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PurposeTo investigate the relationship between pathological brain iron deposition and white matter hyperintensities (WMHs) in cerebral small vessel disease (CSVD), via Monte Carlo simulations of magnetic susceptibility imaging and a novel imaging marker called the Expected Iron Coefficient (EIC).MethodsA synthetic pathological model of a different number of impenetrable spheres at random locations was employed to represent pathological iron deposition. The diffusion process was simulated with a Monte Carlo method with adjustable parameters to manipulate sphere size, distribution, and extracellular properties. Quantitative susceptibility mapping (QSM) was performed in a clinical dataset to study CSVD to derive and evaluate QSM, R2*, the iron microenvironment coefficient (IMC), and EIC in the presence of WMHs.ResultsThe simulations show that QSM signals increase in the presence of increased tissue iron, confirming that the EIC increases with pathology. Clinical results demonstrate that while QSM, R2*, and the IMC do not show differences in brain iron, the EIC does in the context of CSVD.ConclusionThe EIC is more sensitive to subtle changes in brain iron deposition caused by pathology, even when QSM, R2*, and the IMC do not.

BACKGROUND: The association between subclinical hypothyroidism (SCH) and cerebral small vessel disease (CSVD) in the stroke-free population is currently unclear. METHODS: A total of 354 individuals without a history of stroke were enrolled in this study. Demographic data, medical history, vascular risk factors, carotid arteriosclerosis, and the results of laboratory tests were collated. SCH is defined as an elevation in thyroid-stimulating hormone levels, but with normal free thyroxine levels. Magnetic resonance imaging (MRI) was used to assess 4 markers of CSVD, including white matter hyperintensities (WMHs), lacunes, deep microbleeds, and enlarged perivascular spaces (EPVSs). The overall CSVD load was then ranked using an ordinal scale ranging from 0 to 4. Brain atrophy was measured semi-quantitatively on MRI. A binary logistic regression model was used to explore the association of SCH with each CSVD marker after adjusting for confounding factors. The ordinal regression model was used to explore the association of SCH with CSVD burden and brain atrophy after adjusting for confounding factors. RESULTS: The mean age of the participants (66.9% males) was 69.4±12.8 years. SCH was observed in 44 (12.4%) participants. MRI findings revealed 13% of cases with lacunes, 6.2% with microbleeds, 50.3% with confluent WMH, and 49.2% with extensive basal ganglia EPVS. Assessment of total CSVD burden showed that 29.1% scored 1, 30.5% scored 2, 6.5% scored 3, and 2.3% scored ≥3. SCH was associated with extensive basal ganglia EPVS [odds ratio (OR) =2.175; 95% confidence interval (CI): 1.075 to 4.401] and total CSVD load (OR =1.879; 95% CI: 1.028 to 3.438). SCH was not associated with advanced brain atrophy. CONCLUSIONS: SCH is associated with the advanced total burden of CSVD and basal ganglia EPVS in the stroke-free population.

The article deals with investigation of probability of cerebral atrophy (CA) formation according to magnetic resonance markers of cerebral small vessel disease (SVD). During the retrospective cohort study of the data from 308 patients aged 50 to 85 years old with cerebral SVD, CA signs were defined in 60 % of patients, with predominance among males (р = 0.00001). Along with that, CA was not associated with the patients’ age, but it was indirectly associated with cerebral SVD. As for quality of cerebral SVD markers, CA had the closest association with leukoareosis (р

Background This study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI). Methods We retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4. Results In total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level. Conclusions Dysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.

The development of technical documentation of vessels provides that the design, construction and conformity assessment is clearly understood and meets the competent requirements. This paper presents the development process of technical documentation for a small vessel, i.e. a motorboat of project category B (navigation on the high seas), whose hull length is within the range from 2.5 m to 24 m, according to the given norms. For example, the paper will present a boat intended as a polyvalent workboat in service on the Adriatic Sea, whose documentation has been prepared according to standards, i.e. the requirements of the Croatian Register of Shipping (HRN EN ISO Standards)

Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Hypertension and cerebral amyloid angiopathy (CAA) are the most common causes of primary ICH, but the mechanism of hemorrhage in both conditions is unclear. Although fibrinoid necrosis and Charcot-Bouchard aneurysms (CBAs) have been postulated to underlie vessel rupture in ICH, the role and significance of CBAs in ICH has been controversial. First described as the source of bleeding in hypertensive hemorrhage, they are also one of the CAA-associated microangiopathies along with fibrinoid necrosis, fibrosis and "lumen within a lumen appearance." We describe clinicopathologic findings of CBAs found in 12 patients out of over 2700 routine autopsies at a tertiary academic medical center. CBAs were rare and predominantly seen in elderly individuals, many of whom had multiple systemic and cerebrovascular comorbidities including hypertension, myocardial and cerebral infarcts, and CAA. Only one of the 12 subjects with CBAs had a large ICH, and the etiology underlying the hemorrhage was likely multifactorial. Two CBAs in the basal ganglia demonstrated associated microhemorrhages, while three demonstrated infarcts in the vicinity. CBAs may not be a significant cause of ICH but are a manifestation of severe cerebral small vessel disease including both hypertensive arteriopathy and CAA.

Introduction Cerebral small vessel disease (SVD) predicts all-cause mortality in Eastern Asian and Caucasian populations. However, little is known about SVD impact in individuals of different races/ethnic groups. In this study, we sought to estimate the mortality risk according to the total SVD (tSVD) score in older adults of Amerindian ancestry. Methods Participants aged ≥60 years from the prospective population-based Atahualpa Project cohort underwent brain MRI between June 2012 and June 2017. The tSVD score was calculated based on the presence of moderate-to-severe white matter hyperintensities, enlarged perivascular spaces, one or more lacune, and one or more cerebral microbleed. We ascertained all-cause mortality during post-MRI follow-up. Poisson regression and Cox-proportional hazards models adjusted for demographics and cardiovascular risk were obtained to estimate mortality risk according to the tSVD score. Results Analysis included 375 participants with available brain MRI and clinical data (mean age 69.0 ± 8.3 years, 56.3% women). The tSVD score was 0 point in 216 individuals (57.6%), 1 point in 71 (18.9%), 2 points in 53 (14.1%), and 3–4 points in 35 (9.3%). Increasing tSVD score was associated with advancing age, hypertension, low level of education, and physical inactivity. Using tSVD score of 0 as reference, a multivariate Poisson regression model showed an increased mortality for individuals with a tSVD score 3–4 points (IRR: 2.27; 95% CI: 1.20–4.28). Likewise, in the Cox-proportional model adjusted for demographics and cardiovascular risk, participants with a tSVD score 3–4 maintained a greater than two-fold mortality risk when compared to those with tSVD score of 0 points (HR: 2.32; 95% CI: 1.23–4.39). Conclusions High-burden SVD as determined by the tSVD score predicts mortality in community-dwelling older adults of Amerindian ancestry. Incidental diagnosis of covert SVD should prompt aggressive control of cardiovascular health.

Imaging the coronary arteries of children, with their faster heart rates, small vessel size and common inability to lie still or breath-hold, has been a major challenge. With numerous advances in technology, CT examinations can now be performed quickly, often with children free-breathing and with much lower radiation doses than previously. This has led to increased use in children. Care must be taken with technique and choice of electrocardiogram (ECG)-gating technique to obtain adequate imaging for a diagnosis while keeping radiation dose as low as reasonably achievable (ALARA). In this paper, we discuss techniques and tips for CT imaging of the coronary arteries in children, including use of dual-source- and ultrawide-detector CT scanners.

Highlights • Unexplained dizziness in the elderly may result from cerebral small vessel disease. • Dizzy elderly patients differed from controls in EEG power when standing. • EEG power when standing correlated with subjective (perceived) instability., Objective To examine the hypothesis that small vessel disease disrupts postural networks in older adults with unexplained dizziness in the elderly (UDE). Methods Simultaneous electroencephalography and postural sway measurements were undertaken in upright, eyes closed standing, and sitting postures (as baseline) in 19 younger adults, 33 older controls and 36 older patients with UDE. Older adults underwent magnetic resonance imaging to determine whole brain white matter hyperintensity volumes, a measure of small vessel disease. Linear regression was used to estimate the effect of instability on electroencephalographic power and connectivity. Results Ageing increased theta and alpha desynchronisation on standing. In older controls, delta and gamma power increased, and theta and alpha power reduced with instability. Dizzy older patients had higher white matter hyperintensity volumes and more theta desynchronisation during periods of instability. White matter hyperintensity volume and delta power during periods of instability were correlated, positively in controls but negatively in dizzy older patients. Delta power correlated with subjective dizziness and instability. Conclusions Neural resource demands of postural control increase with age, particularly in patients with UDE, driven by small vessel disease. Significance EEG correlates of postural control saturate in older adults with UDE, offering a neuro-physiological basis to this common syndrome.

