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Many lipid biomarkers of stroke have been identified, but the lipid metabolism in elderly patients with leukoaraiosis remains poorly understood. This study aims to explore lipid metabolic processes in stroke among leukoaraiosis patients, which could provide valuable insights for guiding future antithrombotic therapy. In a cohort of 215 individuals undergoing MRI, 13 stroke patients were matched with controls, and 48 stroke patients with leukoaraiosis were matched with 40 leukoaraiosis patients. Serum lipidomics was profiled using UPLC-TOF, and OPLS-DA was applied for metabolite identification. Partial Least Squares Path Model (PLS-PM) assessed pathway weights of novel metabolites in stroke risk, while linear regression explored correlations with clinical outcomes. Lipid profiling identified 168 distinct compounds. From these, 25 lipid molecules were associated with glycerolipid, glycerophospholipid, and sphingolipid metabolism. PLS-PM identified 12 key metabolites, including DG 36:4 (OR = 6.40) as a significant risk factor. Metabolites such as PE 38:5 and FA 16:1;O showed significant correlations with stroke in leukoaraiosis, particularly when the Fazekas score was ≥ 4. Twelve metabolites were identified as key factors in stroke incidence among leukoaraiosis patients. Lipid disturbances in glycerolipids and glycerophospholipids provide valuable insights for further studies on the progression from leukoaraiosis to stroke. [ABSTRACT FROM AUTHOR]

Purpose: Familial cerebral cavernous malformation syndrome (FCCM) is characterized by multiple hemorrhagic lesions and is sometimes mistaken for cerebral amyloid angiopathy (CAA). Methods: We compared clinical and radiologic characteristics in patients with definite (N = 32) and presumed FCCM (n = 76) to patients with definite (N = 29) and probable CAA (N = 21). Results: Patients with CAA were older (78.6 years CAA vs. 43.4 FCCM; p < 0.0001), had cognitive complaints (66.0% CAA vs. 8.3% FCCM; p < 0.0001), and less likely to have a family history (4.0% CAA vs. 50.9% FCCM; p < 0.0001). FCCM patients were more likely to have at least 1 Zabramski type 2 lesion (0 CAA vs. 79.6% FCCM; p < 0.0001). Presence of any subcortical white matter hemorrhagic lesion (23.0% CAA vs. 99.1% FCCM; p < 0.0001), a lesion in either the basal ganglia, internal capsule or cerebellum (28.0% CAA vs 79.6% FCCM; p < 0.0001) and a subcortical white matter to cortical ribbon distribution of hemorrhagic lesions ≥ 1.0 was predictive of FCCM (6.0% CAA vs 83.9% FCCM; p < 0.0001). CAA patients more commonly had white matter disease, sulcal subarachnoid hemorrhage, and severely enlarged perivascular spaces in the centrum. However, none of the latter features were unique to CAA. FCCM patients meeting Boston 2.0 criteria for CAA (n = 14) had additional factors that helped distinguish them from CAA. Conclusions: Patients with FCCM can be reliably distinguished from CAA by accurately applying the Boston 2.0 criteria, assessing hemorrhagic lesion distribution and types, and assessing for clinical features unique to FCCM. FCCM criteria are proposed. The frequent finding of leukoaraiosis and enlarged perivascular spaces in the centrum semiovale in FCCM patients deserves further investigation. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, affect a wide range of cognitive dysfunctions, including spatial neglect. The latter is a disorder of spatial attention and exploration typically after right hemisphere brain damage. To explore the impact of WMH on neglect‐related structural disconnections, the present study investigated the indirectly quantified structural disconnectome induced by either stroke lesion alone, WMH alone, or their combination. Furthermore, we compared different measures of structural disconnection—voxel‐wise, pairwise, tract‐wise, and parcel‐wise—to identify neural correlates and predict acute neglect severity. We observed that WMH‐derived disconnections alone were not associated with neglect behavior. However, when combined with disconnections derived from individual stroke lesions, pre‐stroke WMH contributed to post‐stroke neglect severity by affecting right frontal and subcortical substrates, like the middle frontal gyrus, basal ganglia, thalamus, and the fronto‐pontine tract. Predictive modeling demonstrated that voxel‐wise disconnection data outperformed other measures of structural disconnection, explaining 42% of the total variance; interestingly, the best model used predictors of stroke‐based disconnections only. We conclude that prestroke alterations in the white matter microstructure due to WMH contribute to poststroke deficits in spatial attention, likely by impairing the integrity of human attention networks. [ABSTRACT FROM AUTHOR]

Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood–brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (cSVD) refers to the age-dependent pathological processes involving the brain small vessels and leading to vascular cognitive impairment, intracerebral hemorrhage, and acute lacunar ischemic stroke. Despite the significant public health burden of cSVD, disease-specific therapeutics remain unavailable due to the incomplete understanding of the underlying pathophysiological mechanisms. Recent advances in neuroimaging acquisition and processing capabilities as well as findings from cSVD animal models have revealed critical roles of several age-dependent processes in cSVD pathogenesis including arterial stiffness, vascular oxidative stress, low-grade systemic inflammation, gut dysbiosis, and increased salt intake. These factors interact to cause a state of endothelial cell dysfunction impairing cerebral blood flow regulation and breaking the blood brain barrier. Neuroinflammation follows resulting in neuronal injury and cSVD clinical manifestations. Impairment of the cerebral waste clearance through the glymphatic system is another potential process that has been recently highlighted contributing to the cognitive decline. This review details these mechanisms and attempts to explain their complex interactions. In addition, the relevant knowledge gaps in cSVD mechanistic understanding are identified and a systematic approach to future translational and early phase clinical research is proposed in order to reveal new cSVD mechanisms and develop disease-specific therapeutics. [ABSTRACT FROM AUTHOR]

Introduction: Leukoaraiosis (LA) is a common neuroradiological finding in patients suffering from stroke. Cerebral small-vessel disease (SVD) is one of the primary causes of both ischemic stroke and hemorrhagic stroke (intracerebral hemorrhage, ICH) and the development of LA. Significant evidence that LA predicts the risk of functional dependency and mortality exists. However, studies examining the difference in LA severity between ischemic stroke and hemorrhagic stroke are lacking. We therefore aimed to compare the severity and abundance of LA in the two stroke subgroups. Methods: All patients admitted to the Department of Neurology, Haukeland University Hospital, with an ischemic stroke and intracerebral hemorrhagic (ICH) stroke diagnosed between 2006 and 2020 were included in the study. We collected patient data on risk factors and clinical and radiological findings and outcomes from our local stroke registry. The presence and severity of LA were assessed using the Fazekas score based on CT imaging. We evaluated the outcome using the modified Rankin Score (mRS) 7 days post-stroke. Results: A total of 5,084 patients were included in our analyses: 4437 (87%) with ischemic stroke and 647 (13%) with ICH. LA was present in 2476 (45%) patients. In our ordinal logistic regression model, adjusting for age, sex, known hypertension, known diabetes mellitus, and smoking, LA was more severe and more abundant in ICH patients compared to ischemic stroke patients (Fazekas score: 1, OR: 1.54; Fazekas score: 2, OR: 1.88; and Fazekas score: 3, OR 2.13; p < 0.001). Increasing severity of LA was associated with worse functional outcomes in both groups (ischemic stroke, OR: 1.49; p < 0.001 and ICH, OR: 1.36; p < 0.025). Conclusion: In this study, LA was more severe and abundant in patients with ICH. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the established relationship between WMH burden and age. We found that TrUE-Net was highly reliable at identifying WMH regions with low false positive rates, when compared to semi-manual segmentation as the reference standard. TrUE-Net performed similarly or favorably when compared to the other automated techniques. Moreover, TrUE-Net was able to detect relationships between WMH and age to a similar degree as the reference standard semi-manual segmentation at both the global and regional level. These results support the use of TrUE-Net for identifying WMH at the global or regional level, including in large, combined datasets.

