Search Results (72)

Background/Objectives: This study aimed to investigate the relationship between carotid artery anatomy and geometry and white matter hyperintensities (WMH) and to determine whether it is a risk factor for the disease. Methods: The geometry and anatomy of both carotid arteries were evaluated with the three-dimensional vessel model obtained from the computed tomography angiography (CTA) data, and the segmentation software calculated the geometrical features of the arteries. In this model, vascular diameter, vascular cross-sectional area, carotid bifurcation and internal carotid artery (ICA) angles, as well as ICA tortuosity index (TI) measurements of the common carotid artery (CCA) and ICA were determined. Results: Compared with the non-WMH group, increased carotid bifurcation and ICA angle and higher ICA TI values were found in the WMH group (p < 0.001). In multivariate regression analysis, increased carotid bifurcation angle, higher ICA TI values, age, hypertension, and stroke history were identified as independent risk factors for the development of WMH (p < 0.05). In addition, age, carotid bifurcation angles and ICA angles were found to be associated with the severity of WMH (p < 0.05). Conclusions: Considering the vascular pathologies involved in the pathogenesis of WMH, identifying these risk factors may help determine individuals who are at an increased risk. Full article

Background/Objectives: Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline and dementia. The comparative prognostic value of MRI-based neuroimaging markers and genetic risk factors such as the APOE ε4 allele for cognitive outcomes remains uncertain. The objectives of this study were to estimate the pooled prevalence of cognitive impairment in CSVD, evaluate the associations of key neuroimaging markers (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes) and APOE ε4 with cognitive outcomes, and assess their diagnostic performance. Methods: This study included a systematic review and meta-analysis in accordance with PRISMA and MOOSE guidelines, searching five databases (2005–2025). Eligible studies included adults with CSVD and MRI-visible markers reporting cognitive outcomes (mild cognitive impairment [MCI], global cognitive impairment [GCI], all-cause dementia [ACD], vascular dementia [VaD], and Alzheimer’s disease [AD]). Thirty-nine studies comprising 18,425 participants were included. Pooled prevalence and associations were estimated using random-effects models, and diagnostic accuracy was evaluated. Certainty of evidence was assessed using the GRADE framework. Results: The pooled prevalence of GCI in CSVD was 57% (95% CI: 51–62%), while MCI prevalence was 46% (95% CI: 42–51%). WMHs were strongly associated with VaD (OR 10.35, 95% CI: 7.32–14.64), lacunes with ACD (OR 3.18, 95% CI: 1.24–8.20), and CMBs with AD (OR 1.52, 95% CI: 1.04–2.24). APOE ε4 carriage increased the risk of GCI (OR 1.80, 95% CI: 1.41–2.29). Across markers, diagnostic sensitivity was low, specificity was moderate-to-high, and AUROC values were modest. GRADE certainty ranged from low to moderate, with the highest confidence for WMHs and VaD. Conclusions: CSVD-related MRI markers and APOE ε4 are significantly associated with both early and late cognitive outcomes, supporting the integrated vascular–neurodegenerative continuum. The limited diagnostic sensitivity and variable certainty of evidence highlight the need for harmonized definitions, lesion quantification, and multimodal imaging–genetic approaches to improve early detection and risk stratification of CSVD-related cognitive impairment. Full article

