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Background: Hemoglobin concentration and diffusion-weighted imaging (DWI) ischemic lesions are separately known to be associated with poor intracerebral hemorrhage (ICH) outcomes. While hemoglobin concentrations have known relationships with ischemic stroke, it is unclear whether hemoglobin concentration is associated with DWI ischemic lesions after ICH. We sought to investigate the hypothesis that hemoglobin concentrations would associate with DWI lesions after ICH and further investigated their relationships with clinical outcomes. Methods: Supratentorial ICH patients enrolled between 2010 and 2016 to a prospective, multicenter, observational cohort study (ERICH study [Ethnic/Racial Variations of Intracerebral Hemorrhage]) were assessed. Patients from this study with baseline, admission hemoglobin, and hospitalization magnetic resonance imaging were analyzed. Hemoglobin was examined as the primary exposure variable defined as a continuous variable (g/dL). Magnetic resonance imaging DWI ischemic lesion presence was assessed as the primary radiographic outcome. Primary analyses assessed relationships of hemoglobin with DWI lesions. Secondary analyses assessed relationships of DWI lesions with poor 3-month outcomes (modified Rankin Scale score, 4–6). These analyses were performed using separate multivariable logistic regression models adjusting for relevant covariates. Results: Of 917 patients with ICH analyzed, mean baseline hemoglobin was 13.8 g/dL (±1.9), 60% were deep ICH, and DWI lesions were identified in 27% of the cohort. In our primary analyses, increased hemoglobin, defined as a continuous variable, was associated with DWI lesions (adjusted odds ratio, 1.21 per 1 g/dL change in hemoglobin [95% CI, 1.07–1.37]) after adjusting for sex, race, ICH severity, time to magnetic resonance imaging, and acute blood pressure change. In secondary analyses, DWI lesions were associated with poor 3-month outcomes (adjusted odds ratio, 1.83 [95% CI, 1.24–2.69]) after adjusting for similar covariates. Conclusions: We identified novel relationships between higher baseline hemoglobin concentrations and DWI ischemic lesions in patients with ICH. Further studies are required to clarify the role of hemoglobin concentration on both cerebral small vessel disease pathophysiology and ICH outcomes.

Background: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters. Methods: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event. Results: Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03–2.23], BA aHR, 1.28 [95% CI, 1.02–1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02–3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07–8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes. Conclusions: In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.

El artículo evalúa la pertinencia formativa de los futuros profesionales de la ciudad, a la luz de las competencias que definen al urbanista del siglo XXI. Usando como método el caso de estudio, se analiza el núcleo sustantivo del Plan de Estudios 2015 de la Licenciatura en Planeación Territorial de la Facultad de Planeación Urbana y Regional de Universidad Autónoma del Estado de México para contrastar sus propósitos en el ámbito de las competencias y los ámbitos de desempeño profesional. El análisis revela múltiples retos para la enseñanza en la actualidad y proponer acciones de reforma para fundamentar una visión de los futuros planes de estudios y enfoques educativos que permita el desarrollo de las competencias, habilidades y conocimientos para que los futuros urbanistas estén equipados para teorizar, analizar y gestionar un objeto de estudio que al igual que la sociedad, evoluciona y se transforma de una forma vertiginosa.

We characterized the additive contribution of cerebrovascular biomarkers to amyloid and neurodegeneration biomarkers (AV(N)) when modeling prospective, longitudinal cognitive trajectories within 3 major racial/ethnic groups. Participants (n = 172; age = 69–96 years; 62% women; 31%/49%/20% Non–Hispanic White/Non–Hispanic Black/Hispanic) from the Washington Heights-Inwood Columbia Aging Project were assessed for amyloid (Florbetaben PET), neurodegeneration (cortical thickness, hippocampal volume), and cerebrovascular disease (white matter hyperintensity (WMH), infarcts). Neuropsychological assessments occurred every 2.3 ± 0.6 years for up to 6 visits (follow-up time: 4.2 ± 3.2 years). Linear mixed-effects models were stratified by race/ethnicity groups. Higher amyloid was associated with faster memory decline in all 3 racial/ethnic groups, but was related to faster cognitive decline beyond memory in minoritized racial/ethnic groups. Higher WMH was associated with faster language, processing speed/executive function, and visuospatial ability decline in Non–Hispanic Black participants, while infarcts were associated with faster processing speed/executive function decline in Non–Hispanic White participants. Complementary information from AD, neurodegenerative, and cerebrovascular biomarkers explain decline in multiple cognitive domains, which may differ within each racial/ethnic group. Importantly, treatment strategies exist to minimize vascular contributions to cognitive decline.

