Clinical, Neuropsychological, and Neuroimaging Characteristics of Amyloid- positive vs. Amyloid-negative Patients with Clinically Diagnosed Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

doi:10.2174/1567205018666211001113349

摘要

背景：临床诊断为阿尔茨海默病 (AD) 的很大一部分患者和更高比例的遗忘型轻度认知障碍 (aMCI) 患者在使用淀粉样蛋白结合示踪剂的正电子发射断层扫描 (PET) 上未显示淀粉样蛋白沉积的证据，例如作为 11C 标记的匹兹堡化合物 B (PiB)。目的：本研究旨在确定可能提示临床疑似 AD 或 aMCI 患者出现淀粉样蛋白神经病理学的临床、神经心理学和神经影像学因素。方法：包括在我们的记忆诊所临床诊断并进行 PiB PET 扫描的 40 名轻度至中度 AD 患者和 23 名 aMCI 患者。比较 PiB 阳性和阴性 PET 结果患者的临床、神经心理学和影像学特征，例如 MRI 上的内侧颞叶萎缩 (MTA) 和白质高信号 (WMH) 以及 18F 标记的氟脱氧葡萄糖 (FDG) PET 上的代谢模式分别用于 AD、aMCI 和所有科目的组合。结果：与 PiB 阳性患者相比，PiB 阴性患者有更高的高血压病史，在简易精神状态检查、Rey 听觉语言学习测试和线路定向判断方面的表现更好，MTA 得分较低，并且在 FDG PET 上不太可能出现颞顶为主的低代谢。在诊断为 AD 的 PiB 阴性患者中，情感症状不太常见，而在诊断为 aMCI 的 PiB 阴性患者中，动物流畅性测试得分较高。结论：在临床诊断为 AD 或 aMCI 的患者中，没有高血压病史、语言学习和记忆缺陷、视觉空间功能、语义语言流畅性、情感症状的存在、MRI 上的 MTA 和 FDG PET 上的颞顶代谢减退提示淀粉样蛋白沉积在大脑中。