Introduction: The aim of this study was to test the hypothesis that the attack interval of multiple transient ischemic attacks (TIAs) is correlated with the underlying pathogenesis of ischemia. Methods: Patients with multiple TIAs, defined as 2 or more motor deficits within 7 days, were studied. The attack interval between the last 2 episodes was classified into 3 groups: 2 episodes within an hour (Hour group), over hours within a day (Day group), and over days within a week (Week group). Patients with a lacunar syndrome, no cortical lesions, and no embolic sources were recognized as having a small vessel disease (SVD) etiology for their multiple events. Results: Of 312 TIA patients admitted over a 9-year period, 50 (37 males, 13 females, mean 67.6 years) had multiple TIAs. Twelve patients were classified as being within the Hour group, 23 within the Day group, and 15 within the Week group. Lacunar syndromes were observed in 30 (75%, 35%, and 67%), embolic sources were detected in 28 (25%, 65%, and 67%), and a high signal lesion on diffusion-weighted imaging was depicted in 30 (75%, 48%, and 67%) patients (18 cortical, 11 subcortical, and one cerebellar). Patients in the Hour group had a significantly higher prevalence of SVD etiology (75%) than those in the Day and Week groups (30%, p = 0.0165; 27%, p = 0.0213, respectively). Four patients had a subsequent stroke within 7 days. Conclusion: Attack intervals of multiple TIAs may be correlated with the underlying pathogenesis of ischemia. Two motor deficits within an hour are more likely to suggest a SVD etiology.

Background: Altered white matter brain networks have been extensively studied in cerebral small vessel disease (SVD). However, there exists currently a deficiency of comprehending the performance of changes within the structural networks of the brain in cases with cerebral SVD and depression symptoms. The main aim of the present research is to study the network topology behaviors and features of rich-club organization in SVD patients using graph theory and diffusion tensor imaging (DTI) to characterize changes in the microstructure of the brain. Methods: DTI datasets were acquired from 26 SVD patients with symptoms of depression (SVD + D) and 26 SVD patients without symptoms of depression (SVD − D), and a series of neuropsychological assessments were completed. A structural network was created using a deterministic fiber tracking method. The analysis of rich-club was performed in company with analysis of the global network features of the network to characterize the topological properties of all subjects. Results: DTI data were obtained from SVD patients who manifested symptoms of depression (SVD + D) and from control SVD patients (SVD − D). In comparison with SVD − D patients, SVD + D cases demonstrated a diminished coefficient of clustering along with lower global efficiencies and longer path length characteristics. Rich-club analysis showed SVD + D patients had decreased feeder connectivity and local connectivity strengths compared to SVD − D patients. Our data also showed that the feeder connections in the brain correlated significantly with the severity of depression in SVD + D patients. Conclusions: Our study revealed that SVD patients with depressive symptoms have disrupted white matter networks that characteristically have reduced network efficiency compared to the networks in other SVD patients. Disrupted information interactions among the regions of nonrich-club and rich-club in SVD cases are related to the severity of depression. Our data suggest that DTI may be utilized as an appropriate biomarker for the diagnosis of depression in comorbid SVD patients.

Background: Small vessel disease (SVD) magnetic resonance imaging (MRI) markers including deep and periventricular white matter hyperintensities (PWMH), lacunes, and microbleeds are frequently observed in Alzheimer’s disease (AD) and Lewy body disease (LBD), but their implication has not been clearly elucidated. Objective: To investigate the implication of SVD MRI markers in cognitively impaired patients with AD and/or LBD. Methods: We consecutively recruited 57 patients with pure AD-related cognitive impairment (ADCI), 49 with pure LBD-related cognitive impairment (LBCI), 45 with mixed ADCI/LBCI, and 34 controls. All participants underwent neuropsychological tests, brain MRI, and amyloid positron emission tomography. SVD MRI markers including the severity of deep and PWMH and the number of lacunes and microbleeds were visually rated. The relationships among vascular risk factors, SVD MRI markers, ADCI, LBCI, and cognitive scores were investigated after controlling for appropriate covariates. Results: LBCI was associated with more severe PWMH, which was conversely associated with an increased risk of LBCI independently of vascular risk factors and ADCI. PWMH was associated with attention and visuospatial dysfunction independently of vascular risk factors, ADCI, and LBCI. Both ADCI and LBCI were associated with more lobar microbleeds, but not with deep microbleeds. Conclusion: Our findings suggest that PWMH could reflect degenerative process related with LBD, and both AD and LBD independently increase lobar microbleeds.

