BACKGROUND AND PURPOSE:White matter injury (WMI) is associated with cognitive dysfunction in aging populations; however, a clinicoradiologic discrepancy often arises between WMI and cognition function in clinical practice. Emerging evidence suggests that the glymphatic system plays a crucial role in clearing metabolic waste and maintaining cognitive function. We hypothesize that glymphatic dysfunction may contribute to this discrepancy by moderating the impact of WMI on cognition. MATERIALS AND METHODS:We conducted a retrospective review of community-dwelling residents in our center who underwent multimodal MRI and neuropsychological testing from April 2017 to December 2021. WMI, as indicated by white matter hyperintensities (WMHs) and normal-appearing white matter microstructural injury, along with CBF, were quantified by multimodal MRI. Cognition was assessed by the Mini-Mental State Examination (MMSE). Glymphatic function was evaluated using DTI along the perivascular space (DTI-ALPS). Moderation analyses were performed to explore the potential role of glymphatic function. RESULTS:A total of 947 participants were included in the final analysis. A higher WMH burden was found to be associated with lower MMSE scores in the low DTI-ALPS group (r = -0.261, P < .001), but the correlation was not significant in the high DTI-ALPS group (r = -0.082, P = .07). After adjusting for confounding factors, DTI-ALPS moderated the relationship between WMH burden and the MMSE score (β = 1.792, P = .02), and the moderating effect was significant in participants 60 years of age or younger (β = 2.573, P = .04) without lacunes (β = 2.576, P = .01) or without cerebral microbleeds (β = 3.008, P = .004). Longitudinal analysis demonstrated that DTI-ALPS also moderated the relationship between WMH burden and cognitive decline (β = -3.771, P = .001). Furthermore, DTI-ALPS moderated the relationship between normal-appearing white matter microstructural injury and the MMSE score (β = -20.201, P = .01), but no moderating effect was detected between CBF and the MMSE score (P > .05). CONCLUSIONS:The glymphatic system plays a moderate role in the association between WMI and cognitive impairment, highlighting its potential importance in WMI-related cognitive impairment. Further studies are needed to explore the relative mechanisms.

OBJECTIVE:Cerebral small vessel disease (CSVD) impairs cognitive function, yet its treatment remains challenging due to the variability in MRI findings. This study aimed to investigate the heterogeneous mechanisms underlying CSVD by integrating whole-brain vessel wall imaging (WB-VWI) and blood biomarkers. METHODS:A retrospective analysis was conducted on patients who underwent WB-VWI between January 2020 and September 2024. Vessel wall characteristics and CSVD manifestations, including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (EPVS), were evaluated using MRI. Correlation and regression analyses examined the associations between vessel wall characteristics and CSVD manifestations, while mediation analysis explored the role of vessel wall characteristics in linking blood biomarkers to CSVD. RESULTS:206 patients were analyzed finally. After adjusting for confounders, a higher plaque burden index was associated with greater WMH burden (β = 1.916, padj < 0.001), more lacunes (β = 1.980, padj = 0.013), and increased basal ganglia EPVS (Estimate = 2.910, padj = 0.035). Multivariable regression revealed that only vessel wall enhanced ratio was positively correlated with WMH burden (β = 0.568, padj < 0.001). Additionally, neutrophil percentage correlated with both plaque burden index (r = 0.233, p = 0.001) and WMH burden (r = 0.308, p < 0.001), with plaque burden index mediating the relationship between neutrophils and WMH burden (β = 0.0061, Bootstrapped 95 % CI: 0.0019-0.0105). CONCLUSION:Atherosclerosis may be a common underlying factor in the imaging manifestations of CSVD, with inflammation contributing to its heterogeneity. Further research is needed to clarify these mechanisms.