关键词: 阿尔茨海默病、遗忘性轻度认知障碍、淀粉样蛋白 PET、PiB、认知功能、神经精神症状、内侧颞叶萎缩、FDG PET。

« Previous

[1] 
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. Lancet Neurol  2016; 18: 88-106.
[http://dx.doi.org/10.1016/S1474-4422(18)30403-4] 
[2] 
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement  2018; 14(4): 535-62.
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606] 
[3] 
Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: The IWG-2 criteria. Lancet Neurol  2014; 13(6): 614-29.
[http://dx.doi.org/10.1016/S1474-4422(14)70090-0] [PMID: 24849862] 
[4] 
Nordberg A, Carter SF, Rinne J, et al. A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease. Eur J Nucl Med Mol Imaging  2013; 40(1): 104-14.
[http://dx.doi.org/10.1007/s00259-012-2237-2] [PMID: 22961445] 
[5] 
Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol  2004; 55(3): 306-19.
[http://dx.doi.org/10.1002/ana.20009] [PMID: 14991808] 
[6] 
Ossenkoppele R, Jansen WJ, Rabinovici GD, et al. Prevalence of amyloid PET positivity in dementia syndromes: A meta-analysis. JAMA  2015; 313(19): 1939-49.
[http://dx.doi.org/10.1001/jama.2015.4669] [PMID: 25988463] 
[7] 
Jagust WJ, Bandy D, Chen K, et al. The Alzheimer’s disease neuroimaging initiative positron emission tomography core. Alzheimers Dement  2010; 6(3): 221-9.
[http://dx.doi.org/10.1016/j.jalz.2010.03.003] [PMID: 20451870] 
[8] 
Chételat G, Ossenkoppele R, Villemagne VL, et al. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer’s disease. Brain  2016; 139(Pt 9): 2528-39.
[http://dx.doi.org/10.1093/brain/aww159] [PMID: 27357349] 
[9] 
Ossenkoppele R, Prins ND, Pijnenburg YA, et al. Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement  2013; 9(4): 414-21.
[http://dx.doi.org/10.1016/j.jalz.2012.07.003] [PMID: 23164552] 
[10] 
Wolk DA, Price JC, Saxton JA, et al. Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol  2009; 65(5): 557-68.
[http://dx.doi.org/10.1002/ana.21598] [PMID: 19475670] 
[11] 
Rabinovici GD, Gatsonis C, Apgar C, et al. Association of amyloid positron emission tomography with subsequent change in clinical management among medicare beneficiaries with mild cognitive impairment or dementia. JAMA  2019; 321(13): 1286-94.
[http://dx.doi.org/10.1001/jama.2019.2000] [PMID: 30938796] 
[12] 
Boccardi M, Altomare D, Ferrari C, et al. Assessment of the incremental diagnostic value of florbetapir F 18 imaging in patients with cognitive impairment: The incremental diagnostic value of amyloid PET with [18F]-Florbetapir (INDIA-FBP) study. JAMA Neurol  2016; 73(12): 1417-24.
[http://dx.doi.org/10.1001/jamaneurol.2016.3751] [PMID: 27802513] 
[13] 
Whitwell JL, Przybelski SA, Weigand SD, et al. 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer’s disease. Brain  2007; 130(Pt 7): 1777-86.
[http://dx.doi.org/10.1093/brain/awm112] [PMID: 17533169] 
[14] 
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement  2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250] 
[15] 
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med  2004; 256(3): 183-94.
[http://dx.doi.org/10.1111/j.1365-2796.2004.01388.x] [PMID: 15324362] 
[16] 
Wang Y, Shi Z, Zhang N, et al. Spatial patterns of hypometabolism and amyloid deposition in variants of Alzheimer’s disease corresponding to brain networks: A prospective cohort study. Mol Imaging Biol  2019; 21(1): 140-8.
[http://dx.doi.org/10.1007/s11307-018-1219-6] [PMID: 29869063] 
[17] 
Zhang N, Zhang L, Li Y, et al. Urine AD7c-NTP predicts amyloid deposition and symptom of agitation in patients with Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis  2017; 60(1): 87-95.
[http://dx.doi.org/10.3233/JAD-170383] [PMID: 28777752] 
[18] 
Kato T, Inui Y, Nakamura A, Ito K. Brain fluorodeoxyglucose (FDG) PET in dementia. Ageing Res Rev  2016; 30: 73-84.
[http://dx.doi.org/10.1016/j.arr.2016.02.003] [PMID: 26876244] 
[19] 
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res  1975; 12(3): 189-98.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204] 