Objective: To test the hypothesis that intracranial arterial calcification (IAC) is associated with intracranial large artery stenosis (ILAS) and a higher risk of vascular events and mortality. Method: We leveraged data from two cohorts, the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry Study (NYP/CUIMC-SRS) and the Northern Manhattan Study (NOMAS) to test our hypotheses. We measured IAC using CT scans of participants in both cohorts and expressed IAC as present (vs not) and in tertiles. For the CUIMC-SRS, demographic, clinical and ILAS status was collected retrospectively. In NOMAS, we used research brain MRI and MRA to define asymptomatic ILAS and covert brain infarcts(CBI). We built models adjusted for demographics and vascular risk factors for cross-sectional and longitudinal analyses. Results: Cross-sectionally, IAC was associated with ILAS in both cohorts (OR 1.78, 95% CI: 1.16-2.73 for ILAS-related stroke in the NYP/CUIMC-SRS and OR 3.07, 95%CI 1.13-8.35 for ILAS-related covert brain infarcts in NOMAS). In a meta-analysis of both cohorts, IAC in the upper (HR 1.25, 95%CI 1.01-1.55) and middle tertile (HR 1.27, 95%CI 1.01-1.59) was associated with higher mortality compared with participants with no IAC. There were no longitudinal associations between IAC and risk of stroke or other vascular events. Conclusion: In these multiethnic populations, IAC is associated with symptomatic and asymptomatic ILAS as well as higher mortality. IAC may be a useful marker of higher mortality, the role of IAC as an imaging marker of risk of stroke is less certain.

To study biomarkers of inflammation in cerebrovascular disease, exploring modifiable and non-modifiable biochemical and clinical risk factors associated with the presence of intracranial saccular aneurysms (ISAs) in an HIV-positive cohort.A cross-sectional community-based study was used to study blood biomarkers of inflammation as predictors of cerebrovascular disease, specifically the presence of ISAs in persons with HIV. Potential biochemical and clinical predictors of ISA presence were identified.Time of flight magnetic resonance angiography and magnetic resonance imaging data identified the presence of ISAs in an HIV-positive cohort. Quantitative assays for neuroinflammatory biomarkers were performed on plasma blood samples. Lasso regression models were used to identify neuroinflammatory biomarkers and clinical risk factors associated with ISAs.Eight of 72 participants had radiographically identified ISAs. ISAs were more common in non-Hispanic black participants (18.5% vs. 0% presence in nonblack patients). Participants with well controlled HIV (defined as CD4+ count200 cells/ml and undetectable viral load at time of magnetic resonance imaging) had lower odds of ISAs (odds ratio: 0.19, 95% confidence interval 0.05-0.79) independent of age, sex, ethnicity and vascular risk factors. Macrophage inflammatory protein-1 p, an HIV- suppressive factor detected in participant blood samples, was inversely associated with aneurysm presence.Well controlled HIV is associated with fewer ISAs. The identification of non-modifiable and modifiable risk factors contributing to ISA formation may provide valuable insight to impact clinical practice and inform the pathophysiology underlying ISA formation.

Vascular disease affects many different arterial beds throughout the body. Yet the brain is susceptible to several vascular disorders that either are not found in other parts of the body or when found are much less likely to cause clinical syndromes in other organs. This specific vulnerability of the brain may be explained by structural and functional differences between the vessels of the brain and those of vessels in other parts of the body. In this review, we focus on how cerebrovascular anatomy and physiology may make the brain and its vessels more susceptible to unique vascular pathologies. To highlight these differences, we use our knowledge of five diseases and syndromes that most commonly manifest in the intracranial vasculature. For each, we identify characteristics of the intracranial arteries that make them susceptible to these diseases, while noting areas of uncertainty requiring further research.

