Association of Source of Memory Complaints and Increased Risk of Cognitive Impairment and Cognitive Decline: A Community-Based Study / 中华医学杂志(英文版)

<p><b>Background</b>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.</p><p><b>Methods</b>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.</p><p><b>Results</b>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 after 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).</p><p><b>Conclusions</b>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.</p>

Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's Disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD).</p><p><b>DATA SOURCES</b>Papers in English published in PubMed, Cochrane, and Ovid Nursing databases between January 1988 and November 2016 were searched using the following keywords: PD, nondopaminergic therapy, adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator. We also reviewed the ongoing clinical trials in the website of clinicaltrials.gov.</p><p><b>STUDY SELECTION</b>Articles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review.</p><p><b>RESULTS</b>PD is conventionally treated with dopamine replacement strategies, which are effective in the early stages of PD. Long-term use of levodopa could result in motor complications. Recent studies revealed that nondopaminergic systems such as adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator pathways could include potential therapeutic targets for motor symptoms, including motor fluctuations, levodopa-induced dyskinesia, and gait disorders. Some nondopaminergic drugs, such as istradefylline and amantadine, are currently used clinically, while most such drugs are in preclinical testing stages. Transitioning of these agents into clinically beneficial strategies requires reliable evaluation since several agents have failed to show consistent results despite positive findings at the preclinical level.</p><p><b>CONCLUSIONS</b>Targeting nondopaminergic transmission could improve some motor symptoms in PD, especially the discomfort of dyskinesia. Although nondopaminergic treatments show great potential in PD treatment as an adjunct therapy to levodopa, further investigation is required to ensure their success.</p>

Depression, anxiety, and quality of life in paroxysmal kinesigenic dyskinesia patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder characterized by recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements. Under the condition of psychological burden, some patients' attacks may get worsened with longer duration and higher frequency. This study aimed to assess nonmotor symptoms and quality of life of patients with PKD in a large population.</p><p><b>METHODS</b>We performed a cross-sectional survey in 165 primary PKD patients from August 2008 to October 2016 in Rui Jin Hospital, using Symptom Check List-90-Revised (SCL-90-R), World Health Organization Quality of Life-100 (WHOQoL-100), Self-Rating Depression Scale, and Self-Rating Anxiety Scale. We evaluated the differences of SCL-90-R and WHOQOL-100 scores in patients and Chinese normative data (taken from literature) by using the unpaired Student's t-test. We applied multivariate linear regression to analyze the relationships between motor manifestations, mental health, and quality of life among PKD patients.</p><p><b>RESULTS</b>Compared with Chinese normative data taken from literature, patients with PKD exhibited significantly higher (worse) scores across all SCL-90-R subscales (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism; P= 0.000 for all) and significantly lower (worse) scores of five domains in WHOQoL-100 (physical domain, psychological domain, independence domain, social relationship domain, and general quality of life; P= 0.000 for all). Nonremission of dyskinesia episodes (P = 0.011) and higher depression score (P = 0.000) were significantly associated with lower levels of quality of life. The rates of depression and anxiety in patients with PKD were 41.2% (68/165) and 26.7% (44/165), respectively.</p><p><b>CONCLUSIONS</b>Depression, anxiety, and low levels of quality of life were prevalent in patients with PKD. Co-occurrence of depression and anxiety was common among these patients. Regular mental health interventions could set depression and anxiety as intervention targets. Considering that the motor episodes could be elicited by voluntary movements and sometimes also by emotional stress, and that symptoms may get worsened with longer duration and higher frequency when patients are stressed out, intervention or treatment of depression and anxiety might improve the motor symptoms and overall quality of life in PKD patients.</p>

Parkinson's Disease with Fatigue: Clinical Characteristics and Potential Mechanisms Relevant to α-Synuclein Oligomer

BACKGROUND AND PURPOSE: The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson's disease (PD) patients who experience fatigue. METHODS: PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins-α-synuclein oligomer, β-amyloid (Aβ)(1-42), and tau-were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients. RESULTS: The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of α-synuclein oligomer was higher and that of Aβ1-42 was lower in the fatigue group than in the non-fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the α-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders. CONCLUSIONS: PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased α-synuclein oligomer level in the CSF.

Associations of MRI-lesions and clinical features with disability in Chinese patients with multiple sclerosis

Objective: To analyze associations of MRI-lesions and clinical features with disability in patients with multiple sclerosis (MS) in Shanghai, China. Methods: We studied patients with MS, identified from a survey in Shanghai, whose sites of lesions in the CNS was based on the MRI examinations. Associations between MRI-lesions, various clinical variables and the severity of disability were analyzed with univariate and multivariate logistic regression analysis. Results: There were 210 patients in this study. The disability of the patients with lesions confined to the spinal cord was significantly more severe than those with lesions in the brain (p < 0.008). Current age (OR: 1.041, 95% CI: 1.007~1.077), MS duration (OR: 1.082, 95% CI: 1.011~1.159) and MRI-lesions in the spinal cord (OR: 2.441, 95% CI: 1.039~5.737) were significantly associated with severity of disability on multivariate logistic regression analysis. Conclusion: MRI-lesions in the spinal cord, older age, a longer MS duration were significantly associated with a more severe disability in this MS study in Shanghai China.

Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aß and tau.

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly. Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD. Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear, the current treatments are those drugs that can alleviate the symptoms of AD patients. Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation. Thus the pharmacological mechanism of these drugs may be too simply-evaluated. This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.

Erythropoietin prevents PC12 cells from beta-amyloid-induced apoptosis via PI3K/Akt pathway.

BACKGROUND: Several studies indicated that Erythropoietin (Epo) may provide remarkable neuroprotection in some neurological diseases. It also showed the significant decrease of Epo immunoreactivity in the cerebral cortex and hippocampus in aged rats, suggesting the role of Epo in the pathogenesis of age-related neurodegenerative diseases such as AD. METHODS: The protective effect of Epo was studied in differentiated PC12 cells treated with Abeta. The viability of the cells, the apoptosis of the cells and the level of Bax, Bcl-2, cleaved caspase-3 and cleaved PARP expression were detected by MTT, Hoechst 33258 staining and Western blotting respectively. RESULTS: 20 µM Abeta (25-35) could induce a decreased viability and a increased apoptosis in PC12 cell in a time-dependent manner. However, 20 µM Abeta (35-25) had no effect on cell viability and apoptosis. Western blot analysis also showed that Abeta(25-35) treatment could decrease the expression of Bcl-2 (P < 0.05) and increase the expression of Bax (P < 0.05), Cleaved casapase-3 (P < 0.05), and Cleaved PARP (P < 0.05). The pretreatment of Epo could effectively reverse all the above changes induced by Abeta(25-35) (P < 0.05). Furthermore, the protective effect of Epo could be blocked by PI3K inhibitor LY294002 (P < 0.05). CONCLUSIONS: Epo prevented cell injuries in PC12 cells exposed to the Abeta(25-35) and this effect may depend on the PI3K/Akt pathway. Our study provided an important evidence for the potential application of Epo in the therapy of Alzheimer's disease.

Investigations on prevalence and risk factors of visual hallucination in patients with Parkinson' s disease / 上海第二医科大学学报

Objective To investigate the prevalence and characteristics of visual hallucination among patients with Parkinson's disease (PD), and analyse the potential risk factors. Methods One hundred and twenty-eight patients with PD were administered self-prepared visual hallucination questionnaires, and prevalence of visual hallucination was surveyed. The differences in sex, age, disease duration, Mini Mental State Exam (MMSE) scores, Hoehn & Yahr stage, types of medicine used and levodopa equivalent doses (LDE) were compared between the patients with visual hallucination and those without visual hallucination. The prevalence of rapid eye movement sleep behavior disorder (RBD) was investigated in patients with visual hallucination. Results Eighteen patients (14.06%) experienced visual hallucination, among whom 10 (55.56%) experienced visual hallucination no less than one time per day, 11 (61.11%) "saw" the shadow of human figure and 15(83.33%)were complicated with RBD. There were significant differences in MMSE scores, Hoehn & Yahr stage, female proportion and usage of dopamine agonists between patients with visual hallucination and those without visual hallucination(P<0.05). Conclusion Visual hallucination is a common non-motor symptom among patients with PD, and cognitive function, disease severity and usage of dopamine agonista may be related to visual hallucination.

P2Y6 receptor and immunoinflammation / 神经科学通报·英文版

The immunocytes microglia in the central nervous system (CNS) were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. Previous studies showed that purinoceptor P2Y6 mainly contributed to microglia activation and their later phagocytosis in CNS, while in immune system, it participated in the secretion of interleukin (IL)-8 from monocytes and macrocytes. So there raises a question: whether purinoceptor P2Y6 also takes part in neuroinflammation? Thus, this review mainly concerns about the properties and roles of purinoceptor P2Y6, including (1) structure of purinoceptor P2Y6; (2) distribution and properties of purinoceptor P2Y6; (3) relationships between purinoceptor P2Y6 and microglia; (4) relationships between purinoceptor P2Y6 and immunoinflammation. Itos proposed that purinoceptor P2Y6 may play a role in neuroinflammation in CNS, although further research is still required.

