痴呆与轻度认知障碍的流行病学、发病机制和诊治应用研究——2013年度国家科学技术进步二等奖

doi:10.3969/j.issn.1006-7795.2014.01.001

摘要/Abstract

摘要：

痴呆与轻度认知障碍是我国卫生领域重大疾病，给社会和家庭带来了沉重负担。本项目在国家和省部级40余项基金资助下，对痴呆与轻度认知障碍的流行病学、发病机制和临床诊治进行了系统的研究，建立了国内最系统完整的痴呆与轻度认知障碍的临床信息和生物标本库；明确了中国人群阿尔茨海默病（Alzheimer’s disease，AD）相关的遗传致病/易感基因和重要蛋白功能并在国际首次报道了中国人家族性AD早老素1基因新突变；发现和明确了AD早期诊断的生物学和影像学标志物；主持制定了痴呆与认知障碍诊治指南；研发了抗AD新药，构建了药物研发技术平台。本项目提高了我国痴呆和轻度认知障碍诊治水平，取得了显著的社会效益。

关键词: 轻度认知障碍, 痴呆, 阿尔茨海默病, 药物, 诊断治疗

Abstract:

Dementia and mild cognitive impairment are the most common neurodegenerative disease and the leading cause of dementia in the elderly. Sponsored by over 40 national and provincial funds, we have obtained tremendous achievements through all these years hard work, which included: (1) A large complete system of clinical information and biological specimen dataset of dementia and mild cognitive impairment of Chinese population. (2) The study confirmed the genetic/susceptibility genes and major protein functions associated with Alzheimer's disease(AD) and reported for the first time the novel presenilin 1(V97L and A136G) mutation and SNPs in over 20 susceptibility genes associated with sporadic AD in Chinese population. (3) The study identified and confirmed the biomarkers and images for early diagnosis of AD. (4) The guidelines for the diagnosis and treatment of dementia and cognitive disorders. (5) New drugs for AD were developed and the technology platform for drug was constructed. This project improved the diagnostic and treatment skills for dementia and mild cognitive disorders and achieved significant social benefits.

Key words: mild cognitive disorders, dementia, Alzheimer's disease(AD), drug, diagnosis and treatment

中图分类号:

R741

贾建平. 痴呆与轻度认知障碍的流行病学、发病机制和诊治应用研究——2013年度国家科学技术进步二等奖[J]. 首都医科大学学报, 2014, 35(1): 1-5.

Jia Jianping. This study was awarded with The Second Grade National Prize for Science and Technology Progress—The application study on epidemiology, pathogenesis, diagnosis and treatment of mild cognitive impairment and dementia[J]. Journal of Capital Medical University, 2014, 35(1): 1-5.

参考文献

[1] 孟琛, 汤哲, 陈彪. 老年人认知功能减退影响因素的纵向研究[J]. 中华老年医学杂志, 2000, 19(3):211-214.

[2] 关绍晨, 汤哲, 吴晓光, 等. 北京老年人群轻度认知障碍患病情况及危险因素的抽样调查[J]. 中国脑血管病杂志, 2008, 5(9):395-398.

[3] Wang S, Jia J. Promoter polymorphisms which modulate BACE1 expression are associated with sporadic Alzheimer's disease[J]. Am J Med Genet B Neuropsychiatr Genet, 2010, 153B(1):159-166.

[4] Jia J, Xu E, Shao Y, et al. One novel presenilin-1 gene mutation in a Chinese pedigree of familial Alzheimer's disease[J]. J Alzheimers Dis, 2005, 7(2):119-124. discussion 173-180.

[5] Qin W, Jia J. Down-regulation of insulin-degrading enzyme by presenilin 1 V97L mutant potentially underlies increased levels of amyloid beta 42[J]. Eur J Neurosci, 2008, 27(9):2425-2432.

[6] Xue S, Jia L, Jia J. Association between somatostatin gene polymorphisms and sporadic Alzheimer's disease in Chinese population[J]. Neurosci Lett, 2009, 465(2):181-183.

[7] Lv H, Jia L, Jia J. Promoter polymorphisms which modulate APP expression may increase susceptibility to Alzheimer's disease[J]. Neurobiol Aging, 2008, 29(2):194-202.

[8] Qing H, Zhou W, Christensen M A, et al. Degradation of BACE by the ubiquitin-proteasome pathway[J]. FASEB J, 2004, 18(13):1571-1573.

[9] Sun X, Tong Y, Qing H, et al. Increased BACE1 maturation contributes to the pathogenesis of Alzheimer's disease in Down syndrome[J]. FASEB J, 2006, 20(9):1361-1368.