Background/Objectives: Frank’s sign, a diagonal earlobe crease, may reflect systemic microvascular dysfunction. We investigated whether Frank’s sign serves as a clinical marker of white matter hyperintensity (WMH) burden in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a monogenic model of pure cerebral small vessel disease. Methods: We analyzed 81 genetically confirmed CADASIL patients (61.8 ± 12.6 years, 40.7% female) and 54 age/sex-matched controls (70.3 ± 6.6 years, 48.1% female). Frank’s sign was detected using deep learning from brain MRI-reconstructed 3D facial surfaces. WMH volumes were automatically quantified and adjusted for confounders using Random Forest regression residuals. We compared Frank’s sign prevalence between groups, assessed within-CADASIL associations, and evaluated dose–response relationships across WMH tertiles. Results: Frank’s sign prevalence was significantly higher in CADASIL versus controls (66.7% vs. 42.6%, p = 0.020), with strengthened association after multivariate adjustment (OR = 4.214, 95% CI: 1.128–15.733, p = 0.032). Within CADASIL, Frank’s sign-positive patients showed 72% greater WMH burden (51.5 ± 27.1 vs. 30.0 ± 26.1 mL, p < 0.001) and lower Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) total scores (57.7 ± 19.6 vs. 71.2 ± 22.8, p = 0.006), but similar lacunes, microbleeds, and hippocampal volumes. A robust dose–response relationship emerged across WMH tertiles, with Frank’s sign prevalence increasing from 37.0% (lowest) to 74.1% (highest tertile; adjusted OR = 3.571, 95% CI: 1.134–11.253, p = 0.030). Conclusions: Frank’s sign represents an accessible biomarker of WMH burden in CADASIL, demonstrating disease-specificity and dose–response characteristics independent of vascular risk factors. The automated MRI-based detection method of Frank’s sign enables retrospective analysis of existing neuroimaging databases, transforming a bedside observation into a quantifiable neuroimaging biomarker for genetic small vessel disease stratification. Full article

Background/Objectives: Cardiovascular disease (CVD) contributes to stroke and dementia. Individuals with CVD have high risk for adverse cognitive outcomes and stroke, possibly due to shared risk factors between CVD, stroke, and dementia, which may be attributed to cerebral small vessel disease (CSVD). We aim to determine the association between prevalent CVD and atrial fibrillation (AF) with CSVD. Methods: Composite of CVD [coronary heart disease, heart failure (HF)], its individual components, and AF were assessed. Multi-marker CSVD score was used to reflect increasing CSVD burden (cerebral microbleeds (CMBs), high-burden perivascular spaces, extensive white matter hyperintensity, cortical superficial siderosis, or covert brain infarcts were assigned 1 point each, with a range of 0–5). We related prevalent CVD, its individual components, and AF to multi-marker CSVD score and individual CSVD markers using logistic regression analyses adjusted for age, sex, FHS cohort, time between MRI and clinic exam (model-1), and vascular risk factors (model-2). Results: In 3413 participants (mean age: 59 ± 14 years, 53.4% women), 11% had prevalent CVD or AF, 8% had prevalent CVD, and 4% had prevalent AF. One CSVD marker was seen in 23% participants, and 9% had ≥ 2 markers. In multivariable-adjusted analyses, composite prevalent CVD and AF was associated with the presence of one CSVD marker (OR: 1.38, 95% confidence interval [CI]: 1.05–1.84). The association with ≥2 CSVD markers was not significant. Only CMBs were associated with components of CVD and AF, with the highest odds of association with HF. Conclusions: Prevalent CVD (including AF) is associated with the presence of CSVD, with all components associated with CMBs. Full article

Background: Vascular risk factors (VRFs) are known to influence cerebral small vessel disease (cSVD) burden and progression. However, their specific impact on the presence and distribution of each cSVD imaging marker (white matter hyperintensity [WMH], perivascular spaces [PVSs], lacunes, and cerebral microbleeds [CMBs]) and their spatial distribution remains unclear. Methods: We conducted a retrospective analysis of 93 patients with lacunar stroke with a standardized investigational magnetic resonance imaging protocol using a 3T scanner. WMH and PVSs were segmented semi-automatically, and lacunes and CMBs were manually segmented. We assessed the univariable associations of four common VRFs (hypertension, hyperlipidemia, diabetes, and smoking) with the load of each cSVD marker. Then, we assessed the independent associations of these VRFs in multivariable regression models adjusted for age and sex. Spatial lesion patterns were explored with regional volumetric comparisons using Pearson’s coefficient analysis, which was adjusted for multiple comparisons, and by visually examining heatmap lesion distributions. Results: Hypertension was the VRF that exhibited stronger associations with the cSVD markers in the univariable analysis. In the multivariable analysis, only lacunes (p = 0.009) and PVSs in the basal ganglia (p = 0.014) and white matter (p = 0.016) were still associated with hypertension. In the regional analysis, hypertension showed a higher WMH load in deep structures and white matter, particularly in the posterior periventricular regions. In patients with hyperlipidemia, WMH was preferentially found in hippocampal regions. Conclusions: Hypertension was confirmed to be the VRF with the most impact on cSVD load, especially for lacunes and PVSs, while the lesion topography was variable for each VRF. These findings shed light on the complexity of cSVD expression in relation to factors detrimental to vascular health. Full article

