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）...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 展开更多
Diabetic kidney disease （DKD） is one of the primary causes of end-stage renal disease （ESRD）. Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate （UAER） and glo...Diabetic kidney disease （DKD） is one of the primary causes of end-stage renal disease （ESRD）. Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate （UAER） and glomerular filtration rate （GFR） are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages： normoalbuminuria, microalbuminuria, and macroalbuminuria. However, this clinical paradigm has been questioned recently, as studies have shown that a portion of diabetes mellitus （DM） patients with normoalbuminuria have progressive renal insufficiency, referred to as normoalbuminuric diabetic kidney disease （NADKD） or nonalbuminuric diabetic nephropathy. Epidemiologic research has demonstrated that normoalbuminuric diabetic kidney disease is common, and the large number of NADKD patients suggests that the traditional paradigm needs to be shifted. Currently, the pathogenesis of NADKD remains unclear, but many clinical studies have identified some clinical and pathological features of NADKD. In addition, the long-term outcomes of NADKD patients remain controversial. In this article, we reviewed the latest studies addressing the pathogenesis, pathology, treatment and prevention of NADKD.展开更多
To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases ri...To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.展开更多
Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in bra...Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong（EX-HN1）, Yintang（EX-HN3）, Neiguan（PC6）, Taixi（KI3）, Fenglong（ST40）, and Taichong（LR3）, or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.展开更多
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...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.展开更多
Background:Exercise is a promising nonpharmacological therapy for cognitive dysfunction,but it is unclear which type of exercise is most effective.The objective of this study was to compare and rank the effectiveness ...Background:Exercise is a promising nonpharmacological therapy for cognitive dysfunction,but it is unclear which type of exercise is most effective.The objective of this study was to compare and rank the effectiveness of various exercise interventions on cognitive function in patients with mild cognitive impairment(MCI)or dementia and to examine the effects of exercise on the symptoms relevant to cognitive impairment.Methods:We searched PubMed,Web of Science,Embase,Cochrane Central Register of Controlled Trials,SPORTDiscus,and PsycInfo through September 2019 and included randomized controlled trials that examined the effectiveness of exercise interventions in patients with MCI or dementia.Primary outcomes included global cognition,executive cognition,and memory cognition.Secondary outcomes included activities of daily living,neuropsychiatric symptoms,and quality of life.Pairwise analyses and network meta-analyses were performed using a random effects model.Results:A total of 73 articles from 71 trials with 5606 participants were included.All types of exercise were effective in increasing or maintaining global cognition,and resistance exercise had the highest probability of being the most effective intervention in slowing the decrease in global cognition(standard mean difference(SMD)=1.05,95%confidence interval(95%CI):0.56-1.54),executive function(SMD=0.85,95%CI:0.21-1.49),and memory function(SMD=0.32,95%CI:0.01-0.63)in patients with cognitive dysfunction.Subgroup analyses for patients with MCI revealed different effects,and multicomponent exercise was most likely to be the optimal exercise therapy for preventing the decline of global cognition(SMD=0.99,95%CI:0.44-1.54)and executive function(SMD=0.72,95%CI:0.06-1.38).However,only resistance exercise showed significant effects on memory function for patients with MCI(SMD=0.35,95%CI:0.01-0.69).Exercise interventions also showed various effects on the secondary outcomes.Conclusion:Resistance exercise has the highest probability of being the optimal exercise type for s展开更多
Minimal hepatic encephalopathy is a neuro-cognitive dysfunction which occurs in an epidemic proportion of cirrhotic patients,estimated as high as 80% of the population tested. It is characterized by a specific,complex...Minimal hepatic encephalopathy is a neuro-cognitive dysfunction which occurs in an epidemic proportion of cirrhotic patients,estimated as high as 80% of the population tested. It is characterized by a specific,complex cognitive dysfunction which is independent of sleep dysfunction or problems with overall intelligence. Although named "minimal",minimal hepatic encephalopathy(MHE) can have a far-reaching impact on quality of life,ability to function in daily life and progression to overt hepatic encephalopathy. Importantly,MHE has a profound negative impact on the ability to drive a car and may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history,which is often ignored in routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of care in patients with MHE. The lack of specific signs and symptoms,the preserved communication skills and lack of insight make MHE a difficult condition to diagnose. Diagnostic strategies for MHE abound,but are usually limited by financial,normative or time constraints. Recent studies into the inhibitory control and critical flicker frequency tests are encouraging since these tests can increase the rates of MHE diagnosis without requiring a psychologist. Although testing for MHE and subsequent therapy is not standard of care at this time,it is important to consider this in cirrhotics in order to improve their ability to live their life to the fullest.展开更多
Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived e...Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.展开更多
Summary： This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment （VCI） with the goal of providing a target for t...Summary： This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment （VCI） with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography （CT） were recruited as the ischemic cerebrovascular diseases （ICVD） group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay （ELISA） was employed to detect the levels of hypoxia-inducible factor 1-alpha （HIF-1α）, vascular endothelial growth factor （VEGF）, nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination （MMSE） score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group （P=-0.037 and P=0.000; P=0.023 and P=-0.005）. In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid （r=-0.327, P=0.021; r=-0.585, P=0.046）. In VCI group, HIF-1α level was correlated with NGF level （r=0.589, P=0.044）. HIF-1α and NGF are involved in ischemic and hy- poxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.展开更多
To better understand the potential causes of visibility impairment in autumn and winter in Chengdu,relative humidity(RH),visibility,the concentrations of PM2.5 and its chemical components were on-line measured continu...To better understand the potential causes of visibility impairment in autumn and winter in Chengdu,relative humidity(RH),visibility,the concentrations of PM2.5 and its chemical components were on-line measured continuously in Chengdu from Nov.2016 to Jan.2017.Six obvious haze episodes occurred in Chengdu,with the total time of haze episodes accounted for more than 90%of the total observation period,and higher NO2 concentrations and RH were related to the high particle concentrations in haze episodes.The visibility decreased in a non-linear tendency under different RH conditions with the increase of PM2.5 concentrations,which was more sensitive to RH under lower PM2.5 concentrations.The threshold concentration of PM2.5 got more smaller with the increase of RH.During the entire observation period,organic matter(OM)was the largest contributor(31.12%to extinction coefficient(bext)),followed by NH4NO3 and(NH4)2SO4 with 28.03%and 23.01%,respectively.However,with the visibility impairment from Type I(visibility>10 km)to Type IV(visibility≤2 km),the contribution of OM to bextdecreased from 38.12%to 26.77%,while the contribution of NH4NO3 and(NH4)2SO4 to bextincreased from 19.09%and 20.20%to 34.29%and 24.35%,respectively,and NH4NO3 became the largest contributor to bextat Type IV.The results showed that OM and NH4NO3 were the key components of PM2.5 for visibility impairment in Chengdu,indicating that the control of precursors emissions of carbonaceous species and NH4NO3 could effectively improve the visibility in Chengdu.展开更多
Epidemiological and biological evidences support a link between type 2 diabetes mellitus(DM2) and Alzheimer's disease(AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk o...Epidemiological and biological evidences support a link between type 2 diabetes mellitus(DM2) and Alzheimer's disease(AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. Cognitive deficits in persons with diabetes mainly affect the areas of psychomotor efficiency, attention, learning and memory, mental flexibility and speed, and executive function. The strong epidemiological association has suggested the existence of a physiopathological link. The determinants of the accelerated cognitive decline in DM2, however, are less clear. Increased cortical and subcortical atrophy have been evidenced after controlling for diabetic vascular disease and inadequate cerebral circulation. Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Futuretrials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.展开更多
Alzheimer's disease(AD) is the most common age-related, progressive neurodegenerative disease. It is characterized by memory loss and cognitive decline and responsible for most cases of dementia in the elderly. La...Alzheimer's disease(AD) is the most common age-related, progressive neurodegenerative disease. It is characterized by memory loss and cognitive decline and responsible for most cases of dementia in the elderly. Late-onset or sporadic AD accounts for > 95% of cases, with age at onset > 65 years. Currently there are no drugs or other therapeutic agents available to prevent or delay the progression of AD. The cellular and molecular changes occurring in the brains of individuals with AD include accumulation of β-amyloid peptide and hyperphosphorylated tau protein, decrease of acetylcholine neurotransmitter, inflammation, and oxidative stress. Aggregation of β-amyloid peptide in extracellular plaques and the hyperphosphorylated tau protein in intracellular neurofibrillary tangles are characteristic of AD. A major challenge is identifying molecular biomarkers of the early-stage AD in patients as most studies have been performed with blood or brain tissue samples(postmortem) at late-stage AD. Subjects with mild cognitive impairment almost always have the neuropathologic features of AD with about 50% of mild cognitive impairment patients progressing to AD. They could provide important information about AD pathomechanism and potentially also highlight minimally or noninvasive, easy-to-access biomarkers. MicroRNAs are dysregulated in AD, and may facilitate the early detection of the disease and potentially the continual monitoring of disease progression and allow therapeutic interventions to be evaluated. Four recent reviews have been published of microRNAs in AD, each of which identified areas of weakness or limitations in the reported studies. Importantly, studies in the last three years have shown considerable progress in overcoming some of these limitations and identifying specific microRNAs as biomarkers for AD and mild cognitive impairment. Further large-scale human studies are warranted with less disparity in the study populations, and using an appropriate method to validate the findings.展开更多
Vascular cognitive impairment(VCI)describes all forms of cognitive impairment caused by any type of cerebrovascular disease.Early identification of VCI is quite difficult due to the lack of both sensitive and specific...Vascular cognitive impairment(VCI)describes all forms of cognitive impairment caused by any type of cerebrovascular disease.Early identification of VCI is quite difficult due to the lack of both sensitive and specific biomarkers.Extensive damage to the white matter tracts,which connect the cortical and subcortical regions,has been shown in subcortical VCI(SVCI),the most common subtype of VCI that is caused by small vessel disease.Two specific MRI sequences,including diffusion tensor imaging(DTI)and functional MRI(fMRI),have emerged as useful tools for identifying subtle white matter changes and the intrinsic connectivity between distinct cortical regions.This review describes the advantages of these two modalities in SVCI research and the current DTI and fMRI findings on SVCI.Using DTI technique,a variety of studies found that white matter microstructural damages in the anterior and superior areas are more specific to SVCI.Similarly,functional brain abnormalities detected by fMRI have also been mainly shown in anterior brain areas in SVCI.The characteristic distribution of brain abnormalities in SVCI interrupts the prefrontal-subcortical loop that results in cognitive impairments in particular domains,which further confirms the‘disconnection syndrome’hypothesis.In addition,another MRI technique,arterial spin labelling(ASL),has been used to describe the disconnection patterns in a variety of conditions by measuring cerebral blood flow.The role of the ASL technique in SVCI research is also assessed.Finally,the review proposes the application of multimodality fusion in the investigation of SVCI pathogenesis.展开更多
Our previous ifndings have demonstrated that acupuncture at the Taixi （KI3） acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acu...Our previous ifndings have demonstrated that acupuncture at the Taixi （KI3） acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed signiifcantly between elderly patients with mild cognitive impairment and healthy elderly controls. Results showed that 20 brain regions were activated in both groups of participants, including the bi-lateral anterior cingulate gyrus （Brodmann areas [BA] 32, 24）, left medial frontal cortex （BA 9, 10, 11）, left cuneus （BA 19）, left middle frontal gyrus （BA 11）, left lingual gyrus （BA 18）, right medial frontal gyrus （BA 11）, bilateral inferior frontal gyrus （BA 47）, left superior frontal gyrus （BA11）, right cuneus （BA 19, 18）, right superior temporal gyrus （BA 38）, left subcallosal gyrus （BA 47）, bilateral precuneus （BA 19）, right medial frontal gyrus （BA 10）, right superior frontal （BA 11）, left cingulate gyrus （BA 32）, left precentral gyrus （BA 6）, and right fusiform gyrus （BA 19）. These results suggest that acupuncture at the Taixi acupoint in elderly patients with mild cogni-tive impairment can also activate some brain regions.展开更多
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 ...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.展开更多
In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippo-campi of APP/PS1 transgenic Alzheimer＇s disease model mice. Immunofluorescence staining revealed that the number of newly ge...In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippo-campi of APP/PS1 transgenic Alzheimer＇s disease model mice. Immunofluorescence staining revealed that the number of newly generated （BrdU＋） cells in the subgranular zone of the dentate gyrus in the hippocampus was signiifcantly higher in Alzheimer＇s disease mice after adipose-de-rived mesenchymal stem cell transplantation, and there was also a significant increase in the number of BrdU＋/DCX＋neuroblasts in these animals. Adipose-derived mesenchymal stem cell transplantation enhanced neurogenic activity in the subventricular zone as well. Furthermore, adipose-derived mesenchymal stem cell transplantation reduced oxidative stress and alleviated cognitive impairment in the mice. Based on these ifndings, we propose that adipose-derived mes-enchymal stem cell transplantation enhances endogenous neurogenesis in both the subgranular and subventricular zones in APP/PS1 transgenic Alzheimer＇s disease mice, thereby facilitating functional recovery.展开更多
文摘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
文摘Diabetic kidney disease （DKD） is one of the primary causes of end-stage renal disease （ESRD）. Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate （UAER） and glomerular filtration rate （GFR） are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages： normoalbuminuria, microalbuminuria, and macroalbuminuria. However, this clinical paradigm has been questioned recently, as studies have shown that a portion of diabetes mellitus （DM） patients with normoalbuminuria have progressive renal insufficiency, referred to as normoalbuminuric diabetic kidney disease （NADKD） or nonalbuminuric diabetic nephropathy. Epidemiologic research has demonstrated that normoalbuminuric diabetic kidney disease is common, and the large number of NADKD patients suggests that the traditional paradigm needs to be shifted. Currently, the pathogenesis of NADKD remains unclear, but many clinical studies have identified some clinical and pathological features of NADKD. In addition, the long-term outcomes of NADKD patients remain controversial. In this article, we reviewed the latest studies addressing the pathogenesis, pathology, treatment and prevention of NADKD.
