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【康复前沿】第五期:帕金森病最新文献分享

发布时间:2017-07-20 14:04:40打印本文双击自动滚屏

10种帕金森药物的有效性和耐受性比较。

帕金森患者的饮食习惯对神经功能有什么影响?

星形胶质细胞重编程变身多巴胺神经元!

帕金森病轻度认知障碍的自然病程是怎样的?

帕金森患者认知障碍预测新方法

信息量巨大!

 

1

治疗帕金森病:10种药物的有效性和耐受性比较

Comparison for Efficacy and Tolerability among Ten Drugs for Treatment of Parkinson's Disease: A Network Meta-Analysis.

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帕金森氏病(PD)是一种影响中枢神经系统的长期疾病。此研究旨在确定目前用于PD治疗的现有药物的相对有效性。

首先,研究人员对从在线数据库中检索出来的文献和符合条件的研究进行了一项系统评价,并提取了相关数据。这些药物的有效性通过不同的统一帕金森病评定量表(UPDRS)进行评估。平均差(MD)和比值比(OR)通过成对或网络Meta分析(NMA)确定。最后,研究人员对纳入的药物进行了这些药物的累计排名概率曲线下面积(SUCRA)的聚类分析。

成对Meta分析表明,司来吉兰在UPDRS II、UPDRS III和UPDRS总评分上的排名比溴隐亭和左旋多巴高。司来吉兰比溴隐亭更耐受(OR,0.62;95% CI,0.39~0.98),普拉克索比左旋多巴较不耐受(OR,1.43;95% CI,1.00~2.04)。NMA的结果表明,使用左旋多巴、普拉克索、罗匹尼罗和司来吉兰的患者比使用拉扎贝胺的患者表现出UPDRS III评分的更显着性改善。

总之,左旋多巴、司来吉兰、罗匹尼罗和罗替戈汀因相对较高的有效性和耐受性而推荐用于PD患者。

 

 

摘要原文

 Abstract

    Parkinson’s disease (PD) is a long term disorder affects the central nervous system and we aim to determine the relative efficacy of the current available drugs used in PD. Firstly, we performed a systematic review in current literature and eligible studies were retrieved from online databases, relevant data were extracted. Efficacy of these medications was assessed by different Unified Parkinson’s Disease Rating Scales (UPDRS). Mean difference (MD) and odds ratio (OR) were produced by pairwise or network meta-analysis (NMA). Finally, we performed a cluster analysis for the included medications with respect to their surface under the cumulative ranking curve (SUCRA).

     Pairwise meta-analysis suggests that selegiline had a higher ranking in UPDRS II, UPDRS III and UPDRS total than bromocriptine and levodopa. Selegiline was more tolerable than bromocriptine (OR=0.62, CI: 0.39 to 0.98) and pramipexole was less tolerable than levodopa (OR=1.43, CI=1.00 to 2.04). Results of NMA indicate that patients with levodopa, pramipexole, ropinirole and selegiline exhibited a significantly improved UPDRS III than those with lazabemide. 

    To sum up, levodopa, selegiline, ropinirole and rotigotine were recommended for PD patients as they appeared relatively high efficacy and tolerability.

 

 

 

 

原文出处:Sci Rep. Apr 4 2017

 

 

2

帕金森患者的饮食习惯对神经功能的影响

Dietary habits and neurological features of Parkinson's disease patients: Implications for practice.

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   帕金森患者可以从适当的营养保健尤其是饮食中获益。然而,目前关于饮食习惯对帕金森氏症患者疾病功能影响的证据有限。

一项大的病例对照研究中。600名PD患者接受了系统的营养保健,并且根据年龄、性别、教育、运动情况和66项食物频率问卷调查结果匹配了600名健康对照组。调查帕金森患者的饮食习惯与以下特征的联系:体重、能量平衡、便秘、左旋多巴治疗(剂量)和左旋多巴相关的运动并发症。
   结果显示,相比对照组,帕金森氏症患者有更低的BMI,更高的食物摄入量。BMI与疾病的持续时间、严重程度和左旋多巴相关的运动并发症呈负相关;能量摄入与这些变量呈正相关。在生理需求范围内增加10克蛋白质摄入量(0.8克/公斤/天),左旋多巴剂量对应增加0.7毫克/公斤/天。便秘也与更高左旋多巴需求相关。最后,蛋白质摄入量及其一天中的分布也会影响左旋多巴相关的运动并发症。
   总之,蛋白质摄入和便秘治疗的管理应被视为帕金森病患者护理的一个组成部分。注意力应始终集中在能量摄入上,以维持营养状态,优化左旋多巴的治疗并且最小化左旋多巴相关的运动并发症。

 

 

 

摘要原文

 

 

BACKGROUND & AIMS:

    Parkinson's disease (PD) patients can benefit considerably from appropriate nutritional care, particularly from diet. However, there is limited evidence on the eating habits of PD patients and their relationship with the features of the disease.

METHODS:

    We conducted a large case-control study. Consecutive PD patients (N = 600) receiving systematic nutritional care and healthy controls (N = 600) matched (1:1) for age, gender, education, physical activity level and residence were studied using a 66-item food frequency questionnaire. The relationship between dietary habits and the following features of PD were investigated in patients: body weight, energy balance, constipation, and levodopa therapy (dose) and its related motor complications.

RESULTS:

    PD patients had lower BMI and reported higher food intake than controls. BMI was found to be inversely associated with disease duration and severity, and levodopa-related motor complications, whereas energy intake was positively associated with these variables. An increase in protein intake by 10 g over physiological requirements (0.8 g/kg/day) corresponded to a mean increase in levodopa dose of 0.7 mg/kg/day. Constipation was also associated with higher levodopa requirements. Finally, protein intake and its distribution throughout the day influenced levodopa-related motor complications.

CONCLUSION:

    The management of protein intake and the treatment of constipation should be considered to be an integral part of the care of PD patients. Attention should always be focused on energy intake also. This would result in the maintenance of nutritional status, the optimization of levodopa-therapy and the minimization of its related motor complications.

原文出处:clinical nutrition. July  5 2016

 

 

3

 

星形胶质细胞重编程变身多巴胺神经元

Dietary habits and neurological features of Parkinson's disease patients: Implications for practice.


   

瑞典卡罗林斯卡学院的研究人员近日在寻找帕金森病疗法方面取得了重大进展。论文报告研究组用一种特定分子组合处理非神经元脑细胞可以产生类似多巴胺神经元的细胞,通过操控大脑中的非神经元细胞——星形胶质细胞的基因表达,能够诱导产生新的多巴胺神经元。该研究在小鼠和人类细胞中进行。

细胞替代疗法用于神经退行性疾病的治疗,主要集中在受病理过程影响的细胞类型的移植上。这里描述了一种帕金森氏症的替代策略,即通过直接转换大脑中星形胶质细胞来生成新的多巴胺神经元。利用三个转录因子,NEUROD1、ASCL1和LMX1A、以及microRNA miR218,制成NeAL218混合剂,在体外重编程了人类星形胶质细胞,在体内重编程了小鼠的星形胶质细胞,并诱导它们转化为多巴胺神经元(iDANs)。细胞培养的重编程效率通过促进染色质重塑和激活TGFβ、Shh和Wnt信号通路的小分子来提高。人类星形胶质细胞的重编程效率达到16%,使得诱导出的多巴胺神经元具有适当的中脑标志物和兴奋性。

在帕金森病的小鼠模型中单独喂食NeAL218,成熟的纹状体星形胶质细胞被成功重新编程为有活性的iDANs,小鼠的运动行为症状,如步态障碍得以改善。通过进一步的优化,这种方法或许可以通过传递基因而不是细胞来实现帕金森病的临床治疗。

 

 

摘要原文

Abstract

    Cell replacement therapies for neurodegenerative disease have focused on transplantation of the cell types affected by the pathological process. Here we describe an alternative strategy for Parkinson's disease in which dopamine neurons are generated by direct conversion of astrocytes. Using three transcription factors, NEUROD1, ASCL1 and LMX1A, and the microRNA miR218, collectively designated NeAL218, we reprogram human astrocytes in vitro, and mouse astrocytes in vivo, into induced dopamine neurons (iDANs). Reprogramming efficiency in vitro is improved by small molecules that promote chromatin remodeling and activate the TGFβ, Shh and Wnt signaling pathways. The reprogramming efficiency of human astrocytes reaches up to 16%, resulting in iDANs with appropriate midbrain markers and excitability. In a mouse model of Parkinson's disease, NeAL218 alone reprograms adult striatal astrocytes into iDANs that are excitable and correct some aspects of motor behavior in vivo, including gait impairments. With further optimization, this approach may enable clinical therapies for Parkinson's disease by delivery of genes rather than cells.