Objectives: This study aimed to investigate the relationship between osteoporosis and cerebral small vessel disease (CSVD) burden in stroke-free individuals, as well as its specific imaging markers, including lacunes, enlarged perivascular spaces (EPVSs), white matter hyperintensities (WMHs), and brain atrophy (BA). Methods: A total of 684 stroke-free patients who underwent both bone mineral density (BMD) assessments and brain MRI were included. Clinical data, CSVD burden scores, imaging markers of CSVD, and bone density parameters were collected. Logistic regression models were used to evaluate the relationship between BMD and CSVD burden and imaging markers. Results: Osteoporosis, including hip and vertebral osteoporosis, was independently associated with CSVD burden (OR = 2.332, 95%CI: [1.345, 4.039], p = 0.003; OR = 2.598, 95%CI: [1.540, 4.384], p < 0.001; OR = 1.515, 95%CI: [1.010, 2.272], p = 0.044). Increased BMD in the hip and spine correlated with reduced CSVD burden (OR = 0.929, 95%CI: [0.887, 0.972], p = 0.001; OR = 0.952, 95%CI: [0.917, 0.989], p = 0.012). Hip osteoporosis was a risk factor for lacunes (OR = 2.215, 95%CI: [1.197, 4.1], p = 0.011), multiple lacunes (OR = 2.274, 95%CI: [1.039, 4.980], p = 0.04), severe WMH (OR = 2.611, 95%CI: [1.171, 5.823], p = 0.019), and EPVS ≥ 2 (OR = 1.99, 95%CI: [1.133, 3.495], p = 0.017). No significant association was found between osteoporosis and BA (p = 0.928). In sex-stratified analyses, both hip and vertebral osteoporosis were independently associated with a higher CSVD burden in female patients (hip: OR = 2.529, 95%CI: [1.122, 5.703], p = 0.025; vertebral: OR = 3.129, 95%CI: [1.517, 6.455], p = 0.002; general osteoporosis: OR = 1.755, 95%CI: [1.057, 2.912], p = 0.03), whereas no significant association was observed in male patients (all p > 0.05). Conclusions: Osteoporosis was independently associated with an increased burden of CSVD, particularly evident in female patients. These findings suggest that bone health may be important in CSVD management, particularly for women. Full article

