Vascular Risk Research Articles

ObjectiveTo investigate the effect of enlarged perivascular spaces in the basal ganglia (BG-EPVS) on interstitial fluid (ISF) content in white matter and to assess the mediating role of deep medullary vein (DMV) dysfunction in this relationship among patients with cerebral small vessel disease (CSVD).MethodsMagnetic resonance imaging and clinical data were collected from 166 patients with CSVD. EPVS score (0–4) was evaluated on T2-weighted images on the basis of the number of EPVS in a single slice. DMV score (0–18) was assigned on susceptibility-weighted imaging according to signal continuity and clarity. Free water (FW) values, representing ISF content in white matter, were derived from diffusion tensor imaging.ResultsThe mean age of the participants was 63.6 ± 11.1 years. The median score was as follows: BG-EPVS, 1 (IQR: 1–2); centrum semiovale EPVS (CSO-EPVS), 1 (IQR: 1–2); CSVD score, 1 (IQR: 0–2), and DMV, 4 (IQR: 1–11). The mean FW values were 0.25 ± 0.02. No significant correlation was observed between CSO-EPVS and FW (r = 0.112, p = 0.119). In contrast, BG-EPVS showed a moderate positive correlation with both DMV score (r = 0.594, p < 0.001) and FW (r = 0.521, p < 0.001). DMV score was also moderate positively correlated with FW (r = 0.557, p < 0.001). These associations remained significant after adjusting for age, sex, and vascular risk factors (all p < 0.05). Mediation analysis confirmed that DMV score significantly mediated the relationship between BG-EPVS and FW, independent of covariates.ConclusionHigher BG-EPVS score is significantly associated with increased ISF content in white matter, with DMV dysfunction serving as a key mediator of this association.

Background: Beta-thalassemia major (β-TM) is a severe hemoglobinopathy requiring lifelong transfusions, leading to iron overload and complications. Evidence links β-TM to premature vascular changes, including atherosclerosis, indicated by increased carotid intima-media thickness (CIMT) due to iron overload, chronic inflammation, and oxidative stress. Despite known cardiovascular risks, data on subclinical atherosclerosis in β-TM are scarce. Aims and Objective: This study aims to determine the prevalence of premature subclinical atherosclerosis in transfusion-dependentβ-TM by measuring CIMT and correlating findings with clinical and biochemical parameters for early cardiovascular risk prevention. Materials and Methods: This prospective observational study was conducted at the Department of Pediatrics, Hassan Institute of Medical Sciences, Hassan, over 3 months (May–September 2023), involving 70 children (35 β-TM and 35 controls). Inclusion criteria were transfusion-dependent β-TM (2–18 years) with ≥8 transfusions/year, whereas children with congenital heart disease or familial hypercholesterolemia were excluded. Demographic, clinical, and laboratory data (complete blood count, lipid profile, C-reactive protein, ferritin, and liver enzymes) were recorded. CIMT was measured via B-mode ultrasound. Results: This study revealed a high prevalence of premature subclinical atherosclerosis, with significantly increased carotid and femoral artery intima-media thickness (IMT) (P&lt;0.001) and dyslipidemia (76.3%). Hemoglobin was lower (8.06 vs. 11.37 g/dL, P&lt;0.001), and serum ferritin was elevated (2080.70 vs. 128.03 ng/mL, P&lt;0.001), indicating anemia with iron overload. About 60.5% of patients had both dyslipidemia and increased IMT. Age and serum ferritin significantly predict increased CIMT, with ferritin showing a stronger association, indicating early vascular changes. Conclusion: This study confirms a high prevalence of premature subclinical atherosclerosis in transfusion dependent β-TM patients, evidenced by increased CIMT. These findings justify early cardiovascular screening and intervention to mitigate long-term vascular risks in this vulnerable population.

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.