International audience; Clustered organization of biosynthetic non-homologous genes is emerging as a characteristic feature of plant genomes. The co-regulation of clustered genes seems to largely depend on epigenetic reprogramming and three-dimensional chromatin conformation. In this study, we identified the long non-coding RNA (lncRNA) MARneral Silencing (MARS), localized inside the Arabidopsis marneral cluster, which controls the local epigenetic activation of its surrounding region in response to abscisic acid (ABA). MARS modulates the POLYCOMB REPRESSIVE COMPLEX 1 (PRC1) component LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binding throughout the cluster in a dose-dependent manner, determining H3K27me3 deposition and chromatin condensation. In response to ABA, MARS decoys LHP1 away from the cluster and promotes the formation of a chromatin loop bringing together the MARNERAL SYNTHASE 1 (MRN1) locus and a distal ABA-responsive enhancer. The enrichment of co-regulated lncRNAs in clustered metabolic genes in Arabidopsis suggests that the acquisition of novel non-coding transcriptional units may constitute an additional regulatory layer driving the evolution of biosynthetic pathways

Background: Intracranial large artery stenosis (ILAS) is an important contributor to ischemic stroke in the United States and worldwide. There is evidence to suggest that chronic exposure to certain infectious agents may also be associated with ILAS. We aimed to study this association further in an ethnically diverse, prospective, population-based sample of Northern Manhattan. Methods: We enrolled a random sample of stroke-free participants from an urban, racially, and ethnically diverse community in 1993. Participants have been followed prospectively and a subset underwent brain magnetic resonance angiograms from 2003 to 2008. Intracranial stenoses of the circle of Willis and vertebrobasilar arteries were scored as 0=no stenosis, 1≤50% (or luminal irregularities), 2=50% to 69%, 3≥70% stenosis, and 4=flow gap. We summed the individual score of each artery to produce a global ILAS score (possible range, 0–44). Past infectious exposure to Chlamydia pneumoniae , Helicobacter pylori , cytomegalovirus, and herpes simplex virus 1 and 2 was determined using serum antibody titers. Results: Among 572 NOMAS (Northern Manhattan Study) participants (mean age 71.0±8.0 years, 60% women, 68% Hispanic) with available magnetic resonance angiogram and serological data, herpes simplex virus 2 (beta=0.051, P P P Conclusions: Chronic infectious exposures, specifically herpes simplex virus 2 and cytomegalovirus were associated with asymptomatic ILAS as seen on magnetic resonance angiogram imaging. This may represent an additional target of intervention in the ongoing effort to stem the substantial global burden of strokes related to ILAS.

Despite improved techniques and sophisticated postinterventional care, symptomatic intracranial hemorrhage (sICH) remains the most feared complication of mechanical thrombectomy (MT). Based on peri-interventional parameters, we aimed to discover which patients have a higher risk of sICH.From March 2017 until March 2020 consecutive patients with acute ischemic stroke (AIS) and confirmed large-vessel occlusion who underwent MT were analyzed retrospectively. Demographic, clinical, and radiological variables and parameters specific to thrombectomy were reviewed. A univariate analysis was performed and statistically significant variables were included in a logistic regression model to identify independent factors predictive of sICH.A total of 236 patients with confirmed large-vessel occlusion were included and 22 (9.3%) had sICH. Univariate predictors of sICH included diabetes mellitus, glucose 11.1 mmol/L, creatinine clearance (CrCl) ≤ 30 ml/min/1.73, ASPECTS indicating pretreatment infarct size, acute internal carotid artery (ICA) occlusion, stent implantation, tirofiban use, time from symptom onset to groin puncture 4.5 h and high contrast medium consumption. In the adjusted analysis, ASPECTS 6 (OR 3.673, p = 0.041), and amount of contrast injected ≥ 140 ml (OR 5.412, p = 0.003) were independent predictors of sICH, but not any more baseline glucose 11.1 mmol/L (OR 1.467, p = 0.584), CrCl ≤ 30 ml/min/1.73 (OR 4.177, p = 0.069), acute ICA occlusion (OR 2.079, p = 0.181), stent implantation (OR 0.465, p = 0.512), tirofiban use (OR 5.164, p = 0.167), and time from onset-to-groin puncture (OR 1.453, p = 0.514).The amount of contrast medium used is a modifiable factor associated with sICH. This association is novel and may be related to the neurotoxicity of the contrast medium disrupting the blood-brain barrier.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Background and ObjectivesAge-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer disease. However, in the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA affect volumetric changes in the brain related to neurodegenerative disease remains unclear.MethodsWe performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer's Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between 2 related markers of cerebrovascular disease—MRI-based CMBs and autopsy-based CAA—as independent variables and volumetric markers of neurodegeneration as dependent variables. NOMAS included mostly dementia-free participants age 55 years or older from northern Manhattan. ADNI included participants living in the United States age 55–90 years with a range of cognitive status. EDIS included community-based participants living in Singapore age 60 years and older with a range of cognitive status. BARS included postmortem pathologic samples.ResultsWe included 2,657 participants with available MRI data and 82 autopsy cases from BARS. In a meta-analysis of NOMAS, ADNI, and EDIS, superficial CMBs were associated with larger gray matter (β = 4.49 ± 1.13,p= 0.04) and white matter (β = 4.72 ± 2.1,p= 0.03) volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with 1 CMB (β = 5.17 ± 2.47,p= 0.04) than in those with ≥2 CMBs (β = 1.97 ± 3.41,p= 0.56). In BARS, CAA was associated with increased cortical thickness (β = 6.5 ± 2.3,p= 0.016) but not with increased brain weight (β = 1.54 ± 1.29,p= 0.26).DiscussionSuperficial CMBs are associated with larger morphometric brain measures, specifically white matter volume. This association is strongest in brains with fewer CMBs, suggesting that the CMB/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease.