Background: Hyperintense vessels (HVs) visualized on FLAIR MRI are believed to reflect sluggish antegrade or retrograde flow in leptomeningeal collaterals that develop in response to major intracranial artery stenosis or occlusion. HV is frequently observed in conditions such as Moyamoya disease and symptomatic ICA/MCA steno-occlusion. However, the relationship between HV and cerebral hemodynamics—and the effect of STA-MCA bypass on HV—remains inadequately characterized. This study aimed to investigate the relationship between HV on FLAIR and cerebral vascular hemodynamic status, as measured by SPECT, in patients with Moyamoya disease and symptomatic ICA/MCA occlusion. The secondary goal was to assess the impact of recanalization through STA-MCA bypass surgery on the presence of HV. Methods: We retrospectively analyzed 49 patients with symptomatic ICA or MCA steno-occlusion who underwent STA-MCA bypass between 2015 and 2020. Pre- and postoperative FLAIR MRIs were evaluated, and HV presence was graded as negative (0), minimal (1), or positive (2). SPECT was utilized to assess cerebrovascular reserve (CVR) in regions exhibiting various HV intensities. Follow-up FLAIR imaging was performed 3–14 months postoperatively to correlate HV changes with hemodynamic improvements observed via SPECT. Result: HV was present in 74% (36/49) of affected hemispheres. Regions exhibiting minimal or positive HV demonstrated a significantly lower CVR compared to HV-negative areas, indicating compromised perfusion. Following bypass surgery, HV was reduced or resolved in 65% (32/49) of patients, and this regression corresponded with improved CVR as confirmed by both SPECT and perfusion MRI. Conclusions: HV presence on FLAIR imaging is associated with impaired cerebrovascular hemodynamics in patients with Moyamoya disease or symptomatic large-vessel steno-occlusion. HV-positive territories exhibit reduced CVR, while surgical revascularization via STA-MCA bypass leads to hemodynamic improvement and concurrent HV reduction. These findings support HV as a potential surrogate marker for treatment response. Full article

Background: The brain’s vascular system has recently been shown to provide an important efflux pathway for cerebral waste clearance (CWC). However, little is known about the influence of aging or diabetes on the CWC. The aim of the current study is to investigate the vasculature contribution to CWC under aging and diabetic conditions. Methods: Male Wistar rats under aging and diabetic conditions were evaluated using dynamic intra-cisterna superparamagnetic iron oxide-enhanced susceptibility-weighted imaging (SPIO-SWI). Theoretical analysis of the expected signal intensity using SPIO-SWI was compared with the corresponding dynamic in vivo images. Quantitative susceptibility mapping (QSM) was used to evaluate the iron-based tracer concentration in the venous system. Results: Our data demonstrated that the theoretical analysis predicted the dynamic changes in the signal intensity after SPIO infusion. The distinct hyperintense signals due to the lower concentration of the SPIO over time in cerebrospinal fluid (CSF) and meningeal lymphatic (ML) vessels likely represented the CWC through various efflux pathways, including cerebral vascular and ML vessels. The QSM analysis further revealed reduced CWC from the vasculature in both the aged and diabetic groups compared to the younger group. Conclusions: Our results demonstrated that SPIO-SWI can quantitatively evaluate the CWC efflux contributions from cerebral vascular vessels under aging or diabetic conditions. Full article

Cerebral small vessel disease (cSVD) is a common cause of stroke and dementia. Ageing, hypertension, hyperglycaemia, and smoking make up the biggest risk factors for cSVD. They individually or collectively increase the levels of reactive oxygen species, pro-inflammatory cytokines and matrix metalloproteinases, decrease the bioavailability of nitric oxide, and, in the process, compromise the structural integrity and function of the vascular endothelium, blood–brain barrier, and brain parenchyma. These then appear as white matter hyperintensities, enlarged perivascular spaces, cerebral microbleeds, and atrophy in cerebral imaging. As there is currently no curative therapy for cSVD, prevention or delay of cSVD remains of particular importance to preserve quality of life for as long as possible. Bearing that in mind, this review explores whether drugs used for other neurovascular conditions may prevent neuroinflammation and oxidative damage and effectively maintain endothelial function and blood–brain barrier integrity. It also examines whether potential benefits may be extended to cSVD. The list of drugs includes anti-anginal drugs, acetylcholine esterase inhibitors, β-hydroxy β-methylglutaryl-CoA reductase inhibitors, lithium drugs, phosphodiesterase inhibitors, oral antihyperglycaemic drugs, and tetracycline antibiotics. This review discusses the mechanisms of action of these agents and critically evaluates preclinical, translational, and clinical research pertaining to cSVD. Full article

