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Hypertension-Induced Cerebral Small Vessel Disease Leading to cognitive impairment

Chinese Medical Journal 2018年第5期131卷 615-619页

作者： Yang Liu Yan-Hong Dong Pei-Yuan Lyu Wei-Hong Chen Rui Li Graduate School Hebei Medical University Shijiazhuang Hebei 050017 China Department of Neurology Hebei General Hospital Shijiazhuang Hebei 050051 China

Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and anatomical locations of CSVD and cognitive impairment.

关键词： Cerebral Microbleeds Cerebral Small Vessel Disease cognitive impairment Hypertension

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Is Goshinjo therapy effective in cognitive impairment after severe traumatic brain injury?

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Neural Regeneration Research 2013年第12期8卷 1146-1150页

作者： Keiji Hashimoto Kisho Kida Hashimoto cognitive Research Institute Tokyo 156-0051 Japan Kihodo Head Office Clinic Tokyo 151-0065 Japan

We report a case of a 21-year-old man who had severe traumatic brain injury as a result of an accident at the age of 16 years. Two years and 4 months after the trauma, at the age of 19 years, he still had severe right hemiplegia and cognitive dysfunction including aphasia and attention and memory disturbance. Conventional rehabilitation programs cou（d not resolve all of the neuropsychological problems. He started receiving Goshinjo therapy over a period of 22 months. Following the therapy, significant improvements in verbal intelligence quotient （assessed by the Wechsler Adult Intelligence Scale-Third Edition） and attention and concentration function （using the Wechsler Memory Scale-Revised）, and remission of traumatic epilepsy were observed. Goshinjo therapy is suspected to be effective in the treatment of cognitive dysfunction in the chronic stage after severe traumatic brain injury.

关键词： neural regeneration brain injury traumatic brain injury clinical practice Goshinjo therapy rehabilitation cognitive impairment energy field in human body Jaki neuroregeneration

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An Integrated Analysis of Risk Factors of cognitive impairment in Patients with Severe Carotid Artery Stenosis

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Biomedical and Environmental Sciences 2018年第11期31卷 797-804页

作者： LUO Ru Tao WANG Pei Jiong DENG Xiao Feng ZHOU Shu Jie ZHAO Meng QIAN Jing ZHANG Dong WANG Rong ZHANG Yan Department of Neurosurgery Beijing Children's HospitalCapital Medical UniversityNathgnal Center for Children's HealthBeijing 100045China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050ChinaChina National Clinical Research Center for Neurological Diseases (NCRC-ND) Beijing 100050ChinaCenter of StrokeBeijing Institute for Brain DisordersBeijing 100050ChinaBeijing Key Laboratory of Translational Medicine for Cerebrovascular DiseaseBeijing 100050China Department of Neuropsychology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China

Objective To investigate cognitive dysfunction in patients with carotid artery stenosis(CAS) and potential risk factors related to cognitive-especially memory-dysfunction. Methods Forty-seven patients with carotid artery stenosis were recruited into our study cohort. The Mini-Mental State Examination(MMSE) and the Montreal cognitive Assessment(MoCA) were adopted to assess cognitive function, the Wechsler Memory Scale(WMS) to assess memory function, high-resolution MRI and enhanced ultrasound to evaluate carotid plaques, and computed tomography perfusion(CTP) imaging to evaluate intracranial blood perfusion. Single-factor analysis and multiple-factor regression analysis were used to analyze potential risk factors of cognitive impairment. Results Mini-Mental State Examination test results showed that 22 patients had cognitive impairment, and MoCA test results showed that 10 patients had cognitive impairment. Analysis of various risk factors indicated that the average memory quotient of female patients was higher than that of males(P = 0.024). The cognitive and memory performance of those with an educational background above high school were significantly better than those of participants with high school or lower(P = 0.045). Patients with abnormal intracranial perfusion performed worse on the MMSE test(P = 0.024), and their WMS scores were significantly lower(P = 0.007). The MMSE scores and the memory quotients were significantly lower in patients with a history of cerebral infarction(MMSE, P = 0.047, memory quotient score, P = 0.018). Conclusion A history of cerebral infarction and abnormal cerebral perfusion are associated with decline in overall cognitive function and memory in patients with carotid stenosis. Being female and having an educational background above high school may be protective factors in the development of cognitive dysfunction.