Background:Different white matter hyperintensities (WMHs) distribution patterns exhibit distinct clinical implications, but their underlying mechanisms remain unclear. This study explores vascular risk factors and neuroimaging features to elucidate their heterogeneity. Methods:We retrospectively analyzed WMHs patients who underwent multimodal MRI at Zhejiang Hospital. Neuroimaging features included gray matter volume, white matter microstructure (Fractional anisotropy, FA), and cerebral blood flow (CBF) were assessed. Vascular risk factors and imaging features were compared across four different WMHs distribution patterns [multi-spots, peri-basal ganglia, anterior subcortical (SC) patches, and posterior SC patches]. Mediation analysis was performed to explore the role of imaging features on WMHs related cognitive impairment. Results:A total of 163 patients were included in the final analysis. Among the four WMHs distribution patterns, hypertension was significantly more prevalent in patients with anterior SC patches [48 [85.7%] vs. 71 [66.4%], p = 0.008]. All WMH distribution patterns except multi-spots exhibited reduced gray matter volume (Bonferroni p < 0.0125). Notably, only patients with anterior SC patches exhibited a reduction in white matter FA (0.342 ± 0.049 vs. 0.370 ± 0.043, p < 0.001). Furthermore, patients with posterior SC patches displayed significantly lower CBF in both gray matter (42.65 ± 11.76 vs. 48.02 ± 10.97, p = 0.003) and white matter (35.25 ± 8.81 vs. 38.86 ± 8.07, p = 0.007). Mediation analysis revealed that white matter microstructural injury mediated the association between anterior SC patches WMHs and cognitive impairment [β = -0.371, Bootstrap 95% CI [-0.939, -0.006]]. Conclusion:This study demonstrates heterogeneity in vascular risk factors, gray matter volume, microstructural injury, and hypoperfusion across different WMHs patterns, underscoring the importance of subtype-specific mechanistic and therapeutic research.

Various pathological mechanisms represent distinct therapeutic targets for cognitive disorders, but a balance between clearance and production is essential for maintaining the stability of the brain's internal environment. Thus, the glymphatic system may represent a common pathway by which to address cognitive disorders. Using the established model of the glymphatic system as our foundation, this review disentangles and analyzes the components of its clearance mechanism, including the initial inflow of cerebrospinal fluid, the mixing of cerebrospinal fluid with interstitial fluid, and the outflow of the mixed fluid and the clearance. Each section summarizes evidence from experimental animal models and human studies, highlighting the normal physiological properties of key structures alongside their pathological manifestations in cognitive disorders. The same pathologic manifestations of different cognitive disorders appearing in the glymphatic system and the same upstream influences are main points of interest of this review. We conclude this article by discussing new findings and outlining the limitations identified in current research progress.

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno-associated virus delivery of vascular endothelial growth factor-C (VEGF-C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF-C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.

ObjectiveThis study aimed to investigate the predictive value of the thyroid-stimulating hormone to high-density lipoprotein cholesterol ratio (THR) in identifying specific vulnerable carotid artery plaques.MethodsIn this retrospective analysis, we included 76 patients with carotid plaques who met the criteria for admission to Zhejiang Hospital from July 2019 to June 2021. High-resolution magnetic resonance imaging (HRMRI) and the MRI-PlaqueView vascular plaque imaging diagnostic system were utilized to analyze carotid artery images for the identification of specific plaque components, including the lipid core (LC), fibrous cap (FC), and intraplaque hemorrhage (IPH), and recording of the area percentage of LC and IPH, as well as the thickness of FC. Patients were categorized into stable plaque and vulnerable plaque groups based on diagnostic criteria for vulnerable plaques derived from imaging. Plaques were categorized based on meeting one of the following consensus criteria for vulnerability: lipid core area over 40% of total plaque area, fibrous cap thickness less than 65 um, or the presence of intraplaque hemorrhage. Plaques meeting the above criteria were designated as the LC-associated vulnerable plaque group, the IPH-associated group, and the FC-associated group. Multivariate logistic regression was employed to analyze the factors influencing carotid vulnerable plaques and specific vulnerable plaque components. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serological indices for vulnerable carotid plaques.ResultsWe found that THR (OR = 1.976; 95% CI = 1.094–3.570; p = 0.024) and TSH (OR = 1.939, 95% CI = 1.122–3.350, p = 0.018) contributed to the formation of vulnerable carotid plaques. THR exhibited an area under the curve (AUC) of 0.704 (95% CI = 0.588–0.803) (p = 0.003), and the AUC for TSH was 0.681 (95% CI = 0.564–0.783) (p = 0.008). THR was identified as an independent predictor of LC-associated vulnerable plaques (OR = 2.117, 95% CI = 1.064–4.212, p = 0.033), yielding an AUC of 0.815. THR also demonstrated diagnostic efficacy for LC-associated vulnerable plaques.ConclusionThis study substantiated that THR and TSH have predictive value for identifying vulnerable carotid plaques, with THR proving to be a more effective diagnostic indicator than TSH. THR also exhibited predictive value and specificity in the context of LC-associated vulnerable plaques. These findings suggest that THR may be a promising clinical indicator, outperforming TSH in detecting specific vulnerable carotid plaques.