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). This review paper delves into the hypothesis that atherosclerosis, a prevalent age-related large vessel disease, extends its pathological influence into the cerebral microcirculation, thereby contributing to the development and progression of CSVD, with a specific focus on CMHs. We explore the concept of vascular aging as a continuum, bridging macrovascular pathologies like atherosclerosis with microvascular abnormalities characteristic of CSVD. We posit that the same risk factors precipitating accelerated aging in large vessels (i.e., atherogenesis), primarily through oxidative stress and inflammatory pathways, similarly instigate accelerated microvascular aging. Accelerated microvascular aging leads to increased microvascular fragility, which in turn predisposes to the formation of CMHs. The presence of hypertension and amyloid pathology further intensifies this process. We comprehensively overview the current body of evidence supporting this interconnected vascular hypothesis. Our review includes an examination of epidemiological data, which provides insights into the prevalence and impact of CMHs in the context of atherosclerosis and CSVD. Furthermore, we explore the shared mechanisms between large vessel aging, atherogenesis, microvascular aging, and CSVD, particularly focusing on how these intertwined processes contribute to the genesis of CMHs. By highlighting the role of vascular aging in the pathophysiology of CMHs, this review seeks to enhance the understanding of CSVD and its links to systemic vascular disorders. Our aim is to provide insights that could inform future therapeutic approaches and research directions in the realm of neurovascular health. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular diseases of the brain are usually defined by transient ischemic attacks and strokes. However, they can also cause brain injuries without neurological events. Silent brain infarcts (SBI) and leukoaraiosis are symptoms of both vascular and neurological abnormalities. This study aims to investigate the association between SBI, leukoaraiosis, and middle-aged patients with ischemic stroke. Methods: A single-center retrospective study of 50 middle-aged, ischemic stroke patients were studied from November 2022 and May 2023. The patients were divided into two groups based on the presence or absence of leukoaraiosis. History taking, physical examination, brain CT scan, and MRI were all part of the diagnostic process. Metabolic syndrome (MetS) was also assessed through various factors. The statistical analysis included descriptive statistics, logistic regression analysis, and chi-square test. Results: Out of the cohort comprising 50 patients, characterized by a mean age of 52.26 years (SD 5.29), 32 were male, constituting 64% of the sample. Among these patients, 26 individuals exhibited leukoaraiosis, with 17 of them (65.4%) also presenting with SBI. Moreover, within this cohort, 22 patients were diagnosed with MetS, representing 84.6% of those affected. The Multivariate logistic regression analysis showed a strong and independent association between leukoaraiosis and SBI. Individuals with leukoaraiosis were nearly five times more likely to have SBI compared to those without leukoaraiosis. Conclusion: The study highlights leukoaraiosis as a significant risk factor for SBI, alongside MetS. Advanced imaging techniques have facilitated their detection, revealing a higher prevalence among stroke patients, particularly associated with age and hypertension. Further research is needed to fully understand their complex relationship and develop better management strategies for cerebrovascular diseases, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Leukoaraiosis (LA) appears as white matter hyperintensities on T2-weighted brain magnetic resonance imaging scans. Age and hypertension are considered the primary risk factors for LA, but its pathogenesis remains uncertain. This study aims to investigate the correlation between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and LA. A total of 140 patients with LA and 136 neuroimaging alteration-free controls were recruited in a case–control study. ACE I/D polymorphism was determined using the polymerase chain reaction method. The allele and genotype distributions of the ACE I/D polymorphism were significantly different between subjects with and without LA. Significant difference was observed in the genotypic distribution between LA patients and controls for recessive and additive models. A statistically significant association remained apparent after adjusting for potential risk factors (D/D vs. I/D + I/I: adjusted OR 3.251, 95% CI 1.185–8.918; D/D vs. I/I: adjusted OR 3.277, 95% CI 1.187–9.047). Our results indicate that the D/D genotype and D allele are important risk factors for LA. Future studies with larger populations are needed to validate our results. [ABSTRACT FROM AUTHOR]

Background: Intravenous thrombolysis (IVT) before endovascular treatment (EVT) for acute ischemic stroke might induce intracerebral hemorrhages which could negatively affect patient outcomes. Measuring white matter lesions size using deep learning (DL-WML) might help safely guide IVT administration. We aimed to develop, validate, and evaluate a DL-WML volume on CT compared to the Fazekas scale (WML-Faz) as a risk factor and IVT effect modifier in patients receiving EVT directly after IVT. Methods: We developed a deep-learning model for WML segmentation on CT and validated with internal and external test sets. In a post hoc analysis of the MR CLEAN No-IV trial, we associated DL-WML volume and WML-Faz with symptomatic-intracerebral hemorrhage (sICH) and 90-day functional outcome according to the modified Rankin Scale (mRS). We used multiplicative interaction terms between WML measures and IVT administration to evaluate IVT treatment effect modification. Regression models were used to report unadjusted and adjusted common odds ratios (cOR/acOR). Results: In total, 516 patients from the MR CLEAN No-IV trial (male/female, 291/225; age median, 71 [IQR, 62–79]) were analyzed. Both DL-WML volume and WML-Faz are associated with sICH (DL-WML volume acOR, 1.78 [95%CI, 1.17; 2.70]; WML-Faz acOR, 1.53 95%CI [1.02; 2.31]) and mRS (DL-WML volume acOR, 0.70 [95%CI, 0.55; 0.87], WML-Faz acOR, 0.73 [95%CI 0.60; 0.88]). Only in the unadjusted IVT effect modification analysis WML-Faz was associated with more sICH if IVT was given (p = 0.046). Neither WML measure was associated with worse mRS if IVT was given. Conclusion: DL-WML volume and WML-Faz had a similar relationship with functional outcome and sICH. Although more sICH might occur in patients with more severe WML-Faz receiving IVT, no worse functional outcome was observed. Clinical relevance statement: White matter lesion severity on baseline CT in acute ischemic stroke patients has a similar predictive value if measured with deep learning or the Fazekas scale. Safe administration of intravenous thrombolysis using white matter lesion severity should be further studied. Key Points: White matter damage is a predisposing risk factor for intracranial hemorrhage in patients with acute ischemic stroke but remains difficult to measure on CT. White matter lesion volume on CT measured with deep learning had a similar association with symptomatic intracerebral hemorrhages and worse functional outcome as the Fazekas scale. A patient-level meta-analysis is required to study the benefit of white matter lesion severity-based selection for intravenous thrombolysis before endovascular treatment. [ABSTRACT FROM AUTHOR]

Commonly plaguing in the frigid zone of the world, vitamin D deficiency, as indicated by low levels of 25-hydroxyvitamin D, exacerbated inflammatory responses and impaired endothelial function. Leukoaraiosis (LA) is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses. This study aimed to investigate the impact of vitamin D on the severity of LA.

