A pilot study of the association between leukoaraiosis and cerebral atherosclerosis using synthetic magnetic resonance imaging

Background Leukoaraiosis is a type of lesion characterized by tissue rarefaction or myelin pallor resulting from axons loss and gliosis. Synthetic magnetic resonance imaging (MRI) could yield quantitative T1, T2, proton density (PD) values of leukoaraiosis in addition to information on the volume of the lesion. Purpose To investigate the feasibility of quantifying leukoaraiosis using synthetic MRI and to explore the association between leukoaraiosis and cerebral small vascular diseases and cerebral atherosclerosis. Material and Methods Patients with acute ischemic stroke were enrolled in this study. All participants underwent a conventional T2-weighted image, brain volume, CUBE fluid attenuated inversion recovery, and synthetic MRI acquisition using a 3.0-T MR system. A time-of-flight magnetic resonance angiography was also obtained. We evaluated the T1, T2, PD values and leukoaraiosis volume. Results Analysis of the leukoaraiosis volume ratios demonstrated a positive association with T2 values, a negative association with T1 values, and no association with PD values. Leukoaraiosis volume ratios were independently correlated with age ( P < 0.001), lacunes ( P = 0.022), and cerebral microbleeds ( P = 0.010). A statistical association was found between both age ( P < 0.001) and lacunes ( P = 0.047) and leukoaraiosis T2 values. Conclusion Synthetic MRI may enhance the evaluation of leukoaraiosis, in addition to providing information on its volume. Leukoaraiosis may represent a type of cerebral small vascular disease rather than cerebral atherosclerosis and may share the same pathological mechanism as lacunes and cerebral microbleeds.

Efficacy and Safety of Divaza for the Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial

<b><i>Objective:</i></b> The objective of this study was to determine if Divaza, a drug with nootropic and antioxidant effects, was safe and effective for the correction of oxidative disturbances and to stabilize cognitive impairment in patients with cerebral atherosclerosis. <b><i>Study Design:</i></b> The study design consisted of a 12-week multicenter, randomized, double-blind, placebo-controlled, prospective trial in parallel groups. <b><i>Setting:</i></b> The setting in which the study was conducted comprised 10 clinical centers across the Russian Federation. <b><i>Interventions:</i></b> Patients were randomized into 2 groups and instructed to take either 2 tablets of the study drug or a placebo 3 times per day in conjunction with basic therapy. <b><i>Outcomes:</i></b> The primary outcome was a change in the average endogenous antioxidant potential after the completion of the study. The blood indicators of the oxidative stress (OS) were analyzed at the baseline and then after 12 weeks of therapy using iron-induced chemiluminescence analysis. The Montreal cognitive assessment test was used as a secondary outcome measure to evaluate cognitive impairment at the end of the study. <b><i>Results:</i></b> 124 outpatients with a mean age of 60.7 ± 7.6 years were enrolled and randomly assigned to receive Divaza (<i>n</i> = 65) or a placebo (<i>n</i> = 59). An improvement of cognitive function was observed in all patients of the Divaza group at the end of the treatment; this was significantly better than the placebo group (100 [100] vs. 89.5 [89.1]%, respectively, <i>p</i> = 0.0272 [<i>p</i> = 0.0128]). The administration of Divaza restored the activity of the endogenous antioxidant system. The change in the average level of lipoprotein resistance to oxidation after 12 weeks of therapy, compared to the baseline, was significantly higher in the Divaza group (14.8 ± 14.7 [14.8 ± 14.7] seconds latent period vs. 6.4 ± 16.9 [6.9 ± 16.7] seconds in the placebo group (<i>p</i> = 0.007 [<i>p</i> = 0.0107]). <b><i>Conclusions:</i></b> Divaza is a safe and effective therapeutic option for attenuating OS and recovery of cognitive impairment in patients with cerebral atherosclerosis.

A Genetic Study of Cerebral Atherosclerosis Reveals Novel Associations with NTNG1 and CNOT3

Cerebral atherosclerosis is a leading cause of stroke and an important contributor to dementia. Yet little is known about its genetic basis. To examine the association of common single nucleotide polymorphisms with cerebral atherosclerosis severity, we conducted a genomewide association study (GWAS) using data collected as part of two community-based cohort studies in the United States, the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). Both studies enroll older individuals and exclude participants with signs of dementia at baseline. From our analysis of 1325 participants of European ancestry who had genotype and neuropathologically assessed cerebral atherosclerosis measures available, we found a novel locus for cerebral atherosclerosis in NTNG1. The locus comprises eight SNPs, including two independent significant SNPs: rs6664221 (β = −0.27, 95% CI = (−0.35, −0.19), p = 1.29 × 10−10) and rs10881463 (β = −0.20, 95% CI = (−0.27, −0.13), p = 3.40 × 10−8). We further found that the SNPs may influence cerebral atherosclerosis by regulating brain protein expression of CNOT3. CNOT3 is a subunit of CCR4−NOT, which has been shown to be a master regulator of mRNA stability and translation and an important complex for cholesterol homeostasis. In summary, we identify a novel genetic locus for cerebral atherosclerosis and a potential mechanism linking this variation to cerebral atherosclerosis progression. These findings offer insights into the genetic effects on cerebral atherosclerosis.

Predicting the development of ischemic stroke in patients with cerebral atherosclerosis and diabetes mellitus

Cerebrovascular pathology and metabolic disorders are problems of modern health care, which are of colossal medical and social significance. A high percentage of not only mortality, but also disability determines the extreme urgency of studying their various aspects, and the presence of combined pathology requires the development of a personalized approach to the tactics of managing such patients. The aim of our study is to predict the development of IS based on indicators of the structural and functional state of the heart and cerebral vessels and heart rate variability in patients with cerebral atherosclerosis (CA) and DM2. Materials and methods. The complex clinical and instrumental study involved 229 patients with CA 1–3 degrees. Study design: simple, prospective, non-randomized, sequential enrollment. All patients underwent instrumental examinations: transthoracic echocardiography, electrocardiography ECG, ultrasound Doppler of the vessels of the head and neck, MRI of the brain. All patients took antihypertensive and antidiabetic drugs, antiplatelet agents, statins. Results: Patients were divided into 2 groups: I - with CA 1–2 degrees, II - with CA 3 degrees (after ischemic atherothrombotic stroke (IS)). Average age = 65.1 ± 10.5 and 65.4 ± 9.1 years, respectively. The share of men was 21.2% in the 1st and 52% in the 2nd groups. The number of patients with type 2 diabetes, mean fasting glucose and glycosylated hemoglobin levels were comparable in both groups. At the time of examination, all patients achieved the target BP and T2DM compensation. In our study, for patients with CA, a negative relationship between ischemic stroke and end-diastolic size index and a positive relationship with the thickness of the interventricular septum and male sex was established, which logically explains the important role of LV geometry in the development of ischemic stroke. For patients with T2DM, a negative relationship was found between ischemic stroke and LV diastolic function and positive - with fasting glucose and IM thickness. Conclusion: Based on multivariate regression analysis, in patients with cerebral atherosclerosis with the development of ischemic stroke, the presence of a relationship between the thickness of the interventricular septum, end-systolic size index, end-diastolic size index and the male sex was revealed (AUC = 0.94 (CI 0.91 - 0.97), but in patients with DM2 and CA - fasting glucose level, interventricular septum thickness, intima-media complex thickness and E/A AUC = 0.99 (95% CI 0.94 - 1.00).