Vascular Risk Factors Research Articles

Clinical relevance of critical plasma homocysteine levels in predicting rupture risk for small and medium-sized intracranial aneurysms

Plasma homocysteine (Hcy) has been globally recognized as an independent risk factor for various neurovascular diseases. In this study, the authors investigated the relationship between critical Hcy concentration and the risk of rupture in intracranial aneurysms (IAs). This study collected data from 423 patients with both ruptured and unruptured IAs. We compared demographic data, vascular rupture risk factors, and laboratory test results between the two groups. Multivariable logistic regression analysis was employed to determine the correlation between critical plasma Hcy levels and the risk of rupture in small to medium-sized IAs. A total of 330 cases of ruptured intracranial aneurysms (RIA) and 93 cases of unruptured intracranial aneurysms (UIA) were included. Univariate analysis revealed statistically significant differences between the ruptured and unruptured groups in terms of hypertension, hyperlipidemia, plasma Hcy levels, and IA morphology (all P < 0.05). Multivariable logistic regression analysis indicated that hypertension (odds ratio [OR] 0.504; 95% confidence interval [CI] 0.279–0.911; P = 0.023), hyperlipidemia (OR 1.924; 95% CI 1.079–3.429; P = 0.027), and plasma Hcy levels (OR 1.420; 95% CI 1.277–1.578; P < 0.001) were independently associated with the rupture of small to medium-sized IAs, all with statistical significance (P < 0.05). Our study suggests that critical plasma Hcy levels are an independent risk factor for increased rupture risk in small to medium-sized intracranial aneurysms. Therefore, reducing plasma Hcy levels may be considered a valuable strategy to mitigate the risk of intracranial vascular abnormalities rupture and improve patient prognosis.

Beat-to-beat blood pressure variability, hippocampal atrophy, and memory impairment in older adults.

Visit-to-visit blood pressure variability (BPV) predicts age-related hippocampal atrophy, neurodegeneration, and memory decline in older adults. Beat-to-beat BPV may represent a more reliable and efficient tool for prospective risk assessment, but it is unknown whether beat-to-beat BPV is similarly associated with hippocampal neurodegeneration, or with plasma markers of neuroaxonal/neuroglial injury. Independently living older adults without a history of dementia, stroke, or other major neurological disorders were recruited from the community (N = 104; age = 69.5 ± 6.7 (range 55-89); 63% female). Participants underwent continuous blood pressure monitoring, brain MRI, venipuncture, and cognitive testing over two visits. Hippocampal volumes, plasma neurofilament light, and glial fibrillary acidic protein levels were assessed. Beat-to-beat BPV was quantified as systolic blood pressure average real variability during 7-min of supine continuous blood pressure monitoring. The cross-sectional relationship between beat-to-beat BPV and hippocampal volumes, cognitive domain measures, and plasma biomarkers was assessed using multiple linear regression with adjustment for demographic covariates, vascular risk factors, and average systolic blood pressure. Elevated beat-to-beat BPV was associated with decreased left hippocampal volume (P = .008), increased plasma concentration of glial fibrillary acidic protein (P = .006), and decreased memory composite score (P = .02), independent of age, sex, average systolic blood pressure, total intracranial volume, and vascular risk factor burden. In summary,beat-to-beat BPV is independently associated with decreased left hippocampal volume, increased neuroglial injury, and worse memory ability. Findings are consistent with prior studies examining visit-to-visit BPV and suggest beat-to-beat BPV may be a useful marker of hemodynamic brain injury in older adults.

Staged cerebral and brachiocephalic bypass in a patient with MCA and brachiocephalic steno-occlusion.

Background: Brachiocephalic steal is a rare phenomenon that may lead to hemodynamic abnormalities in the ipsilateral vertebral and carotid arteries. Current treatment includes management of vascular risk factors, endovascular stenting, and surgical management depending on the severity of symptoms. Case Information: We describe a patient with multiple vascular risk factors who presented with mild neurological symptoms and chronic right arm weakness associated with concurrent brachiocephalic steal and right MCA M1 stenosis on neuroimaging. Use of right superficial temporal artery to middle cerebral artery bypass and aorta-right subclavian bypass resulted in improved flow to the right hemisphere on quantitative magnetic resonance angiography and single-photon emission computed tomography, significantly lowering the risk of catastrophic ischemic stroke. Conclusion: Complex steal phenomena increase stroke risk. In cases of high-grade occlusion or advanced symptoms, endovascular or surgical management should be considered for optimal stroke prevention.