Abstract Purpose This study aimed to investigate the feasibility of using computed tomography (CT) attenuation values to differentiate hypodense brain lesions, specifically acute ischemic stroke (AIS) from asymmetric leukoaraiosis (LA) and old cerebral infarction (OCI). Materials and methods This retrospective study included patients with indeterminate hypodense lesions identified via brain CT scans conducted between June 2019 and June 2021. All lesions were confirmed through head MRI/diffusion-weighted imaging within 48 h after CT. CT attenuation values of hypodense lesions and symmetrical control regions were measured. Additionally, CT attenuation value difference (ΔHU) and ratio (RatioHU) were calculated. One-way analysis of variance (ANOVA) was used to compare age and CT parameters (CT attenuation values, ΔHU and RatioHU) across the groups. Finally, receiver operating characteristic (ROC) analysis was performed to determine the cutoff values for distinguishing hypodense lesions. Results A total of 167 lesions from 146 patients were examined. The CT attenuation values for AIS(n = 39), LA(n = 53), and OCI(n = 75) were 18.90 ± 6.40 HU, 17.53 ± 4.67 HU, and 11.90 ± 5.92 HU, respectively. The time interval between symptom onset and CT scans for AIS group was 32.21 ± 26.85 h. ANOVA revealed significant differences among the CT parameters of the hypodense lesion groups (all P

Leukoaraiosis (LA) manifests as cerebral white matter hyperintensities on T2-weighted magnetic resonance imaging scans and corresponds to white matter lesions or abnormalities in brain tissue. Clinically, it is generally detected in the early 40s and is highly prevalent globally in individuals aged >60 years. From the imaging perspective, LA can present as several heterogeneous forms, including punctate and patchy lesions in deep or subcortical white matter; lesions with periventricular caps, a pencil-thin lining, and smooth halo; as well as irregular lesions, which are not always benign. Given its potential of having deleterious effects on normal brain function and the resulting increase in public health burden, considerable effort has been focused on investigating the associations between various risk factors and LA risk, and developing its associated clinical interventions. However, study results have been inconsistent, most likely due to potential differences in study designs, neuroimaging methods, and sample sizes as well as the inherent neuroimaging heterogeneity and multi-factorial nature of LA. In this article, we provided an overview of LA and summarized the current knowledge regarding its epidemiology, neuroimaging classification, pathological characteristics, risk factors, and potential intervention strategies.

Purpose: This study aimed to investigate the feasibility of using computed tomography (CT) attenuation values to differentiate hypodense brain lesions, specifically acute ischemic stroke (AIS) from asymmetric leukoaraiosis (LA) and old cerebral infarction (OCI). Materials and methods: This retrospective study included patients with indeterminate hypodense lesions identified via brain CT scans conducted between June 2019 and June 2021. All lesions were confirmed through head MRI/diffusion-weighted imaging within 48 h after CT. CT attenuation values of hypodense lesions and symmetrical control regions were measured. Additionally, CT attenuation value difference (ΔHU) and ratio (RatioHU) were calculated. One-way analysis of variance (ANOVA) was used to compare age and CT parameters (CT attenuation values, ΔHU and RatioHU) across the groups. Finally, receiver operating characteristic (ROC) analysis was performed to determine the cutoff values for distinguishing hypodense lesions. Results: A total of 167 lesions from 146 patients were examined. The CT attenuation values for AIS(n = 39), LA(n = 53), and OCI(n = 75) were 18.90 ± 6.40 HU, 17.53 ± 4.67 HU, and 11.90 ± 5.92 HU, respectively. The time interval between symptom onset and CT scans for AIS group was 32.21 ± 26.85 h. ANOVA revealed significant differences among the CT parameters of the hypodense lesion groups (all P < 0.001). The AUC of CT values, ΔHU, and RatioHU for distinguishing AIS from OCI were 0.802, 0.896 and 0.878, respectively (all P < 0.001). Meanwhile, the AUC for distinguishing OCI from LA was 0.789, 0.883, and 0.857, respectively (all P < 0.001). Nevertheless, none of the parameters could distinguish AIS from LA. Conclusion: CT attenuation parameters can be utilized to differentiate between AIS and OCI or OCI and LA in indeterminate hypodense lesions on CT images. However, distinguishing AIS from LA remains challenging. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case–control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aβ1–40, Aβ1–42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ1–40 and Aβ1–42 were significantly lower in patients with deep LS (p < 0.0001). Aβ1–42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). Conclusion: The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored. [ABSTRACT FROM AUTHOR]

IntroductionLeukoaraiosis (LA) is a common neuroradiological finding in patients suffering from stroke. Cerebral small-vessel disease (SVD) is one of the primary causes of both ischemic stroke and hemorrhagic stroke (intracerebral hemorrhage, ICH) and the development of LA. Significant evidence that LA predicts the risk of functional dependency and mortality exists. However, studies examining the difference in LA severity between ischemic stroke and hemorrhagic stroke are lacking. We therefore aimed to compare the severity and abundance of LA in the two stroke subgroups.MethodsAll patients admitted to the Department of Neurology, Haukeland University Hospital, with an ischemic stroke and intracerebral hemorrhagic (ICH) stroke diagnosed between 2006 and 2020 were included in the study. We collected patient data on risk factors and clinical and radiological findings and outcomes from our local stroke registry. The presence and severity of LA were assessed using the Fazekas score based on CT imaging. We evaluated the outcome using the modified Rankin Score (mRS) 7 days post-stroke.ResultsA total of 5,084 patients were included in our analyses: 4437 (87%) with ischemic stroke and 647 (13%) with ICH. LA was present in 2476 (45%) patients. In our ordinal logistic regression model, adjusting for age, sex, known hypertension, known diabetes mellitus, and smoking, LA was more severe and more abundant in ICH patients compared to ischemic stroke patients (Fazekas score: 1, OR: 1.54; Fazekas score: 2, OR: 1.88; and Fazekas score: 3, OR 2.13; p