[20] 
Rey A. L’examen clinique in psychologie. Paris: Presses Universitaire de France 1964.
[21] 
Benton AL, Varney NR, Hamsher KD. Visuospatial judgment. A clinical test. Arch Neurol  1978; 35(6): 364-7.
[http://dx.doi.org/10.1001/archneur.1978.00500300038006] [PMID: 655909] 
[22] 
Rosen WG. Verbal fluency in aging and dementia. J Clin Neuropsychol  1980; 2: 135-46.
[http://dx.doi.org/10.1080/01688638008403788] 
[23] 
Kaplan EF, Goodglass H, Weintraub S. The Boston Naming Test.  2nd ed. Philadelphia: Lea & Febiger 1983.
[24] 
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The neuropsychiatric inventory: Comprehensive assessment of psychopathology in dementia. Neurology  1994; 44(12): 2308-14.
[http://dx.doi.org/10.1212/WNL.44.12.2308] [PMID: 7991117] 
[25] 
Liew TM. Symptom clusters of neuropsychiatric symptoms in mild cognitive impairment and their comparative risks of dementia: A cohort study of 8530 older persons. J Am Med Dir Assoc  2019; 20(8): 1054.e1-9.
[http://dx.doi.org/10.1016/j.jamda.2019.02.012] [PMID: 30926409] 
[26] 
Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: Diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry  1992; 55(10): 967-72.
[http://dx.doi.org/10.1136/jnnp.55.10.967] [PMID: 1431963] 
[27] 
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol  1987; 149(2): 351-6.
[http://dx.doi.org/10.2214/ajr.149.2.351] [PMID: 3496763] 
[28] 
Landau SM, Horng A, Fero A, Jagust WJ. Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI. Neurology  2016; 86(15): 1377-85.
[http://dx.doi.org/10.1212/WNL.0000000000002576] [PMID: 26968515] 
[29] 
Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the atherosclerosis risk in communities (ARIC) cohort. JAMA Neurol  2017; 74(10): 1246-54.
[http://dx.doi.org/10.1001/jamaneurol.2017.1658] [PMID: 28783817] 
[30] 
Javanshiri K, Waldö ML, Friberg N, et al. Atherosclerosis, hypertension, and diabetes in Alzheimer’s disease, vascular dementia, and mixed dementia: Prevalence and presentation. J Alzheimers Dis  2018; 65(4): 1247-58.
[http://dx.doi.org/10.3233/JAD-180644] [PMID: 30149459] 
[31] 
Iadecola C, Gottesman RF. Neurovascular and cognitive dysfunction in Hypertension. Circ Res  2019; 124(7): 1025-44.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313260] [PMID: 30920929] 
[32] 
Gottesman RF, Schneider AL, Zhou Y, et al. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA  2017; 317(14): 1443-50.
[http://dx.doi.org/10.1001/jama.2017.3090] [PMID: 28399252] 
[33] 
Zhao Q, Guo Q, Liang X, et al. Auditory verbal learning test is superior to rey-osterrieth complex figure memory for predicting mild cognitive impairment to Alzheimer’s disease. Curr Alzheimer Res  2015; 12(6): 520-6.
[http://dx.doi.org/10.2174/1567205012666150530202729] [PMID: 26027810] 
[34] 
Estévez-González A, Kulisevsky J, Boltes A, Otermín P, García-Sánchez C. Rey verbal learning test is a useful tool for differential diagnosis in the preclinical phase of Alzheimer’s disease: Comparison with mild cognitive impairment and normal aging. Int J Geriatr Psychiatry  2003; 18(11): 1021-8.
[http://dx.doi.org/10.1002/gps.1010] [PMID: 14618554] 
[35] 
Balthazar ML, Yasuda CL, Cendes F, Damasceno BP. Learning, retrieval, and recognition are compromised in aMCI and mild AD: Are distinct episodic memory processes mediated by the same anatomical structures? J Int Neuropsychol Soc  2010; 16(1): 205-9.
[http://dx.doi.org/10.1017/S1355617709990956] [PMID: 19835661] 
[36] 
Putcha D, Brickhouse M, Wolk DA, Dickerson BC. Fractionating the rey auditory verbal learning test: Distinct roles of large-scale cortical networks in prodromal Alzheimer’s disease. Neuropsychologia  2019; 129: 83-92.
[http://dx.doi.org/10.1016/j.neuropsychologia.2019.03.015] [PMID: 30930301] 
[37] 
Ricci M, Graef S, Blundo C, Miller LA. Using the rey auditory verbal learning test (RAVLT) to differentiate Alzheimer’s dementia and behavioural variant fronto-temporal dementia. Clin Neuropsychol  2012; 26(6): 926-41.