[10] Sun X, Wang Y, Qing H, et al. Distinct transcriptional regulation and function of the human BACE2 and BACE1 genes[J]. FASEB J, 2005, 19(7):739-749.

[11] Liu H, Wang P, Song W, et al. Degradation of regulator of calcineurin 1 (RCAN1) is mediated by both chaperone-mediated autophagy and ubiquitin proteasome pathways[J]. FASEB J, 2009, 23(10):3383-3392.

[12] Xue S, Jia L, Jia J. Hypoxia and reoxygenation increased BACE1 mRNA and protein levels in human neuroblastoma SH-SY5Y cells[J]. Neurosci Lett, 2006, 405(3):231-235.

[13] Xing Y, Qin W, Li F, et al. Apolipoprotein E ε4 status modifies the effects of sex hormones on neuropsychiatric symptoms of Alzheimer's disease[J]. Dement Geriatr Cogn Disord, 2012, 33(1):35-42.

[14] Yan C, Gong G, Wang J, et al. Sex-and brain size-related small-world structural cortical networks in young adults: a DTI tractography study[J]. Cereb Cortex, 2011, 21(2):449-458.

[15] Zou Q, Long X, Zuo X, et al. Functional connectivity between the thalamus and visual cortex under eyes closed and eyes open conditions: a resting-state fMRI study[J]. Hum Brain Mapp, 2009, 30(9):3066-3078.

[16] Lo C Y, Wang P N, Chou K H, et al. Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer's disease[J]. J Neurosci, 2010, 30(50):16876-16885.

[17] Bai F, Shu N, Yuan Y, et al. Topologically convergent and divergent structural connectivity patterns between patients with remitted geriatric depression and amnestic mild cognitive impairment[J]. J Neurosci, 2012, 32(12):4307-4318.

[18] 胡忠婕, 王金辉, 朗悦, 等. 两种轻度认知损害患者的神经心理学功能比较(英文)[J]. 上海精神医学, 2011, 23(5):265-271.

[19] Wang J, Zuo X, Dai Z, et al. Disrupted functional brain connectome in individuals at risk for alzheimer's disease[J]. Biol Psychiatry, 2013, 73(5):472-481.

[20] Zhou A, Jia J. A screen for cognitive assessments for patients with vascular cognitive impairment nodementia[J]. Int J Geriatr Psychiatry, 2009, 24(12):1352-1357.

[21] Zhou A, Jia J. The value of the clock drawing test and the mini-mental state examination for identifying vascular cognitive impairment no dementia[J]. Int J Geriatr Psychiatry, 2008, 23(4):422-426.

[22] Lu J, Li D, Li F, et al. Montreal cognitive assessment in detecting cognitive impairment in Chinese elderly individuals: a population-based study[J]. J Geriatr Psychiatry Neurol, 2011, 24(4):184-190.

[23] Li F, Jia XF, Jia J. The Informant Questionnaire on Cognitive Decline in the Elderly individuals in screening mild cognitive impairment with or without functional impairment[J]. J Geriatr Psychiatry Neurol, 2012, 25(4):227-232.

[24] 贾建平. 中国痴呆与认知障碍诊治指南[M]. 北京:人民卫生出版社, 2010.

[25] 中华医学会神经病学分会痴呆与认知障碍学组写作组. 血管性认知障碍诊治指南[J]. 中华神经科杂志, 2011, 44(2):142-147.

[26] 陈莲珍, 李林, 安文林, 等. 参乌胶囊对糖尿病复合脑缺血模型大鼠学习记忆功能和细胞凋亡相关蛋白表达的影响[J]. 中国药学杂志, 2005, 40(1):23-27.

[27] 褚燕琦, 李玮, 张兰, 等. 山茱萸环烯醚萜苷对蛋白磷酸酶抑制剂冈田酸拟阿尔茨海默病细胞模型的作用[J]. 中国药理学通报, 2006, 22(8):960-963.

[28] 楚晋, 李林, 叶翠飞, 等. 淫羊藿黄酮对APP转基因小鼠学习记忆及β-amyloid生成的影响[J]. 中国科技大学学报, 2008, 38(4):339-348.

[29] 楚晋, 张兰, 叶翠飞, 等. 淫羊藿黄酮对转基因小鼠脑内突触相关蛋白的影响[J]. 中华医学杂志, 2008, 88(1):31-35.

[30] Meng Y, Wang R, Yang F, et al. Amyloid precursor protein 17-mer peptide ameliorates hippocampal neurodegeneration in ovariectomized rats[J]. Neurosci Lett, 2010, 468(3):173-177.