BackgroundCerebrovascular diseases of the brain are usually defined by transient ischemic attacks and strokes. However, they can also cause brain injuries without neurological events. Silent brain infarcts (SBI) and leukoaraiosis are symptoms of both vascular and neurological abnormalities. This study aims to investigate the association between SBI, leukoaraiosis, and middle-aged patients with ischemic stroke.MethodsA single-center retrospective study of 50 middle-aged, ischemic stroke patients were studied from November 2022 and May 2023. The patients were divided into two groups based on the presence or absence of leukoaraiosis. History taking, physical examination, brain CT scan, and MRI were all part of the diagnostic process. Metabolic syndrome (MetS) was also assessed through various factors. The statistical analysis included descriptive statistics, logistic regression analysis, and chi-square test.ResultsOut of the cohort comprising 50 patients, characterized by a mean age of 52.26 years (SD 5.29), 32 were male, constituting 64% of the sample. Among these patients, 26 individuals exhibited leukoaraiosis, with 17 of them (65.4%) also presenting with SBI. Moreover, within this cohort, 22 patients were diagnosed with MetS, representing 84.6% of those affected. The Multivariate logistic regression analysis showed a strong and independent association between leukoaraiosis and SBI. Individuals with leukoaraiosis were nearly five times more likely to have SBI compared to those without leukoaraiosis.ConclusionThe study highlights leukoaraiosis as a significant risk factor for SBI, alongside MetS. Advanced imaging techniques have facilitated their detection, revealing a higher prevalence among stroke patients, particularly associated with age and hypertension. Further research is needed to fully understand their complex relationship and develop better management strategies for cerebrovascular diseases, ultimately improving patient outcomes.

After a stroke, individuals with aphasia often recover to a certain extent over time. This recovery process may be dependent on the health of surviving brain regions. Leukoaraiosis (white matter hyperintensities on MRI reflecting cerebral small vessel disease) is one indication of compromised brain health and is associated with cognitive and motor impairment. Previous studies have suggested that leukoaraiosis may be a clinically relevant predictor of aphasia outcomes and recovery, although findings have been inconsistent. We investigated the relationship between leukoaraiosis and aphasia in the first year after stroke. We recruited 267 patients with acute left hemispheric stroke and coincident fluid attenuated inversion recovery MRI. Patients were evaluated for aphasia within 5 days of stroke, and 174 patients presented with aphasia acutely. Of these, 84 patients were evaluated at ∼3 months post-stroke or later to assess longer-term speech and language outcomes. Multivariable regression models were fit to the data to identify any relationships between leukoaraiosis and initial aphasia severity, extent of recovery, or longer-term aphasia severity. We found that leukoaraiosis was present to varying degrees in 90% of patients. However, leukoaraiosis did not predict initial aphasia severity, aphasia recovery, or longer-term aphasia severity. The lack of any relationship between leukoaraiosis severity and aphasia recovery may reflect the anatomical distribution of cerebral small vessel disease, which is largely medial to the white matter pathways that are critical for speech and language function.

Cerebral white matter hyperintensities are an important contributor to ageing brain pathology. Progression in white matter hyperintensity volume is associated with cognitive decline and gait impairment. Understanding the factors associated with white matter hyperintensity progression provides insight into pathogenesis and may identify novel treatment targets to improve cognitive health. We postulated that the immune system interaction with cerebral vessels and tissue may be associated with disease progression, and thus evaluated the relationship of blood leucocyte gene expression to progression of cerebral white matter hyperintensities. A brain MRI was obtained at baseline in 166 patients assessed for a cognitive complaint, and then repeated at regular intervals over a median of 5.9 years (interquartile range 3.5-8.2 years). White matter hyperintensity volumes were measured by semi-automated segmentation and percentage change in white matter hyperintensity per year calculated. A venous blood sample obtained at baseline was used to measure whole-genome expression by RNA sequencing. The relationship between change in white matter hyperintensity volumes over time and baseline leucocyte gene expression was analysed. The mean age was 77.8 (SD 7.5) years and 60.2% of participants were female. The median white matter hyperintensity volume was 13.4 ml (SD 17.4 ml). The mean change in white matter hyperintensity volume was 12% per year. Patients were divided in quartiles by percentage change in white matter hyperintensity volume, which was: -3.5% per year in quartile 1, 7.4% per year in quartile 2, 11.7% in quartile 3 and 33.6% per year in quartile 4. There were 148 genes associated with changing white matter hyperintensity volumes over time (P  |0.2|). Genes and pathways identified have roles in endothelial dysfunction, extracellular matrix remodelling, altered remyelination, inflammation and response to ischaemia. ADAM8, CFD, EPHB4, FPR2, Wnt-B-catenin, focal adhesion kinase and SIGLEC1 were among the identified genes. The progression of white matter hyperintensity volumes over time is associated with genes involved in endothelial dysfunction, extracellular matrix remodelling, altered remyelination, inflammation and response to ischaemia. Further studies are needed to evaluate the role of peripheral inflammation in relation to rate of white matter hyperintensity progression and the contribution to cognitive decline.

Objective: To explore the relationship between the levels of serum uric acid (UA), cystatin C (CysC) and lipoprotein-associated phospholipase A2 (Lp-PLA2) and prognosis of patients with acute cerebral infarction complicated with leukoaraiosis. Methods: 113 patients with acute cerebral infarction complicated with leukoaraiosis admitted to the 960 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from March 2020 to December 2022 were selected, the levels of serum UA, CysC and Lp-PLA2 were detected. Followed up for 1 month, the patients were divided into good prognosis group (0 ~ 2 scores, 75 cases) and poor prognosis group (3 scores and above, 38 cases) according to the modified Rankin Scale (mRS) score. Multivariate Logistic regression was used to analyze the risk factors of poor prognosis in patients with acute cerebral infarction complicated with leukoaraiosis, and receiver operating characteristic curve (ROC) was used to analyze the value of serum UA, CysC and Lp-PLA2 in predicting poor prognosis in patients with acute cerebral infarction complicated with leukoaraiosis. Results: The levels of serum UA, CysC, and Lp-PLA2 in the poor prognosis group were higher than those in the good prognosis group (P<0.05). Multivariate Logistic regression analysis showed that severe white matter lesions, high NIHSS score at admission, and high levels of serum UA, CysC, and Lp-PLA2 were risk factors for poor prognosis in patients with acute cerebral infarction complicated with leukoaraiosis (P<0.05). The area under the curve (AUC) of combined serum UA, CysC, and Lp-PLA2 to predict the prognosis of patients with acute cerebral infarction complicated with leukoaraiosis was 0.916, which was higher than the individual prediction. Conclusion: The elevated levels of serum UA, CysC, and Lp-PLA2 in patients with acute cerebral infarction complicated with leukoaraiosis were associated with poor prognosis, the combination of serum UA, CysC, and Lp-PLA2 had a higher predictive value for poor prognosis in patients with acute cerebral infarction complicated with leukoaraiosis. [ABSTRACT FROM AUTHOR]

