scholarly journals Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study

Oncotarget ◽  
2017 ◽  
Vol 8 (27) ◽  
pp. 44477-44489 ◽  
Author(s):  
Xiao Luo ◽  
Yerfan Jiaerken ◽  
Xinfeng Yu ◽  
Peiyu Huang ◽  
Tiantian Qiu ◽  
...  
2020 ◽  
Vol 11 ◽  
Author(s):  
Kyle D. Murray ◽  
Meera V. Singh ◽  
Yuchuan Zhuang ◽  
Md Nasir Uddin ◽  
Xing Qiu ◽  
...  

Rationale: We provide an in-depth description of a comprehensive clinical, immunological, and neuroimaging study that includes a full image processing pipeline. This approach, although implemented in HIV infected individuals, can be used in the general population to assess cerebrovascular health.Aims: In this longitudinal study, we seek to determine the effects of neuroinflammation due to HIV-1 infection on the pathomechanisms of cerebral small vessel disease (CSVD). The study focuses on the interaction of activated platelets, pro-inflammatory monocytes and endothelial cells and their impact on the neurovascular unit. The effects on the neurovascular unit are evaluated by a novel combination of imaging biomarkers.Sample Size: We will enroll 110 HIV-infected individuals on stable combination anti-retroviral therapy for at least three months and an equal number of age-matched controls. We anticipate a drop-out rate of 20%.Methods and Design: Subjects are followed for three years and evaluated by flow cytometric analysis of whole blood (to measure platelet activation, platelet monocyte complexes, and markers of monocyte activation), neuropsychological testing, and brain MRI at the baseline, 18- and 36-month time points. MRI imaging follows the recommended clinical small vessel imaging standards and adds several advanced sequences to obtain quantitative assessments of brain tissues including white matter microstructure, tissue susceptibility, and blood perfusion.Discussion: The study provides further understanding of the underlying mechanisms of CSVD in chronic inflammatory disorders such as HIV infection. The longitudinal study design and comprehensive approach allows the investigation of quantitative changes in imaging metrics and their impact on cognitive performance.


2021 ◽  
Author(s):  
Li-Kai Huang ◽  
Shu-Ping Chao ◽  
Chaur-Jong Hu ◽  
Yu-Chun Lo ◽  
Yi-Chen Hsieh

Abstract IntroductionPost-stroke cognitive impairment (PSCI) cannot be neglected because it drastically influences the daily life of patients and their families. However, there are no studies exploring the association between preclinical blood biomarkers of neurodegeneration including plasma amyloid-β (Aβ), tau and brain-derived neurotrophic factor (BDNF) together with the risk of PSCI. The present longitudinal study was to investigate whether these blood biomarkers with imaging markers of cerebral small vessel disease can improve the prediction for PSCI. In addition, we also explored the association between blood biomarkers with the trajectories of PSCI.MethodsAdult patients with first ever acute ischemic stroke were recruited, and the cognitive and functional abilities of these patients were evaluated. Furthermore, blood biomarkers of neurodegeneration including plasma Aβ-40, Aβ-42, total tau, phosphorylated tau 181 (p-tau181), and BDNF levels and image markers of cerebral small vessel disease were measured. Each patient was followed up at 3 and 12 months at the outpatient department.ResultsOf 136 patients, 40 and 50 patients developed PSCI at 3 and 12 months after stroke, respectively. In functional trajectories, 27 patients did not have PSCI at 3 months but did at 12 months. By contrast, the PSCI status of 17 patients at 3 months was reversed at 12 months. Patients with high acute plasma p-tau181 had a significantly lower PSCI risk at 3 months (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.40–0.94, p = 0.0243) and 12 months (OR = 0.69, 95% CI = 0.47–0.99, p = 0.0443) after adjustment for covariates and image biomarkers. Discrimination and reclassification statistics indicated that the p-tau181 level can improve discrimination ability for PSCI at 3 and 12 months, respectively. Additionally, the plasma p-tau181 level was the highest in subjects without PSCI followed by those with delayed-onset PSCI and early-onset PSCI with reversal, whereas the lowest plasma p-tau181 level was found among those with persistent PSCI, showing a significant trend test (p = 0.0081).ConclusionsPlasma p-tau181 is a potential biomarker for predicting early- and delayed-onset PSCI. Future studies should incorporate plasma p-tau181 as indicator for timely cognitive intervention in the follow-up of patients with stroke.


2020 ◽  
Vol 5 (2) ◽  
pp. 128-137
Author(s):  
Huimin Chen ◽  
Yuesong Pan ◽  
Lixia Zong ◽  
Jing Jing ◽  
Xia Meng ◽  
...  

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models.ResultsAmong the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability.InterpretationCSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Trial registration numberNCT00979589


2021 ◽  
pp. 0271678X2199262
Author(s):  
Shuai Jiang ◽  
Tian Cao ◽  
Yuying Yan ◽  
Tang Yang ◽  
Ye Yuan ◽  
...  

Recent subcortical infarction (RSI) in the lenticulostriate artery (LSA) territory with a non-stenotic middle cerebral artery is a heterogeneous entity. We aimed to investigate the role of LSA combined with neuroimaging markers of cerebral small vessel disease (CSVD) in differentiating the pathogenic subtypes of RSI by whole-brain vessel-wall magnetic resonance imaging (WB-VWI). Fifty-two RSI patients without relevant middle cerebral artery (MCA) stenosis on magnetic resonance angiography were prospectively enrolled. RSI was dichotomized as branch atheromatous disease (BAD; a culprit plaque located adjacent to the LSA origin) (n = 34) and CSVD-related lacunar infarction (CSVD-related LI; without plaque or plaque located distal to the LSA origin) (n = 18). Logistic regression analysis showed lacunes (odds ratio [OR] 9.68, 95% confidence interval [CI] 1.71–54.72; P = 0.010) and smaller number of LSA branches (OR 0.59, 95% CI 0.36–0.96; P = 0.034) were associated with of BAD, whereas severe deep white matter hyperintensities (DWMH) (OR 0.11, 95% CI 0.02–0.71; P = 0.021) was associated with CSVD-related LI. In conclusion, the LSA branches combined with lacunes and severe DWMH may delineate subtypes of SSI. The WB-VWI technique could be a credible tool for delineating the heterogeneous entity of SSI in the LSA territory.


2021 ◽  
pp. 1-4
Author(s):  
Oscar H. Del Brutto ◽  
Robertino M. Mera

A total of 590 older adults of Amerindian ancestry living in rural Ecuador received anthropometric measurements and a brain magnetic resonance imaging to estimate the total cerebral small vessel disease (cSVD) score. A fully adjusted ordinal logistic regression model, with categories of the total cSVD score as the dependent variable, disclosed significant associations between the waist circumference, the waist-to-hip, and the waist-to-height ratios – but not the body mass index (BMI) – and the cSVD burden. Indices of abdominal obesity may better correlate with severity of cSVD than the BMI in Amerindians. Phenotypic characteristics of this population may account for these results.


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