Background/Objective: Malnutrition and sarcopenia are common complications after ischemic stroke and have a negative impact on prognosis. The C-reactive protein/albumin ratio (CAR) reflects both inflammation and nutritional status, but its predictive role in this setting has not been widely studied. This study aimed to investigate the predictive value of CAR (C-reactive protein/albumin ratio) for malnutrition risk and probable sarcopenia in patients with ischemic stroke. Methods: In this prospective observational study, 197 patients with acute ischemic stroke were evaluated. Patients with chronic renal or hepatic failure, malignancy, active infection, and hand disability preventing grip strength measurement were excluded. Demographic data (age, sex), vascular risk factors, the NIHSS score, and laboratory parameters were recorded. The nutritional status of patients was assessed using the Nutritional Risk Screening-2002 (NRS-2002), and sarcopenia risk was evaluated with the SARC-F questionnaire. Handgrip strength was measured in patients with high SARC-F scores to define probable sarcopenia. CAR was calculated from serum CRP and albumin levels. Logistic regression was applied to identify independent predictors, and receiver operating characteristic (ROC) analyses were performed to determine the discriminatory ability and cut-off values of CAR. The nutritional status of patients admitted to the neurology clinic with acute ischemic stroke was assessed using the Nutritional Risk Screening-2002 (NRS-2002), and sarcopenia risk was evaluated with the SARC-F questionnaire. Handgrip strength was measured in patients with high SARC-F scores to define probable sarcopenia. CAR was calculated from serum CRP and albumin levels. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: Malnutrition risk was identified in 32.5% of patients, and probable sarcopenia was identified in 19.3% of patients. ROC analysis showed that CAR had acceptable discriminatory power for both conditions. In multivariate analysis, CAR was consistently identified as an independent predictor of malnutrition risk and possible sarcopenia. ROC analysis for malnutrition risk showed an AUC of 0.750 (cut-off: 0.306; sensitivity 68.8%; specificity 75.2%). In regression analysis, CAR (OR = 2.13; 95% CI: 1.39-3.26; p < 0.001), age (OR = 1.05; 95% CI: 1.02-1.09; p = 0.003), and NIHSS (OR = 1.11; 95% CI: 1.01-1.23; p = 0.026) were independent predictors. For probable sarcopenia, ROC analysis revealed an AUC of 0.814 (cut-off: 0.320; sensitivity 81.6%; specificity 71.7%). Multivariate analysis identified CAR (OR = 1.73; 95% CI: 1.19-2.52; p = 0.004), age (OR = 1.11; 95% CI: 1.05-1.18; p < 0.001), and NIHSS (OR = 1.19; 95% CI: 1.05-1.35; p = 0.007) as independent predictors. Conclusions: CAR was identified as an independent predictor of both malnutrition risk and probable sarcopenia in ischemic stroke patients. CAR may serve as a reliable biomarker for early nutritional and functional risk stratification in clinical practice.

BackgroundCognitive Frailty (CF), characterized by the co-occurrence of physical frailty and cognitive impairment without dementia, is a significant concern in older adults with Type 2 Diabetes Mellitus (T2DM). This study investigates the prevalence and risk factors of CF in this population, addressing the urgent need for early detection and intervention strategies.MethodsA cross-sectional study was conducted among 713 T2DM patients aged ≥65 years. Participants were assessed using the Clinical Dementia Rating (CDR) for cognitive function and Fried Frailty Phenotype (FP) criteria for physical frailty. CF was defined as CDR = 0.5 and FP score ≥ 3. Multivariable logistic regression identified independent risk factors, adjusting for demographic and clinical variables.ResultsThe prevalence of CF was 24.3%. Cerebrovascular disease (OR: 2.39, 95% CI: 1.44–3.97) and peripheral arterial disease (OR: 1.74, 95% CI: 1.03–2.95) were significant risk factors, while higher education (OR 0.85, 95% CI 0.76–0.94) and later diabetes onset (OR: 0.93, 95% CI: 0.88–0.98) were protective. Early-onset diabetes significantly increased CF risk regardless of education level.ConclusionThis study highlights a markedly increased risk of CF in older adults with T2DM, especially in individuals with CVD, PAD, low education levels, or early-onset diabetes. Notably, early diabetes onset may override the protective effects of cognitive reserve, emphasizing the critical need for early metabolic and vascular risk management in this high-risk population. These findings support integrated screening for cognitive and physical frailty in diabetes care to enable timely interventions.

