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Leukoaraiosis (LA) results from ischemic injury in small cerebral vessels, which may be attributable to decreased vascular density, reduced cerebrovascular angiogenesis, decreased cerebral blood flow, or microcirculatory dysfunction in the brain. In this study, we enrolled 357 patients with mild intracerebral hemorrhage (ICH) from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission, neurological function prognosis at 3 months, and 1-year stroke recurrence. Patients were divided into groups based on Fazekas scale scores: no LA (n = 83), mild LA (n = 64), moderate LA (n = 98) and severe LA (n = 112). More severe LA, larger hematoma volume, and higher blood glucose level at admission were associated with more severe neurological deficit. More severe LA, older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months. In addition, moderate-to-severe LA, admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence. These findings suggest that LA severity may be a potential marker of individual ICH vulnerability, which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH. Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols. This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University (approval No. 12) on March 10, 2011.

BACKGROUND AND PURPOSE White matter hyperintensities (WMHs) are associated with the presence of left ventricular hypertrophy (LVH). It is unclear if periventricular WMH (PV-WMH) and or deep WMH (D-WMH) are associated with LVH. We evaluated the association of PV-WMH and D-WMH with common transthoracic echocardiogram abnormalities, including LVH in acute ischemic stroke. METHODS PV-WMH and D-WMH were graded on a 0-3 score based on the Fazekas scale. Patients were categorized into clinically significant PV-WMH and D-WMH (score 2-3) and controls (score 0-1). Multivariate logistic regression analysis was performed to determine abnormalities on echocardiogram associated with PV-WMH and D-WMH. RESULTS Among 272 patients, 137 patients had PV-WMH and 93 patients had D-WMH with a score of 2-3 on Fazekas scale. Compared to controls, patients with PV-WMH (mean age±standard deviation: 60.8±14.4 vs. 73.8±11.2 years) and D-WMH (63.4±14.4 vs. 75.0±11.1 years) were older. Compared to controls, PV-WMH was associated with history of stroke (22 [16%] vs. 37 [27%], p = .03) and valvular calcification (33 [24%] vs. 61 [45%], p = .0005); D-WMH was associated with history of atrial fibrillation (25 [14%] vs. 22 [24%], p = .04), valvular calcification (50 [28%] vs. 44 [47%], p = .001), and LVH (30 [17%] vs. 25 [27%], p = .049). In multivariate analysis, PV-WMH was associated with age (odds ratio [OR] = 1.09; 95% confidence interval [CI] = 1.06-1.12) and stroke history (OR = 2.1; 95% CI = 1.1-4.1), and D-WMH was associated with age (OR = 1.07; 95% CI = 1.05-1.10) and LVH (OR = 2.0; 95% CI = 1.0-4.0). CONCLUSION LVH is associated with D-WMH but not with PV-WMH. Although valvular calcification is common, it is likely age related than due to WMH.

Background Leukoaraiosis is a type of lesion characterized by tissue rarefaction or myelin pallor resulting from axons loss and gliosis. Synthetic magnetic resonance imaging (MRI) could yield quantitative T1, T2, proton density (PD) values of leukoaraiosis in addition to information on the volume of the lesion. Purpose To investigate the feasibility of quantifying leukoaraiosis using synthetic MRI and to explore the association between leukoaraiosis and cerebral small vascular diseases and cerebral atherosclerosis. Material and Methods Patients with acute ischemic stroke were enrolled in this study. All participants underwent a conventional T2-weighted image, brain volume, CUBE fluid attenuated inversion recovery, and synthetic MRI acquisition using a 3.0-T MR system. A time-of-flight magnetic resonance angiography was also obtained. We evaluated the T1, T2, PD values and leukoaraiosis volume. Results Analysis of the leukoaraiosis volume ratios demonstrated a positive association with T2 values, a negative association with T1 values, and no association with PD values. Leukoaraiosis volume ratios were independently correlated with age ( P < 0.001), lacunes ( P = 0.022), and cerebral microbleeds ( P = 0.010). A statistical association was found between both age ( P < 0.001) and lacunes ( P = 0.047) and leukoaraiosis T2 values. Conclusion Synthetic MRI may enhance the evaluation of leukoaraiosis, in addition to providing information on its volume. Leukoaraiosis may represent a type of cerebral small vascular disease rather than cerebral atherosclerosis and may share the same pathological mechanism as lacunes and cerebral microbleeds.

Background L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder that occurs due to accumulation of L-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF), plasma and urine. The clinical manifestation of L2HGA includes intellectual disability, cerebellar ataxia, epilepsy, speech problems and macrocephaly. Methods In the present study, we ascertained a multigenerational consanguineous Pakistani family with 5 affected individuals. Clinical studies were performed through biochemical tests and brain CT scan. Locus mapping was carried out through genome-wide SNP genotyping, whole exome sequencing and Sanger sequencing. For in silico studies protein structural modeling and docking was done using I-TASSER, Cluspro and AutoDock VINA tools. Results Affected individuals presented with cognitive impairment, gait disturbance, speech difficulties and psychomotor delay. Radiologic analysis of a male patient revealed leukoaraiosis with hypoattenuation of cerebral white matter, suggestive of hypomyelination. Homozygosity mapping in this family revealed a linkage region on chromosome 14 between markers rs2039791 and rs781354. Subsequent whole exome analysis identified a novel frameshift mutation NM_024884.3:c.180delG, p.(Ala62Profs*24) in the second exon of L2HGDH. Sanger sequencing confirmed segregation of this mutation with the disease phenotype. The identification of the most N-terminal loss of function mutation published thus far further expands the mutational spectrum of L2HGDH.

With newer research-based classification systems, the term Vascular Cognitive Impairment (VCI) is now preferred to vascular dementia. VCI is an umbrella term that includes all forms of cognitive deficits ranging from mild cognitive impairment of vascular origin (VaMCI) to vascular dementia (VaD). The new VCI construct takes into account the fact that in addition to single strategic infarcts, multiple infarcts, and leukoaraiosis, there are other mechanisms of cerebrovascular disease such as chronic hypoperfusion that might account for the pattern of cognitive deficits associated with vascular dementia. The key to defining the spectrum of VCI is neuropsychological testing, bedside or office-based clinical examination, and neuroimaging. The lack of specific cognitive tools that are sufficiently sensitive to detect subtle deficits makes the assessment of cognitive impairment difficult. Prospective cross-sectional and longitudinal studies of VCI from different settings are therefore required. Although there have been few published reports, behavioural and psychological symptoms (BPS) are inherently present in VCI from the onset and during the course of the disease. Besides the type of population (i.e. clinical, community or nursing-home settings), the definition of VCI/VaD and the instruments used, and differences in the prevalence and pattern of BPS between various studies, could be due to other, often unconsidered, factors such as gender, age, education, use of medication and VCI/VaD severity.

Ischaemic stroke is characterized by high morbidity, high disability rate, high mortality and high recurrence rate, which can have a grave impact on the quality of life of the patients and consequently becomes an economic burden on their families and society. With the developments in imaging technology in recent years, patients with acute cerebral infarction are predominantly more likely to be diagnosed with leukoaraiosis (LA). LA is a common degenerative disease of the nervous system, which is related to cognitive decline, depression, abnormal gait, ischaemic stroke and atherosclerosis. The aetiology of LA is not clear and there is no gold standard for imaging assessment. Related studies have shown that LA has an adverse effect on the prognosis of cerebral infarction, but some experts have contrary beliefs. Hence, we undertook the present review of the literature on the mechanism and the effect of LA on the prognosis of patients with acute ischaemic stroke.