Introduction It is unclear why cerebral small vessel disease (SVD) leads to lacunar stroke in some and to non–lobar intracerebral hemorrhage (ICH) in others. We investigated differences in MRI markers of SVD in patients with lacunar stroke or non–lobar ICH. Patients and methods We included patients from two prospective cohort studies with either lacunar stroke (RUN DMC) or non–lobar ICH (FETCH). Differences in SVD markers (white matter hyperintensities [WMH], lacunes, cerebral microbleeds [CMB]) between groups were investigated with univariable tests; multivariable logistic regression analysis, adjusted for age, sex, and vascular risk factors; spatial correlation analysis and voxel–wise lesion symptom mapping. Results We included 82 patients with lacunar stroke (median age 63, IQR 57–72) and 54 with non-lobar ICH (66, 59–75). WMH volumes and distribution were not different between groups. Lacunes were more frequent in patients with a lacunar stroke (44% vs. 17%, adjusted odds ratio [aOR] 5.69, 95% CI [1.66–22.75]) compared to patients with a non–lobar ICH. CMB were more frequent in patients with a non–lobar ICH (71% vs. 23%, aOR for lacunar stroke vs non–lobar ICH 0.08 95% CI [0.02–0.26]), and more often located in non–lobar regions compared to CMB in lacunar stroke. Discussion Although we obserd different types of MRI markers of SVD within the same patient, ischemic markers of SVD were more frequent in the ischemic type of lacunar stroke, and hemorrhagic markers were more prevalent in the hemorrhagic phenotype of non-lobar ICH. Conclusion There are differences between MRI markers of SVD between patients with a lacunar stroke and those with a non-lobar ICH.

Background and Purpose: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults. Methods: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001–2004) and follow-ups (2004–2007 and 2007–2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models. Results: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04–0.86]) and lateral ventricular volume (0.58 [0.13–1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, −0.27 to 1.34]) or lacune number (−0.01 [−0.07 to 0.05]). Conclusions: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.

Background: Sulfatides (STs) in cerebrospinal fluid (CSF), as well as magnetic resonance imaging (MRI)-detected white matter hyperintensities (WMHs), may reflect demyelination. Here, we investigated the diagnostic utility of CSF ST levels in the subcortical small vessel type of dementia (SSVD), which is characterized by the presence of brain WMHs. Objective: To study the diagnostic utility of CSF ST levels in SSVD. Methods: This was a mono-center, cross-sectional study of SSVD (n = 16), Alzheimer’s disease (n = 40), mixed dementia (n = 27), and healthy controls (n = 33). Totally, 20 ST species were measured in CSF by liquid chromatography-mass spectrometry (LC-MS/MS). Results: CSF total ST levels, as well as CSF levels of hydroxylated and nonhydroxylated ST species, did not differ across the study groups. In contrast, CSF neurofilament light chain (NFL) levels separated the patient groups from the controls. CSF total ST level correlated with CSF/serum albumin ratio in the total study population (r = 0.64, p