Despite the emergence of anti-amyloid therapies for Alzheimer's disease, targeting modifiable risk factors remains the most effective primary prevention strategy for dementia. While cognitive benefits of multimodal lifestyle interventions have been demonstrated, the underlying effects on brain structure remain unclear, likely due to heterogeneity in brain structure among at-risk individuals. To investigate how distinct subgroups of at-risk individuals, defined by cortical and subcortical grey matter (GM) patterns, differ in their response to the FINGER intervention, as well as in their demographic, vascular, and lifestyle profiles. Observational study employing unsupervised clustering of MRI-based cortical thickness and subcortical volume metrics, followed by longitudinal assessment of a lifestyle intervention. The FINGER randomized controlled trial (RCT), a population-based, multidomain lifestyle intervention targeting older adults (aged 60-77) with elevated cardiovascular risk (CAIDE score ≥ 6) and average to slightly below-average cognitive performance. A total of 120 participants (61 intervention, 59 control) with available baseline MRI data. Participants were randomly assigned (1:1, double-blind) to a 2-year multidomain lifestyle intervention group - targeting diet, physical activity, cognitive training, social engagement, and metabolic and vascular risk management - or to a control group receiving standard health advice. Sociodemographic, vascular, and lifestyle factors, medical comorbidities, and cognitive performance, were assessed at baseline (pre-intervention). Additionally, brain structural outcomes (mean cortical thickness, Alzheimer's disease and resilience-related cortical signatures, hippocampal volume), and cognition (global, executive function, processing speed, memory) were analysed post-intervention using hierarchical linear models stratified by GM cluster. Clusters with diffuse or frontal-predominant cortical thinning, but with more favourable vascular profiles, characterized by lower blood pressure and reduced obesity, showed significantly less cortical thinning (mean thickness, AD-signature, and resilience-signature regions; all p < 0.05) following the intervention. Stratifying at-risk individuals by GM patterns and vascular risk revealed differential brain responses to the FINGER intervention. These findings underscore the value of brain-based subtyping to optimize personalized dementia prevention strategies in heterogeneous at-risk populations. ClinicalTrials.gov Identifier: NCT01041989.

Background and ObjectivesStudies in northern America report lower prevalence of atrial fibrillation (AF) in Black people than in White people despite higher vascular risk factor prevalence. However, it remains unclear whether these differences are driven by biology vs variations in health care access or alcohol use. We aimed to determine whether ethnic differences in AF persist in the United Kingdom, where the National Health Service provides equitable access to care, and whether they are robust to adjustment for deprivation and alcohol use and are also seen for covert paroxysmal AF on ambulatory screening.MethodsWe performed a systematic review of UK-based studies reporting AF and vascular risk factor prevalence across ethnic groups and pooled estimates by random-effects meta-analysis. Findings were validated in a prospective population-based cohort (Oxford Vascular Study, OxVasc) of patients with suspected TIA or stroke in Oxfordshire, United Kingdom (April 2002–March 2023), through logistic regression adjusted for deprivation and alcohol use, and in a subset of participants recruited after October 2010 who were systematically screened for left atrial dilatation and paroxysmal AF.ResultsAmong UK-based studies of patients with stroke, Black and Asian people had lower prevalence of AF (pooled OR, 95% CI, number of studies: 0.25, 0.20–0.32, n = 3; 0.37, 0.28–0.49, n = 6), alcohol consumption (0.42, 0.36–0.49, n = 2; 0.26, 0.13–0.49, n = 3), and smoking (0.70, 0.50–0.97, n = 2; 0.57, 0.44–0.74, n = 5), but higher rates of hypertension (1.95, 1.47–2.60, n = 3; 1.47, 1.02–2.12, n = 6) and diabetes (2.78, 2.40–3.22, n = 3; 4.15, 3.11–5.53, n = 6). In stroke-free populations, similar differences were observed, especially for AF (0.47, 0.12–1.86, n = 2; 0.34, 0.15–0.74, n = 5). Among 7,297 OxVasc participants (47.4% women, 71.0 ± 15.5 years, 335 non-White), AF prevalence was lower in non-White people even after adjustment for age, sex, vascular risk factors, deprivation, and alcohol consumption (adjusted odds ratio [OR] = 0.52, 0.32–0.82, p = 0.005). Among 2,221 participants with routine cardiac investigation, non-White people had lower prevalence of paroxysmal AF (2.3% vs 9.1%, OR = 0.24, 0.07–0.75, p = 0.004) or atrial dilatation (17.7% vs 27.2%, OR = 0.58, 0.34–0.99, p = 0.04).DiscussionAn AF paradox exists in ethnic minority groups in the United Kingdom, for permanent and paroxysmal AF, which is independent of vascular risk factors, deprivation, and alcohol consumption, suggesting different biological susceptibilities.