The relationship between bone health and type of intracranial internal carotid calcifications in patients with ischemic stroke

IntroductionVascular calcifications, primarily in the aorta and its proximal branches, are commonly observed among subjects with impaired bone health. In this study, we sought to determine if a comparable association holds true for the calcifications in the intracranial internal carotid arteries (IICA), in general and also for particular calcification patterns. MethodsA consecutive series of ischemic stroke patients were prospectively enrolled into the study, where computed tomography angiography source images were used to determine the presence and type of IICA calcifications, and dual-energy X-ray absorptiometry was used to determine the bone mineral density in the left femoral neck region. IICA calcifications were categorized as none, intimal, medial, and mixed types based on previously validated classification schemes. Their relationships with femoral bone T-scores were evaluated by bivariate and multivariate analyses. ResultsFemoral neck T-score was highest among patients without any vascular calcifications (n=65), when compared to the bone density measures among patients with any type of calcification (n=185) (p<0.001). After adjustment for age, gender, vascular risk factors, and serum biomarkers related to bone health, the T-score remained significantly associated only with the pattern of intimal calcification [OR 0.63 (0.42 – 0.95), p=0.028]. ConclusionsOur findings suggest that the intracranial vasculature, in particular the internal carotid arteries, is not immune to the interplay between suboptimal bone health and vascular calcifications. This association was most robust for an intimal type of IICA calcification pattern, while no such relationship could be demonstrated for other types of vascular calcifications.

Binge drinking and progression of white matter hyperintensities of presumed vascular origin in older men

BackgroundInformation on trajectories of diffuse subcortical brain damage of vascular origin associated with binge drinking in older adults is limited. We sought to evaluate the impact of this drinking pattern on the progression of white matter hyperintensities (WMH) of presumed vascular origin in individuals aged ≥60 years taken from the community. MethodsFollowing a longitudinal prospective design, participants of the Atahualpa Project Cohort received interviews to assess patterns of alcohol intake as well as baseline and follow-up brain MRIs. Only men were included because alcohol consumption in women is negligible and tend not to engage in binge drinking in our studied population. Poisson regression models were fitted to assess the incidence rate ratio of WMH progression by patterns of alcohol use (binge drinking or not), after adjusting for demographics, level of education and cardiovascular risk factors. ResultsThe study included 114 men aged ≥60 years (mean age: 65.1±5.4 years). Thirty-seven participants (32%) reported binge drinking for more than 30 years. Follow-up MRIs revealed WMH progression in 45 participants (39%) after a median of 7.2 years. In unadjusted analysis, the risk of WMH progression among individuals with binge drinking was 2.08 (95% C.I.: 1.16–3.73). After adjustment for age, education level and vascular risk factors, participants with this drinking pattern were 2.75 times (95% C.I.: 1.42–5.30) more likely to have WMH progression than those who did not. ConclusionsStudy results show an independent association between binge drinking and WMH progression in community-dwelling older men.

Small vessel disease burden predicts incident stroke and all-cause death, but not acute coronary event.