Azizi A Seixas,1,2 Arlener D Turner,2 Omonigho Michael Bubu,1,2 Girardin Jean-Louis,1,2 Mony J de Leon,3 Ricardo S Osorio,2 Lidia Glodzik3 1New York University Grossman School of Medicine, Department of Population Health, New York, NY, 10016, USA; 2New York University Grossman School of Medicine, Department of Psychiatry, New York, NY, 10016, USA; 3Weill Cornell Medicine, Department of Radiology, New York, NY, 10021, USACorrespondence: Azizi A SeixasDepartments of Population Health and Psychiatry, New York University Grossman School of Medicine, 180 Madison Avenue, Office # 715, New York, NY, 10016, USATel +1 646-501-3430Fax +1 212-263-4595Email Azizi.Seixas@nyulangone.orgObjective: Compared to European Americans, research indicates that African Americans have higher white matter hyperintensity (WMH) load; however, the clinical and biological bases underlying this higher burden are poorly understood. We hypothesize that obesity may explain differences in WMH between African and European Americans.Methods: Participants enrolled in longitudinal brain aging studies (n=292; 61% Female; 92% European American; mean age=69.6± 7.7) completed evaluations including medical exams, neuroimaging, and sociodemographic surveys. Overweight/obese status defined as body mass index ≥ 30 kg/m2, and WMH load, captured by FLAIR images, as sum of deep and periventricular volumes, scored using the Fazekas scale (0– 6), WMH≥ 4 considered high.Results: Logistic regression analyses, adjusted for age, sex, hypertension, and smoking history, indicated that age and interaction between race and obesity were significant predictors of WMH, demonstrating that obesity significantly moderated the relationship between race and WMH. Age independently increased the odds of high WMH by 16% (OR=1.16, 95% CI=1.09– 1.23, p< 0.001). Stratified analysis indicates that older European Americans had increased WMH (OR=1.17, 95% CI=1.09– 1.23, p< 0.001), while obese African Americans had increased WMH (OR=27.65, 95% CI=1.47– 519.13, p< 0.05). In a case controlled subgroup matched by age, sex, and education (n=48), African Americans had significantly higher WMH load (27% vs 4%, &KHgr;2=5.3, p=0.02).Conclusion: Results denote that age predicted WMH among European Americans, while obesity predicted WMH among African Americans. Matched sample analyses indicate that obesity increases the odds of WMH, though more pronounced in African Americans. These findings suggest that obesity may explain the differential burden of white matter hyperintensity load, signifying public health and clinical importance.Keywords: white matter hyperintensities, WMH, racial/ethnic differences, African American, obesity

Background Stroke not only substantially increases the risk of incident dementia early after stroke but also the risk remains elevated years after. Aim We aimed to determine the risk factors of dementia onset more than three to six months after stroke or transient ischemic attack. Methods This is a single-center prospective cohort study. We recruited consecutive subjects with stroke/transient ischemic attack without early-onset dementia. We conducted an annual neuropsychological assessment for five years. We investigated the association between baseline demographic, clinical, genetic (APOEɛ4 allele), and radiological factors as well as incident recurrent stroke with delayed-onset dementia using Cox proportional hazards models. Results In total, 1007 patients were recruited, of which 88 with early-onset dementia and 162 who lost to follow-ups were excluded. Forty-nine (6.5%) out of 757 patients have incident delayed-onset dementia. The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline Hong Kong version of the Montreal Cognitive Assessment (MoCA) score were significantly associated with delayed-onset dementia. APOEɛ4 allele, medial temporal lobe atrophy, and recurrent stroke were not predictive. Conclusion The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline MoCA score are associated with delayed-onset dementia after stroke/transient ischemic attack.

Introduction. Typical basis of chronic cerebral ischemia in young people is small vessel disease (SVD) diagnosed by micro-focal lesions and microstructural damage of cerebral white matter (WM), reduction of fractional anisotropy (FA) in diffusion tensor MRI (DT-MRI). Previous studies showed that increased dopplerographic pulsatility and resistivity indices in middle cerebral artery (MCA PI-RI) correlated with SVD manifestations and cognitive impairment in middle-aged and elderly patients. Aim – to determine early markers and predictors of asymptomatic SVD in young and middle-aged individuals without cognitive impairment. Materials and methods. 52 male employees of the EMERCOM, 47.3±7.6 years, without neurological or cognitive deficits were examined. Duplex scanning with MCA PI-RI calculation, MRI with WM damage assessment according to Fazekas scale, DT-MRI FA definition were completed. Results. All those examed showed MRI signs of SVD. Two groups were formed according to Fazekas: 0 points (n-38) and 1-2 points (n-14). The 2nd group showed higher MCA PI-RI (pConclusion. MCA PI-RI are early markers of focal lesions and microstructural changes in WM and predictors of cognitive impairment in the young and middle-aged with asymptomatic SVD.

OBJECTIVE The goal of this systematic review is to evaluate the association between fluid biomarkers and white matter hyperintensities (WMH) in cerebrovascular disease and neurodegenerative disorders. While previous research has examined the etiology of WMH in specific diseases, we propose a comprehensive framework encompassing WMH of both vascular and non-vascular origin. INTRODUCTION Although WMH have been mostly described in aging populations with cerebrovascular disease, extensive lesions also occur in non-vascular diseases. Such lesions are traditionally treated as a separate pathological entity from vascular ones, but recent work has challenged the appropriateness of that framework when probing WMH etiology. Comparing biomarkers associated with WMH across various pathologies may improve our understanding of their etiology. INCLUSION CRITERIA The review will focus on cerebrovascular disease and neurodegenerative disorders and exclude infectious, metabolic, drug-induced, or radiation-induced white matter diseases. Original, peer-reviewed research on the relationship of WMH on magnetic resonance imaging with blood/cerebrospinal fluid biomarkers will be considered for inclusion. Postmortem studies will guide the selection of biomarkers of interest and the interpretation of our findings. Genomic markers will be excluded. METHODS The review will be conducted in accordance with PRISMA and JBI guidelines. English articles of interest published between 2000 and 2020 will be identified in MEDLINE and Embase. Two reviewers will perform abstract and full-text screening, standardized data extraction, and quality assessments of the selected studies. The relationship between each biomarker and WMH burden will be meta-analyzed, if possible, with subgroup or meta-regression analyses to assess differences between diseases. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO CRD42020218298.

The vascular depression hypothesis posits that cerebrovascular diseases are a major risk factor for emotional and behavioral disorders (EBD). Arterial hypertension (AH) is one of the main causes of cerebrovascular diseases. Objective: to assess the relationship between anxiety, depression and apathy in the patients with AH with case history, clinical features and neuroimaging. Patients and methods . 65 hypertensive outpatient were examined (mean age – 57.17±10.76 years). Cognitive status was evaluated with MiniMental State Examination, Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery. EBD was assessed with Beck Depression Scale, Spielberger Anxiety Questionnaire, and Robert's Apathy Scale. The Fazekas scale was used to determine the severity of leukoaraiosis. Results and discussion. Significant depression was present in 66.2%, anxiety – in 41.5%, and apathy – in 80% of hypertensive patients. Blood pressure level (p

Cognitive dysfunction is a degenerative disease of the central nervous system, which often associates with ageing brain as well as neurodegenerative diseases. A growing body of evidence suggests that patients with diabetes mellitus (DM) have a significantly higher risk of cognitive impairment. In recent years, studies have found that patients with diabetes-related cognitive dysfunction have an increased burden of leukoaraiosis (LA), and larger white matter hyperintensity (WMH) volume. With the recent advancement of technologies, multimodal imaging is widely exploited for the precise evaluation of central nervous system diseases. Emerging studies suggest that LA pathology can be used as a predictive signal of white matter lesions in patients with diabetes-related cognitive dysfunction, providing support for early identification and diagnosis of disease. This article reviews the findings, epidemiological characteristics, pathogenesis, imaging features, prevention and treatment of LA pathophysiology in patients with diabetes-related cognitive dysfunction.

Volumetric estimates of subcortical and cortical structures, extracted from T1‐weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) on FreeSurfer gray matter (GM) structure volumes and its possible bias on functional relationships. T1‐weighted images from 1,077 participants (4,321 timepoints) from the Alzheimer's Disease Neuroimaging Initiative were processed with FreeSurfer version 6.0.0. WMHs were segmented using a previously validated algorithm on either T2‐weighted or Fluid‐attenuated inversion recovery images. Mixed‐effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overall WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance. Participants with higher WMH volumes had higher overlaps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (p, Presence of WMHs leads to systematic inaccuracies in GM segmentations, which can also change clinical associations. While specifically measured for the Freesurfer toolkit, this problem likely affects other algorithms.

