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Monoamine Oxidase-B Inhibitor Rasagiline Effects on motor and non-motor symptoms in Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

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Advances in Parkinson's Disease 2024年第3期13卷 27-56页

作者： Paula Abola Mitchell Wolden Department of Clinical Research University of Jamestown Jamestown United States of America

Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on motor and non-motor symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to conduct a systematic review with meta-analysis to investigate the effects that Rasagiline has on motor and non-motor symptoms in individuals with PD. Introduction: Rasagiline is a second-generation monoamine oxidase-B (MAO-B) inhibitor used both as monotherapy and adjunctive therapy for Parkinsons Disease (PD). Methods: A systematic literature search and meta-analysis were performed with randomized control trials that investigated the effects of Rasagiline on motor and non-motor symptoms in individuals with PD. The systematic search was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Results: Fourteen studies were included in our review. There were trivial to small and statistically significant improvements in motor symptoms for individuals with PD treated with Rasagiline compared to placebo. non-motor symptoms showed no significant improvement with Rasagiline compared to placebo in five of six meta-analyses. Results were based on very low to moderate certainty of evidence. Conclusion: 1 mg/day Rasagiline significantly improved Parkinsonian motor symptoms in individuals with PD compared with placebo. For all outcomes, the 1 mg/day Rasagiline group was favored over the placebo group.

关键词： Parkinson’s Disease Monoamine Oxidase-B Inhibitor Rasagiline non-motor symptoms motor symptoms UPDRS PDQ-39 OFF Time

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

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Neural Regeneration Research 2023年第4期18卷 901-907页

作者： Tian-Shuo Yuan Ying-Chuan Chen De-Feng Liu Ruo-Yu Ma Xin Zhang Ting-Ting Du Guan-Yu Zhu Jian-Guo Zhang Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Functional Neurosurgery Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Beijing Key Laboratory of Neurostimulation BeijingChina

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient *** subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still *** aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain *** measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each *** found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months *** legs syndrome was alleviated to a greater extent in men than in *** demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain ***,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in *** conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of *** found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor *** findings may help to guide subthalamic nucleus deep brain stimulation patient selection,progn

关键词： chronic effect deep brain stimulation generalized linear model initial effect motor symptoms non-motor symptoms Parkinson’s disease quality of life sex subthalamic nucleus

Early morning off in patients with Parkinson's disease:a Chinese nationwide study and a 7-question screening scale

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Translational Neurodegeneration 2020年第3期9卷 370-382页

作者： Chao Han Wei Mao Jing An Lifei Jiao Piu Chan on behalf of the China Early Morning Off(EMO)Study Group National Clinical Research Center for Geriatric Disorders Xuanwu Hospital of Capital Medical UniversityBeijingChina Department of Neurobiology Neurology and GeriatricsXuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Beijing Institute of Geriatrics Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Clinical Center for Parkinson's Disease Xuanwu Hospital of Capital Medical University45 Changchun RoadBejjing 100053China Key Laboratories for Neurodegenerative Diseases of the Ministry of Education Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Bejjing Key Laboratory for Parkinson's Disease Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Parkinson Disease Center of Beiing Institute for Brain Disorders Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Advanced Innovative Center for Human Brain Protection Xuanwu Hospital of Capital Medical University45 Changchun RoadBejing 100053China Medical department Lundbeck(Bejjing)Pharmaceutical Co.ItdBeijingChina 不详

Background:Early morning off(EMO)is a common feature of Parkinson's disease(PD).This study aimed to characterize its clinical features and develop a convenient and pragmatic self-assessment instrument in a Chinese nationwide ***:This study was conducted on 942 PD patients admitted to 55 clinic centers for movement disorders between June 2018 and May 2019 in *** logistic regression analyses were performed to determine potential risk factors and the most predictive symptoms of EMO,as well as whether EMO was an independent risk factor of functional dependency in daily *** on this,a 7-question scale was derived for EMO *** accuracy of this scale was assessed from the area under the receiver operative characteristic curve(AUROC)and its 95%confidence intervals(CIs).We further calculated sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for the optimal cutoff ***:EMO occurred in 49.2%of PD patients across all disease *** identified 7 symptoms most predictive of EMO,including bradykinesia or rigidity,excessive sweating or salivation,ificulty in turning on or getting out of bed,muscle cramp,fatigue or sleepiness,frozen state or freezing gait,and *** resulting 7-item scale was confirmed to be of good discrimination with a relatively large AUROC of 0.83,a relatively high sensitivity of 75.7%,specificity of 77.5%,PPV of 76.5%,and NPV of 76.7%.nonideal nighttime sleep,long PD duration,advanced H&Y stages,posture instability gait difficulty-dominant or mixed subtypes,and high levodopa dose were independently associated with increased risk of *** patients were at 87%higher(OR=1.87,95%C:1.07-3.32)risk of experiencing functional dependency in daily living compared with their ***:We demonstrated that EMO is a common feature for PD patients across all disease stages and put forward an EMO-specific screening card of sufficient accuracy and ***

关键词： Parkinson's disease Early morning off motor symptoms non-motor symptoms Screening scale

NF-κB/c-Rel deficiency causes Parkinson’s disease-like prodromal symptoms and progressive pathology in mice

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Translational Neurodegeneration 2019年第1期8卷 183-202页

作者： Edoardo Parrella Arianna Bellucci Vanessa Porrini Marina Benarese Annamaria Lanzillotta Gaia Faustini Francesca Longhena Giulia Abate Daniela Uberti Marina Pizzi Department of Molecular and Translational Medicine University of BresciaViale Europa 1125123 BresciaItaly

Background:Parkinson’s disease(PD),the most common neurodegenerative movement disorder,is characterized by dopaminergic nigrostriatal neuron loss and brain accumulation of Lewy bodies,protein aggregates mainly composed ofα-*** reported that mice deficient for NF-κB/c-Rel(c-rel^(-/-))develop a late-onset *** 18 months of age,c-rel^(-/-)mice showed nigrostriatal degeneration and accumulation ofα-synuclein aggregates associated with a motor impairment responsive to L-DOPA *** c-Rel protein a transcriptional regulator for mitochondrial anti-oxidant and antiapoptotic factors,it has been inferred that its deficiency may affect the resilience of“energy demanding”nigral dopaminergic neurons to the aging *** patients manifest a prodromal syndrome that includes olfactory and gastrointestinal dysfunctions years before the frank degeneration of nigrostriatal neurons and appearance of motor *** to the Braak staging,the onset of non-motor and motor symptoms relates to progressive ascendant diffusion ofα-synuclein pathology in the *** aim of this study was to identify whether c-rel^(-/-)deficiency is associated with the onset of premotor signs of PD and spatio-temporal progression of cerebralα-synuclein ***:Intestinal and olfactory functions,intestine and brainα-synuclein deposition as well as striatal alterations,were assessed in c-rel^(-/-)and control mice from 2 to 18 months of ***:From 2 months of age,c-rel^(-/-)mice displayed intestinal constipation and increasing olfactory *** 2 months,c-rel^(-/-)mice exhibited a mildα-synuclein accumulation in the distal ***,they developed an agedependent deposition of fibrillaryα-synuclein that,starting at 5 months from the olfactory bulbs,dorsal motor nucleus of vagus and locus coeruleus,reached the substantia nigra at 12 *** this age,theα-synuclein pathology associated with a drop of dopamine transporter in the striatum tha

关键词： Parkinson’s disease NF-κB/c-Rel non-motor symptoms α-synuclein pathology progression

Constipation,deficit in colon contractions and alpha-synuclein inclusions within the colon precede motor abnormalities and neurodegeneration in the central nervous system in a mouse model of alphasynucleinopathy

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Translational Neurodegeneration 2019年第1期8卷 48-62页

作者： Lucia Rota Carolina Pellegrini Laura Benvenuti Luca Antonioli Matteo Fornai Corrado Blandizzi Antonino Cattaneo Emanuela Colla Bio@SNS Laboratory Scuola Normale SuperiorePiazza dei Cavalieri 756126 PisaItaly Department of Pharmacy University of PisaVia Roma 5556126 PisaItaly Department of Clinical and Experimental Medicine University of PisaVia Roma 5556126 PisaItaly Neurotrophins and Neurodegenerative Diseases Laboratory Rita Levi-Montalcini European Brain Research InstituteViale Regina Elena 295Rome 00161Italy.

