Early Cerebrovascular Disease Research Articles

Clusters of parental socioeconomic status in early childhood and inherited risk for cerebrovascular disease until mid-life-Northern Finland Birth Cohort 1966.

The incidence of cerebrovascular disease (CVD) is rising among young adults (< 55 years). The risk for CVD starts to form in early childhood and is comprised of genetic and environmental risk factors. The aim of this study is to investigate the relationship between early family socioeconomic status (SES), inherited risk, and CVD until midlife. In the Northern Finland Birth Cohort 1966 of 12,058 children, individuals were followed from gestational period up to 54 years. We used previously published early family SES clusters, based on latent class analysis of a wide set of prenatally collected variables. We investigated inherited risk with polygenic risk score (PRS) and parental CVDs during follow-up. The associations of the five distinct clusters, inherited risk, and consequent risk for various types of CVDs until middle age were analyzed with Cox regression. All analyses were conducted first in the whole sample and then stratified by sex as is recommended in cardiovascular studies. During the follow-up of 586,943 person-years, 512 CVDs occurred. No clear association between SES clusters and CVD were found. Higher PRS associated with any CVD (hazard ratio (HR) per 1 SD increase: 1.15; 95% confidence interval (CI): 1.02-1.31), and ischemic CVD (HR: 1.21; 1.05-1.40). We found no combined associations of early family SES and inherited risk for CVD. Inherited risk was associated with the risk for CVD in mid-life in Finnish population. We found no clear connection with early family SES and CVD. Being born to a specific SES group did not increase the effect of inherited risk. NFBC1966 data are available from the University of Oulu, Infrastructure for Population Studies for researchers who meet the criteria for accessing confidential data. In the use of data, we follow the EU general data protection regulation (679/2016) and Finnish Data Protection Act. Permission to use the data can be applied for research purposes from https://www.oulu.fi/nfbc.

Leukoaraiosis and Gray Matter Volume Alteration in Older Adults: The PROOF Study.

Background and Purpose: Leukoaraiosis, also called white matter hyperintensities (WMH), is frequently encountered in the brain of older adults. During aging, gray matter structure is also highly affected. WMH or gray matter defects are commonly associated with a higher prevalence of mild cognitive impairment. However, little is known about the relationship between WMH and gray matter. Our aim was thus to explore the relationship between leukoaraiosis severity and gray matter volume in a cohort of healthy older adults.Methods: Leukoaraiosis was rated in participants from the PROOF cohort using the Fazekas scale. Voxel-based morphometry was performed on brain scans to examine the potential link between WMH and changes of local brain volume. A neuropsychological evaluation including attentional, executive, and memory tests was also performed to explore cognition.Results: Out of 315 75-year-old subjects, 228 had punctuate foci of leukoaraiosis and 62 had begun the confluence of foci. Leukoaraiosis was associated with a decrease of gray matter in the middle temporal gyrus, in the right medial frontal gyrus, and in the left parahippocampal gyrus. It was also associated with decreased performances in memory recall, executive functioning, and depression.Conclusion: In a population of healthy older adults, leukoaraiosis was associated with gray matter defects and reduced cognitive performance. Controlling vascular risk factors and detecting early cerebrovascular disease may prevent, at least in part, dementia onset and progression.