ObjectiveTo investigate the 2-year change in parenchymal diffusivity, a quantitative marker of microstructural tissue condition, and the relationship with baseline blood-brain barrier (BBB) permeability, in tissue at risk, i.e., the perilesional zone surrounding white matter hyperintensities (WMH) in patients with cerebral small vessel disease (cSVD).MethodsPatients with sporadic cSVD (lacunar stroke or mild vascular cognitive impairment) underwent 3T MRI at baseline, including dynamic contrast-enhanced MRI to quantify BBB permeability (i.e., leakage volume and rate) and intravoxel incoherent motion imaging (IVIM), a diffusion technique that provides parenchymal diffusivity D. After 2 years, IVIM was repeated. We assessed the relation between BBB leakage measures at baseline and change in parenchymal diffusivity (∆D) over 2 years in the perilesional zones (divided in 2-mm contours) surrounding WMH.ResultsWe analyzed 43 patients (age 68 ± 12 years, 58% male). In the perilesional zones, ∆D increased 0.10% (confidence interval [CI] 0.07–0.013%) (p < 0.01) per 2 mm closer to the WMH. Furthermore, ∆D over 2 years showed a positive correlation with both baseline BBB leakage volume (r = 0.29 [CI 0.06–0.52], p = 0.013) and leakage rate (r = 0.24 [CI 0.02–0.47], p = 0.034).ConclusionBBB leakage at baseline is related to the 2-year change in parenchymal diffusivity in the perilesional zone of WMH. These results support the hypothesis that BBB impairment might play an early role in subsequent microstructural white matter degeneration as part of the pathophysiology of cSVD.

ObjectiveTo study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis (LA) and the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in patients with intracerebral haemorrhage (ICH).MethodsThis is a retrospective observational study of patients with nontraumatic ICH. Clinical and biochemical parameters were analysed. sTWEAK levels were measured by ELISA. LA was analysed in the hemisphere without haemorrhage to avoid interference with the acute injury. The main endpoint was the haematoma growth evaluated by the difference in volume between the second and the initial neuroimage. Poor functional outcome, defined as a modified Rankin Scale >2 at 3 months, was considered as secondary endpoint. Receiver operating characteristic curve analysis was performed to stablish the best cut-off for sTWEAK levels associated with haematoma growth.ResultsWe included 653 patients with ICH in our analysis (71.1±11.9 years, 44% women). Haematoma growth was observed in 188 patients (28.8%). sTWEAK levels ≥5600 pg/mL predicted ICH growth with a sensitivity of 84% and a specificity of 87%. sTWEAK levels ≥5600 pg/mL and the presence of LA were associated with haematoma growth (OR: 42.46; (CI 95% 22.67 to 79.52) and OR: 2.73 (CI 95% 1.39 to 5.34), respectively). Also, the presence of LA (OR: 4.31 (CI 95% 2.89 to 6.42)) and the interaction between ICH growth and sTWEAK (OR: 2.23 (CI 95% 1.40 to 3.55)) were associated with poor functional outcome at 3 months.ConclusionsTWEAKs, together with the presence and grade of LA, are biomarkers able to predict ICH growth and poor functional outcome in patients with ICH.

In order to study the mechanism of post-stroke depression (PSD), we used diffusion kurtosis imaging (DKI) to describe the changes in white matter (WM) microstructure in PSD patients, to investigate the association between WM damage in limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuit and PSD, and the utility of DKI in the diagnosis of PSD.Fifty-eight participants were divided into different groups: control group (n=20), stroke patients without depression (Non-PSD, n=21) and PSD group (n=17). All were taken DKI scans. The WM of bilateral superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, temporal lobe, parietal lobe, occipital lobe, the anterior and posterior limb of internal capsule, the genu and splenium of corpus callosum were selected as the regions of interest (ROI) and selected mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK) as the DKI parameters.Compared with control and Non-PSD, MK of PSD group in bilateral superior frontal gyrus, middle frontal gyrus, temporal lobe and the genu of corpus callosum were decreased significantly, as well as the RK in left superior frontal gyrus, bilateral middle frontal gyrus and temporal lobe. But there was no significant difference in AK. Besides, the decrease in MK and RK in frontal and temporal lobe was negatively associated with the severity of PSD.Our research indicated that the damage to WM microstructure in the frontal lobe, temporal lobe and the genu of corpus callosum may be related toPSD. DKI explores the microstructural changes of WM in PSD patients and may be an auxiliary diagnostic method for PSD.

Aim To study the imaging features of leukoaraiosis (LA) and hemorrhage in cerebral amyloid angiopathy (CAA) patients. Methods The earliest MRI images of probable CAA patients and non-CAA patients were collected. The characteristics of LA in the two groups were analyzed. Cerebral micro bleeding (CMB), superficial siderosis (SS), and intracranial hemorrhage (ICH) were recorded in the follow-up study. The space relationship between CMB or SS and ICH was assessed. Results We found that 10/21 (47.6%) patients had occipital prominent LA and 14/21 (66.7%) patients had subcortical punctate LA before the ICH, which was higher than that of the ones in the control group (p = 0.015 and 0.038, respectively). The recurrence rate of ICH was 100% (3/3) in patients with diffuse SS and 36.4% (4/11) in patients without. The recurrence rate of ICH was 60% (3/5) in patients with multiple-lobe CMBs and 44.4% (4/9) in those without. The location of the ICH and CMB was inconsistent. ICH occurred in the ipsilateral cerebral hemisphere of SS in three patients with diffuse SS. Conclusion LA, diffuse SS, and multiple-lobe CMBs are important imaging characteristics of CAA, which may help make early diagnosis and predict the recurrence of ICH.

Objective: To describe the neuroimaging and other methods for assessing vascular contributions to neurodegeneration in the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study, a Canadian multi-center, prospective longitudinal cohort study, including reliability and feasibility in the first 200 participants. Methods: COMPASS-ND includes persons with Alzheimer’s disease (AD; n = 150), Parkinson’s disease (PD) and Lewy body dementias (LBDs) (200), mixed dementia (200), mild cognitive impairment (MCI; 400), subcortical ischemic vascular MCI (V-MCI; 200), subjective cognitive impairment (SCI; 300), and cognitively intact elderly controls (660). Magnetic resonance imaging (MRI) was acquired according to the validated Canadian Dementia Imaging Protocol and visually reviewed by either of two experienced readers blinded to clinical characteristics. Other relevant assessments include history of vascular disease and risk factors, blood pressure, height and weight, cholesterol, glucose, and hemoglobin A1c. Results: Analyzable data were obtained in 197/200 of whom 18 of whom were clinically diagnosed with V-MCI or mixed dementia. The overall prevalence of infarcts was 24.9%, microbleeds was 24.6%, and high white matter hyperintensity (WMH) was 31.0%. MRI evidence of a potential vascular contribution to neurodegeneration was seen in 12.9%–40.0% of participants clinically diagnosed with another condition such as AD. Inter-rater reliability was good to excellent. Conclusion: COMPASS-ND will be a useful platform to study vascular brain injury and its association with risk factors, biomarkers, and cognitive and functional decline across multiple age-related neurodegenerative diseases. Initial findings show that MRI-defined vascular brain injury is common in all cognitive syndromes and is under-recognized clinically.

White matter hyperintensities (WMH) are common in elderly individuals and cause brain network deficits. However, it is still unclear how the global brain network is affected by the focal WMH. We aimed to investigate the diffusion of WMH‐related deficits along the connecting white matters (WM). Brain magnetic resonance imaging data and neuropsychological evaluations of 174 participants (aged 74 ± 5 years) were collected and analyzed. For each participant, WMH lesions were segmented using a deep learning method, and 18 major WM tracts were reconstructed using automated quantitative tractography. The diffusion characteristics of distal WM tracts (with the WMH penumbra excluded) were calculated. Multivariable linear regression analysis was performed. We found that a high burden of tract‐specific WMH was related to worse diffusion characteristics of distal WM tracts in a wide range of WM tracts, including the forceps major (FMA), forceps minor (FMI), anterior thalamic radiation (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus‐parietal (SLFP), superior longitudinal fasciculus‐temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a higher mean diffusivity (MD) of distal tracts was linked to worse attention and executive function in the FMI, right CCG, left ILF, SLFP, SLFT, and UNC. The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions beyond the penumbra and might eventually affect attention and executive function., A high burden of tract‐specific WMH was related to an increased MD of distal WM tracts. A higher MD of distal tracts was linked to worse attention and executive function. The microstructural changes caused by WMH may propagate along tracts to distal regions beyond the penumbra.

