In eukaryotic cells,endoplasmic reticulum (ER) is a locus where the proteins are modified,folded and the calcium is stored.When the harmful factors,such as ischemia/hypoxia,lack of nutrients,viral infections,and toxins cause the homeostasis damage in the endoplasmic reticulum,the accumulation of unfolded or misfolded proteins and the calcium imbalance may result in endoplasmic reticulum stress (ERS).ERS induces the expression of endoplasmic reticulum chaperones and endoplasmic reticulum associated degradation components,and reduces the load of the endoplasmic retlculum by temporarily reducing protein synthesis.Studies have shown that many diseases that can induce cognitive impairment are all associated with ERS.

Neurogenesis is a dynamic process of neural precursor cel self-proliferation and differentiation into new neurons. Studies have confirmed that hippocampal neurogenesis may improve cognitive function, and vascular endothelial growth factor (VEGF) plays an important regulatory role in neurogenesis. This article reviews the mechanism of VEGF promoting neurogenesis and the role of neurogenesis in improving vascular cognitive impalrment.

Oxidative stress plays an important role in pathogeaesis of vascular cognitive impairment (VCI).Increasing studies indicate that NADPH oxidase (NOX) is involved in oxidative stress.This article reviews the relationships between NOX and oxidative stress as well as VCI,in order to provide a new view for the prevention and treatment of VCI.

The significance of the diagnosis of vascular cognitive impairment(VCI)is able to do early intervention and delay or even prevent its progress. How ever, due to the limitations of diagnostic methods and standards, the patients w ith mild VCI often can not get timely and accurate diagnosis. Recent studies have show n that blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) may provide objective indicators for the diagnosis of VCI. This article review s the application of BOLD-fMRI in the diagnosis of VCI.

The significance of identification of mild cognitive impairment (MCI) is to intervene as soon as possible and delay or even prevent its progression to dementia.However,due to the limitations of diagnostic methods and standards,the diagnosis of in patients with MCI is more difficult.In recent years,as an emerging functional neuroimaging technique,resting-state functional magnetic resonance imaging (rsfMRI) has developed rapidly.It has been widely used in the studies of MCI.It may be provide objective biomarkers for the diagnosis of MCI.This article reviews the advances in research on rs-fMRI in MCI.

Subcortical ischemic vascular disease (SIVD) is considered to be the most important and common cause of vascular cognitive impairment (VCI). If patients with subcortical ischemic vascular cognitive impairment (SIVCI) and subcortical vascular cognitive impairment (sVCI) can be found early, it is possible that vascular dementia (VaD) can be identified before occurrence and even reverse the process. Recent studies have shown that resting-state functional magnetic resonance imaging (rsfMRI) may provide the objective basis for the diagnosis of SIVCI. This article reviews the application of rsfMRI in the diagnosis of SIVCI.

Objective To compare the applicability of the Beijing Version of the Montreal Cognitive Assessment (MoCA) and the Mini Mental State Examination (MMSE) in screening for cognitive impairment in patients with acute ischemic stroke for 2-3 weeks.Methods MoCA and MMSE were conducted in 201 patients with acute ischemic stroke within 2 to 3 weeks after the onset of stroke.With MoCA＜23 and MMSE ＜26 as the cut off value,we assessed the clinic effect of the MoCA and MMSE and explored the correlation between two instruments.Results The average scores of MoCA and MMSE scale were (20.5±4.3) and (25.4±3.5) points.The prevalence of cognitive impairment evaluated with MoCA and MMSE were 57.2％and 43.3％,respectively.MoCA showed significant correlation with MMSE score (Pearson's correlation coefficient=0.833,P＜0.001),and an agreement with Kappa values of 0.532 (P＜0.01) in screening for cognitive impairment.Conclusions The prevalence of cognitive impairment assessed with MoCA is higher than that of with MMSE when using MoCA＜23 and MMSE＜26 as the cut off values.Both instruments show a good agreement for screening cognitive impairment in acute ischemic stroke within 2 to 3 weeks following the disease onset.