There are inconsistent data on the long-term risk of dementia after TIA. We used the multidecade Atherosclerosis Risk in Communities (ARIC) study to examine long-term risk of incident dementia and other post-TIA outcomes. The ARIC study recruited participants from 4 US communities-Minneapolis, MN; Jackson, MS; Forsyth County, NC; and Washington County, MD-during the years 1987-1989. Participants have been followed through in-person visits, phone calls, and hospital and death registry surveillance. Our exposure was the first hospitalized TIA event, ascertained between 1987 and 2020. We report on post-TIA incident events ascertained between 1987 and 2020, including adjudicated dementia, stroke, cardiovascular disease (CVD) events, and mortality. We used Cox proportional hazard regression modeling with TIA as a time-dependent exposure to estimate associations with outcome events. Models were adjusted for demographics and vascular risk factors. The ARIC study enrolled 15,792 participants (27% Black) aged 45-64 years. Our analytic sample included 13,721 participants (mean age 54 years, 55.5% women) who were without history of hospitalized TIAs or the outcomes of interest at baseline. There were 536 hospitalized TIAs over a median of 29 years. Incident dementia risk almost doubled after TIA (hazard ratio [HR] 1.96; 95% CI 1.66-2.31). Participants who had a TIA were at high risk of stroke (8.14; 6.87-9.64) and CVD (1.52; 1.28-1.82) compared with those without a TIA. They were also at an elevated risk of all-cause mortality (HR 1.55; 95% CI 1.39-1.73) and CVD mortality (1.82; 1.48-2.22). A sensitivity analysis restricted to participants with TIAs but without stroke showed an elevated risk of dementia (HR 1.67; 95% CI 1.37-2.03). We report an increased risk of dementia after TIA in our multidecade cohort. The elevated risk was present after elimination of stroke as an intermediary variable. Consistent with other studies, we found an increased risk of stroke, CVD, and mortality after TIA. The clinical implications of these results are that in addition to vascular risk factor modification, clinicians should consider incorporating cognitive screening into post-TIA follow-up care.

The triglyceride - glucose (TyG) index is a surrogate of insulin resistance and may predict vascular risk. We evaluated whether baseline TyG is associated with incident stroke and all-cause mortality in adults with diabetes. We analyzed 10,000 UK Biobank participants with diabetes and no baseline cardiovascular disease. TyG was calculated from fasting triglycerides and glucose and categorized into quartiles. Outcomes (stroke; all-cause mortality) were ascertained via hospital and death registries. Cox models estimated hazard ratios (HRs) adjusting for demographic, lifestyle, and clinical covariates. Over a median 12.8 years, 620 strokes and 688 deaths occurred. Compared with Q1, Q4had higher risks of stroke (HR 1.45, 95% CI 1.18-1.80) and mortality (HR 1.42, 95% CI 1.17-1.73). Each 1-SD higher TyG was associated with ~ 19% higher stroke risk (HR 1.19, 95% CI 1.07-1.32) and ~ 16% higher mortality risk (HR 1.16, 95% CI 1.05-1.29). Associations were consistent across age, sex, and BMI subgroups and robust in sensitivity analyses, including extended adjustment. Higher TyG is independently associated with increased risks of stroke and all-cause mortality among individuals with diabetes. As an inexpensive measure derived from routine tests, TyG may aid risk stratification and inform targeted prevention in this high-risk population.

Vascular risk factors (VRFs) such as smoking, hypertension, obesity, and diabetes are associated with dementia, but their importance in Parkinson disease (PD) and PD-dementia (PDD) is less well understood. Previous studies demonstrated that smoking may be protective of PD, but its role in PDD is unclear. The primary objective was to examine the association between midlife VRFs and the risk of developing PD and PDD in older adults. The prospective, longitudinal community-based cohort Atherosclerosis Risk in Communities study recruited Black and White adults (45-64 years old) from Jackson, MS; Forsyth County, NC; Minneapolis suburbs, MN; and Washington County, MD, in 1987-1989. VRFs (smoking status, hypertension, obesity, hypercholesterolemia, and diabetes) were measured at the baseline visit. PD cases were retrospectively adjudicated through 2016 by reviewing participant medications, self-reported physician-made diagnoses, and hospitalization and death surveillance data. Dementia cases were adjudicated using in-person and telephone-based cognitive testing, informant interviews, and hospitalization codes. PDD cases were defined as an adjudicated PD diagnosis followed by an adjudicated dementia diagnosis. Cox proportional hazard models, adjusted for age, race, sex, education level, and APOE ε4 status, evaluated midlife VRFs together in association with PD, with separate models evaluating PD without dementia, PDD, and dementia without PD. Among 13,875 individuals with nonmissing VRF and outcome data with up to 30 years of follow-up (25% Black, 54% female), 179 developed PD at a mean age of 73.4 years, 94 developed PDD at a mean age of 79.2 years, and 1,791 developed dementia without PD at a mean age of 79.7 years. Midlife current smoking (hazard ratio [HR] 0.36, 95% CI 0.21-0.61) was significantly associated with a lower PD rate, independent of other risk factors and demographics. Midlife current smoking was also significantly associated with a lower rate of PDD (HR 0.41, 95% CI 0.18-0.95). Other VRFs were not associated with either PD or PDD. Smoking status in midlife was associated with lower rates of PD and PDD, but other VRFs had no association with PD or PDD. Further studies should evaluate changes of these VRFs over the life course and explore mechanisms for the observed associations.