Total small vessel disease (SVD) score is used to measure the burden of SVD by incorporating four established neuroimaging markers; white matter hyperintensity, lacune, cerebral microbleed, and enlarged perivascular space, ranging from 0 to 4. Whether total SVD scores predict all vascular outcomes remains unclear. This study aimed to clarify the predictive value of the total SVD score for incident stroke, mortality, and acute coronary syndrome in independent outpatients with vascular risk factors. We derived data from The Tokyo Women's Medical University Cerebrovascular Disease registry, a prospective observational registry in which 1011 patients with evidence of cerebral vessel disease on magnetic resonance imaging were enrolled. They were followed up until March 2023. The primary outcomes were stroke, all-cause death, and acute coronary syndrome (ACS). After excluding those with a modified Rankin scale score >1, Mini-mental State Examination score <24, and missing T2* images, 692 patients were included. During a median follow-up period of 4.6 years, stroke, ACS, and all-cause death occurred in 52, 24, and 45 patients, respectively. In multivariate analysis, the total SVD score was independently associated with stroke, and all-cause death but not with acute coronary syndrome. Both cutoff values of the total SVD score for stroke, and all-cause death were 1. In conclusion, the total SVD score could predict stroke and mortality but not acute coronary syndrome. Our results suggest intensive management of patients with a total SVD score ≥1 to prevent stroke and all-cause death. Patients with higher total SVD scores were significantly more likely to have a stroke (A; P = 0.012) than those with lower total SVD scores. However, no association was observed between total SVD scores and acute coronary syndrome (B, P = 0.604). For incident stroke, total SVD scores of 1 and 2 were the cutoff levels.

Assessing blood-brain barrier dysfunction and its association with Alzheimer’s pathology, cognitive impairment and neuroinflammation

BackgroundBlood-brain barrier (BBB) alterations may contribute to AD pathology through various mechanisms, including impaired amyloid-β (Aβ) clearance and neuroinflammation. Soluble platelet-derived growth factor receptor beta (sPDGFRβ) has emerged as a potential biomarker for BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a direct assessment of BBB permeability. However, the relationship between BBB dysfunction, cognitive impairment, and AD pathology remains unclear, with inconsistent findings in the literature.MethodsWe conducted a cross-sectional study using data from the DELCODE and DESCRIBE cohorts to investigate BBB dysfunction in participants with normal cognition (NC), mild cognitive impairment (MCI), and AD dementia. BBB function was assessed using DCE-MRI and sPDGFRβ levels in cerebrospinal fluid and AD biomarkers Aβ and tau were measured. In a subset of patients, the CSF/plasma-ratio of albumin (QAlb) as a standard marker of BBB integrity and markers of neuroinflammation were analyzed.Results91 participants (NC: 44, MCI: 21, AD: 26) were included in the analysis. The average age was 74.4 years, 42% were female. Increased hippocampal BBB disruption was observed in the AD-group (Ktrans: 0.55 × 10− 3 min− 1 ± 0.74 × 10− 3 min− 1) but not the MCI-group (Ktrans: 0.177 × 10− 3 min− 1 ± 0.22 × 10− 3 min− 1), compared to the NC group (Ktrans: 0.19 × 10− 3 min− 1 ± 0.37 × 10− 3 min− 1, p < .01). sPDGFRβ was not significantly different between the cognitive groups. However, sPDGFRβ levels were significantly associated with age (r = .33, p < .01), independent of vascular risk factors. Further, sPDGFRβ showed significant positive associations with soluble Aβ levels (Aβ40: r = .57, p < .01; Aβ42: r = .39, p < .01) and YKL-40 (r = .53, p < .01), a marker of neuroinflammation. sPDGFRβ/DCE-MRI was not associated with overall AD biomarker positivity or APOE-status.ConclusionIn dementia, but not MCI, hippocampal BBB disruption was observed. sPDGFRβ increased with age and was associated with neuroinflammation independent of cognitive impairment. The association between Aβ and sPDGFRβ may indicate a bidirectional relationship reflecting pericytes’ clearance of soluble Aβ and/or vasculotoxic properties of Aβ.