Alzheimer’s disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.

OBJECTIVE:The glymphatic pathway, characterised as a cerebral drainage system, influences cognitive function in neurodegenerative diseases; however, evidence is limited in a normal ageing population. The aim of this study was to investigate the effect of glymphatic function on ageing-related cognitive decline. METHODS:We retrospectively reviewed the Cognitive Impairment, Retinopathy, and Cerebrovascular Lesions in the Elderly (CIRCLE) study, and participants with multi-model magnetic resonance imaging (MRI) scans and Mini-Mental State Examinations (MMSE) were enrolled. Glymphatic function was evaluated via the diffusion tensor imaging along the perivascular space (DTI-ALPS) index. Regression models were used to estimate the impact of the DTI-ALPS index on cognitive decline cross-sectionally and longitudinally. We further analysed the mediation effect of the DTI-ALPS on age and cognitive function. RESULTS:A total of 633 participants were included in this study (48.2% female; mean age, 62.8 ± 8.9 years). The DTI-ALPS index was positively associated with cognitive function cross-sectionally (β = 0.108, P = 0.003), and was an independent protective factor for cognitive decline longitudinally (odds ratio (OR) = 0.029, P = 0.007). The DTI-ALPS index declined progressively with ageing (r = -0.319, P <0.001), and the decrease was more pronounced after 65 years of age. Furthermore, the DTI-ALPS index mediated the relationship between age and MMSE score (β = -0.016, P <0.001). The mediation effect accounted for 21.3%, which was higher in subjects aged over 65 years (25.3%) compared with those aged under 65 years (5.3%). CONCLUSION:Glymphatic function played a protective role in normal ageing-related cognitive decline, which may serve as a potential therapeutic target against cognitive decline in future.

Ventral attention network (VAN), associated with cognitive performance, is one of the functional networks that are most vulnerable in white matter hyperintensity (WMH). Considering the global interaction of networks for cognitive performance, we hypothesized that VAN-related between-network connectivity might play a role in maintaining cognition in patients with WMH. We included 139 participants for both cross-sectional and longitudinal analysis from CIRCLE study (ClinicalTrials.gov ID: NCT03542734) between January 2014 and January 2021. Differences of VAN-related between-network connectivity were compared between normal-cognition (NC) and cognitive-impairment (CI) groups cross-sectionally, and between cognitive-decline (CD) and cognitive non-decline (CND) groups longitudinally by using t-test. False Discovery Rate was used for multiple comparison correction. The relationship between the network connectivity and WMH was tested on linear and quadratic models. Subgroup analysis of different WMH burdens were performed to test the difference of network connectivity between NC and CI groups. Among VAN-related between-network connectivity, only VAN-Visual Network (VN) connectivity was higher both in NC (n = 106) and CND (n = 113) groups versus CI (n = 33) and CD groups (n = 26), respectively. There was an inverted U-shaped relation between periventricular WMH (PWMH) burden and VAN-VN connectivity. Normal-cognition participants had higher VAN-VN connectivity among high, but not low PWMH burden subgroups. These findings suggest that the VAN-VN connectivity plays an important role in maintaining cognitive performance in WMH patients. It may serve as a unique marker for cognitive prediction and a potential target for intervention to prevent cognitive decline in WMH patients.

INTRODUCTIONMetastatic brain tumors are a common complication of systemic cancer. They tend to have a chronic onset and are located at the gray-white junction of the cerebral hemispheres, those larger than 9.4mm in diameter are often accompanied by substantial vasogenic edema. Herein, we report a rare case of calcified metastatic adenocarcinoma with Wallerian degeneration. In addition, we discuss the atypical manifestations of brain metastases.CASE REPORTA 71-year-old man who went through stroke-like onset twice during 8 months with a history of resection of the left pulmonary adenocarcinoma 5 years prior was examined. Diffusion weighted magnetic resonance imaging of the brain showed an enlarged open-ring-shaped hyperintensity on the left periventricular white matter and basal ganglia, with Wallerian degeneration on the left cerebral peduncle. Brain computed tomography revealed nodular calcification of the lesion. The pathology of stereotactic biopsy indicated metastatic adenocarcinoma.CONCLUSIONWhen patients present with acute nervous system symptoms and a previous history of cancer, the possibility of metastases should be considered, even if neuroimaging is atypical.