关键词： Carotid artery stenosis cognitive impairment Memory

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Magnetic resonance spectroscopy in the diagnosis of cognitive impairment in AIDS patients

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Chinese Medical Journal 2011年第9期124卷 1342-1345页

作者： WANG Ling SHI Da-peng HAN Xiong ZHAO Qing-xia YAN Bin LI Hong-jun Department of Radiology People's Hospital of the Henan ProvinceZhengzhou Henan 450003 China Department of Neurology People's Hospital of the Henan ProvinceZhengzhou Henan 450003 China Department of Infectious Disease Henan Province Infectious Disease HospitalZhengzhou Henan 450061 China Department of Digital Circuits Zhengzhou Information Science and Technology Institute Zhengzhou Henan 450002 China Department of Radiology Beijing YouAn Hospital Capital Medical UniversityBeijing 100069 China

Background The pathological abnormalities of the AIDS patients lie in the subcortical regions of the brain, specifically the deep white matter and basal ganglia, while the extent of pathology generally correlates with the severity of cognitive impairments in the white matter and basal ganglia. Brain metabolite changes of these lesions can reflect the pathological abnormalities. The purpose of this study was to assess the value of magnetic resonance spectroscopy （MRS） in the diagnosis of cognitive impairment in AIDS patients.Methods 3.0T MR was used to measure N-acetyl aspartate （NAA）, choline （Cho）, myo-inositol （MI） and creatinine （Cr）in the frontal white matter, basal ganglia and parietal cortex of 21 AIDS patients with dementia complex （ADC）, 19 AIDS patients with neuroasymptomatic （NAS） and 20 seronegative （SN） controls. Then we compared the difference of metabolic rate between AIDS patients and SN groups.Results NAA/Cr （mean=1.2502, SD=0.1600） was significantly decreased and Cho/Cr （mean=1.2028, SD=1.1655） was increased in the frontal white matter in ADC group, while NAA/Cr （mean=1.5334, SD=0.0513） was reduced in NAS group when compared with SN group. NANCr in the basal ganglia was decreased in both ADC and NAS groups （mean=1.2625,SD=0.1615 and mean=1.5278, SD=0.0380, respectively）. Cho/Cr （mean=1. 1631, SD=0.0981） was markedly increased in ADC group. Although NAA/Cr, Cho/Cr and MI/Cr in the parietal cortex had a certain change in both ADC and NAS groups compared with SN group, the differences were not statistically significant.Conclusions The brain metabolite changes of AIDS patients are correlated with cognitive impairments. MRS can be used as a valuable inspection method to assess cognitive impairments in AIDS patients.

关键词： AIDS dementia cerebral metabolites cognitive impairment magnetic resonance spectrum imaging

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Association of Source of Memory Complaints and Increased Risk of cognitive impairment and cognitive Decline： A Community-Based Study

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Chinese Medical Journal 2018年第8期131卷 894-898页

作者： Xue-Mei Qi Lin Go Hui-Dong Tang Sheng-Di Chen Jian-Fang Ma Department of Neurology & Institute of Neurology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Rehabilitation Shanghai Ruijin Rehabilitation Hospital Shanghai 200023 China

Background： Memory complaint is common in the elderly. Recently, it was shown that self-report memory complaint was predictive of cognitive decline. This study aimed to investigate the predictive value of the source of memory complaints on the risk of cognitive impairment and cognitive decline in a community-based cohort. Methods： Data on memory complaints and cognitive function were collected among 1840 Chinese participants （aged ≥55 years old） in an urban community at baseline interview and 5-year follow-up. Incident cognitive impairment was identified based on education-adjusted Mini-Mental State Examination score. Logistic regression model was used to estimate the association between the source of memory complaints and risk of cognitive impairment conversion and cognitive decline, after adjusting for covariates. Results： A total of 1840 participants were included into this study including 1713 normal participants and 127 cognitive impairment participants in 2009. Among 1713 normal participants in 2009, 130 participants were converted to cognitive impairment alter 5 years of follow-up. In 2014, 606 participants were identified as cognitive decline. Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment （odds ratio [OR] - 1.60, 95% confidence interval [CI]： 1.04 2.48） and cognitive decline （OR = 1.30, 95% CI： 1.01-1.68）. Furthermore, this association was more significant in males （OR = 2.10, 95% CI： 1.04-4.24 for cognitive impairment and OR - 1.87, 95% CI：1.20-2.99 for cognitive decline） and in higher education level （OR - 1.79, 95% CI： 1.02-3.15 for cognitive impairment and OR = 1.40, 95% CI：1.02-1.91 for cognitive decline）. Conclusions： Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment conversion and cognitive decline, especially in persons with male gender and high educational background.