Cerebrovascular Involvement in Transthyretin Amyloid Cardiomyopathy

Background: Intracardiac thrombosis is common in transthyretin amyloid cardiomyopathy (ATTR-CM), and patients are at risk for thromboembolic events. However, silent cerebral infarcts and the extent of cerebral small vessel disease in patients with cardiac amyloidosis are unknown. Methods: Thirty-two consecutively selected ATTR-CM patients were prospectively studied by cerebral magnetic resonance imaging (cMRI) and compared with 43 CHA2DS2-VASc-matched controls (Co). Structural clinical standard cMRI sequences and features of cerebral vessel involvement were included and quantified by two board certified neuroradiologists in consensus blinded to clinical status. Group differences were estimated using generalized (logistic) linear regression models adjusting for vascular risk factors based on the CHA2DS2-VASc score. Results: The median CHA2DS2-VASc score was 4 for ATTR-CM and Co (p = 0.905). There were no differences between groups in the frequency of current or former smokers (p = 0.755), body-mass-index &gt; 30 (p = 0.106), and hyperlipidemia (p = 0.869). The number of territorial infarcts (4 vs. 0, p = 0.018) was higher in ATTR-CM compared to Co, as was the mean number of cerebral microbleeds (1.4 vs. 0.3, p ≤ 0.001) and the number of Virchow–Robin spaces (43.8 vs. 20.6, p ≤ 0.001). Lacunar lesion presence was higher in ATTR-CM (6 vs. 2, p = 0.054). CHA2DS2-VASc score, atrial fibrillation, anticoagulation, and the interaction term of CHA2DS2-VASc score and atrial fibrillation did not affect the probability of a territorial ischemic lesion or lacunar lesion in logistic regression modeling. Conclusions: In patients with ATTR-CM free from clinically apparent neurological symptoms, cMRI revealed unreported significant small cerebral vessel disease and territorial ischemia. Our findings may support low thresholds for anticoagulation and cMRI in patients with ATTR-CM.

Quantitative assessment of enlarged perivascular spaces via deep-learning in community-based older adults reveals independent associations with vascular neuropathologies, vascular risk factors, and cognition

Abstract Enlarged perivascular spaces (EPVS) are common in older adults, but their neuropathologic correlates are unclear mainly because most work to date has relied on visual rating scales and/or clinical cohorts. The present study first developed a deep learning model for automatic segmentation, localization and quantification of EPVS in ex-vivo brain MRI, and then used this model to investigate the neuropathologic, clinical, and cognitive correlates of EPVS in 817 community-based older adults that underwent autopsy. The new method exhibited high sensitivity in detecting EPVS as small as 3 mm3, good segmentation accuracy and consistency. Most EPVS were located in the frontal lobe, but the highest density was observed in the basal ganglia. EPVS in the cerebrum and specifically in the frontal lobe were associated with infarcts independent of other neuropathologies, while temporal and occipital EPVS were associated with cerebral amyloid angiopathy. EPVS in most brain lobes were also associated with diabetes mellitus independently of neuropathologies, while basal ganglia EPVS were independently associated with hypertension, supporting the notion of independent pathways from diabetes and hypertension to EPVS. Finally, EPVS were associated with lower cognitive performance independently of neuropathologies and clinical variables, suggesting that EPVS represent additional abnormalities contributing to lower cognition.

Vagus nerve size determined via ultrasonography is associated with white matter lesions in patients with vascular risk factors.

The cross-sectional area (CSA) of the cervical vagus nerve (VN), as assessed through ultrasonography, might be linked to autonomic nervous system dysfunction. Hypertension is the primary factor associated with cerebral white matter lesions (WMLs), but there is also evidence of a connection with autonomic nervous system dysfunction. However, the associations between WMLs and VN size are unclear. Our objective was to investigate the associations between WMLs and VN size in patients with vascular risk factors. The CSA of the VN was evaluated using carotid ultrasonography in patients with a history of stroke (acute or chronic) and comorbidities (n = 196, 70.2 ± 12.7years). Common carotid artery (CCA) intima-media thickness and interadventitial diameter (IAD) were also measured. The severity of the WMLs was assessed by the Fazekas classification and Scheltens' scale. The CSA of the right VN (2.08 ± 0.65mm2) was significantly greater than that of the CSA of the left VN (1.56 ± 0.44mm2) (P < 0.001). Multiple linear regression analyses revealed that older age, hypertension, increased right CCA IAD, and decreased CSA of the right VN (standardized partial regression coefficient [β] -0.226; P < 0.001) were independently associated with the severity of WMLs (Scheltens' scale). A decreased CSA of the left VN was also associated with the severity of WMLs (β = -0.239; P < 0.001). VN size determined via ultrasonography was associated with the severity of WMLs. While these findings do not establish a causal relationship, they suggest that autonomic nervous system dysfunction is involved in the progression of WMLs.

Impact of demographic and clinical factors on in-hospital delays in acute ischemic stroke treatment.