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. This study investigated risk factors for the instability of carotid plaque and the correlation between characteristic components of vulnerable plaque and serological indices.Methods: A total of 76 eligible carotid plaque patients were enrolled. Based on carotid HRMRI results, patients were divided into stable plaque group and vulnerable plaque group. The primary outcome was to discover the risk factors for vulnerable carotid plaque and the correlation between vulnerable plaque components and serological indices.Results: Gender, D-dimer, homocysteine, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and thyroid-stimulating hormone (TSH) were significantly different between the stable plaque group and the vulnerable plaque group (p < 0.05). Multivariate logistic regression analysis adjusted for confounding factors revealed that TSH (OR, 1.948; 95% CI: 1.130-3.358; p = 0.016) was still statistically significant. Spearman correlation analysis showed that lipid core area was positively correlated with higher LDL-C (r = 0.601, p < 0.001), TG (r = 0.318, p = 0.031), and TC (r = 0.405, p = 0.005), and negatively correlated with higher HDL-C (r = -0.379, p = 0.009). Fiber cap area was negatively correlated with high white blood cell (WBC) (r = -0.342, p = 0.020) and neutrophils (r = -0.368, p = 0.012). In addition, intraplastic hemorrhage area was positively correlated with high D-dimer (r = 0.334, p = 0.023), C-reactive protein (CRP) (r = 0.305, p = 0.039), WBC (r = 0.318, p = 0.031), and neutrophils (r = 0.335, p = 0.023).Conclusion: Our study indicated that high level of TSH promoted the risk of plaque instability and may be a risk factor for carotid artery unstable plaque. Besides, there were correlations between different cholesterol and inflammatory markers and carotid plaque composition.

Objectives: White matter hyperintensities (WMH) are highly prevalent in older adults and considered to be a contributor to cognition impairment. However, the strategic WMH lesion distribution related to cognitive impairment is still debated. The aim of this study was to characterize the spatial patterns of WMH associated with cognitive impairment and explore its risk factors.Methods: We retrospectively analyzed patients who underwent T2 fluid attenuated inversion recovery (FLAIR) and mini-mental state examination (MMSE) in two centers. WHM was classified into four patterns based on T2 FLAIR as follows: (1) multiple subcortical spots (multi-spots); (2) peri-basal ganglia (peri-BG); (3) anterior subcortical patches (anterior SC patches); and (4) posterior subcortical patches (posterior SC patches). We cross-sectionally and longitudinally estimated associations between different WMH patterns and all-cause dementia and cognitive decline. Multivariable logistic regression analysis was followed to identify risk factors of WMH patterns related to cognitive impairment.Results: A total of 442 patients with WMH were enrolled, with average age of 71.6 +/- 11.3 years, and MMSE score of 24.1 +/-& nbsp;5.4. Among them, 281 (63.6%), 66 (14.9%), 163 (36.9%) and 197 (44.6%) patients presented multi-spots, peri-BG, anterior SC patches and posterior SC patches, respectively. Patients with anterior SC patches were more likely to have all-cause dementia in cross-sectional study (OR 2.002; 95% CI 1.098-3.649; p 1/4 0.024), and have cognitive decline in longitudinal analysis (OR 3.029; 95% CI 1.270-7.223; p = 0.012). Four patterns of WMH referred to different cognitive domains, and anterior SC patches had the most significant and extensive impact on cognition after Bonferroni multiple comparison correction (allp < 0.0125). In addition, older age (OR 1.054; 95% CI 1.027-1.082; p < 0.001), hypertension (OR 1.956; 95% CI 1.145-3.341; p = 0.014), higher percentage of neutrophils (OR 1.046; 95% CI 1.014-1.080; p = 0.005) and lower concentration of hemoglobin (OR 0.983; 95% CI 0.967-1.000; p = 0.044) were risk factors for the presence of anterior SC patches.Conclusions: Different patterns of subcortical leukoaraiosis visually identified on MRI might have different impacts on cognitive impairment. Further studies should be undertaken to validate this simple visual classification of WMH in different population.