关键词： cognitive Decline cognitive impairment Memory Complaints

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Carotid Atherosclerosis and cognitive impairment in Nonstroke Patients

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Chinese Medical Journal 2017年第19期130卷 2375-2379页

作者： Wei-Hong Chen Wei Jin Pei-Yuan Lyu Yang Liu Rui Li Ming Hu Xiang-Jian Xiao Graduate School Hebei Medical University Shijiazhuang Hebei 050017 China Department of Neurology Hebei General Hospital Shijiazhuang Hebei 050051 China

Objective： As a vascular risk factor, carotid atherosclerosis is crucial to cognitive impairment. While carotid intima-media thickness, carotid artery plaque, and carotid stenosis can reflect carotid atherosclerosis in different stages, this review aimed to explore researches on the role of carotid intima-media thickness, carotid artery plaque, and carotid stenosis in the progress of cognitive impairment in nonstroke patients and tried to illustrate the possible mechanisms. Data Sources： We searched the PubMed database for recently published research articles up to July 2017, with the key words of ＂carotid atherosclerosis,＂＂carotid intima-media thickness,＂＂carotid plaque,＂＂carotid stenosis,＂＂nonstroke,＂ and ＂cognitive impairment.＂Study Selection： Articles were obtained and reviewed to analyze the role of carotid atherosclerosis such as carotid intima-thickness, carotid plaque, and carotid stenosis in the progress of cognitive impairment in nonstroke patients and the possible mechanisms. Results： In recent years, most studies proved that by evaluating carotid atherosclerosis with ultrasonography, carotid atherosclerosis accounts for the development of cognitive decline in nonstroke patients. Carotid atherosclerosis not only impairs the subtle general cognitive function but also decreases the specific domains of cognitive function, such as memory, motor function, visual perception, attention, and executive function. But, it is still controversial. The possible mechanisms of cognitive impairment in nonstroke patients with carotid atherosclerosis can be classified as systemic global cerebrovascular function, small-vessel diseases, and the mixed lesions. Conclusions： Carotid atherosclerosis can be used to predict the risk of cognitive impairment. Furthermore, diagnosing and treating carotid atherosclerosis at early stage might help clinicians prevent and treat vascular cognitive impairment in nonstroke patients.

关键词： Carotid Atherosclerosis Carotid Intima-media Thickness： Carotid Plaque Carotid Stenosis cognitive impairment Nonstroke

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Incidence and Risk Factors of cognitive impairment 3 Months after First-ever Stroke: A Cross-sectional Study of 5 Geographic Areas of China

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第6期32卷 906-911页

作者：张勇张振馨杨百渔李延峰张蕲屈秋民王延平张世红岳卫东谭毓绘张宝荣徐涛 Department of Neurology Liyuan Hospital Tongji Medical College Huazhong University of Science and Technology Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Department of Neurology Renmin Hospital of Wuhan University Department of Neurology the First Affiliated Hospital of Medical College of Xi'an Jiaotong University Department of Neurology the Second Affiliated Hospital of Guangzhou Medical University Department of Neurology West China Hospital West China Medical College Sichuan University Department of Neurology the Second Affiliated Hospital of Harbin Medical University Department of Neurology the People's Hospital of Xinjiang Uygur Autonomous Region Department of Neurology the Second Affiliated Hospital Zhejiang University College of Medicine Departments of Epidemiology and Statistics Institute of Basic Medical Sciences Chinese Academy of Medical Sciences&School of Basic Medicine Peking Union Medical College