Delays in reperfusion treatment, both intravenous thrombolysis (IVT) and endovascular treatment (EVT), adversely affect outcomes in patients with acute ischemic stroke (AIS). To alleviate these delays, it is essential to comprehend how patients' baseline and stroke characteristics impact in-hospital reperfusion delays. While demographic and socioeconomic factors affect stroke outcomes, their impact on in-hospital delays remains unclear. This is retrospective analysis at a tertiary stroke center, encompassing AIS patients receiving IVT and / or EVT between 2019 and 2022 (re-canalization cohort). Outcomes of interest were time intervals of admission to CT and admission to recanalization. Univariable analyses explored age, gender, baseline functional status, socioeconomic status (SES), ethnicity, vascular risk factors, and stroke characteristics. Subsequently, multivariable logistic regression analyses were performed. Altogether, 313 patients treated with IVT and 293 with EVT were included in the re-canalization cohort. No demographic variables were found to be associated with stroke treatment time intervals. Following multivariable analysis, stroke severity (low NIHSS, p < 0.01), arrival to the hospital by other means than ambulance (p < 0.01), and atypical stroke symptoms (p < 0.01), were associated with in-hospital delays, both in the EVT and the IVT groups. Our findings indicate that patients with a more severe ischemic stroke, typical stroke symptoms, and arrival by ambulance have shorter stroke treatment time intervals. These results emphasize that, in atypical cases, even a lower suspicion of stroke should promote urgent workup for stroke diagnosis. Our findings do not indicate any influence of demographic or SES on in-hospital reperfusion delays.

Whole-Brain Vascular Architecture Mapping Identifies Region-Specific Microvascular Profiles in Vivo.

The novel MR imaging technique of vascular architecture mapping allows in vivo characterization of local changes in cerebral microvasculature, but reference ranges for vascular architecture mapping parameters in healthy brain tissue are lacking, limiting its potential applicability as an MR imaging biomarker in clinical practice. We conducted whole-brain vascular architecture mapping in a large cohort to establish vascular architecture mapping parameter references ranges and identify region-specific cortical and subcortical microvascular profiles. This was a single-center examination of adult patients with unifocal, stable low-grade gliomas with multiband spin- and gradient-echo EPI sequence at 3T using parallel imaging. Voxelwise plotting of resulting values for gradient-echo (R2*) versus spin-echo (R2) relaxation rates during contrast agent bolus administration generates vessel vortex curves that allow the extraction of vascular architecture mapping parameters representative of, eg, vessel type, vessel radius, or CBV in the underlying voxel. Averaged whole-brain parametric maps were calculated for 9 parameters, and VOI analysis was conducted on the basis of a standardized brain atlas and individual cortical GM and WM segmentation. Prevalence of vascular risk factors among subjects (n = 106; mean age, 39.2 [SD, 12.5] years; 56 women) was similar to those in the German population. Compared with WM, we found cortical GM to have larger mean vascular calibers (5.80 [SD, 0.59] versus 4.25 [SD, 0.62] P < .001), increased blood volume fraction (20.40 [SD, 4.49] s-1 versus 11.05 [SD, 2.44] s-1; P < .001), and a dominance of venous vessels. Distinct microvascular profiles emerged for cortical GM, where vascular architecture mapping vessel type indicator differed, eg, between the thalamus and cortical GM (mean, -2.47 [SD, 4.02] s-2 versus -5.41 [SD, 2.84] s-2; P < .001). Intraclass correlation coefficient values indicated overall high test-retest reliability for vascular architecture mapping parameter mean values when comparing multiple scans per subject. Whole-brain vascular architecture mapping in the adult brain reveals region-specific microvascular profiles. The obtained parameter reference ranges for distinct anatomic and functional brain areas may be used for future vascular architecture mapping studies on cerebrovascular pathologies and might facilitate early discovery of microvascular changes, in, eg, neurodegeneration and neuro-oncology.

A genome-wide association meta-analysis of all-cause and vascular dementia.

Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.

Markers of Biological Brain Aging Mediate Effects of Vascular Risk Factors on Cognitive and Motor Functions: A Multivariate Imaging Analysis of 40,579 Individuals.