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of β–amyloid peptide 1–42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of β-amyloid peptide 1–42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.

Background and Purpose Intracranial hemorrhage (ICH) is thought to be a rare but probably underestimated presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We conducted a systematic review and meta-analysis with the aim of comprehensively revealing the occurrence of ICH in patients with CADASIL. Methods English-language studies published up to September 30, 2021 were searched for in the MEDLINE (PubMed), Web of Science, and Cochrane Library databases. The design, patient characteristics, occurrence rate of ICH, and associated risk factors were retrieved for each identified relevant study. Results We enrolled 13 studies in the final meta-analysis, which included 1,310 patients with CADASIL. The probability of ICH occurrence in patients with CADASIL was 10.1% (95% confidence interval [CI]=5.6%–18.0%, I2=85.1%). When stratified by geographic region, the occurrence rate of ICH was much higher in Asians (17.7%; 95% CI=11.0%–28.5%, I2=76.3%) than in Europeans (2.0%; 95% CI=0.4%–10.8%, I2=82.8%). A higher burden of cerebral microbleeds (CMBs) and a history of hypertension were the most commonly recorded risk factors for ICH, which were available for three and two of the included studies, respectively. Conclusions Our study suggests that ICH is an important clinical manifestation of CADASIL, especially in Asians. A higher burden of CMBs and the existence of hypertension were found to be associated with a higher probability of ICH occurrence in patients with CADASIL.

ABSTRACT:Anticoagulant treatment increases the risk of intracerebral hemorrhage (ICH), but whether the treatment, more specifically non-vitamin K oral anticoagulants (NOACs), increases the risk of cerebral microbleeds (CMBs) remains uncertain. We performed this study to investigate the development of new CMBs due to NOACs or warfarin treatment in patients with atrial fibrillation (AF).We prospectively recruited AF patients before anticoagulation from June 2016 to June 2018. We performed susceptibility-weighted imaging (SWI) examinations on all enrolled AF patients and re-examined SWI 1 year later. We compared demographic features and new CMBs between the NOACs group and the warfarin group. Univariate analysis of clinical factors was performed according to the development of new CMBs; and age, a HAS-B(L)ED score, warfarin use, and the presence of baseline CMBs were then selected for inclusion in the multivariate logistic regression model.A total of 72 AF patients were recruited, 29 of whom were assigned to the NOACs group and 43 to the warfarin group. Finally, 1 patient in the NOACs group (3.4%) and 9 patients (20.9%) in the warfarin group developed new CMBs after 1 year follow-up (P = .08). Univariate analysis showed that age, a HAS-B(L)ED score ≥4, the presence of baseline CMBs were associated with the development of new CMBs (P < .05). And multivariate regression analysis showed baseline CMBs (P = .03, odds ratio = 6.37, 95% confidence interval 1.15-35.36) was independently related to the increase in new CMBs.AF patients treated with NOACs may have a decreased trend in the development of new CMBs compared with those treated with warfarin. Baseline CMBs increased the frequency of new CMBs during anticoagulant treatment. The development of new CMBs in AF patients with anticoagulation requires further longitudinal studies with longer follow-up in larger samples.

目的 探讨非痴呆老年人脑白质高信号(WMHs)进展的危险因素.方法 从阿尔茨海默病神经影像学倡议(ADNI)-1队列中筛选完成基线及3年随访T2 FLAIR扫描的非痴呆老年人263例,根据WMHs是否进展分为进展组(n=66)与非进展组(n=197).比较两组基线人口学资料、心血管疾病史、载脂蛋白E(apoE)基因型、认知功能、基线WMHs体积及3年随访时的WMHs体积,采用logistic回归分析非痴呆老年人WMHs进展的危险因素.结果 WMHs进展组年龄、冠心病史比例、基线WMHs体积及3年随访时的WMHs体积高于非进展组,听觉词语学习测验即刻记忆评分、连线测验-B评分明显低于非进展组,差异有统计学意义(P<0.05).年龄与基线WMHs体积及3年随访时的WMHs体积均呈正相关(rs=0.273,P<0.001;rs=0.306,P<0.001).多因素logistic回归分析显示,年龄≥80岁和冠心病史是WMHs进展的独立危险因素(OR=2.257,95％CI 1.219～4.178,P=0.010;OR=2.556,95％CI 1.048～6.234,P=0.039).结论 非痴呆老年人WMHs进展的独立危险因素包括年龄≥80岁和冠心病史.