Stroke-associated pneumonia (SAP) is a frequent complication of acute ischemic stroke (AIS) that contributes to poor clinical outcomes. The systemic immune-inflammation index (SII), derived from neutrophil, lymphocyte, and platelet counts, may reflect post-stroke immune imbalance, but its role in predicting SAP remains unclear. In this retrospective study, we analyzed 1,767 AIS patients and evaluated the association between log₂-transformed SII and the occurrence of SAP using multivariable logistic regression, generalized additive models, and two-piecewise regression. SAP developed in 21.3% of patients during hospitalization. Higher SII levels were independently associated with increased SAP risk after adjustment for age, sex, vascular risk factors, comorbidities, baseline National Institutes of Health Stroke Scale (NIHSS) score, and dysphagia assessed by Kubota Water Drinking Test (KWDT). Patients in the highest SII quartile had a significantly greater likelihood of developing SAP compared to those in the lowest quartile (adjusted odds ratio = 2.03, 95% confidence interval: 1.21–3.38, p = 0.0069). A non-linear, threshold-dependent relationship was identified, with SAP risk increasing substantially beyond log₂-SII ≈ 8.5. Receiver operating characteristic (ROC) analysis demonstrated moderate predictive performance of SII for SAP (area under the curve (AUC) = 0.726), while C-reactive protein (CRP) showed superior discrimination (AUC = 0.826 p < 0.0001). Supplementary sensitivity analyses, including a fully adjusted model without NIHSS and KWDT and an alternative model replacing these with the A2DS2 score (Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity), showed consistent results, supporting the robustness of our findings. These findings suggest that SII may serve as a cost-effective and accessible biomarker to aid early identification of high-risk AIS patients.

Cognitive decline can occur following ischaemic stroke. How cognition changes over time and associations with cognitive change are poorly understood. This study aimed to explore these issues over 2 years following ischaemic stroke. This analysis used data from the XILO-FIST study, a clinical trial of allopurinol versus placebo in people with ischaemic stroke according to Tissue-Based Definition. Participants underwent clinical assessment, brain MRI at baseline, and Montreal Cognitive Assessment (MoCA) at baseline, year 1 and year 2. We defined cognitive impairment as a MoCA score < 26 and cognitive change as a difference in MoCA score of 2 points or more at year 1 or year 2 after randomisation. Associations with cognitive impairment and cognitive change were assessed by univariable analysis and multiple logistic regression. Three hundred and sixty participants with complete MoCA data were included. Mean age was 65.4 (SD 8.36) years, and mean baseline MoCA score was 26.4 (SD 2.7). Seventy-seven participants had second-year cognitive improvement. Eighty-four had second-year cognitive decline. After adjustment for age and education year, second-year cognitive improvement was associated with smaller brain volume, lower albumin level, smoking and greater white-matter hyperintensity, and second-year cognitive decline was associated with peripheral arterial disease, higher cholesterol level, small-vessel stroke and greater white-matter hyperintensity. Cognition is dynamic following stroke, with different patterns of change. Brain reserve and vascular risk factors relate to later post-stroke cognitive change. This complex nature of cognitive trajectory has implications for cognitive rehabilitation provision and cognitive impairment detection after stroke.