The increasing global life expectancy brings forth challenges associated with age-related cognitive and motor declines. To better understand underlying mechanisms, we investigated the connection between markers of biological brain aging based on magnetic resonance imaging (MRI), cognitive and motor performance, as well as modifiable vascular risk factors, using a large-scale neuroimaging analysis in 40,579 individuals of the population-based UK Biobank and Hamburg City Health Study. Employing partial least squares correlation analysis (PLS), we investigated multivariate associative effects between three imaging markers of biological brain aging - relative brain age, white matter hyperintensities of presumed vascular origin, and peak-width of skeletonized mean diffusivity - and multi-domain cognitive test performances and motor test results. The PLS identified a latent dimension linking higher markers of biological brain aging to poorer cognitive and motor performances, accounting for 94.7% of shared variance. Furthermore, a mediation analysis revealed that biological brain aging mediated the relationship of vascular risk factors - including hypertension, glucose, obesity, and smoking - to cognitive and motor function. These results were replicable in both cohorts. By integrating multi-domain data with a comprehensive methodological approach, our study contributes evidence of a direct association between vascular health, biological brain aging, and functional cognitive as well as motor performance, emphasizing the need for early and targeted preventive strategies to maintain cognitive and motor independence in aging populations.

Vascular cognitive impairment: Advances in clinical research and management.

Vascular cognitive impairment (VCI) encompasses a wide spectrum of cognitive disorders, ranging from mild cognitive impairment to vascular dementia. Its diagnosis relies on thorough clinical evaluations and neuroimaging. VCI predominately arises from vascular risk factors (VRFs) and cerebrovascular disease, either independently or in conjunction with neurodegeneration. Growing evidence underscores the prevalence of VRFs, highlighting their potential for early prediction of cognitive impairment and dementia in later life. The precise mechanisms linking vascular pathologies to cognitive deficits remain elusive. Chronic cerebrovascular pathology is the most common neuropathological feature of VCI, often interacting synergistically with neurodegenerative processes. Current research efforts are focused on developing and validating reliable biomarkers to unravel the etiology of vascular brain changes in VCI. The collaborative integration of these biomarkers into clinical practice, alongside routine incorporation into neuropathological assessments, presents a promising strategy for predicting and stratifying VCI. The cornerstone of VCI prevention remains the control of VRFs, which includes multi-domain lifestyle modifications. Identifying appropriate pharmacological approaches is also of paramount importance. In this review, we synthesize recent advancements in the field of VCI, including its definition, determinants of vascular risk, pathophysiology, neuroimaging and fluid-correlated biomarkers, predictive methodologies, and current intervention strategies. Increasingly evident is the notion that more rigorous research for VCI, which arises from a complex interplay of physiological events, is still needed to pave the way for better clinical outcomes and enhanced quality of life for affected individuals.

Effects and Thresholds of Young to Midlife Vascular Risks on Brain Health.

Vascular risk factors, particularly hypertension, are important contributors to accelerated brain aging. We sought to quantify vascular risk factor risks over adulthood and assess the empirical evidence for risk thresholds. We used SBP (systolic blood pressure) and diastolic blood pressure, total cholesterol, fasting blood glucose, and body mass index measurements collected from participants in the CARDIA study (Coronary Artery Risk Development in Young Adults) at 2- to 5-year intervals through year 30. The Montreal Cognitive Assessment and domain-specific cognitive tests were performed at year 30. White matter hyperintensity volume was measured by magnetic resonance imaging. We used a 2-step method to fit longitudinal vascular risk factor exposures to optimized spline functions with mixed-effects models, then used the participant-specific random effects that characterized individual exposures over time in cross-sectional models adjusted for sex, race, age, and education to study effects on midlife brain health. Change in SBP up to 33 years of age was negatively associated with Montreal Cognitive Assessment scores (-0.29 Montreal Cognitive Assessment Z score per mm Hg/y change [95% CI, -0.49 to -0.09]; P=0.005), with similar effects for SBP changes from 33 to 49 years of age (-0.08 [95% CI, -0.16 to 0.01]; P=0.08). We observed comparable, significant associations between SBP exposure during those ages, midlife performance on specific cognitive domains, and volume of white matter hyperintensity (all P<0.05). SBP ≤111 mm Hg was the estimated threshold below which no harmful association with midlife cognitive performance was identified. SBP in early adulthood is the vascular risk factor most strongly associated with midlife cognitive performance and white matter hyperintensity burden, with SBP 111 mm Hg suggested as a harm threshold.