Background/Objectives: Low-grade inflammation in the form of microglial activation may be involved in neurodegenerative and vascular dementias. Subcortical small-vessel disease (SSVD) is the main form of vascular dementia, associated with brain barrier dysfunction and endothelial and monocyte activation. IL-6 and IL-17A are known proinflammatory cytokines that contribute to the disruption of blood–brain barrier integrity and microvascular dysfunction, features that are central to SSVD pathophysiological pathways. We herein compared cerebrospinal fluid (CSF) IL-6 and IL-17A concentrations in SSVD and AD patients as well as control subjects and examined the potential associations among IL-6 and IL-17A levels with cognitive and ΜRΙ changes. The albumin quotient (Qalb) was also calculated. Methods: CSF IL-6 and IL-17A (18 SSVD, 17 AD, and 12 healthy controls) were measured with solid-phase sandwich ELISAs, while albumin levels were measured by immunonephelometry. MMSE, FAB, and the CLOX tests were used for cognitive assessment and MRI was used for atrophy and white matter hyperintensities. Results: Significantly elevated CSF levels of Qalb and IL-6 were found in SSVD patients compared to both AD (p = 0.02) and controls (p = 0.002), respectively. Moreover, CSF IL-6 levels displayed a significant inverse correlation with CLOX2 scores (r = −0.641, p = 0.02), as well as a positive correlation with the total normalized CSF volume (r = 0.7, p = 0.01). CSF IL-17A levels were found to be reduced in SSVD patients, compared to controls and AD patients (p < 0.0001 and p = 0.002, respectively). The IL-6/IL-17A ratio with a cut-off value > 1.004 displayed a sensitivity of 83.33% (95%CI; 60.78% to 94.16%) and a specificity of 68.97% (95%CI; 50.77% to 82.72%) for the discrimination of SSVD from AD patients and controls. Conclusions: In the present pilot single-center study, we found increased CSF IL-6 and IL-6/IL-17A ratio levels in SSVD patients that correlated with reduced scores in the CLOX2 test and increased CSF volume. These preliminary findings deserve further evaluation in larger cohorts in order to elucidate their potential as surrogate biomarkers for the discrimination of SSVD from AD pathology. Full article

Background/Objectives: Hemispatial neglect is common after stroke but is often evaluated only after right hemisphere (RH) stroke. We sought to determine the prevalence of two types of neglect, viewer-centered neglect (VCN) and stimulus-centered neglect (SCN), after left hemisphere (LH) and RH strokes. Additionally, we identified lesion load in each vascular territory and areas of hypoperfusion, estimated with FLAIR hyperintense vessels (FVHs) that contribute to neglect. Methods: A series of 233 stroke patients (73 LH and 160 RH) were administered a task to detect VCN and SCN and received brain MRI within 5 days of onset. We used multivariable logistic regression to identify vascular territories where lesion load and/or hypoperfusion contributed to each type of neglect. Results: While VCN was more prevalent after RH stroke, SCN occurred at a similar rate after LH and RH stroke. In RH stroke, lesion load in the middle cerebral artery occipital region and anterior cerebral artery territory and age predicted left VCN, whereas parietal hypoperfusion independently predicted left SCN. In LH stroke, lesion load across regions and age predicted right VCN, while lesion load in posterior cerebral artery occipital and anterior cerebral artery regions, as well as age, predicted right SCN. The addition of information about hypoperfusion improved the prediction of both VCN and SCN. Conclusions: VCN and SCN are each common after RH stroke, and SCN is common after LH stroke. Each type of neglect is accounted for by distinct areas of infarct and hypoperfusion. Results will aid in the detection of neglect after stroke and may guide reperfusion interventions to improve neglect. Full article

