北京大学硕士学位论文中期帕金森病患者视觉空间工作记忆研究姓名：武冬冬申请学位级别：硕士专业：神经病学指导教师：陈海波20060501姓名：院系：学号：北京大学医学部学位论文原创性声明和使用授权说明原创性声明本人郑重声明：所呈交的学位论文，是本人在导师的指导下，独立进行研究工作所取得的成果。
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请选择图书馆发布时间:□即时发布 □一年发布 □二年发布（保密论文在解密后遵守以上规定）论文作者签名：导师签名：日期：年月日中期帕金森病患者视觉空间工作记忆研究中文摘要帕金森病（PD）是一种常见的中枢神经系统缓慢进展的变性疾病，主要见于中老年人，是中老年致残的主要原因之一。
随年龄增长其患病率逐渐增高，其病理改变主要涉及中脑黑质多巴胺（DA）能神经元，呈现细胞脱失死亡。
临床上出现肌强直、肢体静止性震颤和运动减少等症状。
随着认知神经科学的发展，越来越多的研究认为，认知障碍为PD临床症状的一部分。
PD的认知障碍中，前额叶皮层功能障碍（包括工作记忆障碍）是最常见的认知障碍。
大多数学者认为早期PD患者视空间工作记忆受损，而物体工作记忆未受累及。
国内进一步的研究发现空间工作记忆在早期PD患者中也存在相对（距离）空间工作记忆和绝对（位置）空间工作记忆的分离。
根据Bradley 和Kosslyn的理论，国内学者提出空间工作记忆的神经环路的假设。
为明确中期PD对视觉空间工作记忆的影响，我们修订并发展了Smith等工作记忆的检查软件，设定了两个视觉空间工作记忆检查——空间距离工作记忆检查和空间位置工作记忆检查，来检测中期PD对空间距离和位置工作记忆的损伤程度。
同时研究起病年龄、起病侧、病程、文化程度、Webster评分对检查结果的影响及相关性。
实验一：运用空间距离工作记忆检查软件，检查26例中期PD患者（Hoehn －Yahr分级2.5-3级）和26例正常对照。
结果表明PD组正确率(76.19±11.95)较对照组(82.42±8.35)明显降低（P=0.034<0.05）。
右侧起病的患者正确率(72.00±11.72)较对照组(82.42±8.35)明显降低（P=0.003<0.05）。
左侧起病的患者正确率降低较对照组无显著性差异。
左右侧起病的患者正确率相互比较无显著性差异。
利用相关性分析发现PD患者的起病年龄与空间距离工作记忆的正确率呈正相关，病程、受教育时间和Webster评分与空间距离工作记忆正确率无相关性。
实验二：运用空间位置工作记忆检查软件，检查26例中期PD患者（Hoehn －Yahr分级2.5-3级）和26例正常对照。
结果表明PD组正确率（94.46±11.75）较对照组（96.88±3.55）降低无显著性差异（P>0.05）。
左、右侧起病的患者正确率降低较对照组均无显著性差异。
左右侧起病的患者正确率相互比较无显著性差异。
利用相关性分析发现PD患者的起病年龄、病程、受教育时间和Webster评分与空间位置工作记忆正确率均无相关性。
研究结果表明：中期PD患者存在视觉空间工作记忆障碍。
视觉空间位置和视觉空间距离工作记忆的分离现象说明二者受累程度不一致，可能由不同的神经环路参与。
右侧起病的患者视觉空间距离工作记忆检查的成绩明显下降，提示左侧大脑半球对视觉空间距离的加工更占优势。
另外，视觉空间距离工作记忆与起病年龄呈正相关提示PD患者起病越早，视觉空间距离工作记忆障碍越重。
关键词：帕金森病视觉空间距离工作记忆障碍视觉空间位置工作记忆障碍The Research on Visuospatial Working Memoryin Medium-term Parkinson’s Disease PatientsAbstractParkinson’s disease (PD), a common progressive neuro-degenerative disorder, usually occurs among the middle and the aged people, and is one of the main causes for disability. The incidence of PD usually increases with the growth of age. Its pathology change was the loss of nigra dopamine cells inside the midbrain, and takes on rigidity, tremor and bradykinesia as cardinal clinical symptoms. With the development of cognitive neuroscience, lots of studies have shown that PD results in cognitive dysfunction. The dysfunction of prefrontal lobe (including working memory) is the most common one. Most researchers believe that visuospatial working memory in early PD was impaired, while object working memory was relatively spared. Further studies in China have suggested that spatial working memory in early PD also presents a distinction between coordinate spatial working memory and categorical spatial working memory. Based on Bradley and Kosslyn’s theory, domestic researchers advanced the hypothesis on neural loops for spatial working memory. To further investigate the features of visuospatial working memory in medium-term PD patients, the Smith’s working memory software were modified. Two tests on visuospatial working memory, namely, coordinate visuospatial working memory test and categorical visuospatial working memory test were developed to study spatial working memory deficits in medium-term PD. We also investigated the factors that might affect the result, including the age of onset, the side of onset, duration, education duration and Webster Raring Scale.Experiment one: the research of the coordinate visuospatial working memory. We examined twenty-six PD patients in the medium term (Hoehn-Yahr stage 2.5-3) and twenty-six health people as normal controls matched with age, sex, education and intelligence. The results showed that the correct rate (CR) of coordinate visuospatial working memory test was significantly lower in PD patients(76.19±11.95) than in normal controls(82.42±8.35) (P=0.034<0.05). To be more specific, the CR was significantly lower in the right-side-onset PD patients (72.00±11.72) than in controls (82.42±8.35) (P=0.003<0.05), but not in the left-side-onset PD patients. There was no significant difference of CR between right-side-onset and left-side-onset PD patients. There was positive relationship between the CR of coordinate visuospatial working memory and the age of onset. But the CR had no correlation with the side of onset, education duration and Webster Raring Scale.Experiment Two: the research of the categorical visuospatial working memory. The same subjects in experiment one were enrolled in experiment two. The results showed that the CR of categorical visuospatial working memory test was lower in PD (94.46±11.75) than in normal controls (96.88±3.55), but no significant difference between the two groups (P>0.05). There were no significant differences between any combinations of the following three subgroups: the controls, the left-side-onset PD patients, and the right-side-onset PD patients. The CR of categorical visuospatial working memory has no correlation with age of onset, duration, education duration and Webster Raring Scale.The present research went to the conclusion that the visuospatial working memory impairment had its presence in medium-term PD patients. The coordinate visuospatial working memory was impaired, while the categorical visuospatial working memory was relatively spared. They might apply for different neural circuits. The worse performance of the right-side-onset PD patients in the Experiment One implies that the left hemisphere plays a more important role in the coordinate visuospatial working memory.We also noticed that the earlier the age of onset is, the more serious of the coordinate visuospatial working memory impairment.Key words: Parkinson’s diseaseWorking memory中期帕金森病患者视觉空间工作记忆研究前言原发性帕金森病(IPD) 是一种常见的中枢神经系统缓慢进展的变性疾病，主要见于中老年人，是中老年致残的主要原因之一。