BACKGROUND: Leukoaraiosis (LA) is a phenomenon of the brain that is often observed in elderly people. However, little is known about the role of LA in cognitive impairment in neurodegeneration and disease. This cross-sectional, retrospective Leukoaraiosis And Disability (LADIS) study aimed to characterize the relationship between brain white matter connectivity properties with LA ratings in patients with Alzheimer’s disease (AD) as compared with age-matched cognitively normal controls. METHODS: Patients with AD (n=76) and elderly individuals with normal cognitive (NC) function (n=82) were classified into 3 groups, LA1, LA2, and LA3, according to the rating of their white matter changes (WMCs). Diffusion tensor imaging (DTI) data were analyzed by quantifying and comparing the white matter connectivity properties and gray matter (GM) volume of brain regions of interest (ROIs). RESULTS: The rich-club network properties in the AD LA1 and LA2 groups showed significant patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA1 and LA2 groups, respectively. However, the rich-club network properties in the AD LA3 group showed similar patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA3 group, despite there being significant hippocampal and amygdala atrophic differences between AD patients and NC elders. Compared to the NC LA1 group, the characteristic path length of white matter fiber connectivity in the NC LA3 group was significantly increased, and the brain’s global efficiency, clustering coefficient, and network connectivity strength were significantly reduced (P0.05) were observed in characteristic path length, reduced global efficiency, or the clustering coefficient between the NC LA3 and AD LA1 groups, or between the NC LA3 and AD LA2 groups. CONCLUSIONS: Our findings offer some insights into a potential role of LA in cognitive impairment that may predict the development of disability in older adults. The occurrence of LA, an intermediate degenerative change, during neurodegeneration and disease may potentially lead to the remodeling of the brain network through brain plasticity. LA, therefore, representing a possible compensatory mechanism to buffer cognitive decline.

Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase (DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this double-blind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, SmaI restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2 (-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models (GG and CG), while 89.13% of healthy control subjects had dominant genetic models (CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls (P = 0.0002). The frequency of G alleles in the leukoaraiosis patients (71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower (χ2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes (Kruskal–Wallis H = 24.5955, P < 0.0001). In addition, the GG genotype of DDAH2 (-449 G/C) was more common in patients with leukoaraiosis. These findings suggest that the G allele of DDAH2 (-449 G/C) is a risk factor for leukoaraiosis morbidity and is correlated with high levels of asymmetric dimethylarginine. This study was approved by the Institutional Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University of China (approval No. KY2016-177) on July 28, 2016.

Background: Carotid artery plaque, white matter disease (WMD), and silent lacunae infarcts (initial indicators) are associated with symptomatic cerebral infarction (CI) caused by atherosclerosis. We retrospectively examined the association between the initial indicators and risk factors for cerebrovascular disease, considering the primary prevention of symptomatic CI. Methods: We divided 1503 individuals who were neurologically healthy and enrolled in a brain screening program (brain dock) at our institution, into three initial plaque grades (grade 0, 1, and 2) based on having no plaques, having plaques on the right or left carotid artery, or having plaques on both carotid arteries, respectively. We analyzed the risk factors according to the presence/absence of the initial indicators. Results: WMD and the risk factors (low-density lipoprotein [LDL], hemoglobin A1c, systolic blood pressure [BP], and smoking cigarettes) were positively correlated with the initial plaque grades, even when their laboratory values were within normal ranges. Systolic BP (116.5 ± 14.0 mmHg) was significantly lower in group 00 (without carotid plaque and WMD) than that in age-adjusted others (with carotid plaque or WMD). In young participants aged between 40 and 52 years, LDL (132.8 ± 24.5 mg/dl) was significantly higher in subgroup ++ (with carotid plaque and WMD) compared to others (without carotid plaque or WMD). Conclusion: Initial plaque grade and WMD grade as clinical initial indicators of symptomatic CI are associated with risk factors. To avoid deterioration of the initial indicators, it was suggested that the risk factors should be maintained at the lower ends of normal ranges and smoking cessation should be recommended.

Background Parkinson’s disease (PD), frequently accompanied by cognitive impairments, is associated with systemic oxidative stress and abnormal structural changes on brain images. We aimed to identify the correlation between systemic oxidative stress and cognitive function in PD patients with different periventricular white matter hyperintensities (PWMH) and deep white matter hyperintensities (DWMH). Methods A total of 146 participants with idiopathic PD underwent brain MRI, which revealed PWMH and DWMH. The number of lesions were evaluated using the Fazekas criteria. Systemic oxidative stress was determined as early or late phase changes in leukocyte apoptosis and its subsets by flow cytometry. Cognitive functions, including attention, executive function, memory, language, and visual space, were assessed. Results For different DWMH, the leukocyte apoptosis and its subsets were significantly different.. However, there were no significant differences in oxidative stress biomarkers in PD patients with different PWMH. Attention and memory were significantly decreased in patients with more advanced DWMH injuries. Attention, memory, and language were significantly impaired in patients with worse PWMH lesions. Conclusion Significant oxidative stress biomarker alternations in PD patients with DWMH, but not PWMH, might be associated with white matter injury. Systemic inflammatory responses may contribute to deep white matter damage in PD. Further, more cognitive deficits were seen in PD patients with worse deep white matter lesions, especially in moderate to severe periventricular white matter injury. Trial registration Retrospective study.

Background: Low-dose alteplase (LrtPA) has been shown not to be inferior to the standard-dose (SrtPA) with respect to death/disability. Objective: We aim to evaluate the percentage of patients treated with LrtPA at our center after the ENCHANTED trial and the factors associated with the use of this dosage. Methods: Prospective study in consecutive patients with an acute stroke admitted between June 2016 and November 2018. Results: 160 patients were treated with intravenous thrombolysis, 50% female; mean age 65.4±18.5 years. Of these, 48 patients (30%) received LrtPA. In univariate analysis, LrtPA was associated with patient's age (p=0.000), previous modified Rankin scale scores (mRS) (p

Objective To investigate whether elevated serum levels of sTWEAK (soluble tumor necrosis factor‐like inducer of apoptosis) might be involved in a higher frequency of symptomatic hemorrhagic transformation (HT) through the presence of leukoaraiosis (LA) in patients with acute ischemic stroke (IS) undergoing reperfusion therapies. Methods This is a retrospective observational study. The primary endpoint was to study the sTWEAK‐LA‐HT relationship by comparing results with biomarkers associated to HT and evaluating functional outcome at 3‐months. Clinical factors, neuroimaging variables and biomarkers associated to inflammation, endothelial/atrial dysfunction or blood‐brain barrier damage were also investigated. Results We enrolled 875 patients (mean age 72.3 ± 12.2 years; 46.0% women); 710 individuals underwent intravenous thrombolysis, 87 endovascular therapy and 78 both. HT incidence was 32%; LA presence was 75.4%. Patients with poor functional outcome at 3‐months showed higher sTWEAK levels at admission (9844.2 [7460.4–12,542.0] vs. 2717.3 [1489.7–5852.3] pg/mL, P

Background and purpose The aim of the study was to evaluate whether leukoaraiosis (LA) severity is associated with earlier neurological outcome in acute stroke patients undergoing mechanical thrombectomy. Materials and methods In this retrospective multicenter study, we evaluated 273 acute stroke patients treated with mechanical thrombectomy. LA severity was graded as 0–2 (absent-to-moderate) versus 3–4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of early neurological improvement and early neurological deterioration. Early neurological improvement was defined as a decrease of ≥ 4 points on the NIHSS, or an NIHSS score of zero 24 hours after baseline assessment. Early neurological deterioration was defined as an increase of ≥ 4 points on the NIHSS 24 hours after baseline assessment. Results There was a significantly lower early neurological improvement rate (17.1% versus 39.2%; P = 0.006) and non-significantly higher early neurological deterioration rate (29.3% versus 17.7%; P = 0.084) in patients with severe LA (sLA) compared with patients with absent-to-moderate LA. In multivariable analysis, sLA was inversely associated with early neurological improvement (OR, 0.31; 95% CI, 0.13–0.78; P = 0.012). There was no significant association of sLA with early neurological deterioration. However, in patients without symptomatic intracranial hemorrhage, sLA was an independent predictor of early neurological deterioration (OR, 2.65; 95% CI, 1.09–6.45; P = 0.032). Conclusions sLA is a significant negative predictor of early neurological improvement and is an independent predictor of early neurological deterioration in patients without symptomatic intracranial hemorrhage.