Background and purposeAcute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion.Materials and methodsAmong prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis.ResultsGood collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0-2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49-47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02-0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82-0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good collateral status.ConclusionsAmong patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

IntroductionAmong vascular risk factors we hypothesized that an increased prevalence of diabetes in Hispanics would be associated with greater white matter hyperintensity (WMH) volume, which may contribute to cognitive decline.MethodsA total of 1318 participants (60% female; 49% Hispanic, 51% non-Hispanic White; age 66.2 ± 8.9 years) underwent clinical evaluation and brain magnetic resonance imaging (MRI). WMH volume associations were assessed with age, sex, and ethnicity and then with vascular risk factors in a selective regression model.ResultsWMH volume was greater with older age (P

Stroke is the leading cause of functional disability worldwide, with increasing prevalence in adults. Given the considerable negative impact on patients’ quality of life and the financial burden on their families and society, it is essential to provide stroke survivors with a timely and reliable prognosis of stroke recurrence. Leukoaraiosis (LA) is a common neuroimaging feature of cerebral small-vessel disease. By researching the literature of two different databases (MEDLINE and Scopus), the present study aims to review all relevant studies from the last decade, dealing with the clinical utility of pre-existing LA as a prognostic factor for stroke recurrence in stroke survivors. Nineteen full-text articles published in English were identified and included in the present review, with data collected from a total of 34,546 stroke patients. A higher rate of extended LA was strongly associated with stroke recurrence in all stroke subtypes, even after adjustment for clinical risk factors. In particular, patients with ischemic stroke or transient ischemic attack with advanced LA had a significantly higher risk of future ischemic stroke, whereas patients with previous intracerebral hemorrhage and severe LA had a more than 2.5-fold increased risk of recurrent ischemic stroke and a more than 30-fold increased risk of hemorrhagic stroke. Finally, in patients receiving anticoagulant treatment for AF, the presence of LA was associated with an increased risk of recurrent ischemic stroke and intracranial hemorrhage. Because of this valuable predictive information, evaluating LA could significantly expand our knowledge of stroke patients and thereby improve overall stroke care.

Objective: To explore the relationship between serum C peptide (CP), myelin basic protein (MBP), monocyte chemotactic protein-1 (MCP-1) levels and disease severity and prognosis in patients with acute cerebral infarction (ACI) combine with leukoaraiosis (LA). Methods: 117 patients with ACI combine with LA admitted to Suqian Hospital of Nanjing Gulou Hospital Group from March 2021 to March 2023 were selected as observation group, patients were divided into severe group (39 cases), moderate group (40 cases), and mild group (38 cases) according to the severity of LA. 120 healthy individuals who underwent physical examinations during the same period were selected as control group. Detected serum levels of CP, MBP, and MCP-1. Follow up patients with ACI combine with LA 6 months. The influencing factors of poor prognosis in patients with ACI combined with LA were analyzed by multivariate Logistic regression. The predictive value of serum CP, MBP and MCP-1 in ACI patients with LA was analyzed by receiver operating characteristic(ROC) curve. Results: Compared with control group, observation group had higher levels of MBP and MCP-1, lower levels of CP (P<0.05). Serum CP in severe group was lower than that in mild and moderate groups, and the levels of MBP and MCP-1 were higher than those in mild and moderate groups; Serum CP in moderate group was lower than that in mild group, and the levels of MBP and MCP-1 were higher than those in mild group (all P<0.05). Compared with good prognosis group, poor prognosis group had lower CP and higher MBP and MCP-1 (P<0.05). Multivariate logistic regression analysis showed that elevated NIHSS score, MBP, and MCP-1 were independent risk factors for poor prognosis in patients with ACI combine with LA, and elevated CP was a protective factor (P<0.05). ROC analysis results showed that the area under the curve (AUC) of CP, MBP, and MCP-1 combined predicting poor prognosis in patients with ACI combine with LA was 0.916, significantly higher than CP, MBP and MCP-1 alone. Conclusion: The serum CP of patients with ACI combine with LA is lower than that in healthy group, and the serum MBP and MCP-1 levels are higher than those in healthy group, and there is a close relationship between CP, MBP, and MCP-1 and the severity of the patient's condition. The combined detection of serum CP, MBP, and MCP-1 has high predictive value for the prognosis of patients with ACI combine with LA. [ABSTRACT FROM AUTHOR]

Leukoaraiosis (LA) is a disease manifested by demyelination and gliosis in white matter, mainly caused by cerebrovascular diseases. LA is closely related to the expression level of inflammatory factors, oxidative stress, and vascular endothelial dysfunction in patients. Vitamin E may play antioxidant and anti-inflammatory roles in various diseases. We aimed to explore the effects of vitamin E on the patients with LA. A total of 160 patients with LA were recruited in this research. Matrix metalloproteinase-9 (MMP-9), MMP-2, C-reactive protein (CRP), complement 3 (C3), C4, nitric oxide (NO), and endothelin (ET) levels were evaluated by ELISA. The Mini-Mental State Examination (MMSE) was used for cognitive impairment assessment. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were analyzed by commercial kits. The levels of CRP, C3, and C4 significantly decreased in the serum of LA patients after the administration of vitamin E. The levels of MMP-2 and MPP-9 showed a significant decrease in the administered group. Vitamin E significantly inhibited the expression of MDA, while significantly upregulated the expression of SOD. Significant increase in NO production and significant downregulation of ET expression occurred in vitamin E groups. MMSE score was significantly increased by vitamin E. In conclusion, vitamin E showed effects on the alleviation of inflammatory response, oxidative stress, endothelial damage, and cognitive dysfunction. Thus, vitamin E could be a potential drug for the clinical treatment of LA patients. [ABSTRACT FROM AUTHOR]

Background/objectivesTo examine the association between white matter hyperintensities (WMH) and cognitive domains such as memory and executive function (EF) across different clinical and biomarker categories of Alzheimer's disease (AD).DesignCross-sectional study.SettingAlzheimer's Disease Neuroimaging Initiative.ParticipantsA total of 216 cognitively normal (CN) participants and 407 participants with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) at baseline.MeasurementsBased on the 2018 research framework, participants were classified using AT(N) (amyloid-β deposition [A], pathologic tau [T], and neurodegeneration [(N)]) biomarkers into one of three categories: biomarker negative [A - T- (N)-], amyloid negative but other biomarker positive [A - T ± (N)+ or A - T + (N)±] or amyloid positive [A + T ± (N)±]. Linear regression models were then used to examine the association between WMH and memory composite scores and EF composite scores.ResultsHigher WMH burden was associated with worse EF in both CN and MCI subgroups while a significant association between WMH and memory was only found in the MCI subgroup. Furthermore, WMH was associated with EF in the group with A - T ± (N)+ or A - T + (N)± biomarker category, but not for A - T - (N)- (normal biomarker) and A + T ± (N) ± (AD pathology). The association between higher WMH and worse memory was independent of amyloid levels in individuals with MCI with evidence of AD pathology.ConclusionVascular disease, as indexed by WMH, independent of AD pathology affects cognitive function in both CN and MCI subgroups. Future studies using the AT(N) research framework should consider white matter lesions as a key biomarker contributing to the clinical presentation of AD.