Genetic predisposition to inflammation: a new risk factor of Alzheimer's disease / 神经科学通报·英文版

Inflammation has been shown to play an important role in the progression of Alzheimer's disease (AD). Recent epidemical study indicates that the incidence of AD in some populations is substantially influenced by the gene polymorphisms of the inflammation mediators. Meanwhile, an ensured risk factor, the ApoE epsilon4 allele is also reported to directly promote inflammation. Accordingly, it appears that an individual genetic background has partly determined his predisposition for AD by the extent of the inflammation response to the chronic stimulus by beta-amyloid peptide (Abeta) deposits and other antigen stressor in the elderly. Hence we present a hypothesis that the inflammation genotypes may contribute to AD susceptibility. This may provide a new orientation both for future identification of individuals at risk and for personalized medication.

The prevalence of LRRK2 Gly2385Arg variant in Chinese Han population with Parkinson's disease.

We conducted a case-control study to determine the prevalence of the LRRK2 Gly2385Arg variant in patients with Parkinson's disease in Han population in mainland China. Heterozygous LRRK2 Gly2385Arg variant was identified in 14 of 235 patients with Parkinson's disease (5.69%), but not in 214 unrelated healthy controls. Multivariate analysis indicated the frequency of Gly2385Arg variant in the female patients with early age at onset is higher than their male counterparts. The founder haplotype analysis showed the variant carriers shared the same founder. Clinically, the LRRK2 Gly2385Arg carriers presented with classical Parkinson's disease symptoms. Our study indicates that the LRRK2 Gly2385Arg variant is a potential ethnic-specific genetic risk factor of Parkinson's disease within Chinese Han ethnicity.

ATP-sensitive potassium channels: novel potential roles in Parkinson's disease / 神经科学通报·英文版

The ATP-sensitive potassium (K(ATP)) channels which extensively distribute in diverse tissues (e.g. vascular smooth muscle, cardiac cells, and pancreas) are well-established for characteristics like vasodilatation, myocardial protection against ischemia, and insulin secretion. The aim of this review is to get insight into the novel roles of K(ATP) channels in Parkinson's disease (PD), with consideration of the specificities K(ATP) channels in the central nervous system (CNS), such as the control of neuronal excitability, action potential, mitochondrial function and neurotransmitter release.

Insulin and Alzheimer's disease / 上海第二医科大学学报

Recently,the incidence of Alzheimer's disease has been significantly increasing.However,the pathogenesis of Alzheimer's disease remains unknown.It is presumed that insulin and insulin receptor may be involved in the pathogenesis of Alzheimer's disease.The relationship between insulin and cerebral glucose metabolism,the relationship between insulin,insulin receptor,insulin resistance and pathogenesis of Alzheimer's disease as well as the possible mechanism are reviewed in this paper,and the progress of treatment of AD is also described.

Application of UMSARS-Ⅰ in evaluation of illness severity in patients with multiple system atrophy / 上海第二医科大学学报

Objective To investigate the reliability of a novel rating scale, unified multiple system atrophy rating scale, section Ⅰ(UMSARS-Ⅰ) in the evaluation of illness severity in patients with multiple system atrophy (MSA). Methods A retrospective analysis and a prospective follow-up study were conducted by using UMSARS-Ⅰ in 46 patients with MSA, and the Schwab and England scale was employed and illness severity was graded. The reliability, validity and sensitivity to change of UMSARS-Ⅰ in evaluating the illness severity of MSA were estimated. Results UMSARS-Ⅰ enjoyed high internal consistency (standard Crohnbach's ?=0.88) and sound content, criterion-related, construct and discriminant validity in the evaluation of illness severity of MSA, and a moderate sensiti-vity to change was found(effect size=0.61). Conclusion UMSARS-Ⅰ is a reliable and multidimensional semi-quantitative scale in the measurement of severity and progression of impairment in MSA.

Research and Development on Immunotherapy of Alzheimer's Disease / 上海第二医科大学学报

Alzheimer's disease(AD),the most common form of dementia,it is lack of effective cure or preventive treatment.Dementias in the elder are an increasing medical,social and economic problems and current treatments are only mildly effective.Recently,amyloid-beta protein(A?) has become a major therapeutic target.A? vaccine treatment can improve cognition in the patients with AD,but adverse events,such as meningencephalitis were observed in clinical study.The passive A? immunotherapy in humans is effective with possible safety.However,patients need to be monitored carefully.

Regulating Proteins Participating in Neurotransmitter Release of Synaptic Vesicles at Nerve Terminals / 上海第二医科大学学报

Neurotransmitter release is controlled by groups of proteins associated with the membranes of synaptic vesicles and the presynaptic membranes.It is a highly dynamic process which is spatially and temporally regulated via a cascade of protein-protein interactions.These proteins participate in each step of the synaptic vesicle circulation at nerve terminals including the formation of soluble N-ethylmaleimide-sensitive factor-attachment protein receptors complex,the targeted trafficking of synaptic vesicles,the vesicle docking,the neurotransmitter release and finally the reuse of the proteins.This article focuses on the physiological function and the interactions of these regulating proteins.

The role of DJ-1 in the pathogenesis of Parkinson's disease / 神经科学通报·英文版

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder characterized clinically by bradykinesia, rigidity, tremor, gait dysfunction, and postural instability. Several genes have been identified for monogenic disorders that variably resemble Parkinson's disease. Here, we focus on PARK7, a gene relates to an autosomal recessive form of early-onset Parkinsonism and encodes a protein named DJ-1. Though the exact role of DJ-1 needs to be elucidated, it is generally thought to be functioned as a molecular chaperone and an oxidative sensor (or antioxidative factor). We will review the protective role of DJ-1 to prevent dopaminergic neurons in the substantia nigra pars compacta (SNpc) from degeneration and how its dysfunction would lead to neurodegeneration.

The role of synphilin-1 in the pathogenesis of Parkinson's disease / 神经科学通报·英文版

Parkinson's disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplasmic inclusions are highly enriched with ubiquitin, synphilin-1, alpha-synuclein and parkin. Synphilin-1 is an alpha-synuclein-binding protein and a major component of LBs. It is widely accepted that synphilin-1 is involved in the pathogenic process of PD. This review will provide an overall view of the role of synphilin-1 in the pathogenesis of Parkinson's disease and the latest findings in this field.

Therapeutic effect of neuropeptide PACAP27 on Parkinson's disease in mice / 中华神经科杂志

Objective To investigate the effects of different doses of pituitary adenylate cyclase- activating polypeptide(PACAP)on the functional and morphological outcome in a mice model of Parkinson' s disease(PD)rendered by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods Male mice were treated with PACAP 0.02, 0.20 or 2.00 ?g by iv bolus for 7 days after MPTP was administered, and were compared with the saline-treated mice.The immunohistochemistry and Western blot were used to detect the alterations of PD biomarker including tyrosine hydroxylase(TH), dopamine transporter(DAT)and vesicular monoamine transporter2(VAMT2).In addition, monoamine neurotransmitters in the striatum of mice were measured by the high performance liquid chromatography (HPLC).Results TH immunohistochemistry indicated that the number of TH-positive neurons in the substantia nigra was increased in all PACAP-treated mice(PACAP(0.02 ?g/d)group was 93.33?4.87, F=85.85,P

Calbindin-28 in rats of Parkinson's disease after deep brain stimulation to subthaiamus nucleus / 中华神经科杂志

Objective To explore the mechanism of deep brain stimulation(DBS)therapy to Parkinson's disease(PD).Methods We produced hemi-parkinsonian rat model with stereotaxically injecting 6-OHDA to right medial forebrain bundle(MFB)and stimulated ipsilateral subthalamu nucleus (STN)with platinum electrodes chronically to investigate the influence of DBS to the expression of Calbindin-28,synaptophysin and tyrosine dioxydase(TH)in Striatum by Western blot.In addition,slices of bilateral PD rats after DBS were stained to observe the expression of Calbindin-28 and synaptophysin in substantia nigra by Immunohistochemistry.Results High frequency stimulation impaired the rotational frequency 31% of unilateral PD rats triggered by apomophine;Long-term DBS increased the expression of TH in innocent striatum of unilateral PD rats 78.6%?9.5%,since the ipsilateral striatum(lesion side) was TH depleted by 6-OHDA insults;Calbindin-28 expression in ipsilateral striatum of hemi-PD rats raised up 75.4%?15.0% and long-term DBS reduced the effect by 43.0%?7.1%,meanwhile Calbindin-28 positive neurons in substantia nigra compacta in sham,PD and DBS rats were 74.5?10.2,75.7?15.6, 33.1?7.8.However,Synaptophysin expression in substantia nigra and striatum kept stable even after long- term DBS.Conclusions Consistent to the treatment to PD patients,DBS to STN alleviated the motor disorder of PD rats,the treatment might be based on regulating the expression of Calbindin-28 and TH.