Highlights • About a third of patients with neuroimaging in acute/subacute phase show brain abnormalities suggestive of COVID-19 etiology. • Cerebral white matter hyperintensities/hypodensities comprise the primary neuroimaging feature in COVID-19 patients. • Brain abnormalities are diffused across the cerebral hemispheres rather than region-specific., Objective This systematic review aimed to synthesize early data on typology and topography of brain abnormalities in adults with COVID-19 in acute/subacute phase. Methods We performed systematic literature search via PubMed, Google Scholar and ScienceDirect on articles published between January 1 and July 05, 2020, using the following strategy and key words: ((covid[Title/Abstract]) OR (sars-cov-2[Title/Abstract]) OR (coronavirus[Title/Abstract])) AND (brain[Title/Abstract]). A total of 286 non-duplicate matches were screened for original contributions reporting brain imaging data related to SARS-Cov-2 presentation in adults. Results The selection criteria were met by 26 articles (including 21 case reports, and 5 cohort studies). The data analysis in a total of 361 patients revealed that brain abnormalities were noted in 124/361 (34%) reviewed cases. Neurologic symptoms were the primary reason for referral for neuroimaging across the studies. Modalities included CT (-angiogram, -perfusion, -venogram), EEG, MRI (-angiogram, functional), and PET. The most frequently reported brain abnormalities were brain white matter (WM) hyperintensities on MRI 66/124 (53% affected cases) and hypodensities on CT (additional 23% affected cases), followed by microhemorrhages, hemorrhages and infarcts, while other types were found in

Subcortical ischemic white matter injury (SIWMI), pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging, is a common cause of cognitive decline in elderly. Despite its high prevalence, it remains unknown how various components of the white matter degenerate in response to chronic ischemia. This incomplete knowledge is in part due to a lack of adequate animal model. The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components. The SIWMI animal models are categorized into 1) chemically induced SIWMI models, 2) vascular occlusive SIWMI models, and 3) SIWMI models with comorbid vascular risk factors. Chemically induced models display consistent lesions in predetermined areas of the white matter, but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities. Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified. When combined with comorbid vascular risk factors (specifically hypertension), however, they can produce progressive and definitive white matter lesions including diffuse rarefaction, demyelination, loss of oligodendrocytes, and glial activation, which are by far the closest to those found in human white matter hyperintensities lesions. However, considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models. In the meantime, in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury. Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.

The paper presents the current etiopathogenetic classification of chronic cerebrovascular diseases (CVD) and discusses the role of hypertension, cerebral amyloid angiopathy, and genetically determined syndromes in the development of this pathological condition. It gives recommendations for the neuroradiological diagnosis of chronic CVD in accordance with the international standards. The paper discusses the clinical manifestations of chronic CVD, primarily vascular cognitive impairment. It discusses international guidelines for the examination and treatment of patients with chronic CVD, as well as the rules for stroke prevention in this patient cohort. The possibilities of pathogenetically based therapy in decreasing the severity of vascular cognitive impairment in the presence of chronic CVD are also highlighted.

Objective To investigate regional white matter fibers loss in Leukoaraiosis (LA) and its relationship with cognitive impairments. Methods Fifty‐six participants with LA and 38 healthy controls underwent clinical evaluations and MR scans. Participants with LA were classified as cognitively normal (LA‐NC, n = 18), vascular cognitive impairment of none dementia (LA‐VCIND, n = 24), and vascular dementia (LA‐VaD, n = 14) by Mini‐Mental State Examination and Clinical Dementia Rating. Cognitive domains including visual‐spatial, naming, attention, language, abstraction, memory, and orientation were assessed. With the use of Tract‐based spatial statistics, mean fractional anisotropy (FA) of major white matter fiber tracts were compared between LA and controls and among LA groups with varying levels of cognitive impairments. Regression analyses were performed to evaluate relationships between FA values and cognitive performance. Results Participants showed significant FA reduction in the corpus callosum (CC), bilateral corona radiata, anterior limb of the internal capsule, external capsule, posterior thalamic radiation, and superior longitudinal fasciculus compared to controls and across LA groups. The LA‐VaD group showed consistent damage in the body and genu of CC compared to the LA‐NC and LA‐VCIND groups. A positive correlation between visual‐spatial and FA reduction in right anterior corona radiates in LA‐VCIND and body of CC in LA‐ VaD. Interpretation We found regional fiber loss in the CC across the cognitive spectrum in patients with LA and correlations between FA and visuospatial impairment in the anterior corona radiata in patients with LA‐VCIND and in the body of CC in patients with LA‐VaD.

Previous studies have reported a significant increase in age-related magnetic resonance imaging (MRI) changes in relatively younger people living with HIV (PLWH). However, there is little data available for brain changes in Asian PLWH. The data to differentiate HIV specific brain change from usual aging change was also sparse. To clarify them, we assessed the presence of leukoaraiosis and brain atrophic changes on MRI in young and middle-aged Japanese PLWH.We reviewed data from well-controlled PLWH (age: 20-64 years) and coeval controls. We evaluated the presence of leukoaraiosis, as well as the extent of whole-brain grey matter (GM) atrophy and parahippocampal atrophy on brain MRI and determined between-group differences. Moreover, we evaluated the severity of parahippocampal atrophy based on the voxel-based specific regional analysis system for Alzheimer's disease.We enrolled 40 PLWH and 33 controls (median age: 40.15 and 48.00 years, respectively, [Aging changes in the brain were significantly more prevalent in well-controlled Japanese PLWH. However, the process of atrophic brain changes might differ between HIV and one of age-related diseases, Alzheimer's disease.

It is assumed that most cases of embolic stroke of undetermined source (ESUS) are of cardioembolic origin. The data about outcome after the treatment with intravenous thrombolysis (IVT) for this type of acute ischemic stroke (AIS) are limited. We aimed to compare clinical characteristics and outcomes after IVT for AIS between patients with ESUS and cardioembolic stroke (CS). This study was a single center retrospective analysis of stroke patients treated with IVT. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish stroke etiology subtype at 3 months, while ESUS was considered a subset of stroke of undetermined etiology, defined according to 2014 international criteria. Functional outcome was assessed at 3 months and defined as excellent (modified Rankin scale 0–1) and favorable (modified Rankin scale 0–2). Total of 394 patients were treated with IVT; 113 had a cardioembolism, 88 had undetermined stroke subtype, of which 62 met the ESUS criteria. Patients with ESUS were on average younger (63.7 years versus 69.7 years, p = 0.001), had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission (12 versus 15, p = 0.002) and lower prevalence of antiplatelets use (27.4% versus 42.5%, p = 0.04) compared with CS patients. Favorable outcome was more likely in ESUS patients, at discharge (48.4% versus 24.0%, p = 0.002) and after 3 months (71.0% versus 37.2%, p

Objective The objective of this study was to assess the relationship between white matter hyperintensities (WMH) and the occurrence and progression of apathy in Parkinson’s disease (PD). Methods We recruited patients with PD who underwent baseline evaluation, which included apathy assessment and magnetic resonance imaging (MRI) head scans. After 2.5 years of follow‐up, we re‐evaluated patient apathy symptoms. The severity and location of WMH were assessed with fluid‐attenuated inversion recovery (FLAIR) sequences using the Fazekas visual rating scale. Logistic regression and linear regression analyses of baseline WMH characteristics were conducted to explore the potential association between apathy and WMH. Results A total of 141 PD patients were recruited. The apathy group had a higher proportion of male patients, advanced disease, and depression, which was coupled with a lower quality of life. Morever, higher WMH severity was significantly associated with apathy. Logistic regression analyses demonstrated that WMH severity was a risk factor for apathy. In addition, linear regression analysis also suggests that apathy severity is positively correlated with baseline WMH Fazekas scales (ϐ = 0.959, P

Background Leukoaraiosis (LA) severity is associated with poor outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) caused by large vessel occlusion. This meta-analysis aimed to assess the association of LA severity with AIS-related risk factors and outcomes of MT. Methods PubMed, Web of Science, EMBASE, and Cochrane Collaboration Database was searched for studies on MT for AIS with LA. We conducted a random-effects meta-analysis for the prevalence of stroke risk factors and the MT outcome in the absent to moderate LA and severe LA groups. Results We included seven cohort studies involving 1294 participants (1019 with absent to moderate LA and 275 with severe LA). The absent to moderate LA group had a significantly lower prevalence of coronary artery disease (odds ratio [OR] 0.43; 95% CI 0.29–0.66), atrial fibrillation (OR, 0.26; 95% CI 0.17–0.38), hypertension (OR, 0.39; 95% CI 0.24–0.61), and ischemic stroke (OR, 0.27; 95% CI 0.15–0.50) than the severe LA group. There were no significant between-group differences in symptom onset to recanalization time (364.4 versus 356.2 min, mean difference 19.4; 95% CI − 28.3 to 67.2), final recanalization rate (modified thrombolysis in cerebral infarction score of 2b/3; OR, 0.87; 95% CI 0.55–1.38), and symptomatic intracranial hemorrhage (OR, 0.62; 95% CI 0.34–1.11). The absent to moderate LA group had a higher good functional outcome (modified Rankin Scale score of 0–2 at 90 days; OR, 4.55; 95% CI 3.20–6.47) and a lower mortality rate (179/1019 vs 108/275; OR, 0.28; 95% CI 0.20–0.39). Conclusion There are unique differences in the characteristics of risk factors and clinical outcomes of ischemic stroke across patients with LA of different severity. Patients with severe LA are more likely to be associated with risk factors for cerebrovascular disease and have a poor post-MT outcome.

