阿尔茨海默病的诊断与治疗

doi:10.6040/j.issn.1671-7554.0.2017.319

摘要/Abstract

摘要： 阿尔茨海默病(AD)是一种致残性、致死性很高的神经退行性疾病。随着我国人口老龄化的加剧,AD患病率逐年上升,给患者、家庭和社会带来沉重负担。目前,AD研究进展迅速,生物标志物已经逐步应用于临床诊断,并且针对β淀粉样蛋白(Aβ)、tau蛋白、胰岛素通路等的药物也正在研究中。未来,早期诊断生物标志物的应用及综合生活方式干预、药物治疗、非药物治疗的全面管理将使AD患者最大程度获益。

关键词: 阿尔茨海默病, 诊断, 标记物, 治疗

Abstract: Alzheimers disease(AD)is a disabling and fatal neurodegenerative disease. AD prevalence is rapidly increasing as the trend of aging population aggravates, which brings about great burden to patients, families and the 山东大学学报 (医学版)55卷10期 -杜怡峰,等.阿尔茨海默病的诊断与治疗 \=-society. The field of AD research is rapidly growing. Biomarkers and functional imaging are entering clinical practice. Drugs targeting Aβ, tau, insulin pathway and other pathways are under research. In the future, comprehensive therapy combing lifestyle prevention, pharmaceutical treatment and non-pharmacological interventions will bring unprecedented benefits to AD patients.

Key words: Alzheimers disease, Diagnosis, Biomarkers, Treatment

中图分类号:

R741.04

杜怡峰,井然. 阿尔茨海默病的诊断与治疗[J]. 山东大学学报（医学版）, 2017, 55(10): 7-13.

DU Yifeng, JING Ran. Diagnosis and treatment of Alzheimers disease[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 7-13.

