities were rated on a Fazekas 0-3 scale by a medical specialist of the department of radiology blind to clinical diagnosis. Cognitive function was assessed by using Cognitive Assessment and Reference Diagnoses System. RESULTS : No significant differences between demographic characteristics and vascular risk factors were revealed comparing AD, MCI and controls. The frequencies of AD were significantly higher than those of MCI and normal control in Grade 2 and 3 of periventricular hyperintensity and Grade 3 of deep white matter hyperintensity. The scores of amnesia, executive function and attention were significantly lower in Grade 2 and 3 of periventricular hyperintensity than in Grade 0 and 1. The scores of attention were significantly lower in Grade 3 of deep white matter hyperintensity than in Grade 0, 1 and 2. CONCLUSION : Periventricualr hyperintensities are associated with cognitive decline in amnesia, executive function and attention, while deep white matter hyperintensities are associated with cognitive decline in attention.

The Association of Cognitive Dysfunction with White Matter Hyperintensity in Alzheimer's Disease and Mild Cognitive Impairment / 신경정신의학

OBJECTIVES : We investigated the relationship between periventricular and deep white matter hyperintensity and cognitive function in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS : T2-weighted MRI scans were performed in 41 subjects with AD 38 subjects with mild cognitive impairment and 38 control subjects. Periventricular and deep white matter hyperintensities were rated on a Fazekas 0-3 scale by a medical specialist of the department of radiology blind to clinical diagnosis. Cognitive function was assessed by using Cognitive Assessment and Reference Diagnoses System. RESULTS : No significant differences between demographic characteristics and vascular risk factors were revealed comparing AD, MCI and controls. The frequencies of AD were significantly higher than those of MCI and normal control in Grade 2 and 3 of periventricular hyperintensity and Grade 3 of deep white matter hyperintensity. The scores of amnesia, executive function and attention were significantly lower in Grade 2 and 3 of periventricular hyperintensity than in Grade 0 and 1. The scores of attention were significantly lower in Grade 3 of deep white matter hyperintensity than in Grade 0, 1 and 2. CONCLUSION : Periventricualr hyperintensities are associated with cognitive decline in amnesia, executive function and attention, while deep white matter hyperintensities are associated with cognitive decline in attention.

MR Study of White Matter Hyperintensity in Patient with Cerebrovascular Disease / 实用放射学杂志

Objective To quantify the white matter hyperintensity (WMH) with serial MRI in elderly people with cerebrovascular disease, and to evaluate the risk factors that may have impact on their progression.Methods One hundred and thirty-eight patients with cerebrovascular disease underwent twice MRI scans with a 1.5T MR scanner at least one year apart (mean = 13.8 months). The clinical data of all patients, including age, gender, systolic blood pressure, blood glucose level, serum lipid level, alcohol consumption and smoking were recorded at baseline, as well as the historical informations concerning hypertension, diabetes mellitus and hypercholesterolemia. Besides, the overall severity of cognitive impairment and neural deficit of patients were rated by Mini-Mental State Examination (MMSE) and the National Institute of Health Stroke Scale (NIH). MRI measures included volume of gray matter infarction, volume of white matter infarction, and baseline volume of WMH. The volumetric changes of WMH between the twice scans were assessed using a semi-automated software. The influence of risk factors on changes of WMH volume was analyzed. Correlation coefficients were calculated between clinical scales and the change of WMH volume. Results The Baseline WMH volume was(13155?18782) mm3, and the volumetric change of WMH was(7687?9079) mm3. Multiple regression analyses revealed that the occurrence of infarction in cortex and in white matter was significantly associated with the volumetric change of WMH, as well as the baseline WMH volume. The volumetric changes of WMH were related to MMSE and NIH score (r=-0.266,P=0.002; r=0.257,P=0.002). The total infarcted volumes were associated with the volumetric change of WMH (r=0.416,P