QOL-12. CLINICAL SIGNIFICANCE OF RADIATION-INDUCED CEREBROVASULAR DISEASE IN CHILDHOOD BRAIN TUMOR SURVIVORS

BACKGROUNDChildhood brain tumor survivors have a high risk of early cerebrovascular disease, but currently its clinical significance is unknown.METHODSIn a nation-wide study, we investigated 68 childhood brain tumor survivors treated with radiotherapy by using magnetic resonance imaging (MRI) and neuropsychological examination after median follow-up time of 20.6 years (range 5.0 – 33.1 years) since radiotherapy. Associations between imaging markers of cerebrovascular disease, white matter hyperintensities and the results of neuropsychological examination were investigated.RESULTSMajority (65 %) of the survivors was diagnosed with cerebrovascular disease at median age of 27.1 years (range16.2 – 43.8 years). The presence of imaging markers of cerebrovascular disease or white matter hyperintensities was associated with poorer performance in verbal (VIQ) and performance (PIQ) intelligent quotient, working and semantic memory, executive functions, visuospatial ability, and immediate and general auditive memory (P < 0.05). Survivors with microbleeds performed worse in PIQ, processing speed, executive functions, and visuospatial ability (P <0.05). Lacunar infarcts were associated with difficulties in visuospatial ability (P <0.05). Survivors with white matter hyperintensities in MRI had higher impairment of working and semantic memory, visuospatial ability, and general auditive memory (P < 0.05). Cerebrovascular and small-vessel disease burden associated with poorer neurocognitive performance.CONCLUSIONThe imaging markers of cerebrovascular disease and white matter hyperintensities were related to poorer cognitive performance in radiation-treated long-term survivors of childhood brain tumor. Longitudinal studies are urgently needed to investigate how cerebrovascular disease and related cognitive impairment progress in the survivors.

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors.

BackgroundCranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy.MethodsSeventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients’ files.ResultsForty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts.ConclusionsTreating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.

White Matter Lesion Penumbra Shows Abnormalities on Structural and Physiologic MRIs in the Coronary Artery Risk Development in Young Adults Cohort.

White matter lesions are 1 age-related manifestation of cerebrovascular disease, but subthreshold abnormalities have been identified in nonlesional WM. We hypothesized that structural and physiologic MR imaging findings of early cerebrovascular disease can be measured in middle-aged subjects in tissue adjacent to WM lesions, termed "penumbra." WM lesions were defined using automated segmentation in 463 subjects, 43-56 years of age, from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal observational cohort study. We described 0- to 2-mm and 2- to 4-mm-thick spatially defined penumbral WM tissue ROIs as rings surrounding WM lesions. The remaining WM was defined as distant normal-appearing WM. Mean signal intensities were measured for FLAIR, T1-, and T2-weighted images, and from fractional anisotropy, mean diffusivity, CBF, and vascular reactivity maps. Group comparisons were made using Kruskal-Wallis and pair-wise t tests. Lesion volumes averaged 0.738 ± 0.842 cm3 (range, 0.005-7.27 cm3). Mean signal intensity for FLAIR, T2, and mean diffusivity was increased, while T1, fractional anisotropy, and CBF were decreased in white matter lesions versus distant normal-appearing WM, with penumbral tissues showing graded intermediate values (corrected P < .001 for all group/parameter comparisons). Vascular reactivity was significantly elevated in white matter lesions and penumbral tissue compared with distant normal-appearing white matter (corrected P ≤ .001). Even in relatively healthy 43- to 56-year-old subjects with small white matter lesion burden, structural and functional MR imaging in penumbral tissue reveals significant signal abnormalities versus white matter lesions and other normal WM. Findings suggest that the onset of WM injury starts by middle age and involves substantially more tissue than evident from focal white matter lesions visualized on structural imaging.

Blunted cerebral oxygenation during exercise in women with gestational diabetes mellitus: associations with macrovascular function and cardiovascular risk factors