文摘To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.
基金supported by the National Natural Science Foundation of China,No.81173354a grant from the Science and Technology Plan Project of Guangdong Province of China,No.2013B021800099a grant from the Science and Technology Plan Project of Shenzhen City of China,No.JCYJ20150402152005642
文摘Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong（EX-HN1）, Yintang（EX-HN3）, Neiguan（PC6）, Taixi（KI3）, Fenglong（ST40）, and Taichong（LR3）, or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.
基金supported by grants from Bayer Healthcare,Co., Ltd.,GermanyEisai Co.,Ltd.,Japan
文摘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.
基金financial support from the National Natural Science Foundation of Chinafunded by the National Natural Science Foundation of China(81871854)。
文摘Background:Exercise is a promising nonpharmacological therapy for cognitive dysfunction,but it is unclear which type of exercise is most effective.The objective of this study was to compare and rank the effectiveness of various exercise interventions on cognitive function in patients with mild cognitive impairment(MCI)or dementia and to examine the effects of exercise on the symptoms relevant to cognitive impairment.Methods:We searched PubMed,Web of Science,Embase,Cochrane Central Register of Controlled Trials,SPORTDiscus,and PsycInfo through September 2019 and included randomized controlled trials that examined the effectiveness of exercise interventions in patients with MCI or dementia.Primary outcomes included global cognition,executive cognition,and memory cognition.Secondary outcomes included activities of daily living,neuropsychiatric symptoms,and quality of life.Pairwise analyses and network meta-analyses were performed using a random effects model.Results:A total of 73 articles from 71 trials with 5606 participants were included.All types of exercise were effective in increasing or maintaining global cognition,and resistance exercise had the highest probability of being the most effective intervention in slowing the decrease in global cognition(standard mean difference(SMD)=1.05,95%confidence interval(95%CI):0.56-1.54),executive function(SMD=0.85,95%CI:0.21-1.49),and memory function(SMD=0.32,95%CI:0.01-0.63)in patients with cognitive dysfunction.Subgroup analyses for patients with MCI revealed different effects,and multicomponent exercise was most likely to be the optimal exercise therapy for preventing the decline of global cognition(SMD=0.99,95%CI:0.44-1.54)and executive function(SMD=0.72,95%CI:0.06-1.38).However,only resistance exercise showed significant effects on memory function for patients with MCI(SMD=0.35,95%CI:0.01-0.69).Exercise interventions also showed various effects on the secondary outcomes.Conclusion:Resistance exercise has the highest probability of being the optimal exercise type for s
文摘Minimal hepatic encephalopathy is a neuro-cognitive dysfunction which occurs in an epidemic proportion of cirrhotic patients,estimated as high as 80% of the population tested. It is characterized by a specific,complex cognitive dysfunction which is independent of sleep dysfunction or problems with overall intelligence. Although named "minimal",minimal hepatic encephalopathy(MHE) can have a far-reaching impact on quality of life,ability to function in daily life and progression to overt hepatic encephalopathy. Importantly,MHE has a profound negative impact on the ability to drive a car and may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history,which is often ignored in routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of care in patients with MHE. The lack of specific signs and symptoms,the preserved communication skills and lack of insight make MHE a difficult condition to diagnose. Diagnostic strategies for MHE abound,but are usually limited by financial,normative or time constraints. Recent studies into the inhibitory control and critical flicker frequency tests are encouraging since these tests can increase the rates of MHE diagnosis without requiring a psychologist. Although testing for MHE and subsequent therapy is not standard of care at this time,it is important to consider this in cirrhotics in order to improve their ability to live their life to the fullest.
基金sponsored by CONACYT scholarship#487713Fondo Mixto de Ciencia y Tecnología del Estado de Jalisco grant JAL-2014-0-250508
文摘Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.
基金supported by the National Natural Science Foundation of China (No. 81171029)
文摘Summary： This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment （VCI） with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography （CT） were recruited as the ischemic cerebrovascular diseases （ICVD） group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay （ELISA） was employed to detect the levels of hypoxia-inducible factor 1-alpha （HIF-1α）, vascular endothelial growth factor （VEGF）, nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination （MMSE） score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group （P=-0.037 and P=0.000; P=0.023 and P=-0.005）. In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid （r=-0.327, P=0.021; r=-0.585, P=0.046）. In VCI group, HIF-1α level was correlated with NGF level （r=0.589, P=0.044）. HIF-1α and NGF are involved in ischemic and hy- poxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.
基金supported by Sichuan Science and Technology Program (Nos. 2018SZ0316, 2018SZDZX0023)the Research on Forecasting Technology of Heavy Pollution Weather
文摘To better understand the potential causes of visibility impairment in autumn and winter in Chengdu,relative humidity(RH),visibility,the concentrations of PM2.5 and its chemical components were on-line measured continuously in Chengdu from Nov.2016 to Jan.2017.Six obvious haze episodes occurred in Chengdu,with the total time of haze episodes accounted for more than 90%of the total observation period,and higher NO2 concentrations and RH were related to the high particle concentrations in haze episodes.The visibility decreased in a non-linear tendency under different RH conditions with the increase of PM2.5 concentrations,which was more sensitive to RH under lower PM2.5 concentrations.The threshold concentration of PM2.5 got more smaller with the increase of RH.During the entire observation period,organic matter(OM)was the largest contributor(31.12%to extinction coefficient(bext)),followed by NH4NO3 and(NH4)2SO4 with 28.03%and 23.01%,respectively.However,with the visibility impairment from Type I(visibility>10 km)to Type IV(visibility≤2 km),the contribution of OM to bextdecreased from 38.12%to 26.77%,while the contribution of NH4NO3 and(NH4)2SO4 to bextincreased from 19.09%and 20.20%to 34.29%and 24.35%,respectively,and NH4NO3 became the largest contributor to bextat Type IV.The results showed that OM and NH4NO3 were the key components of PM2.5 for visibility impairment in Chengdu,indicating that the control of precursors emissions of carbonaceous species and NH4NO3 could effectively improve the visibility in Chengdu.
文摘Epidemiological and biological evidences support a link between type 2 diabetes mellitus(DM2) and Alzheimer's disease(AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. Cognitive deficits in persons with diabetes mainly affect the areas of psychomotor efficiency, attention, learning and memory, mental flexibility and speed, and executive function. The strong epidemiological association has suggested the existence of a physiopathological link. The determinants of the accelerated cognitive decline in DM2, however, are less clear. Increased cortical and subcortical atrophy have been evidenced after controlling for diabetic vascular disease and inadequate cerebral circulation. Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Futuretrials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.
文摘Alzheimer's disease(AD) is the most common age-related, progressive neurodegenerative disease. It is characterized by memory loss and cognitive decline and responsible for most cases of dementia in the elderly. Late-onset or sporadic AD accounts for > 95% of cases, with age at onset > 65 years. Currently there are no drugs or other therapeutic agents available to prevent or delay the progression of AD. The cellular and molecular changes occurring in the brains of individuals with AD include accumulation of β-amyloid peptide and hyperphosphorylated tau protein, decrease of acetylcholine neurotransmitter, inflammation, and oxidative stress. Aggregation of β-amyloid peptide in extracellular plaques and the hyperphosphorylated tau protein in intracellular neurofibrillary tangles are characteristic of AD. A major challenge is identifying molecular biomarkers of the early-stage AD in patients as most studies have been performed with blood or brain tissue samples(postmortem) at late-stage AD. Subjects with mild cognitive impairment almost always have the neuropathologic features of AD with about 50% of mild cognitive impairment patients progressing to AD. They could provide important information about AD pathomechanism and potentially also highlight minimally or noninvasive, easy-to-access biomarkers. MicroRNAs are dysregulated in AD, and may facilitate the early detection of the disease and potentially the continual monitoring of disease progression and allow therapeutic interventions to be evaluated. Four recent reviews have been published of microRNAs in AD, each of which identified areas of weakness or limitations in the reported studies. Importantly, studies in the last three years have shown considerable progress in overcoming some of these limitations and identifying specific microRNAs as biomarkers for AD and mild cognitive impairment. Further large-scale human studies are warranted with less disparity in the study populations, and using an appropriate method to validate the findings.
基金This work was supported by the National Natural Science Foundation of China(grant number 81671665)Jiangsu Provincial Key Medical Talents(grant number ZDRCA2016085)the Natural Science Foundation of Jiangsu Province(grant number BK20160071).
文摘Vascular cognitive impairment(VCI)describes all forms of cognitive impairment caused by any type of cerebrovascular disease.Early identification of VCI is quite difficult due to the lack of both sensitive and specific biomarkers.Extensive damage to the white matter tracts,which connect the cortical and subcortical regions,has been shown in subcortical VCI(SVCI),the most common subtype of VCI that is caused by small vessel disease.Two specific MRI sequences,including diffusion tensor imaging(DTI)and functional MRI(fMRI),have emerged as useful tools for identifying subtle white matter changes and the intrinsic connectivity between distinct cortical regions.This review describes the advantages of these two modalities in SVCI research and the current DTI and fMRI findings on SVCI.Using DTI technique,a variety of studies found that white matter microstructural damages in the anterior and superior areas are more specific to SVCI.Similarly,functional brain abnormalities detected by fMRI have also been mainly shown in anterior brain areas in SVCI.The characteristic distribution of brain abnormalities in SVCI interrupts the prefrontal-subcortical loop that results in cognitive impairments in particular domains,which further confirms the‘disconnection syndrome’hypothesis.In addition,another MRI technique,arterial spin labelling(ASL),has been used to describe the disconnection patterns in a variety of conditions by measuring cerebral blood flow.The role of the ASL technique in SVCI research is also assessed.Finally,the review proposes the application of multimodality fusion in the investigation of SVCI pathogenesis.
基金supported by the National Natural Science Foundation of China,No.81173354the Natural Science Foundation of Guangdong Province,No.10451810101005862+1 种基金a grant from Guangdong Administration of Traditional Chinese Medicine,No.20111032,20132019the Science and Technology Plan Project of Baoan District,Shenzhen City,No.200902159
文摘Our previous ifndings have demonstrated that acupuncture at the Taixi （KI3） acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed signiifcantly between elderly patients with mild cognitive impairment and healthy elderly controls. Results showed that 20 brain regions were activated in both groups of participants, including the bi-lateral anterior cingulate gyrus （Brodmann areas [BA] 32, 24）, left medial frontal cortex （BA 9, 10, 11）, left cuneus （BA 19）, left middle frontal gyrus （BA 11）, left lingual gyrus （BA 18）, right medial frontal gyrus （BA 11）, bilateral inferior frontal gyrus （BA 47）, left superior frontal gyrus （BA11）, right cuneus （BA 19, 18）, right superior temporal gyrus （BA 38）, left subcallosal gyrus （BA 47）, bilateral precuneus （BA 19）, right medial frontal gyrus （BA 10）, right superior frontal （BA 11）, left cingulate gyrus （BA 32）, left precentral gyrus （BA 6）, and right fusiform gyrus （BA 19）. These results suggest that acupuncture at the Taixi acupoint in elderly patients with mild cogni-tive impairment can also activate some brain regions.
文摘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.
基金supported by the National High-Tech Research and Development Program of China(863 Program),No.2012AA020905Tsinghua-Yue-Yuen Medical Sciences Fund,No.20240000514
文摘In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippo-campi of APP/PS1 transgenic Alzheimer＇s disease model mice. Immunofluorescence staining revealed that the number of newly generated （BrdU＋） cells in the subgranular zone of the dentate gyrus in the hippocampus was signiifcantly higher in Alzheimer＇s disease mice after adipose-de-rived mesenchymal stem cell transplantation, and there was also a significant increase in the number of BrdU＋/DCX＋neuroblasts in these animals. Adipose-derived mesenchymal stem cell transplantation enhanced neurogenic activity in the subventricular zone as well. Furthermore, adipose-derived mesenchymal stem cell transplantation reduced oxidative stress and alleviated cognitive impairment in the mice. Based on these ifndings, we propose that adipose-derived mes-enchymal stem cell transplantation enhances endogenous neurogenesis in both the subgranular and subventricular zones in APP/PS1 transgenic Alzheimer＇s disease mice, thereby facilitating functional recovery.