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

The opinion on whether a patient with an anterior open bite should be treated surgically or not is controversial. These patients generally suffer from associated discomfort due to their occlusal instability and musculoskeletal pain.A 60-year-old woman visited the clinic with dental mobility of her upper central incisors as her chief complaint. She had a severe anterior open bite, with a history of continuous grinding and multiple dental restorations in poor condition. Additionally, she suffered neck pain with movement restrictions.Dentists can evaluate and treat patients with an anterior open bite using this integrative model (physical therapy/dentistry) as a possible alternative as part of the treatment for anterior open bite patients.

Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade the extracellular matrix and are responsible for many physiological and pathological processes. We aim to review the MMP inhibition from a clinical perspective and its possible therapeutic use in the future. MMPs play a role in various neurodegenerative and cerebrovascular diseases such as large artery atherosclerosis and ischemic stroke; for example, MMPs increase blood-brain barrier permeability favoring neuroinflammation. Synthetic MMPs inhibitors have been tested mostly in oncological trials and failed to demonstrate efficacy; some of them were discontinued because of the severe adverse reactions. Tetracyclines, in submicrobial doses, act as an MMP inhibitor, although tetracyclines have not yet been proven effective in several neurological conditions in which they were tested against placebo; it is uncertain whether there may be a use for tetracyclines in cerebrovascular disease, as a neuroprotective agent or in dolichoectasia.

The water balance in boreal forests is dominated by snow in winter and rain in summer, but is expected to change in unpredictable ways by forecasted temperature rise and irregular precipitation patterns. Here we use 30 years of hydrological and environmental data representative of a mixed boreal forest including precipitation, tree transpiration (T), evapotranspiration (ET), vapor pressure deficit, and discharge, combined with a reconstructed 150-year historic climatic record. We show that contrasting seasonal conditions and their lag effects, common in high latitude ecosystems, reduce, buffer, or amplify the boreal forest’s response to extreme weather. Additionally, the season when extreme weather occurs and its preexisting conditions, define how the water balance is partitioned. We show that similarly hot-summer years, (e.g., 2018, 2021), can result in contrasting water balances, primarily because when precipitation is reduced, summer ET returns it rapidly to the atmosphere. Early snowmelt in spring due to high temperatures, accompanied with increased T during spring, reduces summer watershed discharge, storage, and can lower groundwater depths, several months after snowmelt. Using long-term tree T and environmental data, we show the individual importance of seasons in the partitioning of water balance, and highlight the major role boreal forests will play under future climate.

