您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (8): 22-27,33.doi: 10.6040/j.issn.1671-7554.0.2020.0399

• 脑科学与类脑智能研究专题 • 上一篇    下一篇

脑深部电刺激术在阿尔兹海默病中的应用进展

余新光*(),张艳阳   

  1. 解放军总医院第一医学中心神经外科学部，北京 100853
  • 收稿日期:2020-03-20 出版日期:2020-08-07 发布日期:2020-08-07
  • 通讯作者: 余新光 E-mail:yuxinguang_301@163.com
  • 作者简介:余新光，主任医师、教授。现任全军神经外科专业委员会主任委员、中国医师协会神经外科医师分会副会长、中国医师协会脑胶质瘤专业委员会副主任委员、中华医学会神经外科学分会委员兼脊柱脊髓外科学组组长、北京医学会神经外科学分会副主任委员兼转化医学组组长,专业涉及颅底和脑深部肿瘤、颅颈交界畸形和脑机接口等领域。在国内首先提出“中央颅底”的概念。指导团队在国内完成首例DBS技术治疗痴呆，在人体成功实现脑机接口“意念”打字。主持科技部重大科研项目、多个国家自然科学基金项目。以第一完成人获得军队科技进步一等奖和军队医疗成果二等奖。与清华大学合作荣获国家科技进步一等奖。
  • 基金资助:
    国家自然科学基金(81871087)

Advances on the treatment of Alzheimer's disease with deep brain stimulation

Xinguang YU*(),Yanyang ZHANG   

  1. Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
  • Received:2020-03-20 Online:2020-08-07 Published:2020-08-07
  • Contact: Xinguang YU E-mail:yuxinguang_301@163.com

RichHTML

25

PDF (PC)

628

摘要：

阿尔兹海默病(AD)是一种脑网络疾病，至今尚无有效治疗方法，对社会产生严重负担。脑深部电刺激(DBS)可调控靶点相关的脑网络，为AD的治疗带来希望。DBS在AD治疗中的应用尚处于探索阶段，如何选择合适的手术病例、手术的最优靶点、电刺激参数以及DBS治疗AD的确切临床疗效等仍待进一步的研究。本文拟对DBS治疗AD的适应证、手术靶点、刺激参数、作用机制以及未来发展趋势进行综述。

关键词: 阿尔兹海默病, 脑深部电刺激, 脑网络, 神经影像

Abstract:

Alzheimer's disease (AD) has been increasingly considered as a large-scale network disconnection syndrome. Currently, AD remains unchecked, and the economic burden on society is huge. Deep brain stimulation (DBS) engaging circuits and networks in the brain of AD patients is proved potentially therapeutic, but still in the infant stage. This article reviews the indications, stimulation targets and parameters, mechanism and future trends of DBS in the treatment of AD.

Key words: Alzheimer's Disease, Deep brain stimulation, Brain network, Neuroimaging

中图分类号: 