参考文献

[1] Thies B, Truschke E, Morrison-Bogorad M. Consensus report of the Working Group on molecular and biochemical markers of Alzheimers disease[J]. Neurobiol Aging, 1999, 20(2): 247.
[2] Blennow K, Hampel H, Weiner M. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease[J]. Nat Rev Neurol, 2010, 6(3): 131-144.
[3] Hansson O, Zetterberg H, Buchhave P, et al. Association between CSF biomarkers and incipient Alzheimers disease in patients with mild cognitive impairment: a follow-up study[J]. Lancet Neurol, 2006, 5(3): 228-234.
[4] Blennow K. CSF markers for incipient Alzheimers disease[J]. Lancet Neurol, 2003, 2(10): 605-613.
[5] Mattsson N, Zetterberg H, Hansson O, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment[J]. JAMA, 2009, 302(4): 385-393.
[6] Fagan AM, Head D, Shah AR, et al. Decreased cerebrospinal fluid Abeta(42)correlates with brain atrophy in cognitively normal elderly[J]. Ann Neurol, 2009, 65(2): 176-183.
[7] Buchhave P, Minthon L, Zetterberg H, et al. Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia[J]. Arch Gen Psychiatry, 2012, 69(1): 98-106.
[8] Zetterberg H, Wilson D, Andreasson U, et al. Plasma tau levels in Alzheimers disease[J]. Alzheimers Res Ther, 2013, 5(2): 9.
[9] van Oijen M, Hofman A, Soares HD, et al. Plasma Abeta(1-40)and Abeta(1-42)and the risk of dementia: a prospective case-cohort study[J]. Lancet Neurol, 2006, 5(8): 655-660.
[10] Evin G, Barakat A. BACE: Therapeutic target and potential biomarker for Alzheimers disease[J]. Int J Biochem Cell Biol, 2010, 42(12): 1923-1926.
[11] Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia(an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology[J]. Neurology, 2001, 56(9): 1154-1166.
[12] Jack CR, Petersen RC, Xu YC, et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment[J]. Neurology, 1999, 52(7): 1397-1403.
[13] Anchisi D, Borroni B, Franceschi M, et al. Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease[J].Arch Neurol, 2005, 62(11): 1728-1733.
[14] Devanand DP, VanHeertum RL, Kegeles LS, et al.(99m)Tc hexamethyl-propylene-aminoxime single-photon emission computed tomography prediction of conversion from mild cognitive impairment to Alzheimer disease[J].Am J Geriatr Psychiatry, 2010, 18(11): 959-972.
[15] Herholz K. Clinical amyloid imaging in Alzheimers disease[J]. Lancet Neurol, 2011, 10(7): 667-670.
[16] Marchant NL, Reed BR, DeCarli CS, et al.Cerebrovascular disease, β-amyloid, and cognition in aging[J].Neurobiol Aging, 2012, 33(5): 1006.e25-36.
[17] Villemagne VL, Doré V, Bourgeat P, et al. Aβ-amyloid and tau imaging in dementia[J]. Semin Nucl Med, 2017, 47(1): 75-88.
[18] Dronse J, Fliessbach K, Bischof GN, et al. In vivo patterns of tau pathology, amyloid-β burden, and neuronal dysfunction in clinical variants of Alzheimers disease[J].J Alzheimers Dis, 2017, 55(2): 465-471.
[19] Kumar-Singh S, Theuns J, VanBroeck B, et al. Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40[J]. Hum Mutat, 2006, 27(7): 686-695.
[20] Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium[J]. JAMA, 1997, 278(16): 1349-1356.
[21] Tsolaki AC, Kosmidou V, KompatsiarisI Y, et al. Brain source localization of MMN and P300 ERPs in mild cognitive impairment and Alzheimers disease: a high-density EEG approach[J]. Neurobiol Aging, 2017, 55: 190-201.doi: 10.1016/j.neurobiolaging.2017.03.025.
[22] Shi M, Caudle WM. Biomarker discovery in neurodegenerative diseases: a proteomic approach[J]. Neurobiol Dis, 2009, 35(2): 157-164.
[23] Wong MW, Braidy N, Poljak A, et al. Dysregulation of lipids in Alzheimers disease and their role as potential biomarkers[J]. Alzheimers Dement, 2017, 13(7): 810-827.
[24] Shi M, Sui YT, Peskind ER, et al. Salivary tau species are potential biomarkers of Alzheimers disease[J]. J Alzheimers Dis, 2011, 27(2): 299-305.
[25] Zhang J, Zhang CH, Li RJ, et al. Accuracy of urinary AD7c-NTP for diagnosing Alzheimers disease: a systematic review and meta-analysis[J]. J Alzheimers Dis, 2014, 40(1): 153-159.
[26] Peng Q, Bakulski KM, Nan B. Cadmium and Alzheimers disease mortality in US adults: updated evidence with a urinary biomarker and extended follow-up time[J].Environ Res, 2017, 157: 44-51. doi: 10.1016/j.envres.2017.05.011.
[27] Mitchell AJ, Beaumont H, Ferguson D, et al. Risk of dementia and mild cognitive impairment in older people with subjective memory complaints: meta-analysis[J].Acta Psychiatr Scand, 2014, 130(6): 439-451.
[28] Armstrong R. Oculo-visual changes and clinical considerations affecting older patients with dementia[J].Ophthalmic Physiol Opt, 2015, 35(4): 352-376.
[29] Wu N, RaoX, Gao Y, et al. Amyloid-β deposition and olfactory dysfunction in an Alzheimers disease model[J].J Alzheimers Dis, 2013, 37(4): 699-712.
[30] Demnitz N, Zsoldos E, Mahmood A, et al. Associations between mobility, cognition, and brain structure in healthy older adults[J]. Front Aging Neurosci, 2017, 9: 155.doi: 10.3389/fnagi.2017.00155
[31] Hugo J. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment[J]. Clin Geriatr Med, 2014, 30(3): 421-442.
[32] Khachaturian ZS. Revised criteria for diagnosis of Alzheimers disease: National Institute on Aging-Alzheimers Association diagnostic guidelines for Alzheimers disease[J]. Alzheimers Dement, 2011, 7(3): 253-256.
[33] Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimers disease: the IWG-2 criteria[J]. Lancet Neurol, 2014, 13(6): 614-629.
[34] Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimers disease[J]. N Engl J Med, 2006, 355(15): 1525-1538.
[35] Abbott A. Failed Alzheimers trial does not kill leading theory of disease[J]. Nature, 2016, 540(7631): 15-16.
[36] Vaillancourt DE. Aducanumab reduces Aβ plaques in Alzheimers disease[J]. Mov Disord, 2016, 31(11): 1631.
[37] Ghosh AK, Osswald HL. BACE1(β-secretase)inhibitors for the treatment of Alzheimers disease[J]. Chem Soc Rev, 2014, 43(19): 6765-6813.
[38] Claxton A, Baker LD, Hanson A, et al. Long acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimers disease dementia[J]. J Alzheimers Dis, 2015, 45(4):1269-1270.
[39] Hardenacke K, Hashemiyoon R, Visser-Vandewalle V, et al. Deep brain stimulation of the nucleus basalis of meynert in Alzheimers dementia: potential predictors of cognitive change and results of a long-term follow-up in eight patients[J]. Brain Stimul, 2016, 9(5): 799-800.
[40] Spector A, Thorgrimsen L, Woods B, et al. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial[J]. Br J Psychiatry, 2003, 183: 248-254.
[41] Kivipelto M, Solomon A, Ahtiluoto S, et al. The finnish geriatric intervention study to prevent cognitive impairment and disability(FINGER): study design and progress [J]. Alzheimers Dement, 2013, 9(6): 657-665.