The demand for energy, water and food in Africa continues to increase, resulting in growing pressure on contentious multi-sector resources like the Nile. The Nile conflict becomes a zero-sum game if addressed from a water-centric viewpoint. An understanding of how energy changes impact water infrastructure systems introduces new opportunities to solve water conflicts. Sharing water benefits between the Nile Basin countries rather than disputing water volumes has been promoted to advance collaboration, but over the last two decades it has not provided actionable solutions to the toughest Nile negotiations. Here we develop a detailed integrated energy-river basin system simulator of 13 East African countries, including the Nile Basin, and show how new electricity trade agreements between Ethiopia, Sudan, and Egypt could help resolve the ongoing water dispute over the Grand Ethiopian Renaissance Dam. Results demonstrate that actionable transboundary benefit-sharing solutions require accurately and spatially quantifying river-energy system interdependencies to convince decision-makers of the viability of such solutions.

Introduction: Dolichoectasia of brain arteries has significant clinical implications. It can be measured with automated imaging software such as LKEB Automated Vessel Analysis (LAVA). However, this is not currently used as part of standard clinical practice. Non-automated alternatives such as a Picture Archiving Communication System like RadiAnt are more widely accessible in clinical settings Method: In this validation study, we included 600 participants of the Northern Manhattan Study (NOMAS) and 260 participants of the Atahualpa project. Both studies obtained 1.5T, 3-dimensional time-of-flight brain MRAs. Using RadiAnt (version 2022.1), three independent readers (general practitioner (GP), neurology resident (NR), and vascular neurologist (VN)) measured the diameter of the internal carotid artery (ICA); the most proximal 5 mm of the middle cerebral artery (MCA) and anterior cerebral artery (ACA); and the most proximal portion of the basilar artery (BA). The same vessels were also measured by LAVA. We calculated the intraclass correlation of each rater’s diameters versus those obtained with LAVA (version 5.10.0). GP and NR measured the NOMAS cohort. VN measured the Atahualpa project cohort. Results: The intraclass correlations between diameters obtained by GP and LAVA were stronger for the BA, left ICA, and right ICA (table 1). For VN and LAVA, the same correlations were also significant. For NR and LAVA, correlations were more significant for BA and left MCA. Rater-LAVA correlations for the remaining vessels failed to reach 60%. There is a strong correlation between diameters obtained by GP and NR for the BA and right ACA. Conclusion: Our results suggest that manual measurements of the diameter of the ICAs and BA regardless of training status are reliable and could be used to identify dilated brain arteries using diameter cutoffs for possible interventions. The associations with the remaining vessels were too variable to support the same conclusion.

Objectives: Brain arterial dilation is an increasingly recognized cerebrovascular disease marker. However, demographic and anatomical factors may influence brain arterial diameters within the normal spectrum. We hypothesize that age, sex, height, total cranial volume (TCV) and fetal posterior cerebral arteries (fPCA) presence correlate with brain arterial diameters across diverse populations. Methods: We included participants with available time-of-flight MRA from 9 cohort studies across the United States (4), Ecuador (1), Venezuela (1), South Africa (1) and Singapore (2). Arterial diameters of the basilar artery (BA), cavernous internal carotid arteries (ICAs) and middle cerebral arteries (MCAs) were measured using LKEB Automated Vessel Analysis (LAVA) software. Linear regression models were fitted to assess the association between brain arterial diameters and exposures. The R-squared was calculated to assess the extent of brain arterial diameter variation explained by the variables studied. Results: The sample included 6,269 participants (mean age 68 years; 42% men). Unilateral fPCA was found in 12.6% and bilateral fPCAs in 3.0%. Older age, male sex and TCV were uniformly correlated with larger BA, ICA and MCA diameters (Table). Unilateral and bilateral fPCAs showed a negative correlation with BA diameter and a positive correlation with ICA diameters in a dose-dependent manner. Models fitted for age, sex, TCV, and fPCA presence explained on average 24, 16 and 12 % of the BA, ICAs and MCA diameter interindividual variation, respectively. Using height instead of TCV decreased the R-squared by 2% on average. Conclusions: In this pooled analysis of cohort studies, we found brain arterial diameters consistently correlate with age, sex, TCV and fPCA presence. These factors should be considered to define abnormal arterial diameter cut-offs across populations. If resources are limited or if bedside applicability is desired, height could be used instead of TCV.

Background: A history of pregnancy-induced hypertension (PIH) is associated with higher risk of developing cerebrovascular disease. Data are lacking on the relationship between PIH, chronic hypertension, and MRI markers of cerebral small vessel disease (CSVD) in older people. Methods: We recruited parous individuals without dementia from the Northern Manhattan Study and the Washington Heights-Inwood Washington Heights-Hamilton Heights-Inwood Columbia Aging Project, two long-running prospective cohort studies in New York City. Detailed obstetric and medical histories were obtained by interview. We defined history of PIH as self-report of at least one pregnancy complicated by gestational hypertension, preeclampsia or eclampsia. We categorized participants as having no hypertension, current hypertension without history of PIH, or current hypertension with history of PIH. Number and location of infarcts and white matter hyperintensity (WMH) volume was assessed by MRI. We used generalized linear models to compare imaging outcomes between groups, adjusting for demographics and cardiovascular risk factors. To account for the effects of early onset hypertension, we performed a sensitivity analysis in NOMAS participants only, adjusting for hypertension as a time varying covariate. Results: A total of 221 participants were interviewed (mean age 69 years [SD 7.5]; 22% white, 28% non-Hispanic Black, 48% Hispanic) of whom 128 (58%) had current hypertension without history of PIH, and 16 (7%) had current hypertension with history of PIH. Adjusting for covariates, hypertensive participants with a history of PIH had higher WMH volume, but no difference in deep silent brain infarcts (Table). Conclusions: In a multiethnic cohort of older parous individuals, those with hypertension and a history of PIH had the highest volume of WMH, suggesting a higher burden of CSVD.

Introduction: Hematocrit at both low and high extremes can result in both hypoxia and thrombosis respectively. While both scenarios may predispose to ischemia, it is unclear whether hematocrit associates with small vessel cerebrovascular lacunar infarcts. Hypothesis: Hematocrit levels will associate with both asymptomatic and symptomatic cerebrovascular lacunar infarcts in stroke-free participants and ischemic stroke patients, respectively. Methods: A cross sectional observational analysis of a prospective, population-based cohort study of stroke-free, older adult (>50) participants from the Northern Manhattan study (NOMAS) receiving baseline hematocrit testing and MRI between 2003-2008 were analyzed. A second, single center prospective cohort of admitted adult ischemic stroke patients receiving baseline hematocrit testing and MRI between 2005-2018 was evaluated. Associations of hematocrit with covert, asymptomatic chronic lacunar infarcts from stroke-free participants in NOMAS were assessed using general additive models after adjusting for relevant covariates. Separate analyses were performed to assess associations of hematocrit with symptomatic acute lacunar infarct stroke etiology using similar adjusted models for patients admitted and enrolled into the ischemic stroke registry. Results: Of 1218 NOMAS participants analyzed, 6% had covert chronic lacunar infarcts. The association between hematocrit and covert chronic lacunar infarcts was U-shaped (X2: 9.21; p-value: 0.03). In the 1489 patients from the ischemic stroke registry, 23% were identified to have symptomatic acute lacunar infarcts. Linear relationships were identified with higher hematocrit and symptomatic acute lacunar infarct etiology (adjusted coefficient beta: 0.020; standard error: 0.009; p=0.03). Conclusions: We identified relationships of hematocrit with both asymptomatic and symptomatic lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. There may be a relevant role of red blood cell volumes with ischemic cerebral small vessel disease pathophysiology. However, further studies are required to clarify the mechanisms behind these relationships.

Introduction: Vascular aging is characterized by structural and functional changes in blood vessels that lead to reduced perfusion pressure to distal organs and high blood pressure (BP). Cerebrovascular aging is strongly associated with high BP, however, systemic BP is constituted by the steady and pulsatile components. We aimed this study to investigate the association of intracranial artery stenosis in relation to the steady and pulsatile components of the systemic BP - such association remains undocumented. Methods: We used cross-sectional data from 292 participants from the Maracaibo Aging Study who underwent ambulatory BP monitoring, magnetic resonance angiography, and MRI between 2011 to 2016. The stenosis of eleven intracranial arteries was measured using magnetic resonance angiography scans and encompassed the right and left sides of the anterior (ACA), middle (MCA), posterior (PCA) cerebral arteries, and internal carotid arteries (ICA), vertebral arteries, and the basilar artery. The steady BP component included the 24-hour mean arterial pressure (MAP) while the pulsatile component included the 24-hour pulse pressure (PP). We performed multivariable logistic regression models to assess the association between intracranial artery stenosis and BP components. Models were accounted for age, sex, head circumference, years of education, body mass index, total and high-density cholesterol ratio, creatinine, diabetes mellitus, and antihypertensive treatments. Results: Mean age was 57.5±11 years, 75% women. After adjustment for confounders, 24-hour pulse pressure was associated (P≤ 0.020) with the stenosis of ICA (Odds ratios [OR], 2.00 per every 5 mmHg of PP; 95% confidence interval [CI], 1.49-2.69), ACA (OR, 1.50; 95% CI, 1.23-1.84), MCA (OR, 1.46; 95%, CI, 1.21-1.77), PCA (OR, 1.55; 95% CI, 1.26-1.91), basilar artery (OR, 1.28; 95% CI, 1.03-1.59) and vertebral arteries (OR, 1.42; 95% CI, 1.14-1.78). The ORs of ICA, ACA, MCA, PCA, basilar artery, and vertebral arteries in relation to high 24-hour MAP levels (P≤ 0.040) ranged from 1.27 (95% CI, 1.00-1.61) to 1.48 (95% CI, 1.15 - 1.91). Conclusion: Elevated levels in the steady and pulsatile components of the systemic BP are associated with intracranial artery stenosis.

Introduction: Based on the Poiseuille’s law (blood flow= [pressure gradient* [Pi*radius 4 ]]/[8*blood viscosity*length]) larger brain arterial diameter should associate with a proportional increase in cerebral blood flow. We have reported that larger brain arterial diameters are associated with higher risk of dementia and cerebrovascular disease, but the flow correlates of larger brain arterial diameters have not been studied. Methods: We leveraged an existing data repository of 325 unselected volunteers recruited to validate phase contrast quantitative magnetic resonance angiography (QMRA). Imaging was performed in a 3.0 Tesla MRI Scanner (Signa VHi to HDx, General Electric Medical Systems, later GE Healthcare, Milwaukee, WI, USA) using either a four-channel or eight-channel neurovascular coil. The volume flow rate measurements were acquired with the Noninvasive Optimal Vessel Analysis software (VasSol,Chicago, IL, USA). Brain arterial diameters of the circle of Willis were measured using LKEB Automated Vessel Analysis (LAVA) software. Adjusted models by age, sex, race/ethnicity and height were built to explore the association between blood flow and the diameters of the basilar, middle, and anterior cerebral arteries. Results: We include 325 participants (mean age 48 ± 15 years, 52% female, 64% non-Hispanic white). As expected, arterial luminal diameters are associated with proportionally higher cerebral blood flow. Among people with the largest diameters in this sample, however, the corresponding cerebral blood flow was lower than predicted[MRS1] and this non-linear association was significant in three out of the five arteries studied (Figure 1). Conclusions: In a sample of relatively healthy individuals, those with the largest diameters had lower-than-expected cerebral blood flow. Further studies are needed to better understand the physiopathology by which larger brain arterial diameters relate to cerebrovascular disease.

Introduction: Hemoglobin concentrations and diffusion weighted imaging (DWI) lesions are separately known to be associated with poor intracerebral hemorrhage (ICH) outcomes. Though hemoglobin concentrations are related to both hypoxia and thrombosis at their extremes, it is unknown whether hemoglobin concentrations relate to DWI lesions after ICH. Methods: Spontaneous, supratentorial ICH patients with available baseline hemoglobin and hospitalized MRI data enrolled into a multicenter cohort study between 2010-2016 were analyzed. Baseline hemoglobin was assessed as both a continuous variable (g/dL) and categorical variable (/=15 g/dL). Primary analyses assessed relationships of baseline hemoglobin with MRI DWI lesions. Secondary analyses assessed independent relationships of hemoglobin and DWI lesions with poor 3-month outcomes (modified Rankin Scale [mRS] 4-6). Separate multivariable regression models assessed these relationships after adjusting for relevant covariates. Results: Of 917 ICH patients analyzed, the mean baseline hemoglobin was 13.8 g/dL (+/-1.9), 60% were deep ICH, and DWI lesions were identified in 27% of the cohort. In our primary analyses, increased hemoglobin, defined as a continuous variable, was associated with DWI lesions (adjusted OR 1.21, 95% CI: 1.07-1.37) after adjusting for sex, race, ICH severity, time to MRI, and blood pressure treatment change. In secondary analyses, DWI lesions were associated with poor 3-month outcomes (adjusted OR 1.83, 95% CI: 1.24-2.69) adjusting for similar covariates. We identified associations of low hemoglobin categories, when referenced to hemoglobin 13 to /=15 g/dL) with poor outcomes were smaller and imprecise (adjusted OR 1.39, 95% CI: 0.89-2.17). Conclusions: We identified novel relationships between higher baseline hemoglobin concentrations and DWI lesions in ICH patients. Further studies are required to clarify the role of hemoglobin concentrations on both cerebral small vessel disease pathophysiology and ICH outcomes.