Cerebral amyloid angiopathy (CAA) categorized as a cerebral small vessel disease can cause lobar intracerebral hemorrhage (ICH), convexity subarachnoid hemorrhage (SAH) and ischemic stroke (IS). The purpose of this study was to evaluate the differences in the diagnosis of CAA based on hospital characteristics and to assess the discharge outcomes of patients with CAA admitted for IS, ICH and SAH. Adult patients admitted with secondary diagnosis of CAA were identified in National Inpatient Sample in 2016 and 2017. Multivariable logistic regression analysis was performed to evaluate outcomes. A total of 16,040 patients had a secondary diagnosis of CAA. Among CAA patients, 1810 (11.3%) patients were admitted for IS, 4765 (29.7%) for ICH and 490 (3.1%) for SAH. Diagnosis of CAA was five-fold higher among patients admitted to urban teaching hospitals (aOR = 5.4;95% CI = 4.1–7.2) compared to rural hospitals and two-fold higher in large bed size hospitals (aOR = 2.3;95% CI = 2.0–2.7) compared to small bed size hospitals. Compared to non-CAA group, patients with history of CAA had lower odds of in-hospital mortality among patients admitted for ICH (10% vs 23%, aOR = 0.35; 95%CI = 0.27–0.44) and SAH (6% vs 19%, aOR = 0.24; 95%CI = 0.10–0.55); and higher odds of discharge to home among patients admitted for ICH (17% vs 18%, aOR = 1.27; 95%CI = 1.05–1.53). CAA diagnosis is less common in rural and small bed size hospitals compared to urban and large bedside hospitals, respectively. Patients with CAA admitted for ICH have better discharge outcomes compared to non-CAA patients admitted for ICH.

Arterial pseudoaneurysm formation after transradial cardiac catheterization is a rare post-procedural complication occurring in less than 0.1% of radial arterial access. While the data on the management of femoral pseudoaneurysms is extensive, few studies have evaluated how these techniques apply for small vessel arterial pseudoaneurysms. We present the case of an octogenarian man with a radial artery pseudoaneurysm after transradial coronary intervention that failed initial compression therapy, and surgical intervention was avoided by applying continuous compression therapy with a TR Band® radial compression device.

Chronic cerebral hypoperfusion, a major vascular contributor to vascular cognitive impairment and dementia, can exacerbate small vessel pathology. Connexin43, the most abundant gap junction protein in brain tissue, has been found to be critically involved in the pathological changes of vascular cognitive impairment and dementia caused by chronic cerebral hypoperfusion. However, the precise mechanisms underpinning its role are unclear. We established a mouse model via bilateral common carotid arteries stenosis on connexin43 heterozygous male mice and demonstrated that connexin43 improves brain blood flow recovery by mediating reparative angiogenesis under chronic cerebral hypoperfusion, which subsequently reduces the characteristic pathologies of vascular cognitive impairment and dementia including white matter lesions and irreversible neuronal injury. We additionally found that connexin43 mediates hypoxia inducible factor-1α expression and then activates the PKA signaling pathway to regulate vascular endothelial growth factor-induced angiogenesis. All the above findings were replicated in bEnd.3 cells treated with 375 µM CoCl2 in vitro. These results suggest that connexin 43 could be instrumental in developing potential therapies for vascular cognitive impairment and dementia caused by chronic cerebral hypoperfusion.

Perivascular space facilitates cerebral interstitial water clearance. However, it is unclear how dilated perivascular space (dPVS) affects the interstitial water of surrounding white matter. We aimed to determine the presence and extent of changes in normal-appearing white matter water components around dPVS in different populations. Twenty healthy elderly subjects and 15 elderly subjects with severe cerebral small vessel disease (CSVD, with lacunar infarction 6 months before the scan) were included in our study. And other 28 healthy adult subjects were enrolled under a different scanning parameter to see if the results are comparable. The normal-appearing white matter around dPVS was categorized into 10 layers (1 mm thickness each) based on their distance to dPVS. We evaluated the mean isotropic-diffusing water volume fraction in each layer. We discovered a significantly reduced free-water content in the layers closely adjacent to the dPVS in the healthy elderlies. however, this reduction around dPVS was weaker in the CSVD subjects. We also discovered an elevated free-water content within dPVS. DPVS played different roles in healthy subjects or CSVD subjects. The reduced water content around dPVS in healthy subjects suggests these MR-visible PVSs are not always related to the stagnation of fluid.