Asymptomatic intracranial atherosclerotic stenosis (ICAS) is frequently identified in stroke screening programs, particularly in Asian populations. However, the prognosis and management strategies for incidentally detected asymptomatic ICAS in hospital-based, stroke-free populations remain unclear. This study aimed to investigate the incidence of symptomatic transition and associated long-term prognostic evolution in this population, providing evidence to inform primary stroke prevention. We conducted a prospective cohort study that included 1004 patients with asymptomatic ICAS (⩾50%) screened by transcranial Doppler ultrasound (TCD) between January 2016 and May 2022, with follow-up through August 2023. Using the Fine and Gray competing risk model, we analyzed the incidence of symptomatic transition, defined as a first-ever ischemic stroke or transient ischemic attack occurring within the ICAS territory. Post-transition outcomes, including recurrent stroke, major adverse cardiovascular events (MACE), disability (modified Rankin Scale score > 2), and patient-reported cognitive decline (Everyday Cognition-12 score ⩾ 2), were evaluated by comparative analysis. Over a median follow-up of 3.7 years (IQR 2.4-5.2), 43 (4.3%) patients with asymptomatic ICAS experienced a symptomatic transition under routine clinical surveillance, yielding a 5-year cumulative transition rate of 5.6%. After adjusting for potential confounders, hypertension (hazard ratio (HR) 3.33, 95% CI 1.25-8.87) and hyperlipidemia (HR 2.71, 95% CI 1.28-5.74) were independent predictors of the transition. Through extended follow-up, post-transition risks significantly increased for ischemic stroke (HR 3.37, 95% CI 1.17-9.68), MACE (HR 4.48, 1.83-10.99), disability (odds ratio (OR) 4.80, 2.17-10.64), and patient-reported cognitive decline (OR 3.43, 1.19-9.94). Asymptomatic ICAS detected by TCD incidentally in hospital-based, stroke-free populations carries a substantial risk of symptomatic transition and subsequent adverse outcomes. These findings underscore the prognostic importance of identifying asymptomatic ICAS clinically and highlight the necessity for intensive vascular risk factor management in this under-recognized group to guide primary stroke prevention strategies.

To identify clinical and radiological features of cerebral amyloid angiopathy-related inflammation (CAA-ri), and compare these features with those of sporadic CAA, to improve the understanding, diagnosis, and clinical care of CAA-ri. We retrospectively reviewed routine clinical data from 37 patients with CAA-ri and 158 patients with sporadic CAA, including conventional vascular risk factors and comorbidities. We assessed brain magnetic resonance imaging for: radiological markers of CAA; features of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) including parenchymal white matter hyperintensities, sulcal hyperintensities, and gyral swelling; and evidence of neurodegeneration (medial temporal atrophy and global cortical atrophy). Compared with patients with sporadic CAA, patients with CAA-ri had more numerous lobar cerebral microbleeds (median 207[IQR 33-811] vs 19[IQR 7-58], p < 0.001), and higher rates of medial temporal and global cortical atrophy. In comparison with sporadic CAA, all ARIA-E features were much more common in patients with CAA-ri (parenchymal hyperintensities 89% vs 3%, sulcal hyperintensities 78% vs 9%, and gyral swelling 86% vs 0.6%), as were conventional vascular risk factors (hypertension, dyslipidemia) and long-term comorbidities (inflammatory and infectious disorders, autoimmune or connective tissue disorders, or malignancies). Features of ARIA-E (parenchymal white matter hyperintensities, sulcal hyperintensities, and gyral swelling) are more common in CAA-ri in comparison with "non-inflammatory" sporadic CAA, suggesting shared mechanisms with Alzheimer's disease immunotherapy and a potential role in improving diagnostic accuracy for CAA-ri. The high prevalence of atrophy and lobar cerebral microbleeds suggests a potential mechanistic role for capillary CAA, Alzheimer's disease, or both, in CAA-ri. Cardiovascular risk factors and other long-term comorbidities may also be relevant to the underlying mechanisms of CAA-ri. ANN NEUROL 2025 ANN NEUROL 2025.

BackgroundWhite matter hyperintensities (WMH), a key imaging marker of cerebral small vessel disease, are associated with stroke, cognitive decline, and mortality in aging populations, yet current magnetic resonance imaging (MRI)-based assessments are costly and unsuitable for large-scale monitoring. Owing to shared microvascular characteristics between the retina and brain, ocular imaging offers a non-invasive alternative, but most studies have examined single-modal retinal metrics or total WMH volume, with little attention to multimodal biomarkers and lobe-specific WMH. This study aims to explore the associations between multimodal ocular imaging biomarkers and WMH volume to enable earlier, non-invasive detection of cerebral small vessel disease.MethodsParticipants (age: 23–83 years) in the KaiLuan Study underwent comprehensive ophthalmic and neuroimaging evaluations, including optical coherence tomography (OCT) for measuring macular retinal nerve fiber layer (mRNFL), macular ganglion cell-inner plexiform layer (mGCIPL), macular inner nuclear layer (mINL), macular ganglion cell complex (mGCC), and total macular thickness. Fundus photography was used to assess central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriole/venular ratio (AVR), fractal dimension (FD), global vein width, and global artery width. MRI was employed to quantify WMH volume. Generalized linear regression models were used to analyze associations between ocular biomarkers and WMH, with adjustments for demographics and vascular risk factors.ResultsThe study included 761 participants (average age 55 years, 54.4% women). Thinner mGCIPL and mGCC were significantly associated with greater WMH volume in the total brain (P<0.02), temporal lobes (P≤0.02), and occipital lobes (P≤0.003). Reduced mINL correlated with larger WMH in the total brain and specific lobes (P<0.04). No significant associations were found for mRNFL or total macular thickness (all P>0.05). Smaller AVR, narrower CRAE, and wider CRVE were linked to higher WMH volume in the occipital lobe (P<0.02). Lower FD complexity and wider global vein width demonstrated significant associations with increased WMH volume in the total brain and individual lobes (frontal, occipital, and temporal lobes; all P<0.01). Sex-stratified analysis showed that these associations were stronger in females, with thinner mGCIPL, mINL, and wider global vein width associated with greater total and lobe-specific WMH (P<0.05).ConclusionsIt is suggested that parameters from OCT and fundus photography are independently associated with WMH volume. These parameters may serve as potential biomarkers for the early detection and longitudinal monitoring of WMH, enabling precise identification and ongoing surveillance of white matter alterations.