ObjectivesTo evaluate the frequency, clinical and etiologic features, and short- and long-term outcomes of early recurrent TIA.MethodsThis prospective observational cohort study enrolled all consecutive patients with TIA referred to our emergency department and diagnosed by a vascular neurologist. Expedited assessment and best secondary prevention were performed within 24 hours. Primary endpoints were stroke and a composite outcome including stroke, acute coronary syndrome, and vascular death at 3, 12, and, for a subset of patients, 60 months; secondary outcomes were TIA relapse, cerebral hemorrhage, new-onset atrial fibrillation, and death resulting from other causes. Concordance between index TIA and subsequent stroke etiologies was also evaluated.ResultsA total of 1,035 patients (822 with a single TIA, 213 with recurrent TIA = 21%) were enrolled from August 2010 to December 2017. Capsular warning syndrome and large artery atherosclerosis showed the strongest relationship with early recurrent TIA. The risk of stroke was significantly higher in the early recurrent TIA subgroup at each follow-up, and most stroke episodes occurred within 48 hours of index TIA. TIAs with lesion, dysarthria, and leukoaraiosis were the 3- and 12-month independent predictors of stroke incidence after early recurrent TIA subgroup. Index TIA and subsequent stroke etiologies showed substantial concordance. An ABCD3 score >6 predicted a higher risk of stroke recurrence over the entire follow-up.ConclusionsOur study evaluated long-term outcome after early recurrent TIA. Our observations support the importance of promptly detecting and treating patients with early recurrent TIAs to reduce the high early and long-term risk of poor clinical outcomes.

Cerebral small vessel disease (CSVD) is a common cause of stroke (25 % of all strokes) and has a significant contribution to development dementia, functional loss and increases the risk of death. Validation of methods for assessing the total cerebral small vessel disease burden on CT and MRI makes it possible to more accurately and fully assess the impact of the cumulative effect of cerebrovascular pathology on the development and consequences of stroke after 3 months. The aim of our study was to investigate the prognostic value of the total CSVD burden and its individual features (leukoaraiosis, lacunes, brain atrophy) on the course and outcome of stroke at 90 days. 131 patients with ischemic stroke, diagnosed according to TOAST criteria, were enrolled. All patients underwent computed tomography on a General Electric CT/e device (Italy) with a slice thickness of 3–7 mm. Leukoaraiosis was diagnosed and scored by the visual scale of Fazekas and von Swieten. Brain atrophy was assessed separately in central and cortical regions by validated standard template. Lacunes were defined according to the standard protocol. We calculated the total CSVD burden (composed leukoaraiosis, lacunes, brain atrophy) with and without brain atrophy. We assessed the severity of neurological deficit by the NIHSS scale. The functional outcome and the degree of disability or dependence in the daily activities we measured by modified Rankin scale and Barthel index. MMSE was used to assess cognitive function. Statistical analyses were performed by SPSS 25.0 software (IBM Corp., Armonk, NY, USA). We used Student’s t-test or Mann-Whitney U test, Pearson or Spearman correlation and regression analysis. Our data have shown that cerebral small vessel disease is negatively correlated with the consequences of stroke and reflect brain frailty and impair regenerative potential. The degree of cognitive deficit was associated with negative prognostic consequences of stroke. The total cerebral small vessel disease burden is a valuable prognostic marker of stroke prognosis and can be used as a tool for the assessment of effectiveness of preventive and curative measures.

OBJECTIVE: Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. METHODS: BIOCARD Study participants were cognitively normal and primarily middle-aged (M=57 years) at baseline and have been followed with annual cognitive and clinical assessments (M=13 years). Baseline cognitive reserve was indexed with a composite score combining education with reading and vocabulary scores. Baseline vascular risk (N=229) was assessed with a composite risk score reflecting five vascular risk factors. Baseline white matter hyperintensity load (N=271) was measured with FLAIR magnetic resonance imaging. Cox regression models assessed risk of progression from normal cognition to onset of clinical symptoms of Mild Cognitive Impairment. Longitudinal mixed effects models measured the relationship of these variables to cognitive decline, using a global composite score, and executive function and episodic memory sub-scores. RESULTS: Both vascular risk and white matter hyperintensities were associated with cognitive decline, particularly in executive function. Higher vascular risk, but not white matter hyperintensity burden, was associated with an increased risk of progression to Mild Cognitive Impairment. Higher cognitive reserve was associated with a reduced risk of symptom onset and higher levels of baseline cognition but did not modify the associations between the vascular risk score and white matter hyperintensities with clinical progression or cognitive decline. INTERPRETATION: Although cognitive reserve has protective effects on clinical and cognitive outcomes, it does not mitigate the negative impact of vascular risk and small vessel cerebrovascular disease on these same outcomes.

Cerebrovascular disease is one of the most important problems of clinical neurology, which is a significant cause of cognitive impairment and depression. Chronic forms of cerebrovascular insufficiency are most often associated with cerebral microangiopathy or a disease of small vessels, which is characterized by the presence of lacunae, microinfarction and microbleeding, leukoaraiosis and dilated perivascular spaces. One of the main and most common clinical symptoms is vascular cognitive impairment. They are characterized by extremely variable cognitive deficits, highly dependent on the location and severity of vascular damage. However, clinical manifestations associated with impaired frontal circulation are usually observed. Recent international criteria for vascular cognitive impairment presented by the VASCOG (International Society for Vascular Behavioral and Cognitive Disorders) working group emphasize the particular importance of impaired information processing speed, attention, and/or frontal regulatory functions, often in combination with personality or emotional disorders. The frequency of vascular depression in chronic cerebrovascular insufficiency reaches 70%. The addition of affective disorders significantly aggravates the existing cognitive deficit, increases the risk of dementia. This is due to the fact that depression itself leads to the development of cognitive impairment, causes multiple functional disorders of cerebral microcirculation and a number of other mechanisms. The presence of cerebral microangiopathy underlying this pathology makes the use of drugs with vascular effects in the treatment of these patients. The use of preparations with multimodal action, in particular the combined drug and, is most preferable.