Diverging Trends in Survival and Functional Outcome between Males and Females after Intracerebral Hemorrhage.

Compared to ischemic stroke, sex differences in patient outcomes following intracerebral hemorrhage (ICH) are underreported. We aimed to determine sex differences in mortality and functional outcomes in a large, unselected Swedish cohort. In this observational study, data on 22,789 patients with spontaneous ICH registered in the Swedish Stroke Register between 2012 and 2019 were used to compare sex differences in 90-day mortality and functional outcome using multivariable Cox and logistic regression analyses, adjusting for relevant confounders. Multiple imputation was used to impute missing data. The crude 90-day mortality rate was 36.7% in females (3,820/10,405) and 31.7% in males (3,929/12,384) (female hazard ratio [HR] 1.20 95% confidence interval [CI]: 1.15-1.25). In multivariable analysis, the HR for 90-day mortality following ICH in females was 0.89 (95% CI: 0.85-0.94). Age was an important driving factor for the effect of sex on mortality. After adjustment for age, vascular risk factors, and stroke severity, the 90-day functional outcome in pre-stroke independent patients was worse in females compared to males (odds ratio: 1.27 95% CI: 1.16-1.40). In this large observational study, despite lower 90-day mortality, the female sex was independently associated with a worse functional outcome compared to males after ICH, even after adjusting for significant covariates. These diverging trends have not been previously reported for ICH. Given the observational design, our findings should be interpreted with caution, thus further external validation is warranted.

Encephaloduroarteriosynangiosis for Symptomatic Intracranial Atherosclerotic Arterial Steno-Occlusive Disease: Clinical and Radiological Outcomes.

This study investigated the long-term clinical and angiographic outcomes of encephaloduroarteriosynangiosis treatment for symptomatic intracranial atherosclerotic arterial steno-occlusive disease to further evaluate the potential therapeutic role of encephaloduroarteriosynangiosis in this population. A total of 152 adult patients with symptomatic intracranial atherosclerotic arterial steno-occlusive disease who were treated with encephaloduroarteriosynangiosis and intensive medical management across 3 tertiary centers in China between January 2011 and September 2019 were retrospectively included. The primary outcomes were defined as postoperative cerebrovascular events, including ischemic and hemorrhagic stroke. The postoperative neovascularization was analyzed qualitatively and quantitatively by using angiography. Clinical, radiological, and long-term follow-up data were analyzed using Cox regression, logistic regression, and linear regression analyses. Primary outcome rates were 3.2% (5/152) within 30 days, 6.6% (10/152) within 2 years, 9.2% (14/152) within 5 years, and 11.1% (17/152) during a median 9.13 years follow-up. Initial infarction symptoms were positively associated with recurrent ischemic stroke. Additionally, posterior circulation involvement and coexisting cardiac disease indicated poorer neurological status, whereas encephaloduroarteriosynangiosis neovascularization efficacy was negatively associated with older age and vascular risk factors but positively associated with posterior circulation involvement. Encephaloduroarteriosynangiosis plus intensive medical management appears efficacious and safe for symptomatic intracranial atherosclerotic arterial steno-occlusive disease, with low perioperative risk and favorable long-term results. Further prospective trials are needed to verify its efficacy and determine the optimal patient selection criteria.

High-resolution MR Angiographic Cerebrovascular Findings in a Tri-Ethnic Population.