Objective: to study the level of inflammatory biomarkers and growth factors in the peripheral blood of patients with chronic cerebrovascular disease (CCVD) and anamnesis of coronavirus infection COVID-19.Material and methods. The study included patients with CCVD (n=41), 26 of them had a documented anamnesis of coronavirus infection within 4 months before inclusion in the study, 15 people did not have COVID-19. The control group consisted of 20 apparently healthy individuals of the same age. Neuroimaging was performed using a Philips Achieva 1.5 T device. Pro-inflammatory cytokines were determined in blood serum – tumor necrosis factor α (TNF α ), interleukin 6 (IL6), IL18, interferon γ (IFN γ ); chemokines – monocytic chemoattractant protein 1 (MCP-1), IL8; growth factors – vascular endothelial growth factor type A (VEGF-A), transforming growth factor β 1 (TGF β 1).Results. In patients with CCVD, compared with the control group, an increase in the level of proinflammatory cytokines (TNF α , IL6, IL18), chemokines (MCP1 and IL8), a decrease in the concentration of IFN γ , and divergent changes in the content of growth factors (VEGF-A and TGF β 1) were noted. Patients who recovered from COVID-19 showed an increase in the level of IL6 and a decrease in the level of IFN γ compared with those who had not been ill, which indicates a persistently high activity of immunoinflammatory processes and an insufficient humoral immune response.Conclusion. Postponed coronavirus infection COVID-19 aggravates the existing endothelial dysfunction and intravascular inflammation in patients with CCVD, which may probably require changes in their treatment and prevention strategies in the future.

Abstract Background and objective The recruitment of collateral circulation correlates with a balance of the microvasculature. Uncertainty remains to be made about the association of leukoaraiosis with leptomeningeal collaterals. To explore the effect of leukoaraiosis on leptomeningeal collaterals in patients treated with endovascular therapy. Methods Observational studies exploring the correlation between leukoaraiosis and leptomeningeal collaterals in large vessel occlusion treated with endovascular therapy were searched from PubMed, EMBASE, and Cochrane Libraries databases. Two independent reviewers retrieved eligible literature, extracted purpose-related data, and utilized the Newcastle–Ottawa Scale to evaluate the risk of bias. A Mantel–Haenszel method was used to calculate the odds ratio (OR). Meta-regression and subgroup analyses were conducted to clarify heterogeneity. Results Data from 10 studies with 1606 patients were extracted for pooled analysis. Compared to non-severe leukoaraiosis, patients with severe leukoaraiosis showed significant relevance to poor leptomeningeal collaterals (OR, 2.13; 95% confidence interval [1.27–3.57]; P = 0.004). Meta-regression indicated that sample size (coefficient = -0.007299, P = 0.035) and the number of female patients (coefficient = -0.0174709, P = 0.020) were sources of heterogeneity. Furthermore, all of the countries (USA versus France versus China, Q = 3.67, P = 0.159), various assessment scales of leukoaraiosis (the Fazekas scale versus Non-Fazekas scales, Q = 0.77, P = 0.379), and different imaging methods of leukoaraiosis (computed tomography versus magnetic resonance imaging, Q = 2.12, P = 0.146) and leptomeningeal collaterals (computed tomography angiography versus digital subtraction angiography, Q = 1.21, P = 0.271) showed no contribution to the effect size. Conclusion Severe leukoaraiosis is associated with poor leptomeningeal collaterals in patients treated with endovascular therapy. Further studies may focus on whether the finding applies to different stroke subtypes.

Background: White matter hyperintensities (WMH) are a prevalent radiographic finding in the aging brain studies. Research on WMH association with motor impairment is mostly focused on the lower-extremity function and further investigation on the upper-extremity is needed. How different degrees of WMH burden impact the network of activation recruited during upper limb motor performance could provide further insight on the complex mechanisms of WMH pathophysiology and its interaction with aging and neurological disease processes. Methods: 40 healthy elderly subjects without a neurological/psychiatric diagnosis were included in the study (16F, mean age 69.3 years). All subjects underwent ultra-high field 7 T MRI including structural and finger tapping task-fMRI. First, we quantified the WMH lesion load and its spatial distribution. Secondly, we performed a data-driven stratification of the subjects according to their periventricular and deep WMH burdens. Thirdly, we investigated the distribution of neural recruitment and the corresponding activity assessed through BOLD signal changes among different brain regions for groups of subjects. We clustered the degree of WMH based on location, numbers, and volume into three categories; ranging from mild, moderate, and severe. Finally, we explored how the spatial distribution of WMH, and activity elicited during task-fMRI relate to motor function, measured with the 9-Hole Peg Test. Results: Within our population, we found three subgroups of subjects, partitioned according to their periventricular and deep WMH lesion load. We found decreased activity in several frontal and cingulate cortex areas in subjects with a severe WMH burden. No statistically significant associations were found when performing the brain-behavior statistical analysis for structural or functional data. Conclusion: WMH burden has an effect on brain activity during fine motor control and the activity changes are associated with varying degrees of the total burden and distributions of WMH lesions. Collectively, our results shed new light on the potential impact of WMH on motor function in the context of aging and neurodegeneration.

Background: The relative contribution of changes in the cerebral white matter (WM) and cortical gray matter (GM) to the transition to dementia in patients with mild cognitive impairment (MCI) is not yet established. In this longitudinal study, we aimed to analyze MRI features that may predict the transition to dementia in patients with MCI and T2 hyperintensities in the cerebral WM, also known as leukoaraiosis. Methods: Sixty-four participants with MCI and moderate to severe leukoaraiosis underwent baseline MRI examinations and annual neuropsychological testing over a 2 year period. The diagnosis of dementia was based on established criteria.We evaluated demographic, neuropsychological, and several MRI features at baseline as predictors of the clinical transition. The MRI features included visually assessed MRI features, such as the number of lacunes, microbleeds, and dilated perivascular spaces, and quantitative MRI features, such as volumes of the cortical GM, hippocampus, T2 hyperintensities, and di_usion indices of the cerebral WM. Additionally, we examined advanced quantitative features such as the fractal dimension (FD) of cortical GM and WM, which represents an index of tissue structural complexity derived from 3D-T1 weighted images. To assess the prediction of transition to dementia, we employed an XGBoost-based machine learning system using SHapley Additive exPlanations (SHAP) values to provide explainability to the machine learning model. Results: After 2 years, 18 (28.1%) participants had transitioned from MCI to dementia. The area under the receiving operator characteristic curve was 0.69 (0.53, 0.85) [mean (90% confidence interval)]. The cortical GM-FD emerged as the top-ranking predictive feature of transition. Furthermore, aggregated quantitative neuroimaging features outperformed visually assessed MRI features in predicting conversion to dementia. Discussion: Our findings confirmthe complementary roles of cortical GM and WM changes as underlying factors in the development of dementia in subjects with MCI and leukoaraiosis. FD appears to be a biomarker potentially more sensitive than other brain features. [ABSTRACT FROM AUTHOR]