Objective — to study the effect of leukoaraiosis (LA) severity on the functional recovery of patients with atherothrombotic ischemic stroke (IS) 90 days after the onset of the disease.Methods and subjects. We performed a cohort prospective study of 82 patients with acute atherothrombotic IS. 37 men and 45 women (mean age 71.1 ± 9.4 years) were examined. The inclusion criteria were the first IS, atherothrombotic variant (according to the TOAST criteria), hospitalization outside of the «therapeutic window». The degree of impairment of neurological functions was assessed by the NIHSS scale, the degree of functional impairment was estimated using the modified Rankin scale (mRS). The severity of the LA was evaluated based by Fazekas scale. For statistical analysis, patients were distributed into two groups according Fazekas score: 0 — 1 point (mild LA) and 2 — 3 points (severe LA).Results. A significant difference has been revealed in prevalence of the main cerebrovascular risk factors between the groups: patients with severe LA were older in age (p = 0.005), they were more likely to have arterial hypertension (p = 0.028), diabetes mellitus (p = 0.019) or coronary heart disease (p = 0.010). It was shown that in the group with mild LA, functional recovery was significantly better in 90 days after IS. It is evidenced that the severe LA is an independent determinant of the negative prognosis regarding functional recovery for 3 months after the atherothrombotic IS (p = 0.003; OR 3.1; 95 % CI 1.5 — 6.4).Conclusions. The study showed that severe degree of LA negatively affects the functional recovery of patients with atherothrombotic IS. It is an independent prognostic factor of an unfavorable functional outcome. Considering the high percentage of patients with poor functional recovery, the role of LA in recovery from IS requires further investigation., Цель — изучить влияние выраженности лейкоареоза на функциональное восстановление больных с атеротромботическим ишемическим инсультом через 90 дней после начала заболевания.Материалы и методы. Проведено когортное проспективное исследование 82 больных с острым атеротромботическим ишемическим инсультом (37 мужчин и 45 женщин в возрасте от 61 до 89 лет (средний возраст — (71,1 ± 9,4) года). Критериями включения были первый ишемический инсульт, атеротромботический вариант (по критериям TOAST), госпитализация за пределами «терапевтического окна». Степень нарушения неврологических функций оценивали по шкале NIHSS, степень функциональных нарушений — по модифицированной шкале Ренкина. Выраженность лейкоареоза определяли на основании визуальной оценки Fazekas. Для статистического анализа больных разделили на две группы: 0 — 1 балл (легкий лейкоареоз) и 2 — 3 балла (выраженный лейкоареоз).Результаты. Выявлена статистически значимая разница по распространенности основных цереброваскулярных факторов риска в группах: больные с выраженным лейкоареозом были старше по возрасту (р = 0,005), у них чаще имели место артериальная гипертензия (р = 0,028), сахарный диабет (р = 0,019) и ишемическая болезнь сердца (р = 0,010). Через 90 дней после ишемического инсульта в группе с легким лейкоареозом отмечено статистически значимо лучшее функциональное восстановление больных. Доказано, что выраженный лейкоареоз является независимым фактором, определяющим негативный прогноз относительно функционального восстановления в течение 3 мес после атеротромботического ишемического инсульта (p = 0,003; отношение шансов — 3,1, 95 % доверительный интервал — 1,5 — 6,4).Выводы. Выраженный лейкоареоз негативно влияет на функциональное восстановление больных с атеротромботическим ишемическим инсультом, будучи независимым прогностическим фактором неблагоприятного функционального исхода. Из‑за большой доли пациентов с плохим функциональным восстановлением влияние лейкоареоза на восстановление после ишемического инсульта требует дальнейшего изучения., Мета — вивчити вплив вираженості лейкоареозу на функціональне відновлення хворих з атеротромботичним ішемічним інсультом через 90 днів після початку захворювання.Матеріали і методи. Проведено когортне проспективне дослідження 82 хворих із гострим атеротромботичним ішемічним інсультом (37 чоловіків та 45 жінок віком від 61 до 89 років (середній вік — (71,1 ± 9,4) року). Критеріями залучення були перший ішемічний інсульт, атеротромботичний варіант (за критеріями TOAST), госпіталізація поза межами «терапевтичного вікна». Ступінь порушення неврологічних функцій оцінювали за шкалою NIHSS, ступінь функціональних порушень — за модифікованою шкалою Ренкіна. Вираженість лейкоареозу визначали на підставі візуальної оцінки за Fazekas. Для статистичного аналізу хворих поділили на дві групи: 0 — 1 бал (легкий лейкоареоз) та 2 — 3 бали (виражений лейкоареоз).Результати. Виявлено статистично значущу різницю за поширенням основних цереброваскулярних чинників ризику у групах: хворі з вираженим лейкоареозом були старшими за віком (р = 0,005), у них частіше мали місце артеріальна гіпертензія (р = 0,028), цукровий діабет (р = 0,019) та ішемічна хвороба серця (р = 0,010). Через 90 днів після ішемічного інсульту в групі з легким лейкоареозом відзначено статистично значущо краще функціональне відновлення хворих. Доведено, що виражений лейкоареоз є незалежним чинником, який визначає негативний прогноз щодо функціонального відновлення протягом 3 міс після атеротромботичного ішемічного інсульту (p = 0,003; відношення шансів — 3,1, 95 % довірчий інтервал — 1,5 — 6,4).Висновки. Виражений лейкоареоз негативно впливає на функціональне відновлення хворих з атеротромботичним ішемічним інсультом, будучи незалежним прогностичним чинником несприятливого функціонального виходу. Через велику частку пацієнтів з поганим функціональним відновленням вплив лейкоареозу на відновлення після ішемічного інсульту потребує подальшого вивчення.

A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.

BackgroundTo assess if leukoaraiosis severity is associated with outcome in patients with acute ischemic stroke (AIS) following endovascular thrombectomy, and to propose a leukoaraiosis-related modification to the ASPECTS score.MethodsA retrospective review was completed of AIS patients that underwent mechanical thrombectomy for anterior circulation large vessel occlusion. The primary outcome measure was 90-day mRS. A proposed Leukoaraiosis-ASPECTS (“L-ASPECTS”) was calculated by subtracting from the traditional ASPECT based on leukoaraiosis severity (1 point subtracted if mild, 2 if moderate, 3 if severe). L-ASEPCTS score performance was validated using a consecutive cohort of 75 AIS LVO patients.Results174 patients were included in this retrospective analysis: average age: 68.0±9.1. 28 (16.1%) had no leukoaraiosis, 66 (37.9%) had mild, 62 (35.6%) had moderate, and 18 (10.3%) had severe. Leukoaraiosis severity was associated with worse 90-day mRS among all patients (P=0.0005). Both L-ASPECTS and ASPECTS were associated with poor outcomes, but the area under the curve (AUC) was higher with L-ASPECTS (PConclusionsLeukoaraiosis severity on pre-mechanical thrombectomy NCCT is associated with worse 90-day outcome in patients with AIS following endovascular recanalization, and is an independent risk factor for worse outcomes. A proposed L-ASPECTS score had stronger association with outcome than the traditional ASPECTS score.

The clinical significance of FLAIR vascular hyperintensity (FVH), a marker of collateral circulation in ischaemic stroke, remains controversial. We hypothesised that the association between FVH and outcomes varies with the severity of leukoaraiosis (LA), another marker of collaterals, and that their combined significance may vary with time. We included 459 consecutive patients with middle cerebral artery (MCA) stroke. Proximal and distal FVHs were distinguished based on location. LA was divided into two grades, according to Fazekas scores of 0–2 and 3–6. Symptom-to-MRI time was divided into two categories: ≤ 14 days and ≥ 15 days. We found no difference in FVH proportion according to LA grade. Multivariate analysis revealed that LA and FVH status were independently associated with unfavourable outcomes (modified Rankin scale ≥ 2) in patients with symptom-to-MRI times ≤ 14 days (P = 0.008), but not in those with symptom-to-MRI times ≥15 days (P = 0.61). In the group with symptom-to-MRI times ≤14 days, patients with LA 3–6 and FVH(+) (OR, 3.044; 95% CI, 1.116–8.305) were more likely to have unfavourable clinical outcomes compared with patients with LA 0–2 and FVH(+) but not compared with those with LA 0–2 and FVH(−) or LA 3–6 and FVH(−). In addition, FVH location did not influence the relationship between FVH and outcomes. The association between FVH and outcomes was influenced by the degree of LA in the acute but not in the subacute and chronic stages of MCA infarction. FVH predicts clinical outcomes independently only in those with more extensive LA.

Background and Purpose Left ventricular hypertrophy (LVH) is associated with the risk of stroke and dementia independently of other vascular risk factors, but its association with cerebral small vessel disease (CSVD) remains unknown. Here, we employed a systematic review and meta-analysis to address this gap.Methods Following the MOOSE guidelines (PROSPERO protocol: CRD42018110305), we systematically searched the literature for studies exploring the association between LVH or left ventricular (LV) mass, with neuroimaging markers of CSVD (lacunes, white matter hyperintensities [WMHs], cerebral microbleeds [CMBs]). We evaluated risk of bias and pooled association estimates with random-effects meta-analyses.Results We identified 31 studies (n=25,562) meeting our eligibility criteria. In meta-analysis, LVH was associated with lacunes and extensive WMHs in studies of the general population (odds ratio [OR]lacunes, 1.49; 95% confidence interval [CI], 1.12 to 2.00) (ORWMH, 1.73; 95% CI, 1.38 to 2.17) and studies in highrisk populations (ORlacunes: 2.39; 95% CI, 1.32 to 4.32) (ORWMH, 2.01; 95% CI, 1.45 to 2.80). The results remained stable in general population studies adjusting for hypertension and other vascular risk factors, as well as in sub-analyses by LVH assessment method (echocardiography/electrocardiogram), study design (cross-sectional/cohort), and study quality. Across LV morphology patterns, we found gradually increasing ORs for concentric remodelling, eccentric hypertrophy, and concentric hypertrophy, as compared to normal LV geometry. LVH was further associated with CMBs in high-risk population studies.Conclusions LVH is associated with neuroimaging markers of CSVD independently of hypertension and other vascular risk factors. Our findings suggest LVH as a novel risk factor for CSVD and highlight the link between subclinical heart and brain damage.