Aim/HypothesisThis cross-sectional, observational, controlled study examined cerebral oxygenation during exercise, an index of cerebrovascular function and cortical activation, in pregnancies complicated by gestational diabetes mellitus (GDM) and unaffected pregnancies. The association of cerebral oxygenation with macrovascular and cardiovascular function indices was also evaluated. Material and MethodsVascular function and structure [aortic pulse-wave-velocity (PWV), augmentation index (AI), carotid intima-media thickness], as well as 24-hour ambulatory blood pressure (BP) were assessed in women with GDM (n = 21) and uncomplicated pregnancies (n = 16), at 26–32 gestational weeks. Changes in cerebral oxygenation [oxy- (O2Hb), deoxy- (HHb) and total- (tHb) hemoglobin] were continuously recorded by near-infrared spectroscopy (NIRS) during intermittent handgrip exercise. Beat-by-beat BP and systemic vascular resistance (SVR) were assessed (Finapres). ResultsWomen with GDM had higher AI than controls. During exercise, women with GDM maintained a smaller force (p < 0.05), despite similar ratings of perceived exertion. Despite similar increases in BP during exercise, the GDM group exhibited a lower average and total (AUC) increase in cerebral-O2Hb than controls (p < 0.05). In addition, GDM exhibited a slower rate of cerebral-O2Hb decay during recovery (p < 0.05). SVR was lower in GDM compared to controls throughout the protocol (p < 0.01). Cerebral oxygenation indices were correlated with PWV and AI (p < 0.05). ConclusionsThis study provided novel evidence for blunted cerebral oxygenation during exercise in women with GDM compared to uncomplicated pregnancies, suggesting a link between reduced cerebrovascular function with exercise intolerance in GDM. Cerebral oxygenation during physical stress was correlated with macrovascular function and cardiovascular risk factors. More studies are needed to examine whether this impaired cerebral oxygenation reflects early cerebrovascular disease.

Early Cerebrovascular Disease—Clinical Characteristics and Aspects. Description of a Clinical Case

The etiology, pathogenesis, clinical findings and actual therapeutic questions in the patients under the age of 45 with ischemic attacks of cerebral blood circulation form a varied and complex nature of syndrome of early cerebrovascular disease. The epidemiologic peculiarties of the affected contingent and the scale social aspects of the disease are at the root of large amount of multifactor examinations and tracing of the described problem. A case is presented of a 39-year old female patient with early cerebrovascular disease on the ground of isolated stenoses of both medial cerebral arteries-high-grade stenosis (70%) for the left arteria cerebri media (MCA) and low-grade stenosis (40%) for the right MCA. In the process of the wide differential diagnostic plan, no risk and etiological factors have been specified, excepting described intracranial stenoses for the first appearance of cerebral infarctions in the young age. A short analysis has been accomplished of conventional and specific etiological factors for ischemic anomalies of cerebral blood circulation in the age group under 45 as well as a review of the therapeutic possibilities in the medical algorithm of the cerebrovascular disease.

Early cerebrovascular disease in a 2-year-old with extreme obesity and complete metabolic syndrome due to feeding of excessively high amounts of energy

A 2-year-old morbidly obese boy presented with early manifestation of vascular disease associated with several obesity-related features of the metabolic syndrome due to massive overfeeding. Ultrasound of the carotid arteries showed significant thickening of the intima media, perfusion magnetic resonance spectroscopy indicated cerebral microcirculation disturbance, and echocardiography revealed left ventricular hypertrophy. Thorough assessment of morbidly obese children seems to be of importance from early childhood on. Studies evaluating the prevalence of obesity-related metabolic and vascular comorbidities in very young morbidly obese children are warranted.

Assessment of the antiplatelet effects of low to medium dose aspirin in the early and late phases after ischaemic stroke and TIA