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder frequently accompanied by cerebral small vessel disease (CSVD). However, the influence of CSVD on the brain functional connectivity in subjects along the AD continuum is still largely unknown. The current study combined the static and dynamic functional network connectivity (FNC) to explore the underlying mechanism. Materials and Methods: In this study, we included 182 healthy controls, 27 individuals with subjective cognitive decline (SCD), 27 with SCD+CSVD, 104 with mild cognitive impairment (MCI), 123 with MCI+CSVD, 16 with AD, and 62 with AD+CSVD. We examined the static and dynamic FNC within the default mode, salience, and cognitive control domains. We also assessed the association between atypical FNC patterns and cognitive impairments, as well as the pathologies. Results: Static FNC results showed progressively increased within-domain connectivity and decreased between-domain connectivity along the AD continuum, especially in CSVD subjects. Dynamic FNC in CSVD subjects showed more occurrences in a highly modularized state and fewer occurrences in the diffusely connected state. Further analysis showed that neuropathology and CSVD burden divergently affect the FNC changes. Conclusions: The overall results demonstrate divergent abnormalities of FNC in CSVD and non-CSVD individuals along the AD continuum, which were divergently affected by neuropathology and CSVD burden. Specifically, those with CSVD show more static and dynamic FNC impairments, associated with cognitive decline. These findings may advance our understanding of the effect of CSVD on AD onset and progression, and provide potential hints for clinical treatment. IMPACT STATEMENT: By combining the static and dynamic brain functional network connectivity (FNC), our study explored the effect of vascular pathology on FNC in subjects along the Alzheimer's disease (AD) continuum. Results demonstrate divergent FNC abnormalities in individuals with/without cerebral small vessel disease (CSVD) along the AD continuum, which could be divergently affected by neuropathology (amyloid and tau) and CSVD burden. Notably, AD-continuum subjects with CSVD show more static and dynamic FNC impairments, associated with cognitive decline. Conclusively, these findings may advance our understanding of the effect of vascular pathology on AD onset and progression, and provide potential hints for clinical treatment.

Introduction Small vessel disease (SVD) commonly causes stroke and dementia. Early clinical predictors of disease progression are lacking. We aimed to determine whether informant reports of chronic cognitive/functional decline, prerequisites for dementia diagnosis, are associated with (a)baseline SVD burden, measured by Fazekas scores and (b)SVD change, measured by incident subcortical Diffusion-weighted Imaging (DWI) lesions. Method We prospectively recruited patients with mild ischaemic stroke, performed diagnostic MRI, and invited participants to repeat MRI 3- to 6-monthly. Informants completed the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) prior to baseline visit, a 16-item questionnaire which assesses patients’ cognitive and functional decline in the preceding ten years. Scores range from 1–5: a score above 3.3 has high sensitivity/specificity for dementia post-stroke. We conducted linear regression with IQCODE as the dependent variable, adjusting for age, sex, baseline MoCA, disability (modified Rankin Scale). Results We recruited 106 participants (mean age 67 years;range 40–86;33% female). Ninety-three informant questionnaires were returned. IQCODE associated with baseline Fazekas score; Fazekas 6 (β = 0.28, p = 0.04) vs. Fazekas 3 (β = 0.03, p = 0.67), R2 = 0.11, adjusted for age, sex, baseline MoCA, disability. Incident DWI lesions were common (15/106; 14/15 subcortical; no active embolic sources; median 67 days post-stroke). Four were asymptomatic, two reported stroke-like symptoms and nine had neuropsychiatric/non-focal symptoms. IQCODE was higher in those with a new lesion vs. without (β = 0.21, p = 0.02), R2 = 0.09, while age (β = −0.004, p = 0.19), MoCA (β = −0.006, p = 0.56) and disability (β = 0.06, p = 0.2) were not. Conclusions Higher SVD burden and incident, mostly “silent” stroke lesions associate more strongly with informant concerns of cognitive/functional decline than age or objective cognitive tests. These findings are novel in an ischaemic stroke population and the first to assess IQCODE/SVD progression. Future work should determine whether combining informant reports with imaging features of small vessel disease improves early detection of dementia.