Background:Gastrointestinal dysfunction can affect Parkinson’s disease(PD)patients long before the onset of motor ***,little is known about the relationship between gastrointestinal abnormalities and the development of *** to other animal models,the human A53T alpha-synuclein(αS)transgenic mice,Line G2–3,developsαS-driven neurological and motor impairments after 9 months of age,displaying a long presymptomatic phase free of central nervous system(CNS)***:To determine whether this line can be suitable to study constipation as it occurs in prodromal PD,gastrointestinal functionality was assessed in young mice through a multidisciplinary approach,based on behavioral and biochemical analysis combined with electrophysiological recordings of mouse intestinal ***:We found that the A53TαS mice display remarkable signs of gastrointestinal dysfunction that precede motor abnormalities andαS pathology in the CNS by at least 6 ***αS mice show a drastic delay in food transit along the gastrointestinal tract,of almost 2 h in 3 months old mice that increased to more than 3 h at 6 *** impairment was associated with abnormal formation of stools that resulted in less abundant but longer pellets excreted,suggesting a deficit in the intestinal *** agreement with this,electrically evoked contractions of the colon,but not of the ileum,showed a reduced motor response in both longitudinal and circular muscle layers inαS mice already at 3 months of age,that was mainly due to an impaired cholinergic transmission of the underlying enteric nervous ***,the presence of insoluble and aggregatedαS was found in enteric neurons in both myenteric and submucosal plexi only in the colon of 3 months oldαS mice,but not in the small intestine,and exacerbated with age,mimicking the increase in transit delay and the contraction deficit showed by behavioral and electrical recordings ***:Gastrointest

关键词： Alpha-synuclein Constipation Gastrointestinal dysfunction Bowel dysmotility non-motor symptoms Parkinson’s disease Enteric nervous system Alpha-synucleinopathy

Deep Clinical Phenotyping of Parkinson’s Disease: Towards a New Era of Research and Clinical Care

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Phenomics 2022年第5期2卷 349-361页

作者： Zhiheng Xu Bo Shen Yilin Tang Jianjun Wu Jian Wang Department of Neurology and National Research Center for Aging and Medicine&National Center for Neurological Disorders State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghai 200040China

Despite recent advances in technology,clinical phenotyping of Parkinson’s disease(PD)has remained relatively limited as current assessments are mainly based on empirical observation and subjective categorical judgment at the clinic.A lack of comprehensive,objective,and quantifiable clinical phenotyping data has hindered our capacity to diagnose,assess patients’conditions,discover pathogenesis,identify preclinical stages and clinical subtypes,and evaluate new ***,deep clinical phenotyping of PD patients is a necessary step towards understanding PD pathology and improving clinical *** this review,we present a growing community consensus and perspective on how to clinically phenotype this disease,that is,to phenotype the entire course of disease progression by integrating capacity,performance,and perception approaches with state-of-the-art *** also explore the most studied aspects of PD deep clinical phenotypes,namely,bradykinesia,tremor,dyskinesia and motor fluctuation,gait impairment,speech impairment,and non-motor phenotypes.

关键词： Parkinson’s disease Deep phenotyping motor symptoms non-motor symptoms

Magnetic resonance morphometry of the loss of gray matter volume in Parkinson's disease patients

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Neural Regeneration Research 2013年第27期8卷 2557-2565页

作者： Jianguo Xia Juan Wang Weizhong Tian Hongbin Ding Qilin Wei Huanxin Huang Jun Wang Jinli Zhao Hongmei Gu Lemin Tang Department of Radiology Taizhou People's Hospital of Nantong University Department of Medical Image Engineering Medical School of Nantong University Department of Geriatrics Affiliated Hospital of Nantong University Department of Radiology Affiliated Hospital of Nantong University

Voxel-based morphometry can be used to quantitatively compare structural differences and func-tional changes of gray matter in subjects. In the present study, we compared gray matter images of 32 patients with Parkinson’s disease and 25 healthy controls using voxel-based morphometry based on 3.0 T high-field magnetic resonance T1-weighted imaging and clinical neurological scale scores. Results showed that the scores in Mini-Mental State Examination and Montreal Cognitive Assessment were lower in patients compared with controls. In particular, the scores of visuospatial/executive function items in Montreal Cognitive Assessment were significantly reduced, but mean scores of non-motor symptoms significantly increased, in patients with Parkinson’s dis-ease. In addition, gray matter volume was significantly diminished in Parkinson’s disease patients compared with normal controls, including bilateral temporal lobe, bilateral occipital lobe, bilateral parietal lobe, bilateral frontal lobe, bilateral insular lobe, bilateral parahippocampal gyrus, bilateral amygdale, right uncus, and right posterior lobe of the cerebel um. These findings indicate that voxel-based morphometry can accurately and quantitatively assess the loss of gray matter volume in patients with Parkinson＇s disease, and provide essential neuroimaging evidence for multisystem pathological mechanisms involved in Parkinson’s disease.

关键词： neural regeneration neuroimaging neurodegeneration voxel-based morphometry Parkinson'sdisease MRI dopamine non-motor symptoms gray matter abnormality region of interest Mini-Mental State Examination Montreal Cognitive Assessment neurodegenerative disease grants-supported paper neuroregeneration

Clinical features and relative factors of constipation in a cohort of Chinese patients with Parkinson's disease

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2021年第1期12卷 21-31页

作者： Bai-Hua Sun Tao Wang Nian-Ying Li Qiong Wu Jin Qiao Department of Neurology the First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061Shaanxi ProvinceChina Department of Neurology Xi'an Third HospitalXi'an 710021Shaanxi ProvinceChina Department ofNeurology the Shaanxi Sengong HospitalXi'an 710300Shaanxi ProvinceChina Department of Rehabilitation Medicine the First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061Shaanxi ProvinceChina

BACKGROUND Constipation as a most common non-motor symptom of Parkinson's disease(PD),has a higher prevalence compared to the general *** etiologies of constipation in PD are *** addition to physical weakness and other factors of disease,the lifestyles and eating habits are also important ***,the prevalence and influencing factors of constipation may vary among different *** To determine the prevalence of constipation and analyze relative factors in a cohort of Chinese patients with *** All the patients diagnosed with PD according to the movement disorders society criteria were consecutively collected by a self-developed *** III diagnostic criteria were used to assess functional constipation and Wexner score was used to estimate the severity of ***-motor symptoms(NMS)were assessed with the non-motor symptoms assessment scale(NMSS).Unified Parkinson's disease Rating Scale III(UPDRS III)was used to evaluate the severity of motor *** modified Hoehn-Yahr stage was used to evaluate the severity of *** function was assessed using Montreal cognitive assessment(MoCA).Depression and anxiety were rated with the Hamilton depression scale(HAMD)and the Hamilton anxiety scale(HAMA).Quality of life was assessed using the Parkinson’s disease Questionnaire-39 items(PDQ-39).RESULTS Of 166 patients enrolled,87(52.41%)were accompanied with constipation,and 30(34.48%)experienced constipation for 6.30±5.06 years before motor symptoms ***,Hoehn-Yahr stage,disease duration,levodopa medication times,incidence of motor complications,the scores of UPDRS total,UPDRS III,NMSS,HAMD,HAMA,and PDQ-39 in the constipation group were higher than those in the non-constipation group(P0.05).There was a higher incidence of depression in patients with constipation(P<0.05),but there were no di

关键词： Parkinson’s disease non-motor symptoms Constipation Clinical characteristics Quality of life Depression

Sleep Disturbance in Parkinson’s Disease Varies with Age of Onset and Family History

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Advances in Parkinson's Disease 2016年第4期5卷 103-117页

作者： Divya Madhusudhan Daniella Sisniega Andrew Ferree Janice Weinberg Marie Saint-Hilaire Samuel Ellias Anna DePold Hohler Boston University School of Medicine Boston USA Boston University School of Public Health Boston USA Department of Neurology Boston University Medical Center Boston USA

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.

关键词： Parkinson’s Disease (PD) Sleep Disorders Rapid Eye Movement Behavior Disorder (RBD) Age non-motor symptoms Familial PD