  • R741
1 Querfurth HW , LaFerla FM . Alzheimer's disease[J]. N Engl J Med, 2010, 362 (4): 329- 344.
doi: 10.1056/NEJMra0909142
2 GBD 2016 Dementia Collaborators . Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet Neurol, 2019, 18 (1): 88- 106.
doi: 10.1016/S1474-4422(18)30403-4
3 张建国. 脑深部电刺激治疗阿尔茨海默病的现状和进展[J]. 中华神经创伤外科电子杂志, 2018, 4 (6): 379- 381.
ZHANG Jianguo . Status and prospect of deep brain stimulation for the treatment of Alzheimer's disease[J]. Chinese Journal of Neurotraumatic Surgery, 2018, 4 (6): 379- 381.
4 Long JM , Holtzman DM . Alzheimer disease: an update on pathobiology and treatment strategies[J]. Cell, 2019, 179 (2): 312- 339.
5 Schneider L . A resurrection of aducanumab for Alzheimer's disease[J]. Lancet Neurol, 2020, 19 (2): 111- 112.
doi: 10.1016/S1474-4422(19)30480-6
6 余新光, 张艳阳. 神经外科参与脑科学研究的机遇与挑战[J]. 中国现代神经疾病杂志, 2019, 19 (12): 915- 919.
YU Xinguang , ZHANG Yanyang . Opportunities and challenges for neurosurgeon in the brain-research era[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2019, 19 (12): 915- 919.
7 Poo MM , Du JL , Ip NY , et al. China brain project: basic neuroscience, brain diseases, and brain-inspired computing[J]. Neuron, 2016, 92 (3): 591- 596.
doi: 10.1016/j.neuron.2016.10.050
8 张艳阳, 余新光. 人脑连接组学在神经外科中的应用进展[J]. 中国医学影像学杂志, 2017, 25 (10): 789- 793.
ZHANG Yanyang , YU Xinguang . Connectomics: a new paradigm for understanding brain disease in neurosurgery[J]. Chinese Journal of Medical Imaging, 2017, 25 (10): 789- 793.
9 Jagust W . Imaging the evolution and pathophysiology of Alzheimer disease[J]. Nat Rev Neurosci, 2018, 19 (11): 687- 700.
doi: 10.1038/s41583-018-0067-3
10 Okun MS . Deep-brain stimulation-entering the era of human neural-network modulation[J]. N Engl J Med, 2014, 371 (15): 1369- 1373.
doi: 10.1056/NEJMp1408779
11 Laxton AW , Tang-Wai DF , McAndrews MP , et al. A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease[J]. Ann Neurol, 2010, 68 (4): 521- 534.
doi: 10.1002/ana.22089
12 Smith GS , Laxton AW , Tang-Wai DF , et al. Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease[J]. Arch Neurol, 2012, 69 (9): 1141- 1148.
13 Kuhn J , Hardenacke K , Lenartz D , et al. Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia[J]. Mol Psychiatry, 2015, 20 (3): 353- 360.
doi: 10.1038/mp.2014.32
14 Sharma M , Deogaonkar M , Rezai A . Assessment of potential targets for deep brain stimulation in patients with Alzheimer's disease[J]. J Clin Med Res, 2015, 7 (7): 501- 505.
doi: 10.14740/jocmr2127w
15 Khan IS , D'Agostino EN , Calnan DR , et al. Deep brain stimulation for memory modulation: a new frontier[J]. World Neurosurg, 2019, 126: 638- 646.
doi: 10.1016/j.wneu.2018.12.184
16 Gratwicke J , Kahan J , Zrinzo L , et al. The nucleus basalis of Meynert: a new target for deep brain stimulation in dementia?[J]. Neurosci Biobehav Rev, 2013, 37 (10 Pt 2): 2676- 2688.
17 Koulousakis P , Andrade P , Visser-Vandewalle V , et al. The nucleus basalis of meynert and its role in deep brain stimulation for cognitive disorders: a historical perspective[J]. J Alzheimers Dis, 2019, 69 (4): 905- 919.
doi: 10.3233/JAD-180133
18 Turnbull IM , McGeer PL , Beattie L , et al. Stimulation of the basal nucleus of Meynert in senile dementia of Alzheimer's type: a preliminary report[J]. Appl Neurophysiol, 1985, 48 (1-6): 216- 221.
19 Dougherty DD , Rezai AR , Carpenter LL , et al. A randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression[J]. Biol Psychiatry, 2015, 78 (4): 240- 248.
doi: 10.1016/j.biopsych.2014.11.023
20 Scharre DW , Weichart E , Nielson D , et al. Deep brain stimulation of frontal lobe networks to treat Alzheimer's disease[J]. J Alzheimers Dis, 2018, 62 (2): 621- 633.
doi: 10.3233/JAD-170082
21 Deeb W , Salvato B , Almeida L , et al. Fornix-region deep brain stimulation-induced memory flashbacks in Alzheimer's disease[J]. N Engl J Med, 2019, 381 (8): 783- 785.
doi: 10.1056/NEJMc1905240
22 Hamani C , McAndrews MP , Cohn M , et al. Memory enhancement induced by hypothalamic/fornix deep brain stimulation[J]. Ann Neurol, 2008, 63 (1): 119- 123.
doi: 10.1002/ana.21295
23 Ponce FA , Asaad WF , Foote KD , et al. Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial[J]. J Neurosurg, 2016, 125 (1): 75- 84.
doi: 10.3171/2015.6.JNS15716
24 Mao ZQ , Wang X , Xu X , et al. Partial improvement in performance of patients with severe Alzheimer's disease at an early stage of fornix deep brain stimulation[J]. Neural Regen Res, 2018, 13 (12): 2164- 2172.
doi: 10.4103/1673-5374.241468
25 Senova S , Chaillet A , Lozano AM . Fornical closed-loop stimulation for Alzheimer's disease[J]. Trends Neurosci, 2018, 41 (7): 418- 428.
doi: 10.1016/j.tins.2018.03.015
26 Aldehri M , Temel Y , Alnaami I , et al. Deep brain stimulation for Alzheimer's disease: an update[J]. Surg Neurol Int, 2018, 9: 58.
doi: 10.4103/sni.sni_342_17
27 Buckner RL , Snyder AZ , Shannon BJ , et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory[J]. J Neurosci, 2005, 25 (34): 7709- 7717.
doi: 10.1523/JNEUROSCI.2177-05.2005
28 Sankar T , Chakravarty MM , Bescos A , et al. Deep brain stimulation influences brain structure in Alzheimer's disease[J]. Brain Stimul, 2015, 8 (3): 645- 654.
29 凌至培, 毛之奇, 潘隆盛, 等. 脑深部电刺激术治疗痴呆的初步临床结果[J]. 中华神经医学杂志, 2017, 16 (1): 55- 59.
LING Zhipei , MAO Zhiqi , PAN Longsheng , et al. Deep brain stimulation therapy for patients with severe dementia[J]. Chinese Journal of Neuromedicine, 2017, 16 (1): 55- 59.
30 Supekar K , Menon V , Rubin D , et al. Network analysis of intrinsic functional brain connectivity in Alzheimer's disease[J]. PLoS Comput Biol, 2008, 4 (6): e1000100.
doi: 10.1371/journal.pcbi.1000100
31 Buckner RL , Sepulcre J , Talukdar T , et al. Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease[J]. J Neurosci, 2009, 29 (6): 1860- 1873.
doi: 10.1523/JNEUROSCI.5062-08.2009
32 He Y , Chen Z , Evans A . Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer's disease[J]. J Neurosci, 2008, 28 (18): 4756- 4766.
doi: 10.1523/JNEUROSCI.0141-08.2008
33 Lo CY , Wang PN , Chou KH , 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.
doi: 10.1523/JNEUROSCI.4136-10.2010
34 Gondard E , Chau HN , Mann A , et al. Rapid modulation of protein expression in the rat hippocampus following deep brain stimulation of the fornix[J]. Brain Stimul, 2015, 8 (6): 1058- 1064.
doi: 10.1016/j.brs.2015.07.044
35 Fox MD , Buckner RL , Liu H , et al. Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases[J]. Proc Natl Acad Sci USA, 2014, 111 (41): E4367- 4375.
doi: 10.1073/pnas.1405003111
36 Via a J , Vickers JC , Cook MJ , et al. Currents of memory: recent progress, translational challenges, and ethical considerations in fornix deep brain stimulation trials for Alzheimer's disease[J]. Neurobiol Aging, 2017, 56: 202- 210.
doi: 10.1016/j.neurobiolaging.2017.03.001
37 Hescham S , Jahanshahi A , Schweimer JV , et al. Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus[J]. Brain Struct Funct, 2016, 221 (8): 4281- 4286.
doi: 10.1007/s00429-015-1144-2
38 Sarah Hescham , Yasin Temel , Sandra Schipper , et al. Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis[J]. Brain Struct Funct, 2017, 222 (2): 1069- 1075.
39 Elise Gondard , Hien N Chau , Amandeep Mann , et al. Rapid modulation of protein expression in the rat hippocampus following deep brain stimulation of the fornix[J]. Brain Stimul Nov-Dec, 2015, 8 (6): 1058- 1064.
doi: 10.1016/j.brs.2015.07.044
40 Aurelie Leplus , Inger Lauritzen , Christophe Melon . Chronic fornix deep brain stimulation in a transgenic Alzheimer's rat model reduces amyloid burden, inflammation, and neuronal loss[J]. Brain Struct Funct, 2019, 224 (1): 363- 372.
41 Huang C , Chu H , Ma Y , et al. The neuroprotective effect of deep brain stimulation at nucleus basalis of Meynert in transgenic mice with Alzheimer's disease[J]. Brain Stimul, 2019, 12 (1): 161- 174.
doi: 10.1016/j.brs.2018.08.015
[1] 尹义龙,袭肖明,孟宪静. 阿尔兹海默病的智能诊断方法[J]. 山东大学学报 (医学版), 2020, 58(8): 14-21.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 58(7): 1 -6 .
[2] 张宝文,雷香丽,李瑾娜,罗湘俊,邹容. miR-21-5p靶向调控TIMP3抑制2型糖尿病肾病小鼠肾脏系膜细胞增殖及细胞外基质堆积[J]. 山东大学学报 (医学版), 2020, 58(7): 7 -14 .
[3] 龙婷婷,谢明,周璐,朱俊德. Noggin蛋白对小鼠脑缺血再灌注损伤后学习和记忆能力与齿状回结构的影响[J]. 山东大学学报 (医学版), 2020, 58(7): 15 -23 .
[4] 付洁琦,张曼,张晓璐,李卉,陈红. Toll样受体4抑制过氧化物酶体增殖物激活受体γ加重血脂蓄积的分子机制[J]. 山东大学学报 (医学版), 2020, 58(7): 24 -31 .
[5] 马青源,蒲沛东,韩飞,王超,朱洲均,王维山,史晨辉. miR-27b-3p调控SMAD1对骨肉瘤细胞增殖、迁移和侵袭作用的影响[J]. 山东大学学报 (医学版), 2020, 58(7): 32 -37 .
[6] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 58(7): 38 -46 .
[7] 史爽,李娟,米琦,王允山,杜鲁涛,王传新. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报 (医学版), 2020, 58(7): 47 -52 .
[8] 肖娟,肖强,丛伟,李婷,丁守銮,张媛,邵纯纯,吴梅,刘佳宁,贾红英. 两种甲状腺超声数据报告系统诊断效能的比较[J]. 山东大学学报 (医学版), 2020, 58(7): 53 -59 .
[9] 丁祥云,于清梅,张文芳,庄园,郝晶. 胰岛素样生长因子II在84例多囊卵巢综合征患者颗粒细胞中的表达和促排卵结局的相关性[J]. 山东大学学报 (医学版), 2020, 58(7): 60 -66 .
[10] 徐玉香,刘煜东,张蓬,段瑞生. 101例脑小血管病患者脑微出血危险因素的回顾性分析[J]. 山东大学学报 (医学版), 2020, 58(7): 67 -71 .
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发