Incidental findings on brain MR and variation of the circle of Willis (CoW) are relatively common among the general population. Ethnic differences have been described before, but few studies have explored the prevalence of incidental intracranial cerebrovascular findings and CoW variants in the setting of a single multi-ethnic cohort. The purpose of this investigation is to describe both incidental cerebrovascular findings and the morphology of the CoW on high-resolution 3T time-of-flight MR angiography (ToF MRA) in a UK tri-ethnic population-based cohort and to present updated prevalence estimates and morphologic reference values. We studied participants from the UK Southall and Brent Revisited (SABRE) study who underwent 3T brain MRI between 2014-2018. ToF MRA images were assessed for the presence of incidental cerebrovascular imaging findings and used to determine CoW anatomy. 750 participants (mean age: 71.28 ± 6.46 years, range [46-90], 337 female), 322 White Europeans, 253 South Asians, and 175 African Caribbeans, were included. Incidental cerebrovascular findings were observed in 84 subjects (11.2%, 95% CI [9.0-13.7]; 38 women, 45.24%, 95% CI [34.34-56.48]), cerebral aneurysms being the most frequent, followed by intracranial arterial stenoses (ICAS) with highest prevalence among South Asians compared to White European (OR: 2.72, 95% CI [1.22-6.08], p = .015) and African Caribbean subjects (OR: 2.79, 95% CI [1.00-7.82], p = .051). Other findings included arteriovenous malformations and infundibula. The CoW was found to be more often complete in women than in men (25.22% compared to 18.41%, p = .024), and in African Caribbean (34.86%), compared to White European (19.19%), and South Asian (14.23%) subjects (p <0.001 each). ICAS were independently associated with ethnicity after adjusting for vascular risk factors, having the highest prevalence among South Asians. The prevalence of aneurysms was higher than in previous population-based studies. We observed anatomical differences in the CoW configuration between women, men, and ethnicities. BP = Blood pressure; ICAS = Intracranial arterial stenoses; CoW = Circle of Willis; CVM = Cerebral vascular malformations; OR = Odds ratio; ToF MRA = Time-of-flight MR angiography.

Study of the impact of the vascular systemic risk factors on peripapillary vascular density by optical coherence tomography angiography.

The focus of therapeutic tools in glaucoma has been mainly to control of intraocular pressure. Recently there has been a growing interest in investigating the relationship of vascular risk factors in the development of glaucoma. The aim of this study was to assess the association between systemic arterial hypertension, diabetes mellitus and hypercholesterolemia, and peripapillary vascularization measured by Optical Coherence Tomography Angiography (OCTA) in glaucoma and healthy subjects. In this unicenter, observational, cross-sectional study, 212 subjects, 118 glaucoma patients and 94 controls were consecutively recruited. Of these, 86 participants were excluded due to poor OCTA image quality. Therefore, 146 subjects were included in the final analysis, 74 glaucoma patients and 72 controls. Using a linear regression model, with 95% confidence and 80% statistical power, the effect of vascular risk factors on OCTA parameters in the 146 subjects included in the final analysis was studied. No significant impact of vascular risk factors on OCTA measurements was found. Diabetic patients tended to show a lower peripapillary perfusion vascular density than subjects without diabetes (β 0.016, 95%CI 0.003;0.030, p 0.016). Similarly, hypercholesterolemia patients appeared to show less peripapillary flow index than non-hypercholesterolaemic patients (β 0.029, 95%CI 0.013;0.046, p 0.001). Glaucoma patients had 0.02% lower peripapillary perfusion vascular density (β 0.020, 95% CI 0.011;0.029, p < 0.001), 0.04% lower peripapillary flow index (β 0.036, 95%CI 0.022;0.051, p < 0.001) and 9.62% thinner retinal nerve fibre layer (β 9.619, 95%CI 5.495;13.744, p < 0.001). In conclusion glaucoma has greater effect on peripapillary vascular density parameters than any of the vascular risk factors analyzed. What is known: • Vascular disfunction plays an important role in the development of glaucoma. • Optical coherence tomography angiography makes it possible to assess the retinal microvasculature and the role that its alterations could have in the development of glaucoma. • Decrease of the peripapillary microcirculation seems to be more related to the increase in intraocular pressure and the glaucoma itself than to the presence of cardiovascular risk factors. • The effect of having diabetes, systemic arterial hypertension or hypercholesterolaemia on vascular parameters or nerve fibre layer thickness was low. • There was also no relevant impact of the systemic medication used for these diseases on the peripapillary vascular parameters studied or on nerve fibre layer thickness.