Background and objectives: It has been suggested that white matter hyperintensity lesions (WMHs), which typically progress over time, can also regress, and that this might be associated with favorable cognitive performance. We determined the prevalence of WMH regression in patients with cerebral small vessel disease (SVD) and examined which demographic, clinical, and radiological markers were associated with this regression. Methods: We used semi-automated lesion marking methods to quantify WMH volume at multiple timepoints in three cohorts with symptomatic SVD; two with moderate-to-severe symptomatic SVD (the SCANS observational cohort and the control arm of the PRESERVE interventional trial) and one with mild-to-moderate SVD (the RUN DMC observational cohort). Mixed-effects ordered logistic regression models were used to test which factors predicted participants to show WMH regression. Results: No participants (0/98) in SCANS, 6/42 (14.3%) participants in PRESERVE, and 6/276 (2.2%) in RUN DMC showed WMH regression. On multivariate analysis, only lower WMH volume (OR: 0.36, 95% CI: 0.23–0.56) and better white matter microstructural integrity assessed by fractional anisotropy using diffusion tensor imaging (OR: 1.55, 95% CI: 1.07–2.24) predicted participant classification as regressor versus stable or progressor. Discussion: Only a small proportion of participants demonstrated WMH regression across the three cohorts, when a blinded standardized assessment method was used. Subjects who showed regression had less severe imaging markers of disease at baseline. Our results show that lesion regression is uncommon in SVD and unlikely to be a major factor affecting the use of WMH quantification as an outcome for clinical trials. [ABSTRACT FROM AUTHOR]

Neuroticism is a major risk factor for neurodegenerative disorders, such as Alzheimer's disease and related dementias. This study investigates whether neuroticism is associated with white matter hyperintensities and whether this measure of brain integrity is a mediator between neuroticism and cognitive function. Middle-aged and older adults from the UK Biobank (N = 40,602; aged 45–82 years, M = 63.97, SD = 7.66) provided information on demographic and health covariates, completed measures of neuroticism and cognition, and underwent magnetic resonance imaging from which the volume of white matter hyperintensities was derived. Regression analyses that included age and sex as covariates found that participants who scored higher on neuroticism had more white matter hyperintensities (β = 0.024, 95% CI 0.015 to 0.032; p <.001), an association that was consistent across peri-ventricular and deep brain regions. The association was reduced by about 40% when accounting for vascular risk factors (smoking, obesity, diabetes, high blood pressure, heart attack, angina, and stroke). The association was not moderated by age, sex, college education, deprivation index, or APOE e4 genotype, and remained unchanged in sensitivity analyses that excluded individuals with dementia or those younger than 65. The mediation analysis revealed that white matter hyperintensities partly mediated the association between neuroticism and cognitive function. These findings identify white matter integrity as a potential neurobiological pathway that accounts for a small proportion of the association between neuroticism and cognitive health. [ABSTRACT FROM AUTHOR]

Objective: Leukoaraiosis and other brain MRI‐assessed parameters were shown to be associated with recurrent stroke in this population. We aimed to develop an MRI‐based predictive tool for risk stratification of ESUS patients. Methods: We retrospectively assessed consecutive patients who were diagnosed with ESUS and underwent brain MRI and performed a multivariable analysis with the outcome of recurrent stroke/TIA. Based on the coefficient of each covariate, we generated an integer‐based point scoring system. The discrimination and calibration of the score were assessed using the area under the receiver operator characteristic curve, net reclassification improvement, integrated discrimination improvement, calibration curve, and decision curve analysis. Also, we compared the new score with a previously published score (ALM score). Results: Among 176 patients followed for an overall period of 902.3 patient‐years (median of 74 months), there were 39 recurrent ischemic stroke/TIAs (4.32 per 100 patient‐years). Fazekas score (HR: 1.26, 95% CI: 1.03–1.54), enlarged perivascular space (EPVS) (HR: 2.76, 95% CI: 1.12–6.17), NIHSS at admission (HR: 1.11, 95% CI: 1.02–1.18), and infarct subtypes (HR: 2.88, 95% CI: 1.34–6.17) were associated with recurrent stroke/TIA. Accordingly, a score (FENS score) was developed with AUC‐ROC values of 0.863, 0.788, and 0.858 for 1, 3, and 5 years, respectively. These were significantly better than the AUC‐ROC of ALM score (0.635, 0.695, and 0.705, respectively). The FENS score exhibited better calibration and discrimination ability than the ALM score (Hosmer–Lemeshow test χ2: 4.402, p = 0.819). Conclusion: The MRI‐based FENS score can provide excellent predictive performance for recurrent stroke/TIA and may assist in risk stratification of ESUS patients. [ABSTRACT FROM AUTHOR]

Stroke is the leading cause of functional disability worldwide, with increasing prevalence in adults. Given the considerable negative impact on patients' quality of life and the financial burden on their families and society, it is essential to provide stroke survivors with a timely and reliable prognosis of stroke recurrence. Leukoaraiosis (LA) is a common neuroimaging feature of cerebral small-vessel disease. By researching the literature of two different databases (MEDLINE and Scopus), the present study aims to review all relevant studies from the last decade, dealing with the clinical utility of pre-existing LA as a prognostic factor for stroke recurrence in stroke survivors. Nineteen full-text articles published in English were identified and included in the present review, with data collected from a total of 34,546 stroke patients. A higher rate of extended LA was strongly associated with stroke recurrence in all stroke subtypes, even after adjustment for clinical risk factors. In particular, patients with ischemic stroke or transient ischemic attack with advanced LA had a significantly higher risk of future ischemic stroke, whereas patients with previous intracerebral hemorrhage and severe LA had a more than 2.5-fold increased risk of recurrent ischemic stroke and a more than 30-fold increased risk of hemorrhagic stroke. Finally, in patients receiving anticoagulant treatment for AF, the presence of LA was associated with an increased risk of recurrent ischemic stroke and intracranial hemorrhage. Because of this valuable predictive information, evaluating LA could significantly expand our knowledge of stroke patients and thereby improve overall stroke care. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is the most common clinical manifestation of ischemic leukoaraiosis (ILA), but the underlying neurobiological pathways have not been well elucidated. Recently, it was thought that ILA is a "disconnection syndrome". Disorganized brain connectome were considered the key neuropathology underlying cognitive deficits in ILA patients. Objective: We aimed to detect the disruption of network hubs in ILA patients using a new analytical method called voxel-based eigenvector centrality (EC) mapping. Methods: Subjects with moderate to severe white matters hyperintensities (Fazekas score ≥3) and healthy controls (HCs) (Fazekas score = 0) were included in the study. The resting-state functional magnetic resonance imaging and the EC mapping approach were performed to explore the alteration of whole-brain network connectivity in ILA patients. Results: Relative to the HCs, the ILA patients exhibited poorer cognitive performance in episodic memory, information processing speed, and executive function (all ps < 0.0125). Additionally, compared with HCs, the ILA patients had lower functional connectivity (i.e., EC values) in the medial parts of default-mode network (i.e., bilateral posterior cingulate gyrus and ventral medial prefrontal cortex [vMPFC]). Intriguingly, the functional connectivity strength at the right vMPFC was positively correlated with executive function deficit in the ILA patients. Conclusion: The findings suggested disorganization of the hierarchy of the default-mode regions within the whole-brain network in patients with ILA and advanced our understanding of the neurobiological mechanism underlying executive function deficit in ILA. [ABSTRACT FROM AUTHOR]