This study examined the incidence, neuropsychological characteristics and risk factors of cognitive impairment 3 months after stroke in China. Five regions that differed in geography and economy in China were selected. Patients from the hospitals located in the five regions were prescreened at admission, and the demographic data, vascular risk factors and clinical characteristics of stroke were obtained. A battery of cognitive-specific domain tests was performed in the patients who failed to pass cognitive screening 3 months post stroke. Patients were diagnosed as having post-stroke cognitive impairment (PSCI) or no cognitive impairment (NCI) based on the results of the neuropsy-chological tests. Univariate analysis was performed for suspect risk factors, and significant variables were entered in multivariable logistic regression analysis. Our results showed that a total of 633 patients were recruited 3 months after stroke; complete cognitive tests were performed in 577 of the stroke pa-tients. The incidence of PSCI in these Chinese patients was 30.7%. There were 129 (22.4%) patients with visuospatial impairment, 67 (11.6%) with executive impairment, 60 (10.4%) with memory impairment and 18 (3.1%) with attention impairment. The risk factors associated with PSCI were older age (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.20–2.58), low education level (OR 2.45, 95% CI 1.65–3.64), depressive symptom (OR 1.69, 95% CI 1.09–2.61), obesity (OR 2.57, 95% CI 1.41–4.71), stroke severity 3 months post stroke (OR 1.62, 95%CI 1.10–2.37) and cortex lesion (OR 1.55, 95% CI 1.04–2.31). It was concluded that PSCI occurs commonly 3 months after first-ever stroke in Chinese patients. Visuospatial ability may be the most frequently impaired cognitive domain for the patients with stroke. The critical risk factors of PSCI are older age, low education level, depressive symptom, obesity, stroke severity 3 months post stroke and cortex lesion.

关键词： stroke cognitive impairment frequency neuropsychological characteristics determinants China

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C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental post-stroke cognitive impairment by enhancing microglia/macrophage M2 polarization

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World Journal of Stem Cells 2020年第2期12卷 152-167页

作者： Huai-Chun Yang Min Zhang Rui Wu Hai-Qing Zheng Li-Ying Zhang Jing Luo Li-Li Li Xi-Quan Hu Department of Rehabilitation Medicine the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina Department of Andrology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells.However,the effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUC-MSCs)(ExoCtrl)on post-stroke cognitive impairment(PSCI)have rarely been reported.Moreover,whether exosomes derived from C-C chemokine receptor type 2(CCR2)-overexpressing HUC-MSCs(ExoCCR2)can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied.AIM To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI.METHODS Transmission electron microscopy,qNano®particles analyzer,and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2.ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2(CCL2)in vivo.After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats,the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze.Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy.QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization.The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis.RESULTS CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes.The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference.ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding.Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI,oligodendrogenesis,remyelination,and microglia/macrophage polarization,ExoCCR2 exhibited a significantly superior beneficial effect.We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activatio

关键词： cognitive impairment Stroke Exosomes C-C chemokine receptor type 2 Microglia/macrophage polarization Remyelination

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Microarray-based analyses of monocytes from Chinese Uygur patients with Parkinson＇s disease and cognitive impairment

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Chinese Medical Journal 2014年第12期127卷 2386-2388页

作者： Luo Qin Xia Huan Yang Xinling Department of Neurology Center First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiang 830054China Cadre Wards Cancer Hospital of Xinjiang Medical UniversityUrumqiXinjiang 830000China

Parkinson＇s disease （PD）, a complex neurodegenerative disease, is characterized by the loss of dopamine neurons in the substantia nigra ot the midbraln. PD patients have varying degrees of cognitive impairment （CI） that we term PD-CI. However, the etiology of these changes remains unexplained. We chose three Uygur male patients with PD-CI and three healthy controls of the same of nationality and sex to explore the pathogenesis of Xinjiang Uygur PD-CI using microarray-based gene expression profiling of monocytes.

关键词： microarray Uygur Parkinson＇s disease cognitive impairment

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Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

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Neural Regeneration Research 2008年第11期3卷 1161-1167页

作者： Dezhi Kang Zhang Guo Department of Neurosurgery First Affiliated Hospital Fujian Medical University Fuzhou 350005 Fujian Province China

BACKGROUND： In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor （BDNF） can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE： To explore changes in BDNF expression and cognitive function in rats after brain injury. DESIGN, TIME AND SETTING： The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University （China） from July 2007 to July 2008. MATERIALS： A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS： Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney＇s method （n = 24, each group）. A bone window was made in rats from the sham operation group （n = 24）, but no attack was conducted. MAIN OUTCOME MEASURES： At days 1, 2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry （streptavidin-biotin-peroxidase complex method）. Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS： cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups （P 〈 0.05）. CONCLUSION： BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats following injury.

关键词： brain-derived neurotrophic factor cognitive impairment traumatic brain injury

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