Migraine: advances in treatment.

Transgender individuals represent a vulnerable population with unique healthcare needs. Despite facing health disparities, there is limited research on the characteristics and stroke risk factors among transgender stroke survivors. We extracted and analyzed data from the 2020–2022 Behavioral Risk Factor Surveillance System (BRFSS) to study stroke risk factors among transgender stroke survivors and to compare them to cisgender stroke survivors. cisgender stroke survivors were paired with transgender stroke survivors using a 1:2 propensity score matching (PSM) ratio. Demographic characteristics, lifestyle factors, and vascular risk factors were assessed using univariate and multivariate logistic regression models. Out of 29,628 individuals with a history of stroke, we identified 189 transgender stroke survivors and matched them with 378 cisgender stroke survivors. Transgender individuals exhibited a higher odds of reporting a history of stroke compared to cisgenders (adjusted odds ratio[aOR]=1.692, 95% CI 1.645–1.741). Hypertension (57.8%), depression (54.3%), hypercholesterolemia (52%), and obesity (44.7%) were the most common risk factors for transgender stroke survivors. Transgender stroke survivors had higher odds of lifestyle risk factors such as e-cigarette smoking (aOR=3.651, 95%CI 1.373–9.705), binge drinking (aOR=2.519, 95%CI 1.088–5.832), alcohol consumption (aOR=2.147, 95%CI 1.049–4.395), and tobacco smoking (aOR=2.030, 95%CI 1.214–3.395). In conclusion, transgender stroke survivors may face significant challenges due to elevated modifiable risk factors, especially lifestyle-related ones. Recognizing these specific risk factors is crucial for targeted interventions for transgender stroke survivors.

Background: Concurrent atherosclerosis (AS) in peripheral arteries may worsen the prognosis of ischemic cerebrovascular disease (ICVD) patients. Although cervicocephalic atherosclerotic burden (AB) has demonstrated strong risk stratification capabilities, whether peripheral arterial evaluation provides incremental prognostic value remains unclear. This study aimed to determine whether cervicocephalic–peripheral AB (CPAB) improves risk stratification in ICVD patients. Methods: This prospective cohort study consecutively included acute ICVD patients. AB scores for intracranial, cervical, renal, and lower extremity arteries were assigned as 0 (no stenosis), 1 (significant stenosis in one segment), or 2 (significant stenosis in ≥2 segments). The total score (range 0–8) was trisected into low, medium, and high CPAB levels. The primary endpoint was a composite of ischemic stroke, acute coronary syndrome, and vascular death. Model performance was evaluated using Harrell’s C and Somers’ D. Results: Among 403 patients (mean follow-up: 9.6 ± 5.4 months), 41 primary endpoints occurred, and 21 (5.2%) were lost to follow-up. Of 382 patients analyzed, 30.6% had significant peripheral AS. Patients with concurrent peripheral-cervicocephalic AS had a higher risk of vascular events (p = 0.001) than those with single-territory AS. CPAB was independently associated with the primary endpoint (HR = 2.22, p < 0.001) and stroke recurrence (HR = 1.90, p = 0.013). While cervicocephalic AB also independently predicted outcomes, the CPAB-based multivariate Cox model had improved discriminative performance (Harrell’s C = 0.678 vs. 0.653 for primary endpoint, p = 0.02; 0.646 vs. 0.634 for stroke recurrence, p = 0.03). Conclusions: Peripheral AS is common in ICVD patients and contributes independently to vascular risk. The CPAB score, which integrates atherosclerotic burden from both cervicocephalic and peripheral territories, could improve prognostic stratification compared to single-territory or cervicocephalic AB alone, supporting comprehensive multiterritorial AS assessment to guide risk-based management strategies.