PURPOSE:Parkinson's disease (PD) is a neurodegenerative disease that usually leads to memory impairment, cognitive decline and dementia. Previous studies have reported that plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms play important roles in cardiovascular diseases, obesity, inflammation and other diseases. However, the role of PAI-1 in the diagnosis of Parkinson's disease has not been reported so far.METHODS:This study was a case-control study. This study included 131 PD patients and 97 healthy volunteers. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphic loci of five different regions in PAI-1 gene (rs2227631, rs1799889, rs6092, rs2227694 and rs7242). 60 PD patients and 60 healthy volunteers were selected to detect the plasma PAI-1 concentration. The allele and genotype frequencies of SNPs were assessed using the SHEsis program.RESULTS:We found that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in the PD patients. Statistically significant difference for rs1799889 could be observed in overdominant model. In subgroup analysis, a significant difference in genotype frequency distribution and allele frequency was found for rs2227631 and rs1799889 between early-onset PD group and the control group. For cognitive dysfunction, the subcomponent showed that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in normal cognition group. The codominant model of rs1799889 was significantly different between the cognitive impairment group and the control group. In addition, the expression of PAI-1 in plasma of PD patients was significantly higher than that of controls, and further analysis showed that the expression of PAI-1 in patients with cognitive impairment was significantly higher than that in patients with cognitive normal.CONCLUSION:Our results indicate that the PAI-1 gene rs2227631 and rs1799889 polymorphisms were significantly associated with PD susceptibility in the Chinese Han population. PAI-1 has the potential to become a new therapeutic target and diagnostic marker.

Alzheimer’s disease (AD) is one of the most common types of dementia among the elderly. Previous studies had revealed that the dysregulation of lncRNAs played important roles in human diseases, including AD. However, there is still a lack of comprehensive analysis of differently expressed long non-coding RNAs (lncRNAs) in different distinct regions related to AD. In present study, we identified a total of 678, 593, 941, 1445, 1179, 466 differently expressed lncRNAs that were found in entorhinal cortex (EC), middle temporal gyrus(MTG), hippocampus (HIP), superior frontal gyrus (SFG), posterior cingulate (PC), cortex and primary visual cortex (VCX) AD samples, respectively. Furthermore, we constructed lncRNA–mRNA co-expression networks in AD to explore the potential roles of these lncRNAs. Differentially expressed (DE) lncRNAs were involved in regulating metabolic process, respiratory electron transport chain and ATP metabolic process showed by GO analysis. Interestingly, KEGG analysis revealed these lncRNAs were associated with neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease and Parkinson’s disease. Four lncRNAs (LOC100507557, LOC101929787, NEAT1, and JAZF1-AS1) were identified as key lncRNAs in AD progression and dysregulated in different distinct regions related to AD. Our study has uncovered several key lncRNAs in AD, which would give novel underlying therapeutic and prognostic targets for AD.

目的 了解心房颤动患者脑微出血(CMBs)的比例和分布,分析房颤脑微出血患者的相关危险因素.方法 选取2015年1月～2017年6月在我院住院且行头颅磁敏感加权成像检查的132例房颤患者.对所有患者采集一般临床资料,并对CMBs的数量和分布进行分析;采用Logistic回归分析房颤患者的相关危险因素.结果 本研究中38例房颤患者(28.9％)合并有CMBs,其中9例患者(23.7％)CMBs病灶数为1个,17例患者(44.7％)病灶数为2～4个,12例患者(31.6％)病灶数≥5个.房颤CMBs患者总病灶数为183个,其中102个病灶(55.7％)位于脑叶,57个病灶(31.2％)位于深部,24个病灶(13.1％)位于幕下.回归分析提示年龄(OR=1.102,P=0.001,95％CI1.044～1.163)和抗凝治疗(OR =3.006,P=0.033,95％CI 1.091～8.281)是房颤患者CMBs的独立危险因素.结论 房颤患者脑微出血病灶主要位于脑叶,对于年龄大且需要抗凝的房颤患者,建议行头颅磁敏感加权成像监测脑微出血.