Background and Purpose: There is increasing recognition of the importance of cortical microinfarcts to overall brain health, cognition, and Alzheimer dementia. Cerebral small vessel pathologies are associated with microinfarcts and frequently coexist with Alzheimer disease; however, the extent to which Aβ (amyloid beta) and tau pathology modulates microvascular pathogenesis is not fully understood. Study objective was to examine the relationship of small vessel pathologies, arteriolosclerosis, and cerebral amyloid angiopathy, with cortical microinfarcts in people with differing levels of Aβ or tau tangle burden. Methods: Participants were 1489 autopsied older people (mean age at death, 89 years; 67% women) from 1 of 3 ongoing clinical-pathological cohort studies of aging. Neuropathological evaluation identified cortical Aβ and tau tangle burden using immunohistochemistry in 8 brain regions, provided semiquantitative grading of cerebral vessel pathologies, and identified the presence of cortical microinfarcts. Logistic regression models adjusted for demographics and atherosclerosis and examined whether Aβ or tau tangle burden modified relations between small vessel pathologies and cortical microinfarcts. Results: Cortical microinfarcts were present in 17% of older people, moderate-to-severe cerebral amyloid angiopathy pathology in 36%, and arteriolosclerosis in 34%. In logistic regression models, we found interactions with Aβ and tau tangles, reflecting that the association between arteriolosclerosis and cortical microinfarcts was stronger in the context of greater Aβ (estimate, 0.15; SE=0.07; P =0.02) and tau tangle burden (estimate, 0.13; SE=0.06; P =0.02). Interactions also emerged for cerebral amyloid angiopathy, suggesting that the association between cerebral amyloid angiopathy and cortical microinfarcts is more robust in the presence of higher Aβ (estimate, 0.27; SE=0.07; P P =0.005). Conclusions: These findings suggest that in the presence of elevated Aβ or tangle pathology, small vessel pathologies are associated with greater microvascular tissue injury, highlighting a potential link between neurodegenerative and vascular mechanisms.

During COVID-19 pandemic, a wide variety of stroke typologies have been described in patients affected by SARS-CoV-2. Investigating the case reports of acute stroke in COVID-19 patients, published since the beginning of the pandemic, we tried to trace the pathogenic mechanisms of stroke during SARS-CoV-2 infection. We conducted a systematic review analyzing demographic data, cerebrovascular risk factors, NIHSS score, vascular territory involvement and laboratory findings of 168 patients described in 89 studies, from a pool of 1243 records. Based on our results, we have identified different stroke profiles: (1) cerebral large vessel disease (CLVD) profile with a low disability, simultaneous onset of COVID-19 and stroke symptoms, good outcome and low serum levels of D-dimer and CRP; (2) intracranial bleeding (IB) profile with high disability, poor outcome and low levels of serum markers of inflammation and coagulopathy; (3) CLVD profile with a short time-lapse between COVID-19 symptoms and stroke onset, high neurological disability and very high systemic inflammatory markers; (4) multiple thrombo-embolic disease (MTED) profile with older patients, many comorbidities, disabling stroke, poor outcome, evident alteration of coagulation tests and high serum levels of both D-dimer and CRP. We therefore summarized these different profiles in a spectrum similar to that of visible light, where the violet–blue band included IB and CSVD with low inflammation and prothrombotic activity, the green–yellow band included CLVD with high inflammation and moderate prothrombotic activity and the orange–red band for MTED with moderate-high levels of inflammation and very high prothrombotic activity.

Objective: Cerebral small vessel disease (CSVD) and chronic kidney disease (CKD) may be part of a multisystem small-vessel disorder. Since the kidney and brain share unique susceptibilities to vascular injury, kidney impairment may be predictive of the presence and severity of CSVD. This study explored the relationship between CSVD and CKD. Methods: Between December 2015 and December 2017 (follow-up 10–20 months) 52 patients with chronic nephritis and CKD were classified into a progressive group (n = 17) and stable group (n = 35). Age, gender, hypertension, diabetes and smoking were matched between groups. CSVD features of both groups, including enlarged Virchow-Robin spaces (VRS), white matter lesions (WML), lacunar infarcts (LI), and cerebral microbleeds (CMB) were evaluated by magnetic resonance (MR) imaging. Results: WML and CMB in the progressive group were exacerbated at follow-up compared to initial exam (p = 0.004 and 0.041, respectively). There was no significant change in VRS, WML, LI, or CMB in the stable group at follow-up compared to initial exam. CMB were significantly different between the progressive group and stable group at follow-up.etimtaed Glomerular filtration rate (eGFR) was significantly correlated with VRS, WML, and CMB at follow-up (p = 0.037, 0.041, and 0.009, respectively). Conclusions: Patients with progressive CKD have a higher prevalence and severity of CSVD, which correlates with deterioration of renal function as assessed by decreased eGFR. Thus EGFR may also be of value in the prediction of cerebral small vessel disease.

Age-related sporadic cerebral small vessel disease (CSVD) has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population. The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers' understanding in the in vivo evolution of CSVD, its impact upon the brain, its risk factors, and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD. In this review, we aimed to provide an update on the pathophysiology, risk factors, biomarkers, and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

Introduction: Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed. Methodology: We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test. Results: For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades. Conclusion: The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification.