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Background: Compromised cerebral blood flow can contribute to future ischemic events in patients with symptomatic carotid artery disease. However, there is limited knowledge of the effects on cerebral hemodynamics resulting from a reduced internal carotid artery (ICA) blood flow rate (BFR). Purpose: Investigate how reduced ICA-BFR, relates to BFR in the cerebral arteries. Study Type: Prospective. Subjects: Thirty-eight patients, age 72 ± 6 years (11 female). Field Strength/Sequence: 3-Tesla, four-dimensional phase-contrast magnetic resonance imaging (4D-PCMRI). Assessment: Patients with ischemic stroke or transient ischemic attack were evaluated regarding the degree of stenosis. 4D-PCMRI was used to measure cerebral BFR in 38 patients with symptomatic carotid stenosis (≥50%). BFR in the cerebral arteries was assessed in two subgroups based on symptomatic ICA-BFR: reduced ICA-flow (<160 mL/minutes) and preserved ICA-flow (≥160 mL/minutes). BFR laterality was defined as a difference in the paired ipsilateral-contralateral arteries. Statistical Tests: Patients were grouped based on ICA-BFR (reduced vs. preserved). Statistical tests (independent sample t-test/paired t-test) were used to compare groups and hemispheres. Significance was determined at P < 0.05. Results: The degree of stenosis was not significantly different, 80% (95% confidence interval [CI] = 73%–87%) in the reduced ICA-flow vs. 72% (CI = 66%–76%) in the preserved ICA-flow; P = 0.09. In the reduced ICA-flow group, a significantly reduced BFR was found in the ipsilateral middle cerebral artery and anterior cerebral artery (A1), while significantly increased in the contralateral A1. Retrograde BFR was found in the posterior communicating artery and ophthalmic artery. Significant BFR laterality was present in all paired arteries in the reduced ICA-flow group, contrasting the preserved ICA-flow group (P = 0.14–0.93). Data Conclusions: 4D-PCMRI revealed compromised cerebral BFR due to carotid stenosis, n

Background Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer's disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group). Methods We recruited a population-based cohort of 217 individuals (all aged 70 years, 53% female participants, 119 SCD-memory individuals, 23 SCD-concentration individuals, and 89 controls). AD and CVD were assessed through cerebrospinal fluid levels of the A beta 42/40 ratio and phosphorylated tau, and white matter signal abnormalities on magnetic resonance imaging, respectively. Associations between biomarkers, depressive symptomatology, and SCD were tested via logistic regression and correlation analyses. Results We found a significant association between depressive symptomatology with SCD-memory and SCD-concentration. Depressive symptomatology was not associated with AD and CVD biomarkers. Both the phosphorylated tau biomarker and depressive symptomatology predicted SCD-memory, and the A beta 42/40 ratio and depressive symptomatology predicted SCD-concentration. Conclusions The role of depressive symptomatology in SCD may differ depending on the stage within the spectrum of preclinical AD (as determined by amyloid-beta and tau positivity), and does not seem to reflect AD pathology. Our findings contribute to the emerging field of subclinical depressive symptomatology in SCD and clarify the association of different types of subjective complaints with distinct syndromic and biomarker profiles.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76–0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74–0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81–0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78–0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Cinco son los artículos científicos que conforman la presente tesis doctoral, titulada “Efectos de la Terapia en Espejo vs. Ejercicio Terapéutico Cognoscitivo en la mejora de las funciones del miembro superior en pacientes con ictus”, que sigue la modalidad por compendio de publicaciones. La rehabilitación de pacientes post-ictus representa un desafío significativo en la atención médica actual, dada la complejidad de las secuelas neurológicas que afectan la funcionalidad y la calidad de vida (CV) de los individuos. En este contexto, la investigación sobre los avances en la rehabilitación post-ictus se ha centrado en varios aspectos cruciales para mejorar los resultados clínicos. Como aspecto principal, para la aplicación de una intervención adecuada y adaptada se ha investigado la efectividad comparativa de la Terapia en Espejo (TE) vs. el Ejercicio Terapéutico Cognoscitivo (ETC), combinadas con Terapia Orientada a Tareas (TOT), en la mejora de la funcionalidad, la motricidad, la autonomía y CV de los pacientes post-ictus. Otro punto importante a considerar es la evaluación, siendo esencial comprender las características psicométricas de los instrumentos de evaluación. Algunos de estos, como el ARAT y MAL-30, están específicamente diseñados para evaluar a pacientes con ictus, por lo que es fundamental garantizar su validez y confiabilidad en la población española. Además, se ha investigado la relación entre diferentes variables demográficas y clínicas con la funcionalidad y la CV un mes después del ictus, lo que proporciona datos cruciales para adaptar los tratamientos de manera personalizada. Con el objetivo de estudiar nuevos avances en la rehabilitación post-ictus, se llevó a cabo un estudio longitudinal enfocado a probar la efectividad de la combinación de estas terapias. Así mismo, dentro de este estudio longitudinal, se utilizó un diseño transversal, analizando los datos en un punto concreto del proceso para determinar las propiedades psicométricas de las esca, There are five scientific articles that make up the present doctoral thesis, entitled "Effects of Mirror Therapy vs. Cognitive Therapeutic Exercise on Improving Upper Limb Functions in Stroke Patients," which follows the compilation of publications modality. The rehabilitation of post-stroke patients represents a significant challenge in current medical care, given the complexity of the neurological sequelae that affect individuals' functionality and quality of life (QoL). In this context, research on advances in post-stroke rehabilitation has focused on several crucial aspects to improve clinical outcomes. As a primary aspect, comparative effectiveness research has been conducted on Mirror Therapy (MT) vs. Cognitive Therapeutic Exercise (CTE), combined with Task-Oriented Therapy (TOT), in improving functionality, motor skills, autonomy, and QoL in post-stroke patients. Another important point to consider is evaluation, as it is essential to understand the psychometric characteristics of assessment instruments. Some of these, such as the ARAT and MAL-30, are specifically designed to assess stroke patients, so it is crucial to ensure their validity and reliability in the Spanish population. Furthermore, the relationship between different demographic and clinical variables with functionality and QoL one month after stroke has been investigated, providing crucial data for personalized treatment adaptation. In order to study new advances in post-stroke rehabilitation, a longitudinal study was conducted to test the effectiveness of combining these therapies. Within this longitudinal study, a cross-sectional design was used to analyze data at a specific point in the process to determine the psychometric properties of the scales and identify the characteristics and determining factors of functional independence and QoL in these patients. Our findings suggest that both techniques, Mirror Therapy (MT) and Cognitive Therapeutic Exercise (CTE) combined with Task-Oriented Thera, Doctorado en Avances en Ciencia y Biotecnología Alimentarias

Cerebrovascular disease is the world's second major cause of mortality and disability, and the fourth major cause of mortality and disability in South Africa. Cerebrovascular disease occurs due to issues of the brain's blood supply, either the blood supply is cut off or a blood artery within the brain bursts. Radiologists have the responsibility to detect cerebrovascular disease. We now have technology which can help them to better detect this disease. Medical imaging plays an important role in detecting diseases. This study presents implementation of a detection system using artificial intelligence model, namely, convolutional neural networks to help in detecting cerebrovascular disease from magnetic resonance imaging (MRI) scans. Brain images using MRI was obtained from kaggle pub-lic dataset. Segmentation process was applied in this study to normalise images since the images came in different sizes. The effectiveness of the concept was demonstrated using a confusion matrix. The accuracy rate was plotted using the Receiver Operating Characteristics (ROC) curve. The evaluation results show that the Convolutional Neural Network (CNN) model detect cerebrovascular disease successfully with validation accu-racy rate of 90% and test accuracy rate of 80%. The training procedure could be improved by using a larger MRI dataset., IBM ETDP SITA

Background: Studies have established that radiotherapy for childhood brain tumors (BTs) increases the risk of cerebrovascular disease (CVD); however, it is unclear how this will affect cognitive function. This study aimed to investigate the associations between radiotherapy-induced CVD, white matter hyperintensities (WMHs), and neurocognitive outcomes in adult survivors of childhood BTs. Methods: In a cross-sectional setting, we conducted a national cohort that included 68 radiotherapy-treated survivors of childhood BTs after a median follow-up of 20 years. Markers of CVD and WMHs were evaluated using brain MRI, and the sum of CVD-related findings was calculated. Additionally, the associations among CVD findings, WMHs, and neuropsychological test results were analyzed. Results: Of the 68 childhood BT survivors, 54 (79%) were diagnosed with CVD and/or WMHs at a median age of 27 years. CVD and/or WMHs were associated with lower scores for verbal intelligence quotient, performance intelligence quotient (PIQ), executive function, memory, and visuospatial ability (P < .05). Additionally, survivors with microbleeds had greater impairments in the PIQ, processing speed, executive function, and visuospatial ability (P < .05). WMHs and CVD burden were associated with greater difficulties in memory function and visuospatial ability (P < .05). Small-vessel disease burden was associated with PIQ scores, processing speed, working memory, and visuospatial ability. Conclusions: The study results suggest that markers of radiotherapy-induced CVD, the additive effect of CVD markers, and risk factors of dementia are associated with cognitive impairment, which may suggest that the survivors are at a high risk of developing early-onset dementia.

Background and aims: Guidelines no longer recommend low-fat diets and currently recommend more plant-based diets to reduce atherosclerotic cardiovascular disease (ASCVD) risk. Furthermore, these guidelines have consistently recommended salt-reduced diets. This article describes current self-reported use and time-trends in the self-reported use of low-fat, low-salt and vegetarian diets in ASCVD patients and examines patient characteristics associated with each diet. Methods and results: 9005 patients with ASCVD included between 1996 and 2019 in the UCC-SMART cohort were studied. The prevalence of self-reported diets was assessed and multi-variable logistic regression was used to identify the determinants of each diet. Between 1996-1997 and 2018–2019, low-fat diets declined from 22.4 % to 3.8 %, and low-salt diets from 14.7 % to 4.6 %. The prevalence of vegetarian diets increased from 1.1 % in 1996–1997 to 2.3 % in 2018–2019. Patients with cerebrovascular disease (CeVD) and peripheral artery disease or an abdominal aortic aneurysm (PAD/AAA) were less likely to report a low-salt diet than coronary artery disease (CAD) patients (OR 0.62 [95%CI 0.49–0.77] and 0.55 [95%CI 0.41–0.72]). Conclusion: In the period 1996 to 2019 amongst patients with ASCVD, the prevalence of self-reported low-fat diets was low and decreased in line with changes in recommendations in major guidelines. The prevalence of self-reported vegetarian diets was low but increased in line with societal and guideline changes. The prevalence of self-reported low-salt diets was low, especially in CeVD and PAD/AAA patients compared to CAD patients, and decreased over time. Renewed action is needed to promote low-salt diets in ASCVD patients.

Objectives Quantitative regional cerebral perfusion (rCBF) measurements using [15O]H2O PET with arterial cannulation and acetazolamide (ACZ) challenge have been reserved to identify high-risk patients that are candidates for by-pass operation. We aimed to assess the prognostic value of various parameters in quantitative [15O]H2O PET measurements in patients not subsequently undergoing surgery. Methods We identified 32 eligible patients who underwent [15O]H2O brain PET imaging for suspicion of hemodynamic insufficiency between 2009 and 2020. Cerebrovascular events were defined as new ischemic lesions on MRI, stroke, transient ischemic attack, vascular dementia. Follow-up period was 91 months (range: 26-146). rCBF before (rCBFbase) and after (rCBFacz) ACZ challenge and the relative increase (CVR), were examined in the anterior (ACA), middle (MCA), and posterior (PCA) cerebral artery territories of the affected hemisphere, and the most recent MRI scans were scored for infarcts and white matter lesions. Results Receiver operating characteristic (ROC) curve analysis showed higher prognostic accuracy for rCBFacz(AUC:0.82) compared to CVR (AUC:0.72) and rCBFbase (AUC:0.77). ROC AUC, optimal thresholds (and corresponding sensitivity/specificity/accuracy) for rCBFacz after ACZ in individual territories were 0.79 and 37.8 mL 100g−1 min−1 (0.81/0.63/0.72) for the ACA, 0.84 and 32 mL 100g−1 min−1 (0.81/0.75/0.78) for the MCA, and 0.70 and 43.9 ml/(mL 100g−1 min−1 (0.81/0.43/0,62) for the PCA. Kaplan Meier survival curve showed longer event-free survival in patients with rCBFacz below cut-off (p=0.007). In multivariate analysis rCBFacz remained a significant predictor when correcting for age. Conclusion Quantitative rCBF measurements after ACZ challenge with [15O]H2O PET provided high prognostic value for future cerebrovascular events., Objectives: Quantitative regional cerebral perfusion (rCBF) measurements using [15O]H2O PET with arterial cannulation and acetazolamide (ACZ) challenge have been reserved to identify high-risk patients that are candidates for by-pass operation. We aimed to assess the prognostic value of various parameters in quantitative [15O]H2O PET measurements in patients not subsequently undergoing surgery. Methods: We identified 32 eligible patients who underwent [15O]H2O brain PET imaging for suspicion of hemodynamic insufficiency between 2009 and 2020. Cerebrovascular events were defined as new ischemic lesions on MRI, stroke, transient ischemic attack, vascular dementia. Follow-up period was 91 months (range: 26-146). rCBF before (rCBFbase) and after (rCBFacz) ACZ challenge and the relative increase (CVR), were examined in the anterior (ACA), middle (MCA), and posterior (PCA) cerebral artery territories of the affected hemisphere, and the most recent MRI scans were scored for infarcts and white matter lesions. Results: Receiver operating characteristic (ROC) curve analysis showed higher prognostic accuracy for rCBFacz(AUC:0.82) compared to CVR (AUC:0.72) and rCBFbase (AUC:0.77). ROC AUC, optimal thresholds (and corresponding sensitivity/specificity/accuracy) for rCBFacz after ACZ in individual territories were 0.79 and 37.8 mL 100g−1 min−1 (0.81/0.63/0.72) for the ACA, 0.84 and 32 mL 100g−1 min−1 (0.81/0.75/0.78) for the MCA, and 0.70 and 43.9 ml/(mL 100g−1 min−1 (0.81/0.43/0,62) for the PCA. Kaplan Meier survival curve showed longer event-free survival in patients with rCBFacz below cut-off (p=0.007). In multivariate analysis rCBFacz remained a significant predictor when correcting for age. Conclusion: Quantitative rCBF measurements after ACZ challenge with [15

PCSK9 inhibitors (Proprotein convertase subtilisin-kexin9 inhibitors) not only have a good lipid-lowering effect but also have the effects of improving cardiovascular outcome, anti-inflammation, reducing oxidative stress and improving vascular endothelium. In recent years, the continuous research and development of PCSK9 inhibitors have provided new ideas for the treatment of cardiovascular diseases. This article reviews the multiple action mechanisms of PCSK9 inhibitors and their research in kidney disease and cerebrovascular diseases.

Background: The COVID-19 pandemic seemed to mainly involve the respiratory system, but it was realized that it could affect any organ, including the CNS. The pandemic has followed a wave-like trend, with its peaks being due to the COVID-19 different variants and the introduction of the vaccine, which led to an apparent reduction in hospitalizations but also brought about perplexities related to its adverse effects. The aim of this study was to analyze the changes in the use of head CT/contrast CT and their impacts on the onset of cerebrovascular disease in our emergency department during the COVID-19 period and the vaccine rollout. Methods: Patients >= 18 years old admitted to our emergency department from January 2018 to September 2021 were enrolled. The patients were divided into three groups. The COVID-19 period included patients who visited our emergency department from 1 March 2020 to 31 January 2021; the vaccine period was considered to range from 1 February 2021 to 30 September 2021. The patients who visited the emergency department from 1 January 2018 to 31 January 2020 were considered the controls. Results: We found an increase in head CT/contrast CT requests during the COVID-19 period and increase in head contrast CT during the vaccine period, without an increase in the incidence of cerebrovascular disease. Conclusions: The uncertainty regarding the possible thrombotic events associated with COVID-19 and its vaccine increased the relative use of head CT/contrast CT by about 20% compared to the control period

Background Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time. Methods A total of 4943 participants (mean age = 64.6 +/- 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used. Results A smaller total brain volume (beta = -0.107, 95% CI -0.192 to -0.022), larger white matter hyperintensities volume (beta = 0.047, 95% CI 0.010-0.084), presence of cortical infarcts (beta = 0.194, 95% CI 0.047-0.341), and higher MD levels (beta = 0.060, 95% CI 0.022-0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (beta = -0.091, 95% CI -0.167 to -0.015) and presence of cortical infarcts (beta = 0.168, 95% CI 0.022-0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages. Conclusions Neuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatolo

The study aimed to determine the predictors of death (in the first 21 days) in patients with spontaneous subarachnoid hemorrhage; for this, an observational, descriptive-correlational study was carried out, which included 79 patients with spontaneous subarachnoid hemorrhage between 2016 and 2021. Fatality due to the disease and its relationship with various variables were determined, for which bivariate and multivariate analysis (logistic regression) was performed; The Odds Ratio and its confidence interval were used as statisticians. Among the main results are the following: 29 patients (36.7%) died. Mortality was higher in older adults (40% vs 33%, not significant), in females (43% vs 29%, not significant) and in patients admitted within the first 48 hours of diagnosis (43% vs 7%, OR 9.8[1.2;79.7]); also in whom the cause of the bleeding could not be identified (64%), and in the clinical presentation with a predominance of alterations in the state of consciousness (OR 3.3[1.03;10.5]). In the clinical and imaging scales used, a progressive increase in lethality from low to high grades was found (Hunt and Hess: OR 13.6[4.3;43.2]; Fisher: OR 14.4[1.8;115.3]). As conclusions of the investigation, the lethality at 21 days in the series studied is considered high, and was associated with the clinical presentation with a predominance of alterations in the state of consciousness, the greater intensity of the initial bleeding (Fisher IIIIV), the occurrence of neurological complications and the superimposed respiratory infection. The importance of rebleeding in the occurrence of death is verified, as well as the condition of death predictor of the Hunt and Hess scale., El estudio tuvo como objetivo determinar los factores predictivos de muerte (en los primeros 21 días) en pacientes con hemorragia subaracnoidea espontánea; para esto se realizó un estudio observacional, descriptivo-correlacional, que incluyó a 79 pacientes con hemorragia subaracnoidea espontánea entre 2016 y 2021. Se determinó la letalidad por la enfermedad y su relación con diversas variables, para lo cual se realizó análisis bivariado y multivariado (regresión logística); se utilizó como estadígrafo el Odds Ratio y su intervalo de confianza. Entre los principales resultados se encuentran los siguientes: fallecieron 29 pacientes (36,7%). La letalidad fue superior en adultos mayores (40% vs 33%, no significativo), en el sexo femenino (43% vs 29%, no significativo) y en los pacientes que ingresaron en las primeras 48 horas del diagnóstico (43% vs 7%, OR 9,8[1,2;79,7]); también en quienes no pudo ser identificada la causa del sangramiento (64%), y en la presentación clínica con predominio de alteraciones del estado de conciencia (OR 3,3[1,03;10,5]). En las escalas clínica e imagenológicas utilizadas se constató un incremento progresivo de la letalidad de los grados bajos a los altos (Hunt y Hess: OR 13,6[4,3;43,2]; Fisher: OR 14,4[1,8;115,3]). Como conclusiones de la investigación, la letalidad a los 21 días en la serie estudiada se considera elevada, y estuvo asociada a la presentación clínica con predominio de alteraciones en el estado de conciencia, la mayor intensidad del sangramiento inicial (Fisher IIIIV), la ocurrencia de complicaciones neurológicas y la infección respiratoria sobreañadida. Se comprueba la importancia del resangrado en la ocurrencia de muerte, así como la condición de predictor de fallecimiento de la escala de Hunt y Hess.

BackgroundWhite matter hyperintensities (WMH) that occur in the setting of vascular cognitive impairment and dementia (VCID) may be dynamic increasing or decreasing volumes or stable over time. Quantifying such changes may prove useful as a biomarker for clinical trials designed to address vascular cognitive-impairment and dementia and Alzheimer's Disease.ObjectiveConducting multi-site cross-site inter-rater and test-retest reliability of the MarkVCID white matter hyperintensity growth and regression protocol.MethodsThe NINDS-supported MarkVCID Consortium evaluated a neuroimaging biomarker developed to track WMH change. Test-retest and cross-site inter-rater reliability of the protocol were assessed. Cognitive test scores were analyzed in relation to WMH changes to explore its construct validity.ResultsICC values for test-retest reliability of WMH growth and regression were 0.969 and 0.937 respectively, while for cross-site inter-rater ICC values for WMH growth and regression were 0.995 and 0.990 respectively. Word list long-delay free-recall was negatively associated with WMH growth (p < 0.028) but was not associated with WMH regression.ConclusionsThe present data demonstrate robust ICC validity of a WMH growth/regression protocol over a one-year period as measured by cross-site inter-rater and test-retest reliability. These data suggest that this approach may serve an important role in clinical trials of disease-modifying agents for VCID that may preferentially affect WMH growth, stability, or regression.

Producción Científica, We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10−2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = −0.04, p-value = 1.3 × 10−3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10−4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10−2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection., Consejo Superior de Investigaciones Científicas (CSIC), Fondos COVID-19 - (grant CSIC202020E086), Comisión Europea—NextGenerationEU - (grant EU 2020/2094), Instituto de Salud Carlos III, proyecto iBioStroke - (grant AC19/00106 Eranet-Neuron, European research grants), Instituto de Salud Carlos III - (RICORS RD21/0006/0006), Fondo Europeo de Desarrollo Regional (FEDER), NextGeneration EU - PREVICTUS project (PMP21/00165), and COPYCTUS project (PI21/01088), Instituto de Salud Carlos III, PFIS Contract (Contratos Predoctorales de Formación en Investigación en Salud) - (grant FI19/00309), Instituto de Salud Carlos III, y Fondo Europeo de Desarrollo Regional (FEDER), Contrato Sara Borrel - (grant CD20/00043)

The respiratory virus SARS-CoV-2, responsible for the multi-system illness known as COVID-19 and resulting global pandemic of 2020, is increasingly recognized  for its ability to cause cerebrovascular complications. This series of four cases from a single institution during the height of the pandemic is presented to illustrate the virus’s uniquely diverse pathophysiology and corresponding clinical and radiologic manifestations. As no neurologic manifestation specific to SARS-CoV-2 has been identified, it remains of upmost importance that clinicians and radiologists alike maintain a high index of suspicion for these complications, especially when neurological findings present in the young or otherwise atypical demographics.

Background Adverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome. Methods Patients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014–2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale. Results In total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69). Conclusion Intraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.

IntroductionThe Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for Alzheimer's disease (AD) clinical trials. To improve generalizability, ADNI4 aims to enroll 50-60% of its new participants from underrepresented populations (URPs) using new biofluid and digital technologies. ADNI4 has received funding from the National Institute on Aging beginning September 2022.MethodsADNI4 will recruit URPs using community-engaged approaches. An online portal will screen 20,000 participants, 4000 of whom (50-60% URPs) will be tested for plasma biomarkers and APOE. From this, 500 new participants will undergo in-clinic assessment joining 500 ADNI3 rollover participants. Remaining participants (∼3500) will undergo longitudinal plasma and digital cognitive testing. ADNI4 will add MRI sequences and new PET tracers. Project 1 will optimize biomarkers in AD clinical trials.Results and discussionADNI4 will improve generalizability of results, use remote digital and blood screening, and continue providing longitudinal clinical, biomarker, and autopsy data to investigators.

Brain changes at the end-stage of fragile X-associated tremor/ataxia syndrome (FXTAS) are largely unknown due to mobility impairment. We conducted a postmortem MRI study of FXTAS to quantify cerebrovascular disease, brain atrophy and iron content, and examined their relationships using principal component analysis (PCA). Intracranial hemorrhage (ICH) was observed in 4/17 FXTAS cases, among which one was confirmed by histologic staining. Compared with seven control brains, FXTAS cases showed higher ratings of T2-hyperintensities (indicating cerebral small vessel disease) in the cerebellum, globus pallidus and frontoparietal white matter, and significant atrophy in the cerebellar white matter, red nucleus and dentate nucleus. PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus and amygdala, that were independent from a highly correlated number of regions with ICH and iron content in subcortical nuclei. Post-hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus and amygdala in FXTAS cases compared to controls, after adjusting for T2-hyperintensity ratings. These findings indicate that both ischemic and hemorrhagic brain damage may occur in FXTAS, with the former being marked by demyelination/iron depletion and atrophy, and the latter by ICH and iron accumulation in basal ganglia.

American football players and other individuals exposed to repetitive head impacts can exhibit a constellation of later-life cognitive and neuropsychiatric symptoms. While tau-based diseases such as chronic traumatic encephalopathy can underpin certain symptoms, contributions from non-tau pathologies from repetitive head impacts are increasingly recognized. We examined cross-sectional associations between myelin integrity using immunoassays for myelin-associated glycoprotein and proteolipid protein 1 with risk factors and clinical outcomes in brain donors exposed to repetitive head impacts from American football. Immunoassays for myelin-associated glycoprotein and proteolipid protein 1 were conducted on dorsolateral frontal white matter tissue samples of 205 male brain donors. Proxies of exposure to repetitive head impacts included years of exposure and age of first exposure to American football play. Informants completed the Functional Activities Questionnaire, Behavior Rating Inventory of Executive Function-Adult Version (Behavioral Regulation Index), and Barratt Impulsiveness Scale-11. Associations between myelin-associated glycoprotein and proteolipid protein 1 with exposure proxies and clinical scales were tested. Of the 205 male brain donors who played amateur and professional football, the mean age was 67.17 (SD = 16.78), and 75.9% (n = 126) were reported by informants to be functionally impaired prior to death. Myelin-associated glycoprotein and proteolipid protein 1 correlated with the ischaemic injury scale score, a global indicator of cerebrovascular disease (r = -0.23 and -0.20, respectively, Ps < 0.01). Chronic traumatic encephalopathy was the most common neurodegenerative disease (n = 151, 73.7%). Myelin-associated glycoprotein and proteolipid protein 1 were not associated with chronic traumatic encephalopathy status, but lower proteolipid protein 1 was associated with more severe chronic traumatic encephalopathy (P = 0.03). Myelin-associated glycop

Cerebrovascular disease is a sudden neurological impairment attributable to a focal vascular cause. The definition of ischemic is oriented when it is due to an obstruction that causes a decrease or absence of blood flow, generally due to a thrombus in the vasculature in situ or an embolization from another place, causing a neuronal energy deficit with subsequent death of the affected neurons. Age is the most important demographic risk factor and although the incidence of cerebrovascular disease has decreased in recent years, the lifetime risk of stroke has increased due to the aging of the population. The clinical manifestations will correspond to the location of the ischemia, but are generally absent or decreased sensory, motor function or both in one half of the body, loss of speech or understanding, vision changes, gait disturbance, and sudden severe headache. The most common etiologies are cardioembolic, arterioarterial embolism and stenosis that limits the flow of a large extracranial vessel. Within the diagnostic tools, the first study of choice is still computed tomography without contrast, basically to show or not a bleeding process to rule out hemorrhagic cerebrovascular disease that may explain the patient's presentation. Lastly, seek the continuous education of our patients, guiding them towards a healthy lifestyle and be attentive in our consultations to see the clinical evolution of these patients., La enfermedad cerebrovascular es una deficiencia neurológica repentina atribuible a una causa vascular focal. La definición de isquémica se orienta cuando se debe a una obstrucción que provoca una disminución o ausencia del flujo sanguíneo, generalmente por un trombo en la vasculatura in situ o una embolización proveniente de otro lugar, llevando a cabo un déficit energético neuronal con la posterior muerte neuronal afectada. La edad es el factor de riesgo demográfico más importante, y aunque la incidencia de la enfermedad cerebrovascular ha disminuido en los últimos años, el riesgo de ictus a lo largo de la vida ha aumentado debido al envejecimiento de la población. Las manifestaciones van a corresponder a la localización de la isquemia, pero generalmente son ausencia o disminución de la función sensitiva, motora o ambas en la mitad del cuerpo, pérdida del habla o de la comprensión, cambios en la visión, alteración de la marcha y cefalea intensa inesperada. Las etiologías más comunes son cardioembólicas, embolismo arterioarteriales y estenosis que limita el flujo de un gran vaso extracraneal. Dentro de las herramientas diagnósticas, el primer estudio de elección todavía sigue siendo la tomografía computarizada sin contraste, básicamente para evidenciar o no un proceso hemorrágico para descartar la enfermedad cerebrovascular hemorrágica que pueda explicar la presentación del paciente. Por último, se debe buscar la educación continua de los pacientes, orientándolos hacia un estilo de vida saludable, y se debe prestar atención en las consultas para ver la evolución clínica de estos pacientes.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, progressive, premature aging syndrome with early morbidity due to cardiovascular and cerebrovascular diseases. The clinical symptoms are very diverse, including non-specific symptoms such as growth retardation, scleroderma, alopecia and osteoporosis, as well as hypertension and cardiovascular diseases that occur in childhood and adolescence due to accelerated vascular aging, is caused by a sporadic mutation of a LMNA single base, resulting in an abnormal form of the inner membrane protein lamin A, also known as progerin. Progerin is expressed in cell types that are essential for vascular function and structure, such as vascular smooth muscle cells, endothelial cells, and adventitial fibroblasts. The presence of the syndrome generates a high risk of developing cerebrovascular events among other comorbidities. We present below a case of a 21-year-old male from Santander Colombia with a diagnosis of Progeria and 2 lacunar cerebrovascular events. This is a male in his third decade of life with a clinical picture of 2 hospital admissions for cerebrovascular disease presenting with left motor hemiparesis, modified Rankin of 1, in the CASCADE protocol studies, embolic, atherothrombotic and hypercoagulability sources were ruled out. A lacunar infarction was evidenced in brain resonance at the level of the right and left hemisphere. Lacunar infarcts are expressed by four stereotyped lacunar syndromes: pure motor hemiparesis, pure sensory syndrome, femoral paresis with ipsilateral ataxia, later called ataxic hemiparesis or ataxia-hemiparesis, and clumsy hand dysarthria. The patient presents a pure left motor hemiparesis-type event with currently minimal limitations. This case is anecdotal and would be the first report in the Colombian literature of this type of association with progeria., El síndrome de progeria de Hutchinson-Gilford (SPHG) es un síndrome de envejecimiento prematuro, progresivo y poco frecuente con morbilidad temprana debido a enfermedades cardiovasculares y cerebrovasculares. Los síntomas clínicos son muy diversos, incluyendo síntomas inespecíficos como retraso del crecimiento, esclerodermia, alopecia y osteoporosis, así como hipertensión y enfermedades cardiovasculares que se presentan en la infancia y la adolescencia debido al envejecimiento vascular acelerado, es causado por una mutación esporádica de una sola base de LMNA, que da como resultado una forma anormal de la proteína lamina A de la membrana interna, también conocida como progerina. La progerina se expresa en tipos de células que son fundamentales para la función y estructura vascular, como las células del músculo liso vascular, las células endoteliales y los fibroblastos adventiciales. La presencia del síndrome genera un riesgo elevado para desarrollar eventos cerebrovasculares entre otras comorbilidades. Presentamos a continuación un caso de un masculino de 21 años de edad proveniente de Santander Colombia con diagnóstico de Progeria y con 2 eventos cerebrovasculares lacunares. Se trata de un masculino de la tercera década de la vida con cuadro clínico de 2 ingresos hospitalarios por enfermedad cerebrovascular cursando con hemiparesia motora izquierda, Rankin modificado de 1, en los estudios del protocolo CASCADE se descartaron fuentes embolicas, aterotrombóticas y de hipercoagulabilidad. Se evidencio infarto lacunar en resonancia cerebral a nivel del hemisferio derecho e izquierdo. Los infartos lacunares se expresan por cuatro síndromes lacunares estereotipados: hemiparesia motora pura, síndrome sensitivo puro, paresia crural con ataxia homolateral, que más tarde se llamaría hemiparesia atáxica o ataxia-hemiparesia, y disartria mano torpe. El paciente presenta un evento tipo hemiparesia motora pura izquierda con minimas limitaciones actualmente. El presente caso es a

Hypertension is associated with the presence of vascular abnormalities, including remodeling and rarefaction. These processes play an important role in cerebrovascular disease development; however, the mechanistic changes leading to these diseases are not well characterized. Using data-independent acquisition–based mass spectrometry analysis, here we determined the protein changes in cerebral arteries in pre- and early-onset hypertension from the spontaneously hypertensive rat (SHR), a model that resembles essential hypertension in humans. Our analysis identified 125 proteins with expression levels that were significantly upregulated or downregulated in 12-week-old spontaneously hypertensive rats compared to normotensive Wistar Kyoto rats. Using an angiogenesis enrichment analysis, we further identified a critical imbalance in angiogenic proteins that promoted an anti-angiogenic profile in cerebral arteries at early onset of hypertension. In a comparison to previously published data, we demonstrate that this angiogenic imbalance is not present in mesenteric and renal arteries from age-matched SHRs. Finally, we identified two proteins (Fbln5 and Cdh13), whose expression levels were critically altered in cerebral arteries compared to the other arterial beds. The observation of an angiogenic imbalance in cerebral arteries from the SHR reveals critical protein changes in the cerebrovasculature at the early onset of hypertension and provides novel insights into the early pathology of cerebrovascular disease.

Objective: To examine the relationship between periodontitis and subclinical intracranial atherosclerosis. The association of periodontitis with preclinical markers of atherosclerosis in other vascular territories was also explored. Material and methods: This was a cross-sectional study where 97 elderly subjects with a previous history of hypertension received an ultrasonographic evaluation to assess subclinical atherosclerosis in different vascular territories: (1) cerebral [pulsatility (PI) and resistance index (RI) of the middle cerebral artery], (2) carotid [intima-media thickness (IMT)], and (3) peripheral [ankle-brachial index (ABI)]. Additionally, participants underwent a full-mouth periodontal assessment together with blood sample collection to determine levels of inflammatory biomarkers (leukocytes, fibrinogen, and erythrocyte sedimentation rate), lipid fractions (total cholesterol and high- and low-density lipoprotein), and glucose. Results: Sixty-one individuals had periodontitis. Compared to subjects without periodontitis, those with periodontitis showed higher values of PI (1.24 ± 0.29 vs 1.01 ± 0.16), RI (0.70 ± 0.14 vs 0.60 ± 0.06), and IMT (0.94 ± 0.15 vs 0.79 ± 0.15) (all p < 0.001). No statistically significant differences were found neither for ABI or for other clinical and biochemical parameters. An independent association was found between periodontitis and increased intracranial atherosclerosis (ORadjusted = 10.16; 95% CI: 3.14-32.90, p < 0.001) and to a lesser extent with thicker carotid IMT (ORadjusted = 4.10; 95% CI: 1.61-10.48, p = 0.003). Conclusions: Periodontitis is associated with subclinical atherosclerosis in both intracranial and carotid arteries in elderly subjects with hypertension. Clinical relevance: The association of periodontitis with intracranial atherosclerosis implies that periodontitis patients might have greater chances to develop ischemic stroke in the future

Introduction and objectives: Exposure to environmental tobacco smoke (ETS) is associated with increased mortality and morbidity. The objective of this study was to estimate the impact of ETS exposure in Spain on mortality in 2020 in the population aged 35 years and over. Methods: A method of estimating attributable mortality (AM) based on the prevalence of ETS exposure was applied. Prevalence data were obtained from a representative study conducted in Spain and the relative risks were derived from a meta-analysis. AM point estimates are presented along with 95% confidence intervals (95% CI), calculated using a bootstrap naive procedure. AM, both overall and by smoking habit, was estimated for each combination of sex, age group, and cause of death (lung cancer and ischemic heart disease). A sensitivity analysis was performed. Results: A total of 747 (95% CI 676–825) deaths were attributable to ETS exposure, of which 279 (95% CI 256–306) were caused by lung cancer, and 468 (95% CI 417–523) by ischemic heart disease. Three quarters (75.1%) of AM occurred in men and 60.9% in non-smokers. When chronic obstructive pulmonary disease and cerebrovascular disease are included, the burden of AM is estimated at 2242 deaths. Conclusions: ETS exposure is associated with 1.5% of all deaths from lung cancer and ischemic heart disease in the population aged 35 and over. These data underline the need for health authorities to focus on reducing exposure to ETS in all settings and environments

Background Somatosensory evoked potentials (SEP) may add substantial prognostic value in patients with acute ischemic stroke (AIS) and contribute to the selection of patients that may benefit from revascularization therapies beyond the accepted therapeutic time windows. We aimed to study the prognostic accuracy of N20 SEP component of the ischemic hemisphere in patients with anterior large vessel occlusion undergoing endovascular thrombectomy (EVT). Methods: Presence and amplitude of the N20 response were recorded before and after EVT. Its adjusted predictive value for functional independence (modified Rankin scale score, =2) at day 7 was analysed by binary logistic regression adjusting by age, mean arterial blood pressure, NIHSS, ASPECTS score and serum glucose. N20 predictive power was compared with that of clinical and imaging models by using Receiving Operating Characteristics Curve (ROC) analysis. Results: 223 consecutive patients were studied (mean age, 70y; median NIHSS, 18). SEP recordings identified presence of N20 in 110 (49.3%), absence in 58 (26%) and not assessable in 55 patients due to radiofrequency interferences in the angiography room. Prior to EVT, N20 predicted functional independence with a sensitivity of 93% (95%CI, 78-98%) and negative predictive value of 93% (80-98%). The adjusted odds ratio for functional independence was 9.9 (95%CI, 3.1-44.6). In ROC analysis, N20 amplitude showed a higher area under the curve than models using pre-hospital or in-hospital variables, including advanced imaging. Sensitivity increased to 100% (95% CI, 0.85-1) at the end of EVT. Conclusions: SEP monitoring is a non-invasive and bedside technique that could help eligibility of AIS patients for EVT and predict functional recovery., Peer Reviewed, Postprint (published version)

Introducció: L'ictus és una síndrome clínica causada per una lesió cerebral focal o generalitzada que dura més de 24 hores o que porta a la mort, i no té cap altra causa que la vascular. Ocorre quan de manera sobtada es trenca o s’obstrueix un vas sanguini que irriga el cervell, llavors les neurones de l’àrea afectada no reben prou oxigen i moren, provocant dany cerebral. Una de les múltiples seqüeles de l’ictus és l’afectació en la visió. Objectiu:Realitzar una revisió bibliogràfica sobre la discapacitat visual derivada de l'ictus per identificar publicacions científiques recents sobre el tema. Metodologia: S'ha dut a terme una cerca bibliogràfica a través de Pubmed en revistes revisades per parells, restringint la cerca a articles publicats en anglès entre els mesos de gener de 2002 i desembre de 2022. S’ha utilitzat les següents paraules clau: ''Stroke AND visual impairment'', ''Stroke AND vision'' i ''Stroke AND visual rehabilitation”. Resultats: Després d’aplicar els criteris d’inclusió i exclusió, s’ha seleccionat 41 articles. La discapacitat visual afecta gairebé el 60% de les persones que han patit un ictus, sobretot en forma de pèrdua del camp visual, però també negligència visual, alteracions de la motilitat ocular, reducció de l'agudesa visual i/o problemes de percepció visual. Els mètodes de rehabilitació depenen de les necessitats i dificultats visuals de cada pacient. Conclusions: La rehabilitació de la discapacitat visual subjacent a un ictus és un gran desafiament, doncs té unes repercussions importants en les activitats de vida diària de la persona, i en la seva qualitat de vida., Introducción: El ictus es un síndrome clínico causado por una lesión cerebral focal o generalizada que dura más de 24 horas o que lleva a la muerte, y no tiene otra causa que la vascular. Ocurre cuando de forma repentina se rompe o se obstruye un vaso sanguíneo que irriga el cerebro, entonces las neuronas del área afectada no reciben suficiente oxígeno y mueren, provocando daño cerebral. Una de las múltiples secuelas del ictus es la afectación en la visión. Objetivo:Realizar una revisión bibliográfica sobre la discapacidad visual derivada del ictus para identificar publicaciones científicas recientes sobre el tema. Metodología: Se ha realizado una búsqueda bibliográfica a través de Pubmed en revistas revisadas por pares, restringiendo la búsqueda a artículos publicados en inglés entre los meses de enero de 2002 y diciembre de 2022. Se han utilizado las siguientes palabras clave: ''Stroke AND visual impairment'', ''Stroke AND vision'' y ''Stroke AND visual rehabilitation”. Resultados: Después de aplicar los criterios de inclusión y exclusión, se han seleccionado 41 artículos. La discapacidad visual afecta a casi el 60% de las personas que han sufrido un ictus, sobre todo en forma de pérdida del campo visual, pero también negligencia visual, alteraciones de la motilidad ocular, reducción de la agudeza visual y/o problemas de percepción visual. Los métodos de rehabilitación dependen de las necesidades y dificultades visuales de cada paciente. Conclusiones: La rehabilitación de la discapacidad visual subyacente a un ictus es un gran desafío, pues tiene importantes repercusiones en las actividades de vida diaria de la persona, y en su calidad de vida., Introduction: Stroke is a clinical syndrome caused by a focal or generalized brain lesion that lasts more than 24 hours or that leads to death, and has no other cause than vascular. It occurs when a blood vessel supplying the brain ruptures or is suddenly blocked, then the neurons in the affected area do not receive enough oxygen and die, causing brain damage. One of the multiple sequelae of stroke is vision impairment. Objective: To carry out a literature review on visual impairment derived from stroke to identify scientific publications recently on the subject. Methodology: A bibliographic search has been carried out through Pubmed in peer-reviewed journals, restricting the search to articles published in English between January 2002 and December 2022. The following words have been used: ''Stroke AND visual impairment'', ''Stroke AND vision'' and ''Stroke AND visual rehabilitation”. Results: After applying the inclusion and exclusion criteria, 41 articles have been selected. According to recent literature, visual impairment affects almost 60% of people who have suffered a stroke, especially in the form of loss of the visual field, but also visual negligence, alterations of ocular motility, reduced visual acuity and/or visual perception problems. Rehabilitation methods depend on the needs and visual difficulties of each patient. Conclusions: The rehabilitation of visual impairment underlying a stroke is a great challenge, since it has important repercussions on the person's daily life activities, and on their quality of life.

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO2), or if some patients demonstrate reduced CMRO2 related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO2 were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO2 after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.

To examine the effect of childhood adversity on the development of cardiovascular disease (CVD) between ages 16 and 38, specifically focusing on ischaemic heart disease and cerebrovascular disease, Aims To examine the effect of childhood adversity on the development of cardiovascular disease (CVD) between ages 16 and 38, specifically focusing on ischaemic heart disease and cerebrovascular disease. Methods and results Register data on all children born in Denmark between 1 January 1980 and 31 December 2001, who were alive and resident in Denmark without a diagnosis of CVD or congenital heart disease until age 16 were used, totalling 1 263 013 individuals. Cox proportional hazards and Aalen additive hazards models were used to estimate adjusted hazard ratios (HRs) and adjusted hazard differences of CVD from ages 16 to 38 in five trajectory groups of adversity experienced between ages 0 and 15. In total, 4118 individuals developed CVD between their 16th birthday and 31 December 2018. Compared with those who experienced low levels of adversity, those who experienced severe somatic illness and death in the family (men: adjusted HR: 1.6, 95% confidence interval: 1.4-1.8, women: 1.4, 1.2-1.6) and those who experienced very high rates of adversity across childhood and adolescence (men: 1.6, 1.3-2.0, women: 1.6, 1.3-2.0) had a higher risk of developing CVD, corresponding to 10-18 extra cases of CVD per 100 000 person-years in these groups. Conclusions Individuals who have been exposed to childhood adversity are at higher risk of developing CVD in young adulthood compared to individuals with low adversity exposure. These findings suggest that interventions targeting the social origins of adversity and providing support for affected families may have long-term cardio-protective effects.