Background/Objectives: The aim of the study was to evaluate the usefulness of vessel wall imaging and MRI in assessment of the post-COVID-19 changes in the brain. VWI is a progressive MRI technique that provides precise imaging of the pathological process in the wall of the vessel. It might help us to better understand the pathophysiology of COVID-19-related neurological lesions and may have an impact on management protocols. Methods: A total of 43 patients were included in the study; the post-COVID-19 group included 23 patients hospitalized for COVID-19 (mean age of the group: 53.52 years; 26% male, 74% female). The control group consisted of 20 patients from the general population who did not suffer from COVID-19 (mean age: 52.15 years; 35% male, 65% female). MRI examinations were performed on a 3T scanner (Biograph mMR, Siemens). The VW-MRI protocol included T1-weighted SPACE FS black-blood images, FLAIR images, SWI, and MRA. Results: Several radiological changes in post-COVID-19 patients were described: hyperintense foci in the white matter of the brain hemispheres, in the lower parts of the temporal lobes, and in the structures of the posterior cranial fossa; presence of engorgement of deep medullary veins or perivascular enhancement; presence of inflammatory vessel thickening in VWI images; changes in hippocampus size; presence of cortical atrophy; and thickening of the mucous membrane of the paranasal sinuses. The presence of atherosclerotic vessel thickening in VWI and the width of the third ventricle depended on the age of the patient. Conclusions: VWI and MRI may be useful in the assessment of post-COVID-19 lesions in the brain. Full article

Background and Purpose: Perivascular spaces (PVS) are usually enlarged in small vessel disease (SVD). However, the significance of PVS patterns in different locations is uncertain. Hence, we analyzed the distribution of PVS in patients with a recent small subcortical infarct (RSSI) and their correlation with clinical and imaging factors. Materials and Methods: In a cohort of 71 patients with an RSSI with complete clinical data, including the Pittsburgh Sleep Quality Index (PSQI), we segmented PVS in white matter (WM-PVS), basal ganglia (BG-PVS), and brainstems (BS-PVS) on 3T-MRI T2-weighted sequences, obtaining fractional volumes (%), and calculated the WM/BG-PVS ratio. We analyzed the Pearson’s correlation coefficients between PVS regional loads. We used normalized PVS measures to assess the associations with clinical and MRI-SVD features (white matter hyperintensities (WMHs), number of lacunes, and microbleeds) in univariable and multivariable linear regressions adjusted for age, sex, and hypertension. Results: In our cohort (mean age 70 years; 27% female), the Pearson’s correlation coefficients between WM-PVS/BG-PVS, WM-PVS/BS-PVS, and BG-PVS/BS-PVS were 0.67, 0.61, and 0.59 (all p < 0.001). In the adjusted models, BG-PVS were associated with lacunes (p = 0.034), WMHs (p = 0.006), and microbleeds (p = 0.017); WM-PVS with lacunes (p = 0.003); while BS-PVS showed no associations. The WM/BG-PVS ratio was associated with lacunes (p = 0.018) and the PSQI (p = 0.046). Conclusions: PVS burdens in different regions are highly correlated in patients with RSSI but with different SVD patterns. Sleep quality impairment might affect waste removal mechanisms differently in the WM and BG regions. Full article

Background/Objectives: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. Methods: This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD. MRI assessments followed the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE), with a total burden of small-vessel disease (TBSVD) score calculated. Statistical analyses included forward selection and binary logistic regression. Results: TBSVD differed significantly across groups (p < 0.001), except between SAH and IA groups (p = 0.8). Controls had the lowest TBSVD (1.00; 1.22 ± 0.996), followed by SAH (2.00; 2.08 ± 1.013) and IA groups (2.00; 2.04 ± 1.141), with the highest in the CSVD group (1.00; 1.22 ± 0.996). White-matter hyperintensity (WMH) patterns varied with IA rupture status (p = 0.044); type A was prevalent in SAH patients and type D in the IA group. Incorporating MRI CSVD features and TBSVD into risk assessments did not enhance IA prediction or outcome models. Conclusions: IA patients exhibit a higher CSVD burden than controls, suggesting a link between small and large intracranial vessels. WMH patterns distinguish between ruptured and unruptured IA patients, offering potential markers for IA rupture risk assessment and signaling a paradigm shift in understanding IAs and CSVD. Full article