Introduction: The role of “food swamps”, an area characterized by a high-density of establishments selling fast-food and junk food relative to healthier options, on incident stroke is not well studied. Hypothesis We hypothesized that a higher retail food environment index (RFEI), indicative of food swamps, would be associated with greater odds of incident stroke. Methods: The sample comprised of community-dwelling stroke-free participants aged ≥50 years who enrolled in the 2010 epoch of the Health and Retirement Study (HRS), which is representative of the US population. If a participant moved to a new area during follow-up through 2016, we only considered incident strokes reported before relocation. The traditional RFEI is a county’s ratio of the number of fast-food restaurants and convenience stores to the number of grocers. The expanded RFEI additionally includes full-service restaurants as unhealthy food options, and farmers’ markets and specialized food stores as healthy food retailers. We averaged RFEI across all included follow-up years and dichotomized RFEI using a threshold of 5, previously shown to discriminate obesity rates. We used logistic regression models to assess the association between RFEI groups and incident stroke, adjusting for key covariates and weighting to account for survey design. Results: Among 84,023,542 participants (mean age 64±10 years, 54% female, 84% white) in weighted analysis, 3,224,378 (3.8%) reported an incident stroke during follow-up. The average traditional and expanded RFEI were 6.5±2.7 (72% in ≥5 group) and 6.9±2.3 (84% in ≥5 group), respectively. In fully adjusted weighted analyses, the higher traditional RFEI group had greater odds of incident stroke compared to the lower group (OR [95% CI]: 1.135 [1.132-1.138]). We found a similar association with expanded RFEI groups and incident stroke (OR [95% CI]: 1.095 [1.092-1.098]). Conclusions: Among community-dwelling adults in HRS, RFEI was associated with incident stroke, independent of demographics and health characteristics. Results highlight the potential importance of an area’s food options as a structural determinant in stroke, especially given most participants resided in areas with 6 times the amount of relative unhealthy to healthy food choices.

Introduction: Small vessel disease (SVD) is a condition associated with aging and vascular risk factors to which the brain and kidney are susceptible. However, whether kidney dysfunction may directly contribute to brain SVD as opposed to both organs being affected as an epiphenomenon of aging is less clear. We hypothesize that impaired kidney function is differentially associated with brain markers of SVD, and the association is greater with SVD markers restricted to deep, penetrating arteries. Methods: We leveraged existing data from the Columbia University Irving Medical Center/ New York Presbyterian Hospital Stroke Registry. Odds ratio (OR), estimate, confidence intervals (CI), and p values were calculated. We rated visually the presence an anatomical location of cerebral microbleeds and chronic lacunar infarcts and used the Fazekas scale to semi-quantitate white matter hyperintensities. We created linear regression models adjusted for age, sex, race/ethnicity and vascular risk factors to evaluate the relationship between kidney function (defined as self-reported chronic kidney disease or creatinine on admission). Results: We included 973 patients (mean age 65±16 years, 51 % female). The prevalence of self-reported CKD/ESRD was 14% and the mean creatinine on admission was 1.61±2.04 mg/dl. The prevalence of chronic brain infarct was 40%, cerebral microbleeds 24%, and all had some degree of white matter hyperintensity. Conclusion: There is association between previous history of CKD-ESRD and creatinine levels on admission with periventricular WMH. These data also hint a possible association between CMB of deep location with history of CKD-ESRD, but a bigger sample is required for significance.

Item does not contain fulltext 01 juli 2023