运动可能延缓阿氏症

适量规律的运动可能会延缓老人的阿兹海默氏症。这项研究结果是根据超过1700位年纪在65岁以上的老年人发现的．这些人在研究开始时并没有痴呆症状；那些表示每周至少运动三次的人．在过去六年来可能发展痴呆．主要是阿兹海默氏症的机会少了三分之一。

The pathogenesis of Alzheimer and pharmaceutical research on prevention

Senile Dementia is the illness with a symptom of ongoing cognitive obstacle and loss of memory function. With our population aging, dementia and depression in old age is increasing rapidly. It is estimated that by 2020, depressive disorder will become the second largest human disease leading to crippling. By 2040, globally the number of people with dementia will reach 81.1 million while the number of dementia patients in China will be the sum of that in all developed countries. Its incidence increases exponentially with age and the incidence of the elderly over 85 reach up to 8% -10%. Among all dementia patients, people with Alzheimer＇ s disease （Alzheimer＇ s disease, AD） accounted for 50 % -70%, the rest is vascular dementia （vascular dementia, VD） and mixed dementia. In the United States, Alzheimer＇ s disease has become the fourth leading cause of death followed after cardiovascular disease, cancer and stroke. Through comprehensive control strategy, we can improve the mental health level of old people, so as to protect the physical and mental health, improving the life quality of old people.

Neurotoxicity and Biomarkers of Lead Exposure: a Review

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies.Biomarkers are generally classified into three groups:biomarkers of exposure,effect,and susceptibility.The main body compartments that store lead are the blood,soft tissues,and bone;the half-life of lead in these tissues is measured in weeks for blood,months for soft tissues,and years for bone.Within the brain,lead-induced damage in the prefrontal cerebral cortex,hippocampus,and cerebellum can lead to a variety of neurological disorders,such as brain damage,mental retardation,behavioral problems,nerve damage,and possibly Alzheimer’s disease,Parkinson’s disease,and schizophrenia.This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Copper ions influence the toxicity of β-amyloid(1-42) in a concen-tration-dependent manner in a Caenorhabditis elegans model of Alzheimer’s disease

β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often.In the present study,we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006.Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10-3 mol L-1 copper ions.However,the paralysis behavior was dramatically attenuated with exposure to 10-4 mol L-1 copper ions.The exogenous copper treatment also partially changed the homeostatic balance of zinc,manganese,and iron.Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006.The ROS generation induced by Aβ and copper appear to be through sod-1,prdx-2,skn-1,hsp-60 and hsp-16.2 genes.

A fusion of least squares and empirical likelihood for regression models with a missing binary covariate

Multiply robust inference has attracted much attention recently in the context of missing response data. An estimation procedure is multiply robust, if it can incorporate information from multiple candidate models, and meanwhile the resulting estimator is consistent as long as one of the candidate models is correctly specified. This property is appealing, since it provides the user a flexible modeling strategy with better protection against model misspecification. We explore this attractive property for the regression models with a binary covariate that is missing at random. We start from a reformulation of the celebrated augmented inverse probability weighted estimating equation, and based on this reformulation, we propose a novel combination of the least squares and empirical likelihood to separately handle each of the two types of multiple candidate models,one for the missing variable regression and the other for the missingness mechanism. Due to the separation, all the working models are fused concisely and effectively. The asymptotic normality of our estimator is established through the theory of estimating function with plugged-in nuisance parameter estimates. The finite-sample performance of our procedure is illustrated both through the simulation studies and the analysis of a dementia data collected by the national Alzheimer's coordinating center.

A regression approach to ROC surface,with applications to Alzheimer's disease

We consider the estimation of three-dimensional ROC surfaces for continuous tests given covariates.Three way ROC analysis is important in our motivating example where patients with Alzheimer's disease are usually classified into three categories and should receive different category-specific medical treatment.There has been no discussion on how covariates affect the three way ROC analysis.We propose a regression framework induced from the relationship between test results and covariates.We consider several practical cases and the corresponding inference procedures.Simulations are conducted to validate our methodology.The application on the motivating example illustrates clearly the age and sex effects on the accuracy for Mini-Mental State Examination of Alzheimer's disease.

SAR of tricyclic sulfones as γ-secretase inhibitors

Novel tricyclic sulfones as γ-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in vivo efficacies than sulfonamide analogues re- ported previously by this laboratory. Based on the previously reported tricyclic sulfone scaffold, additional SAR studies of C ring were carried out. Various C-ring structures including cyclohexane, pyran, and piperidine were tolerated. Additionally, the 7- and 8- positions of the C-ring were identified as the best sites to introduce substituent for modulating the pharmacokinetic properties of compounds from this series.

A weighted Wilcoxon estimate for the covariate-specific ROC curve

The covariate-specific receiver operating characteristic(ROC) curve is an important tool for evaluating the classification accuracy of a diagnostic test when it is associated with certain covariates. In this paper,a weighted Wilcoxon estimator is constructed for estimating this curve under the framework of location-scale model for the test result. The asymptotic normality is established, both for the regression parameter estimator and the estimator for the covariate-specific ROC curve at a fixed false positive point. Simulation results show that the Wilcoxon estimator compares favorably to its main competitors in terms of the standard error, especially when outliers exist in the covariates. As an illustration, the new procedure is applied to the dementia data from the national Alzheimer's coordinating center.

Therapeutic potential of berberine against neurodegenerative diseases

Berberine(BBR) is an organic small molecule isolated from various plants that have been used in traditional Chinese medicine. Isolation of this compound was its induction into modern medicine, and its usefulness became quickly apparent as seen in its ability to combat bacterial diarrhea, type 2 diabetes, hypercholesterolemia, inflammation, heart diseases, and more. However, BBR's effects on neurodegenerative diseases remained relatively unexplored until its ability to stunt Alzheimer's disease(AD) progression was characterized. In this review, we will delve into the multi-faceted defensive capabilities and bio-molecular pathways of BBR against AD, Parkinson's disease(PD), and trauma-induced neurodegeneration. The multiple effects of BBR, some of which enhance neuro-protective factors/pathways and others counteract targets that induce neurodegeneration, suggest that there are many more branches to the diverse capabilities of BBR that have yet to be uncovered. The promising results seen provide a convincing and substantial basis to support further scientific exploration and development of the therapeutic potential of BBR against neurodegenerative diseases.