Backgroud As the elderly stroke population continues to increase, we will have to confront greater challenges regarding how to choose suitable patients to reduce thrombolysis-related bleeding events and accurately judge their prognosis. Therefore, we evaluated the relationship among leukoaraiosis (LA), haemorrhagic transformation (HT) and the prognosis at 3 months after intravenous (IV) thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction (ACI). Methods We prospectively and consecutively chose 125 elderly patients aged ≥ 60 years with ACI who could accept and be suitable for IV recombinant tissue plasminogen activator (rtPA) after excluding 6 cases. Brain computed tomography(CT) was used to assess LA by using the modified Van Swieten scale (mVSS) before treatment and the modified Rankin scale (mRS) to appraise prognosis at 3 months after IV rtPA. Binary logistic regression was used to analyse the predictors of HT and the prognosis of ACI. Results Our data indicated that by brain CT, 26.4% of all patients showed severe LA, and the rate of HT and symptomatic intracranial haemorrhage (sICH) were 12.0% and 9.6%, respectively. Severe LA was evidently associated with HT (odds ratio [OR] 3.272, 95% confidence interval [CI] 1.010–10.598, P = 0.048) rather sICH (P > 0.05). Moreover, we also found that severe LA was associated with poor functional prognosis (OR 5.266, 95% CI 1.592–17.419, P = 0.006). Conclusion Our results showed that LA was associated with HT and adverse clinical prognosis rather sICH after IV rtPA in elderly patients aged ≥60 years with ACI. Although LA may increase the risk of bleeding but not fatal haemorrhage after IV thrombolysis, therefore, we should actively select an appropriate elderly population for thrombolytic treatment and have reasonable judgments on the outcomes.

Cerebral small vessel disease (SVD) is a common accompaniment to aging. Magnetic resonance imaging (MRI) features of SVD include lacunar infarcts (LI) and white matter hyperintensity (WMH). Brain iron deposition is also a known marker of SVD that is associated with cognitive impairment and can be detected with susceptibility-weighted imaging (SWI) MRI technique. According to recent studies, the pulsation of cerebral blood flow can be one of the main factors of the development of pathological brain changes in elderly patients. The objective of this study was to investigate the relationship between the brain iron deposition, cerebral blood flow pulsation, and cognitive impairment in patients with SVD. For the study, 97 patients with diagnosed SVD were selected. The patients were divided into two groups based on the Montreal Cognitive Assessment (MoCA) test scores. All patients underwent MRI in the SWI sequence. Pulsatility index (PI) and resistivity index (RI) were recorded from the middle cerebral artery bilaterally using transcranial Doppler (TCD). The linear regression model showed that the pulsatility index (PI) and resistivity index (RI) were associated with cognitive impairment and brain iron deposition in basal ganglia. The most significant association was found between left globus pallidus severe hypointensity voxels count and left middle cerebral artery (MCA) RI (p = 0.009). The results of the study provide information that TCD indicators may be associated with brain iron deposition and cognitive decline in patients with SVD. Our findings suggest that both brain iron deposition and cerebral hemodynamics abnormalities may play an important role in the pathophysiological mechanisms of SVD.

Purpose Severity of white matter lesion (WML) is typically evaluated on magnetic resonance images (MRI), yet the more accessible, faster, and less expensive method is computed tomography (CT). Our objective was to study whether WML can be automatically segmented from CT images using a convolutional neural network (CNN). The second aim was to compare CT segmentation with MRI segmentation. Methods The brain images from the Helsinki University Hospital clinical image archive were systematically screened to make CT-MRI image pairs. Selection criteria for the study were that both CT and MRI images were acquired within 6 weeks. In total, 147 image pairs were included. We used CNN to segment WML from CT images. Training and testing of CNN for CT was performed using 10-fold cross-validation, and the segmentation results were compared with the corresponding segmentations from MRI. Results A Pearson correlation of 0.94 was obtained between the automatic WML volumes of MRI and CT segmentations. The average Dice similarity index validating the overlap between CT and FLAIR segmentations was 0.68 for the Fazekas 3 group. Conclusion CNN-based segmentation of CT images may provide a means to evaluate the severity of WML and establish a link between CT WML patterns and the current standard MRI-based visual rating scale.

A study of 104 patients with a transient ischemic attacks (TIA) in the form of visual disorders was conducted to assess the factors that affect the development and probable localization of TIA. Neurological and ophthalmological status, structural characteristics of the brain and major arteries of the head (MAH) with the use of magnetic resonance therapy (MRT) and ultrasonic dopplerography were assessed. The age of patients ranged from 33 to 79years (65.4 years in average). The control group consisted of 46patients with an average age of 67.8years without cerebral ischemic events and visual disorders. During the MRI, the presence of microstructural pathology of the brain was assessed; “leukoaraiosis” was considered; foci up to 2-3 mm that are vascular by genesis. Significant differences in the frequency of TIA occurrence in terms of gender were not detected in all age subgroups. In young patients with TIA, arterial hypertension was associated with signs of microstructural pathology (MSP) of the brain in 85.58% cases. TIA localization did not correlate with the grade of structural disorders of the MAH and the nature of retinopathy in all age groups. Frequency of TIA tended to increase (in the a.ophthalmica pool) with an increase in the grade of stenosis of the MAH and retinopathy. The control group had retinopathy of the 1ststage in 12 or 26.09%, showing a qualitative difference with the group of study. The study did not reveal any differences in the frequency of TIA (according to presentations to a medical institution) in patients of different age groups, which indicates the influence of others factors that are not related to aging, such as TIA factors. The state of the MAH and microcirculation of vessels are their markers and probable causative factors. Determination of markers for the prognosis of the deve­lopment of cortical TIA or TIA in a.ophthalmica pools are still an open issue, as well as the chances of the TIA development in other areas of cerebral blood supply. Thus, according to clinical and anamnestic data, transient ischemia in the patients, who have applied to medical institutions with complaints of transient vision disorder (impairment) and who have been diagnosed with TIA is detected mainly in the a.ophthalmica blood supply pool (89 or 85.58%), more rarely (in 15 or 14.42%) in the cortical areas of visual analyzer without gender and age differences. All age groups had TIA associated with MAH structure impairment, retinopathy, MSP of the brain (in 82% of men and 67% of women), this leads to the interpretation of such TIA as non-random events preceded by systemic disorders, which are the basis for the prediction and prevention of such conditions.

Characterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty‐five adults aged 55 to 85 were recruited and divided into three groups: control (apnea‐hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract‐Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free‐water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p

Background: Previous studies have reported changes in white matter (WM) microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on WM tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients (HKIIPs) who were treated with Jiao-Tai-Wan (JTW) or a placebo to assess the changes in WM tracts.Methods: Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity (MD) and fractional anisotropy (FA) of WM between 75 HKIIPs and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of MD and FA were also performed in 24 HKIIPs (8 males; 16 females; 42.5 ± 10.4 years) with JTW and 26 HKIIPs (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates.Results: HKIIPs showed lower MD and FA values of several WM tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. Specifically, FA values in left corticospinal tract (CST) were increased in HKIIPs. After being treated with JTW, HKIIPs showed a trend towards reduced FA values in the left CST.Conclusions: These results suggest that JTW may reverse WM alterations caused by heart-kidney imbalance insomnia.Trial registration: Chinese Clinical Trial Registry, ChiCTR1800019239; registered on 1 November 2018-retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx, more than a month after the start of the experiment. The delay was due to lack of experience regarding trail, registration with a data sharing website.