相关文章 15

[1]	李波波李道堂刘曙光王兴武. 食管癌患者血清中DKK-1的表达[J]. 山东大学学报(医学版), 2209, 47(6): 58-61.
[2]	徐平于国放李霞. 不同类型甲状腺上动脉PSV对Graves病与桥本氏甲状腺炎鉴别诊断的价值[J]. 山东大学学报(医学版), 2209, 47(6): 62-64.
[3]	王欣，邢春燕，杨艳平. 血清磷酸丙酮酸水合酶检测对诊断侵袭性白念珠菌感染的临床价值[J]. 山东大学学报(医学版), 2209, 47(6): 92-94.
[4]	闫鹏王蓉杜怡峰沈伦乾. 老年性痴呆患者尿中AD7c-NTP含量的研究[J]. 山东大学学报(医学版), 2209, 47(6): 106-.
[5]	巩性军，吴树明，张供，李守先，庞昕焱. 无顶冠状静脉窦综合征的诊断和外科治疗[J]. 山东大学学报(医学版), 2209, 47(6): 129-.
[6]	王凯,沈媛媛,程宪永,李彦敏,史宁. 嗜酸性粒细胞性食管炎1例并文献复习[J]. 山东大学学报 (医学版), 2020, 1(9): 119-121.
[7]	李刚,薛皓,邱伟,赵荣荣. 脑胶质瘤抑制性免疫微环境形成机制及研究进展[J]. 山东大学学报 (医学版), 2020, 1(8): 67-73.
[8]	陈安静,张训. 靶向小类泛素化修饰的胶质瘤治疗新策略[J]. 山东大学学报 (医学版), 2020, 1(8): 88-94.
[9]	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, 1(8): 14-21.
[10]	焉传祝,王伟,纪坤乾,赵玉英. 线粒体与脑疾病[J]. 山东大学学报 (医学版), 2020, 1(8): 34-41.
[11]	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, 1(7): 53-59.
[12]	路璐,孙志钢,张楠. 继发性嗜血细胞综合征1例[J]. 山东大学学报 (医学版), 2020, 1(7): 122-124.
[13]	董伟,邢乃栋,吕家驹,刘帅,孙亮,曹庆伟,董宇昊,刘钊,丁森泰. 靶向抑制有丝分裂驱动蛋白治疗多西紫杉醇耐药前列腺癌的体外疗效[J]. 山东大学学报（医学版）, 2017, 55(9): 23-30.
[14]	赵作辉,李翠玲,王道光,王风芹,曲宏懿,丁森泰,巩晶,吕家驹,杨静华. MnSOD乙酰化对肾透明细胞癌786-O细胞增殖、凋亡的影响[J]. 山东大学学报（医学版）, 2017, 55(9): 31-35.
[15]	底学敏,牛书雷,赵静,杜随,于慧敏,张宏涛,王娟. CT引导下¹²⁵I粒子植入治疗晚期胃癌淋巴结转移[J]. 山东大学学报（医学版）, 2017, 55(9): 79-84.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed