今天是:2019-04-22 星期一

网格细胞空间导航神经环路的衰老和退变特征及其预测AD转化的机制
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注册号:

Registration number:

ChiCTR1900022525 

最近更新日期:

Date of Last Refreshed on:

2019-04-15 

注册时间:

Date of Registration:

2019-04-15 

注册号状态:

补注册  

Registration Status:

Retrospective registration  

注册题目:

网格细胞空间导航神经环路的衰老和退变特征及其预测AD转化的机制 

Public title:

Aging and degeneration characteristics of spatial navigation neural circuits in grid cells and the mechanism of predicting AD transformation 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

网格细胞空间导航神经环路的衰老和退变特征及其预测AD转化的机制 

Scientific title:

Aging and degeneration characteristics of spatial navigation neural circuits in grid cells and the mechanism of predicting AD transformation 

研究课题代号(代码):

Study subject ID:

 

在二级注册机构或其它机构的注册号:

The registration number of the Partner Registry or other register:

 

申请注册联系人:

青钊 

研究负责人:

张冰 

Applicant:

Zhao Qing 

Study leader:

Bing Zhang 

申请注册联系人电话:

Applicant telephone:

+86 13701451581 

研究负责人电话:

Study leader's telephone:

+86 15851803070 

申请注册联系人传真 :

Applicant Fax:

 

研究负责人传真:

Study leader's fax:

 

申请注册联系人电子邮件:

Applicant E-mail:

qz2004012239@sina.com 

研究负责人电子邮件:

Study leader's E-mail:

zhangbing_nanjing@nju.edu.cn 

申请单位网址(自愿提供):

Applicant website(voluntary supply):

 

研究负责人网址(自愿提供):

Study leader's website(voluntary supply):

 

申请注册联系人通讯地址:

江苏省南京市鼓楼区中山路321号南京鼓楼医院 

研究负责人通讯地址:

江苏省南京市鼓楼区中山路321号南京鼓楼医院 

Applicant address:

321 Zhongshan Road, Nanjing, Jiangsu, China 

Study leader's address:

321 Zhongshan Road, Nanjing, Jiangsu, China 

申请注册联系人邮政编码:

Applicant postcode:

 

研究负责人邮政编码:

Study leader's postcode:

 

申请人所在单位:

南京鼓楼医院 

Applicant's institution:

Affiliated Drum Tower Hospital of Nanjing University Medical School 

是否获伦理委员会批准:

是 

Approved by ethic committee:

Yes 

伦理委员会批件文号:

Approved No. of ethic committee:

2017-105-01 

伦理委员会批件附件:

Approved file of Ethical Committee:

查看附件View

批准本研究的伦理委员会名称:

南京大学医学院附属鼓楼医院医学伦理委员会 

Name of the ethic committee:

Medical ethics committee of Affiliated Drum Tower Hospital of Nanjing University Medical School 

伦理委员会批准日期:

Date of approved by ethic committee:

 

伦理委员会联系人:

沙莉莉 

Contact Name of the ethic committee:

Lili Sha 

伦理委员会联系地址:

江苏省南京市鼓楼区中山路321号南京鼓楼医院 

Contact Address of the ethic committee:

321 Zhongshan Road, Nanjing, Jiangsu, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

 

研究实施负责(组长)单位:

南京大学医学院附属鼓楼医院 

Primary sponsor:

Affiliated Drum Tower Hospital of Nanjing University Medical School 

研究实施负责(组长)单位地址:

江苏省南京市鼓楼区中山路321号南京鼓楼医院 

Primary sponsor's address:

321 Zhongshan Road, Nanjing, Jiangsu, China 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

江苏省

市(区县):

南京市

Country:

China

Province:

Jiangsu

City:

Nanjing

单位(医院):

南京大学医学院附属鼓楼医院影像科

具体地址:

江苏省南京市鼓楼区中山路321号

Institution
hospital:

Department of Radiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Address:

321 Zhongshan Road, Nanjing, Jiangsu, China

经费或物资来源:

中国国家自然科学基金 

Source(s) of funding:

Chinese National Natural Science Foundation 

研究疾病:

轻度认知障碍 

Target disease:

mild cognitive impariment 

研究疾病代码:

 

Target disease code:

 

研究类型:

基础科学研究 

Study type:

Basic Science 

研究所处阶段:

其它 

Study phase:

N/A 

研究目的:

以网格细胞“六倍旋转对称特性”任务态fMRI 研究为理论依据,空间导航测试和3D 高分辨BOLD 为关键技术,采用因果推断中介分析法,探讨衰老、基因、神经退行性疾病中网格细胞空间导航神经环路的改变机制 

Objectives of Study:

Based on the theoretical basis of "six-fold rotatory symmetry characteristics" task state fMRI study of grid cells, spatial navigation test and 3D high-resolution BOLD are the key technologies, and the causal inference intermediary analysis method is adopted to explore the change mechanism of spatial navigation neural circuits of grid cells in aging, gene and neurodegenerative diseases 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

析因分组(即根据危险因素或暴露因素分组) 

Study design:

Factorial 

纳入标准:

可能AD(probable AD) 诊断标准:参照《精神疾病诊断及统计手册第四版修订版(DSM - IV)》和美国国立神经研究院沟通障碍、中风- Alzheimer 病及相关障碍协会 (NINCDS - ADRDA) 标准。 a)客观证据表明确有短期或长期记忆损害。 b)有以下8 个认知区域的一种或一种以上认知功能障碍:记忆、语言、注意、执行能力、定向力、抽象思维与判断力损害、其它皮质功能的障碍、人格改变。 c)上述两类认知功能损害明显干扰社交、职业活动或人际关系。 d)总体认知分级量表异常( 教育年龄8 年以上):MMSE ≤24分,20~24分( 轻度) ,16~19分( 中度) ,15分以下( 重度) ;MoCA<19 分;CDR 1分( 轻度) ,2 分( 中度) ,3 分( 重度) ;ADL>20 分,Hachinski 缺血指数表≤4分。 e)右利手,并签署知情同意书。 f) MRI 入组标准:除脑萎缩和深部白质少量脱髓鞘病变(Fazekas scale I 级及以下) 外,无其它异常改变。 MCI 诊断标准:参照2001年美国神经学会质量标准分会推荐的Petersen 等1999年提出的标准。( 各条诊断标准必须同时满足,下同) 。 a)主诉认知功能障碍;有客观认知功能任务受损表现。 b)总体认知分级量表轻度异常( 教育年龄8 年以上): MMSE 25~26 分; MoCA 19~25分;CDR 0.5 分;Hachinski 缺血指数表(Rosen 法) 得分小于等于 4 分,以除外血管性痴呆及混合性痴呆。日常生活能力正常或轻微受损(20 项ADL 量表,正常值20分) 。 c) 右利手,并签署知情同意书。 d) MRI 入组标准同前。 遗忘型 MCI (aMCI) 诊断标准:遗忘型MCI 患者参照Dubois 等提出的基于(Grober和Buschke 的16- 项增强的线索回忆程序测试,G B ’s Te st)的标准。( 各条诊断标准必须同时满足,下同) 。认知水平参照MCI 诊断标准。 a)主诉记忆障碍。 b)记忆测验 ( 语言类AVLT,GB’s Test 或非语言类BVRT) 低于正常对照组1.5 个标准差。 HMCI 诊断标准:参照Dubois 等提出的基于(Grober和Buschke 的 16- 项增强的线索回忆程序测试,GB’s Test)的标准。( 各条诊断标准必须同时满足,下同) 。 自由回忆存在较严重缺陷(尽管有足够的编码)或由于线索效应不足导致总体回忆受损:少于10个词语,或者10~14 个词语中超过30% 为无序自发回忆(总数为16个词语)。反映了对记忆的编码和巩固障碍,与海马功能密切相关。NHMCI诊断标准:参照Dubois 等提出的基于(Grober和Buschke 的16- 项增强的线索回忆程序测试,G B ’s Te st )的标准。( 各条诊断标准必须同时满足,下同) 。 自由回忆受损程度较轻:10~14 个词语中无序自发回忆不超过30%;或在提供线索后趋于正常:回忆15–16个词语(总数为16个词语) 。反映了对记忆的提取障碍,与额叶功能密切相关。 非遗忘型 MCI- (naMCI) 诊断标准:参照MCI 诊断标准。 a)无主诉记忆障碍。 b)注意- 执行功能障碍,语言或视空间功能障碍。 进展型MCI诊断标准 :根据Petersen, R.C. (J Intern Med, 2004)及Whitwell JL (Brain, 2007)文献提示,aMCI每年约12~15%进展为AD,随访6 年后有80% 转化为AD。 ①随访6 年后确诊为AD 或其他类型痴呆者,在其转化为痴呆前的状态可以确诊为进展型MCI 。 ②每年随访MCI 患者,其MMSE 分数持续下降,下降2分以上。 认知正常对照组(Cognitively normal, CN) : 参照2008年美国国家卫生部(U.S. National institutes of health, NIH) 认知功能障碍研究项目提出的对照组标准。 ①无主诉记忆障碍。 ②总体认知分级量表正常:MMSE 27~30 分; MoCA 26~30 分;CDR 0 分;ADL正常20分。Hachinski 缺血指数表≤ 4分。 ③右利手,并签署知情同意书。 ④ MRI入组标准同前。 

Inclusion criteria

Probable AD: It is probable that the diagnostic and statistical manual of mental disorders, dsm-iv, and the nincds-adrda criteria will be considered. 1) objective evidence suggests short-term or long-term memory impairment. 2) one or more of the following cognitive dysfunction in eight cognitive regions: memory, language, attention, executive ability, orientation, impairment of abstract thinking and judgment, other cortical dysfunction, personality change; 3) the above two types of cognitive impairment significantly interfere with social, professional activities or interpersonal relationships; 4) abnormalities in the general cognitive rating scale (education age over 8 years): MMSE 24, 20-24 (mild), 16-19 (moderate), and below 15 (severe); MoCA < 19 points; CDR score: 1 (mild), 2 (moderate), 3 (severe); ADL>20, Hachinski ischemia index table 4; 5) right handedness and signing of the informed consent. 6) MRI inclusion criteria: except for brain atrophy and small amount of demyelinating lesions in deep white matter (Fazekas scale I). No other abnormal changes. Diagnostic criteria for MCI, refer to Petersen, 2001, recommended by the quality standards branch of the American neurological association: 1) chief complaint of cognitive dysfunction; Objective cognitive function task impaired performance. 2) mild abnormalities in the general cognitive rating scale (education age over 8 years): MMSE 25 ~ 26 points; MoCA 19 ~ 25 points; CDR 0.5 points; Hachinski ischemia index (Rosen method) score was less than or equal to 4, except vascular dementia and mixed dementia. Normal or minor impairment of daily living ability (20 items of ADL scale, normal score 20 points); 3) right handedness, and sign the informed consent; 4) MRI inclusion criteria were the same as before. HMCI diagnostic criteria: refer to Dubois, proposed based on (Grober and Buschke 16 - clues to enhance recall program testing, GB Test) 's standards. (all diagnostic criteria must be met simultaneously, the same below). Free recall was severely flawed (despite adequate coding) or impaired overall recall due to insufficient cue effects: less than 10 words, or more than 30% of 10 to 14 words were disordered spontaneous recall (a total of 16 words). It reflects the disorder of encoding and consolidation of memory, which is closely related to hippocampal function. NHMCI diagnostic criteria: refer to the criteria proposed by Dubois et al. (16-item enhanced cue recall procedure test based on Grober and Buschke, G B's Te st). (all diagnostic criteria must be met simultaneously, the same below). The degree of damage of free recall was less: no more than 30% of the disordered spontaneous recall in 10~14 words; Or they tended to be normal after giving clues: 15 to 16 words were recalled (a total of 16 words). It reflects the impairment of memory extraction and is closely related to the function of frontal lobe. Non-amnestic MCI- (naMCI) diagnostic criteria: refer to MCI diagnostic criteria. A) no chief complaint of memory disorder. B) attention - executive dysfunction, language or visuospatial dysfunction. Diagnostic criteria for progressive MCI: according to the literature of Petersen, R.C. (J Intern Med, 2004) and Whitwell JL (Brain, 2007), about 12 ~ 15% of the patients with aMCI developed into AD every year, and 80% of them were converted into AD after 6 years of follow-up. (1) in patients diagnosed with AD or other types of dementia after 6 years of follow-up, progressive MCI can be diagnosed in the state before its conversion to dementia; (2) patients with MCI were followed up every year, and their MMSE scores continued to decline, down by more than 2 points. Cognitively normal control (CN): what tively normal (CN) has