Vascular events commonly recur in stroke patients on aspirin, and may reflect incomplete inhibition of platelet function with aspirin therapy. The platelet function analyser (PFA-100) activates platelets by aspirating a blood sample at a moderately high shear rate through a capillary to a biologically active membrane with a central aperture. The membrane is coated with collagen, and either ADP (C-ADP) or epinephrine (C-EPI). The time taken for activated platelets to adhere, aggregate, and occlude the aperture is called the closure time. Previous studies have shown that aspirin prolongs the C-EPI closure time, without prolongation of the C-ADP closure time, in the majority of control subjects. We hypothesised that the PFA-100 would provide a sensitive assay for the detection of early and convalescent phase cerebrovascular disease (CVD) patients who had incomplete inhibition of platelet function with aspirin. We investigated potential cyclooxygenase-dependent and -independent mechanisms that might influence the responsiveness to aspirin using the PFA-100. Patients were studied during the early (≤4 weeks, n = 57) and convalescent phases (≥3 months, n = 46) after ischaemic stroke or TIA. To investigate potential mechanisms that could contribute to aspirin responsiveness on the PFA-100, we measured von Willebrand factor antigen levels, and carried out platelet aggregometry experiments in platelet-rich plasma in response to sodium arachidonate (1 mM) and ADP (5 µM). Sixty percent of patients in the early phase and 43% of patients in the convalescent phase did not have prolonged C-EPI closure times on 75–300 mg of aspirin daily, and were defined as aspirin non-responders. Median C-ADP closure times were significantly shorter in aspirin non-responders than aspirin-responders in both the early and convalescent phases after symptom onset (P ≤ 0.008), suggesting platelet hyper-reactivity to collagen or ADP in the aspirin non-responder subgroup. There was a significant inverse relationship between plasma von Willebrand factor antigen levels and C-EPI closure times in both early and convalescent phase CVD patients (P ≤ 0.008). Mean von Willebrand factor antigen levels were significantly higher in aspirin non-responders than aspirin responsive patients in the early (P = 0.001), but not convalescent phase (P = 0.2) after stroke and TIA. None of the patients studied were defined as being aspirin-resistant using sodium arachidonate- or ADP-induced platelet aggregometry. A large proportion of ischaemic CVD patients have incomplete inhibition of platelet function with low to medium dose aspirin using the PFA-100. The results suggest that cyclooxygenase-independent mechanisms, including elevated von Willebrand factor antigen levels, play an important role in mediating aspirin non-responsiveness on the PFA-100.

Circulating reticulated platelets in the early and late phases after ischaemic stroke and transient ischaemic attack.

The percentage of reticulated platelets (% RP) could be a useful marker of increased platelet production and/or turnover in patients with increased platelet activation, but few flow cytometric studies have measured the % RP in patients with ischaemic cerebrovascular disease (CVD). Whole blood flow cytometry using thiazole orange was performed to compare the % RP in patients in the early (1-27 d, n = 79) and late phases (79-725 d, n = 70) after ischaemic stroke or transient ischaemic attack (TIA) with controls without CVD (n = 27). The impact of aspirin dose escalation (75-300 mg/d) on the % RP was investigated in 10 patients in the late phase after stroke/TIA. The platelet count and mean platelet volume (MPV) were similar in CVD patients and controls. Compared with controls, the unadjusted % RP was not significantly higher in early or late phase CVD patients (P < or = 0.3). However, having adjusted for age, the % RP was higher in early (P = 0.047) and late phase CVD patients (P = 0.01). There was a positive correlation between % RP and MPV in EDTA- and citrate-anticoagulated blood in both early and late phase CVD patients (P< or = 0.01). The % RP was not significantly influenced by aspirin dose. These data do not convincingly support an excessive stimulus to platelet production in the early or late phases after ischaemic stroke/TIA, but are consistent with the hypothesis that reticulated platelets are larger than more mature 'non-reticulated' platelets in ischaemic CVD.

Electroencephalograms during hypercapnia. Response characteristi for normal aging subjects.

As a sequence to the evaluation of the electroencephalogram (EEG) in normal aging men exposed to mild hypoxia,17a similar study was instituted using carbon dioxide in low concentration as a stress agent toward a better understanding of the normal aging process,16,21and early cerebrovascular disease.2,3,13 We have reviewed the electroencephalographic (EEG) pattern and the relationship of alveolar CO2and pulmonary ventilation to the EEG in normal young and older subjects, whose mean ages were 24.4 years and 60.7 years respectively, during breathing a CO2gas mixture. Particular attention was given to the older subjects whose aging process had been uncomplicated by detectable disease. Analysis of the EEG pattern was made within and just without the normal range, since it became apparent early in the study that 6% CO2inhalation for 10 minutes produced only slight transitory changes and no apparent clinical symptoms. Certain