We investigated the associations among neurological severity, activities of daily living (ADLs), and clinical factors in patients with ischemic stroke in convalescent rehabilitation outcome. The study sample included 723 patients with ischemic stroke (484 men and 239 women; mean age, 73.2 ± 8.5 years) for inpatient convalescent rehabilitation. National Institutes of Health Stroke Scale (NIHSS) was used to measure the neurological severity, and Functional Independence Measure (FIM) was used to assess ADLs at discharge. Leukoaraiosis was graded based on periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on magnetic resonance imaging. The correlations between NIHSS scores and total FIM scores were significant but relatively mild (r = -0.684, P < 0.001). Multiple regression analysis revealed that age and PVH grade significantly decreased their total FIM scores and affected the discrepancies between NIHSS scores at discharge (P < 0.001), but DWMH scores did not affect these results. Factors such as positive history of heart disease (P = 0.008) and bilateral infarction (P = 0.038) additionally decreased their total FIM scores and affected the discrepancies between NIHSS scores. These findings suggest that age, PVH, history of heart disease positive, and bilateral infarction in patients with ischemic stroke affected their performance of ADLs and the discrepancies between their neurological severities in convalescent rehabilitation outcomes, probably because the pathophysiological background of leukoaraiosis and these factors strongly decrease their ADL performance in post-phase ischemic stroke. [ABSTRACT FROM AUTHOR]

ObjectiveExamine 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.MethodsBIOCARD 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.ResultsBoth 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.InterpretationAlthough 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.

BackgroundWe determined the association between ratios of plasma ceramide species of differing fatty-acyl chain lengths and incident dementia and Alzheimer's disease (AD) dementia in a large, community-based sample.MethodsWe measured plasma ceramide levels in 1892 [54% women, mean age 70.1 (SD 6.9) yr.] dementia-free Framingham Offspring Study cohort participants between 2005 and 2008. We related ratios of very long-chain (C24:0, C22:0) to long-chain (C16:0) ceramides to subsequent risk of incident dementia and AD dementia. Structural MRI brain measures were included as secondary outcomes.ResultsDuring a median 6.5 year follow-up, 81 participants developed dementia, of whom 60 were diagnosed with AD dementia. In multivariable Cox-proportional hazards analyses, each standard deviation (SD) increment in the ratio of ceramides C24:0/C16:0 was associated with a 27% reduction in the risk of dementia (HR 0.73, 95% CI 0.56-0.96) and AD dementia (HR 0.73, 95% CI 0.53-1.00). The ratio of ceramides C22:0/C16:0 was also inversely associated with incident dementia (HR per SD 0.75, 95% CI 0.57-0.98), and approached statistical significance for AD (HR 0.73, 95% CI 0.53-1.01, P = 0.056). Higher ratios of ceramides C24:0/C16:0 and C22:0/C16:0 were also cross-sectionally associated with lower white matter hyperintensity burden on MRI (-0.05 ± 0.02, P = 0.02; -0.06 ± 0.02, P = 0.003; respectively per SD increase), but not with other MRI brain measures.ConclusionsHigher plasma ratios of very long-chain to long-chain ceramides are associated with a reduced risk of incident dementia and AD dementia in our community-based sample. Circulating ceramide ratios may serve as potential biomarkers for predicting dementia risk in cognitively healthy adults.

Stroke survivors are at increased risk of developing depression and cognitive decline. Thus, it is crucial for both clinicians and stroke survivors to be provided with timely and accurate prognostication of post-stroke depression (PSD) and post-stroke dementia (PSDem). Several biomarkers regarding stroke patients’ propensity to develop PSD and PSDem have been implemented so far, leukoaraiosis (LA) being among them. The purpose of the present study was to review all available work published within the last decade dealing with pre-existing LA as a predictor of depression (PSD) and cognitive dysfunction (cognitive impairment or PSDem) in stroke patients. A literature search of two databases (MEDLINE and Scopus) was conducted to identify all relevant studies published between 1 January 2012 and 25 June 2022 that dealt with the clinical utility of preexisting LA as a prognostic indicator of PSD and PSDem/cognitive impairment. Only full-text articles published in the English language were included. Thirty-four articles were traced and are included in the present review. LA burden, serving as a surrogate marker of “brain frailty” among stroke patients, appears to be able to offer significant information about the possibility of developing PSD or cognitive dysfunction. Determining the extent of pre-existing white matter abnormalities can properly guide decision making in acute stroke settings, as a greater degree of such lesioning is usually coupled with neuropsychiatric aftermaths, such as PSD and PSDem.

Stroke stands as a major cause of death and disability with increasing prevalence. The absence of clinical improvement after either intravenous thrombolysis (IVT) or mechanical thrombectomy (MT) represents a frequent concern in the setting of acute ischemic stroke (AIS). In an attempt to optimize overall stroke management, it is clinically valuable to provide important insight into functional outcomes after reperfusion therapy among patients presenting with AIS. The aim of the present review is to explore the predictive value of leukoaraiosis (LA) in terms of clinical response to revascularization poststroke. A literature research of two databases (MEDLINE and Scopus) was conducted in order to trace all relevant studies published between 1 January 2012 and 1 November 2022 that focused on the potential utility of LA severity regarding reperfusion status and clinical outcome after revascularization. A total of 37 articles have been traced and included in this review. LA burden assessment is indicative of functional outcome post-intervention and may be associated with hemorrhagic events’ incidence among stroke individuals. Nevertheless, LA may not solely guide decision-making about treatment strategy poststroke. Overall, the evaluation of LA upon admission seems to have interesting prognostic potential and may substantially enhance individualized stroke care.