Objective:To investigate the risk factors for anterior circulation and posterior circulation symptomatic intracranial atherosclerotic stenosis (sICAS).Methods:The clinical data of patients admitted to Hebei General Hospital for ischemic stroke or transient ischemic attack (TIA) and diagnosed with sICAS by digital subtraction angiography from May 2019 to May 2020 were retrospectively included. The patients were divided into anterior circulation group and posterior circulation group according to the stenosis sites, and the distribution of sICAS and its risk factors were analyzed.Results:A total of 134 patients with sICAS were enrolled, including 82 males (61.2%) and 52 females (38.8%). Their age was 60.28±11.46 years; 115 (85.8%) had ischemic stroke and 19 (14.2%) had TIA. There were 92 patients (68.7%) in the anterior circulation group and 42 (31.3%) in the posterior circulation group. Body mass index (BMI), systolic and diastolic blood pressure levels, as well as the proportion of patients with hypertension, diabetes, smoking and drinking in the posterior circulation group were significantly higher than those in the anterior circulation group (all P<0.05). Multivariate logistic regression analysis showed that higher BMI (odds ratio [ OR] 1.191, 95% confidence interval [ CI] 1.029-1.379; P=0.019), hypertension ( OR 4.073, 95% CI 1.135-14.616; P=0.031) and diabetes ( OR 2.783, 95% CI 1.149-6.738; P=0.023) were independently correlated with the posterior circulation sICAS. Conclusions:Compared with anterior circulation, high BMI, hypertension and diabetes are the independent risk factors for posterior circulation sICAS.

Objective:To explore the effect of iron overload on the cognitive function of rats and its possible internal mechanism.Methods:Thirty 8-week-old male Sprague Dawley rats of SPF degree were randomly divided into 2 groups, iron overload group(IO group) and control group(Sham group), with 15 in each group.The rats in IO group were injected intraperitoneally iron dextran(100 mg/(kg·d)) for 28 days.The cognitive function of rats was detected by Morris water maze method. Western blot method was used to detect the expression of TfR1 and autophagy-related protein p-AMPK, LC3 and Beclin1 in the hippocampus of rats. Immunofluorescence was used to observe the expression of LC3 and Beclin1 in the hippocampus of rats. HE staining was used to observe the morphological changes of neurons in the hippocampus. Transmission electron microscopy was used to observe the number of autophagosomes and the morphology of endoplasmic reticulum in hippocampus.The software of SPSS 20.0 was used for repeated measurement ANOVA and t-test. Results:Morris water maze test showed that there were significant interaction between the group factor and training time factor of escape latency( F=3.55, P<0.01). And the simple effect analysis showed that compared with the Sham group((28.09±18.41)s, (21.42±15.53)s, (16.96±8.35)s, (10.24±3.75)s), the average escape latency of rats(2nd-5th day) in IO group((56.68±30.65)s, (58.21±36.09)s, (36.58±13.54)s, (27.29±14.30)s )were significantly longer ( t=8.57, 6.81, 9.51, 7.12, P<0.01). The platform was removed on 6th day of the space exploration experiment, compared with the Sham group ((41.89±3.89)%), the percentage of time spent in the target quadrant of IO group ((25.46±3.56)%) was significantly decreased( t=24.06, P<0.01). Western blot showed that the relative expression levels of (TfR1 (2.10±0.48), p-AMPK (0.74±0.10), LC3 (1.11±0.40), Beclin1 (1.05±0.20)) in IO group in the hippocampus of the rats were significantly higher than those of the Sham group(TfR1(0.11±0.18), p-AMPK(0.19±0.02), LC3(0.22±0.11), Beclin1(0.17±0.02))( t=1.58, 14.58, 10.06, 20.65, P<0.01)). HE staining showed that compared with the Sham group, the neuron in the hippocampus of the IO group were sparsely arranged, morphologically irregular, and the number of the neurons was significantly reduced. Transmission electron microscopy showed that compared with the Sham group, the number of autophagosomes in the hippocampus of IO group was increased. Conclusion:Iron overload may exert its neurotoxic effect by increasing the level of autophagy in the hippocampus, causing cognitive dysfunction.

A number of studies have shown that the enlarged perivascular spaces (EPVS) are associated with various diseases such as cerebral small vessel disease,Alzheimer's disease,post-stroke depression,and post-stroke cognitive impairment.This article reviews the imaging features,pathophysiological mechanisms and clinical significance of EPVS.