 

原文出处:nature biotechnology. 35, 444–452 (2017)

 

 

 

4

 

帕金森病轻度认知障碍的自然病程是怎样的

Natural course of mild cognitive impairment in Parkinson disease

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   此研究旨在评估帕金森病患者5年期间轻度认知功能障碍的发生、发展和逆转。

   该研究以帕金森患者人群为基础的队列,研究对象分别在研究之初(n=178)、1年(n=175)、3年(n=163)和5年(n=150)接受重复的神经心理测试,主要包括注意力、执行功能、记忆力、视觉空间能力。患者根据公布的标准被分为帕金森病轻度认知功能障碍患者和已诊断的老年痴呆症患者。
   在研究之初共有36名患者(20.2%)复合帕金森病轻度认知功能障碍的标准。在研究之初认知功能正常的患者(n=142)中,帕金森病轻度认知功能障碍的累积发生率随访1年后为9.9%,3年后为23.2%,5年后为28.9%。总体而言,在5年的研究期间39.1%的在研究之初已是帕金森病轻度认知功能障碍的患者或期间发生帕金森病轻度认知功能障碍的患者进展为痴呆。帕金森病轻度认知功能障碍持续1年的痴呆转化率为59.1%,而在第一年认知正常的参与者为7.2%(调整后的比值比为16.6,95%可信区间为5.1–54.7,P<0.001)。在研究结束时27.8%的在研究之初已是帕金森病轻度认知功能障碍的患者和24.2%研究期间发展为帕金森病轻度认知功能障碍的患者恢复正常的认知,但在那些持续帕金森病轻度认知功能障碍的患者中连续随访2次恢复率下降至9.4%。与认知功能正常的患者相比,在随访前3年帕金森病轻度认知功能障碍恢复的患者在随后发生痴呆的风险增加(调整后的比值比为10.7,95%可信区间为1.5–78.5,P=0.019)。  

   由此可见,早期帕金森病轻度认知功能障碍,无论是持续或恢复到正常的认知,对于帕金森病患者预测老年痴呆症具有预后判断价值。认知衰退是帕金森病情恶化的临床表现。

   研究人员开发了一种临床-遗传评分来预测患者全脑认知障碍程度。(见下文)

 

 

摘要原文



Objective: To examine the incidence, progression, and reversion of mild cognitive impairment in patients with Parkinson disease (PD-MCI) over 5 years.

Methods: A population-based cohort of patients with incident PD underwent repeated neuropsychological testing of attention, executive function, memory, and visuospatial abilities at baseline (n = 178), 1 year (n = 175), 3 years (n = 163), and 5 years (n = 150). Patients were classified as PD-MCI and diagnosed with dementia according to published criteria.

Results: Thirty-six patients (20.2%) fulfilled criteria for PD-MCI at baseline. Among those with normal cognition at baseline (n = 142), the cumulative incidence of PD-MCI was 9.9% after 1 year, 23.2% after 3 years, and 28.9% after 5 years of follow-up. Overall, 39.1% of patients with baseline or incident PD-MCI progressed to dementia during the 5-year study period. The conversion rate to dementia was 59.1% in patients with persistent PD-MCI at 1 year vs 7.2% in those with normal cognition during the first year (adjusted odds ratio 16.6, 95% confidence interval 5.1–54.7, p < 0.001). A total of 27.8% of patients with baseline PD-MCI and 24.2% of those with incident PD-MCI had reverted to normal cognition at study end, but the reversion rate decreased to 9.4% in those with persistent PD-MCI at 2 consecutive visits. Compared with cognitively normal patients, PD-MCI reverters within the first 3 years of follow-up were at increased risk of subsequently developing dementia (adjusted odds ratio 10.7, 95% confidence interval 1.5–78.5, p = 0.019).

Conclusions: Early PD-MCI, regardless of persistence or reversion to normal cognition, has prognostic value for predicting dementia in patients with PD.

 

 

 

原文出处:Neurology.January 20 2017

 

5

 

帕金森患者认知障碍预测新方法

Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts


   认知衰退是帕金森病情恶化的临床表现。研究人员开发了一种临床-遗传评分来预测患者全脑认知障碍程度。

在这项纵向分析研究中,研究人员根据1986-2016年间北美和欧洲的9项帕金森患者临床研究数据,建立了一个全脑认知功能障碍的预测算法(名为简易精神状态检查[MMSE] ) 。

在1986-2016年间的9项大型帕金森临床研究,共包含3200名患者进行了27022项试验研究。根据MMSE评价法,235名患者基线得分≤25以及135名首次发病时间超过12年的患者被排除在外。模型开发样本患者共1350人,6个研究队列,12.8年随访5165次。发病年龄,基线MMSE、受教育年限、测试成绩、性别、抑郁病情和β-葡糖脑苷脂酶(GBA)突变状态被纳入预测模型。模型检测样本包含1132名患者,随访8.6年进行19127次随访。模型开发组(95% CI 0.82–0.90) 以及检测组(95% CI 0.78–0.91),10年内认知风险评分预测曲线下面积(AUC)均大于0.85。认知风险评分得分最高的1/4患者,较最低的1/4患者,全脑认知功能障碍的风险增加(HR 18.4,95% CI 9.4-36.1)。以0.196最为预测截止点,痴呆或致残性认知功能障碍AUC为0.88 (95% CI 0.79–0.94),阴性预测率0.92(95% 0.88–0.95)且在10000随机抽样子集中保持稳定。

研究为帕金森病患者认知功能完整或受损提供了一个潜在的测试方法,将有助于认知干预试验在帕金森防治中发挥更大的作用。

 

 

摘要原文



Methods

    In this longitudinal analysis, we built a prediction algorithm for global cognitive impairment (defined as Mini Mental State Examination [MMSE] ≤25) using data from nine cohorts of patients with Parkinson's disease from North America and Europe assessed between 1986 and 2016. Candidate predictors of cognitive decline were selected through a backward eliminated Cox's proportional hazards analysis using the Akaike's information criterion. These were used to compute the multivariable predictor on the basis of data from six cohorts included in a discovery population. Independent replication was attained in patients from a further three independent longitudinal cohorts. The predictive score was rebuilt and retested in 10000 training and test sets randomly generated from the entire study population.

Findings

   3200 patients with Parkinson's disease who were longitudinally assessed with 27022 study visits between 1986 and 2016 in nine cohorts from North America and Europe were assessed for eligibility. 235 patients with MMSE ≤25 at baseline and 135 whose first study visit occurred more than 12 years from disease onset were excluded. The discovery population comprised 1350 patients (after further exclusion of 334 with missing covariates) from six longitudinal cohorts with 5165 longitudinal visits over 12·8 years (median 2·8, IQR 1·6–4·6). Age at onset, baseline MMSE, years of education, motor exam score, sex, depression, and β-glucocerebrosidase (GBA) mutation status were included in the prediction model. The replication population comprised 1132 patients (further excluding 14 patients with missing covariates) from three longitudinal cohorts with 19127 follow-up visits over 8·6 years (median 6·5, IQR 4·17·2). The cognitive risk score predicted cognitive impairment within 10 years of disease onset with an area under the curve (AUC) of more than 0·85 in both the discovery (95% CI 0·82–0·90) and replication (95% CI 0·78–0·91) populations. Patients scoring in the highest quartile for cognitive risk score had an increased hazard for global cognitive impairment compared with those in the lowest quartile (hazard ratio 18·4 [95% CI 9·4–36·1]). Dementia or disabling cognitive impairment was predicted with an AUC of 0·88 (95% CI 0·79–0·94) and a negative predictive value of 0·92 (95% 0·88–0·95) at the predefined cutoff of 0·196. Performance was stable in 10000 randomly resampled subsets.

 

 

原文出处:Lancet Psychiatry. June 16 2017

 



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