Systemic disease burden is well reflected in the retinal microvasculature, but it is not established whether optical coherence tomography angiography (OCTA) parameters can reliably reflect coronary atherosclerosis. To assess the association of reduced retinal vascular density and subclinical coronary atherosclerosis in asymptomatic individuals. This cross-sectional cohort study included asymptomatic individuals with elevated cardiovascular risk who self-referred for a health screening program involving coronary computed tomography angiography (CTA) at Asan Medical Center in Seoul, South Korea, and subsequently underwent OCTA as part of ophthalmic evaluations. This study was conducted from October 2015 to December 2020, and data analysis was conducted from January 2021 to May 2025. The primary outcome was the association between OCTA parameters and coronary CTA parameters. A total of 1286 eyes from 1286 participants were analyzed (mean [SD] age, 64.2 [9.9] years; 482 female participants [37.5%]). Coronary artery calcium score (CACS), presence of plaque and its subtypes, obstructive coronary artery disease (CAD), severe CAD, segment stenosis score (SSS), and segment involvement score (SIS) were significantly increased across the quartiles of superficial and deep parafoveal vascular density (PFVD). When modeled as continuous variables, superficial capillary plexus (SCP) and deep capillary plexus (DCP) PFVD were the most significant metrics and correlated with CACS, number of coronary vessels involved, SSS, and SIS. The lowest quartile of SCP PFVD was associated with significantly higher odds of obstructive CAD (adjusted odds ratio [aOR], 2.91; 95% CI, 1.83-4.73), severe CAD (aOR, 3.30; 95% CI, 1.55-7.91), and elevated SSS and SIS scores compared to the highest quartile. Similar but attenuated associations were observed for DCP PFVD. Continuous variable analysis for ORs for unit increase supported a linear inverse association between PFVD and CAD burden. Incorporating PFVD into models with cardiovascular risk factors improved area under the curve (AUC) for identifying severe CAD (AUC, 0.79; 95% CI, 0.75-0.82), obstructive CAD (AUC, 0.78; 95% CI, 0.76-0.81), and SSS of 10 or higher (AUC, 0.77; 95% CI, 0.74-0.80), with SCP yielding superior performance over DCP. In this cross-sectional cohort study, reduced retinal PFVD was independently associated with subclinical coronary atherosclerosis in a population with elevated vascular risk. In this context, decreased PFVD may reflect greater subclinical coronary atherosclerotic burden and help identify individuals who could benefit from further coronary evaluation, beyond traditional risk factors.

Background: While sleep duration’s association with stroke is established, the combined influence of sleep onset time and duration on stroke subtypes remains inadequately explored. Since circadian biology links sleep onset timing to vascular risk via mechanisms operating independently of sleep duration, we quantified their joint contributions to the risk of stroke. Methods: In this population-based cross-sectional study, from 31 December 2021 to 31 March 2022, we recruited 8168 ischemic stroke cases, 3172 intracerebral hemorrhage cases, and 13,458 control participants across 152 survey centers in 28 counties in Hunan Province, China. Standardized computer-assisted interviews collected sleep parameters. Conjoint analysis identified protective sleep profiles. Results: Short sleep duration (<6 h) was consistently associated with elevated ischemic risk across all sleep onset times (p < 0.05 in all cases, i.e., sleep before 10 p.m. [odds ratio (95%CI): 1.886(1.606, 2.214)], 10–11 p.m. [1.740(1.336, 2.265)], 11 p.m.–12 a.m. [2.335(1.190, 4.581)], and after 12 a.m. [2.834(1.193, 6.728)]). A sleep duration of 6–8 h with a sleep onset time between 10 p.m. and 12 a.m. was associated with the lowest ischemic risk (p < 0.001 in all cases). Conversely, prolonged sleep (>8 h) with an early sleep onset time (<10 p.m.) increased ischemic risk (OR 1.194, 95% CI 1.090–1.308, p < 0.001), whereas a late sleep onset time (11 p.m.–12 a.m.) in long sleepers was protective (OR 0.580, 95% CI 0.352–0.956, p < 0.001). Similar trends were observed for ICH, though the effect sizes were attenuated. Conclusion: Sleep duration and onset time interact to influence stroke risk. Optimal cerebrovascular protection requires ≥6 h of sleep, ideally initiated between 10 p.m. and 11 p.m. These findings highlight sleep optimization as a potential modifiable target for high-risk populations.