[http://dx.doi.org/10.1080/13854046.2012.704073] [PMID: 22809061] 
[38] 
Wolk DA, Dickerson BC. Fractionating verbal episodic memory in Alzheimer’s disease. Neuroimage  2011; 54(2): 1530-9.
[http://dx.doi.org/10.1016/j.neuroimage.2010.09.005] [PMID: 20832485] 
[39] 
Sutin AR, Stephan Y, Terracciano A. Verbal fluency and risk of dementia. Int J Geriatr Psychiatry  2019; 34(6): 863-7.
[http://dx.doi.org/10.1002/gps.5081] [PMID: 30729575] 
[40] 
Ska B, Poissant A, Joanette Y. Line orientation judgment in normal elderly and subjects with dementia of Alzheimer’s type. J Clin Exp Neuropsychol  1990; 12(5): 695-702.
[http://dx.doi.org/10.1080/01688639008401012] [PMID: 2258431] 
[41] 
Ismail Z, Smith EE, Geda Y, et al. Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement  2016; 12(2): 195-202.
[http://dx.doi.org/10.1016/j.jalz.2015.05.017] [PMID: 26096665] 
[42] 
Ruthirakuhan M, Herrmann N, Vieira D, Gallagher D, Lanctôt KL. The roles of apathy and depression in predicting Alzheimer disease: A longitudinal analysis in older adults with mild cognitive impairment. Am J Geriatr Psychiatry  2019; 27(8): 873-82.
[http://dx.doi.org/10.1016/j.jagp.2019.02.003] [PMID: 30910421] 
[43] 
Sugarman MA, Alosco ML, Tripodis Y, Steinberg EG, Stern RA. Neuropsychiatric symptoms and the diagnostic stability of mild cognitive impairment. J Alzheimers Dis  2018; 62(4): 1841-55.
[http://dx.doi.org/10.3233/JAD-170527] [PMID: 29614641] 
[44] 
Mori T, Shimada H, Shinotoh H, et al. Apathy correlates with prefrontal amyloid β deposition in Alzheimer’s disease. J Neurol Neurosurg Psychiatry  2014; 85(4): 449-55.
[http://dx.doi.org/10.1136/jnnp-2013-306110] [PMID: 24133289] 
[45] 
Johnson DK, Watts AS, Chapin BA, Anderson R, Burns JM. Neuropsychiatric profiles in dementia. Alzheimer Dis Assoc Disord  2011; 25(4): 326-32.
[http://dx.doi.org/10.1097/WAD.0b013e31820d89b6] [PMID: 22086220] 
[46] 
Tsuno N, Homma A. What is the association between depression and Alzheimer’s disease? Expert Rev Neurother  2009; 9(11): 1667-76.
[http://dx.doi.org/10.1586/ern.09.106] [PMID: 19903025] 
[47] 
Squire LR, Wixted JT. The cognitive neuroscience of human memory since H.M. Annu Rev Neurosci  2011; 34: 259-88.
[http://dx.doi.org/10.1146/annurev-neuro-061010-113720] [PMID: 21456960] 
[48] 
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS-ADRDA criteria. Lancet Neurol  2007; 6(8): 734-46.
[http://dx.doi.org/10.1016/S1474-4422(07)70178-3] [PMID: 17616482] 
[49] 
Harper L, Fumagalli GG, Barkhof F, et al. MRI visual rating scales in the diagnosis of dementia: Evaluation in 184 post-mortem confirmed cases. Brain  2016; 139(Pt 4): 1211-25.
[http://dx.doi.org/10.1093/brain/aww005] [PMID: 26936938] 
[50] 
Biesbroek JM, Weaver NA, Biessels GJ. Lesion location and cognitive impact of cerebral small vessel disease. Clin Sci (Lond)  2017; 131(8): 715-28.
[http://dx.doi.org/10.1042/CS20160452] [PMID: 28385827] 
[51] 
Lee S, Viqar F, Zimmerman ME, et al. White matter hyperintensities are a core feature of Alzheimer’s disease: Evidence from the dominantly inherited Alzheimer network. Ann Neurol  2016; 79(6): 929-39.
[http://dx.doi.org/10.1002/ana.24647] [PMID: 27016429] 
[52] 
Hoffman JM, Welsh-Bohmer KA, Hanson M, et al. FDG PET imaging in patients with pathologically verified dementia. J Nucl Med  2000; 41(11): 1920-8.
[PMID: 11079505] 
[53] 
Silverman DH, Small GW, Chang CY, et al. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. JAMA  2001; 286(17): 2120-7.
[http://dx.doi.org/10.1001/jama.286.17.2120] [PMID: 11694153] 
[54] 
Drzezga A, Grimmer T, Riemenschneider M, et al. Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. J Nucl Med  2005; 46(10): 1625-32.
[PMID: 16204712] 

Rights & Permissions Print Cite

Article Metrics

30

1

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1567205018666211001113349	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828

当代阿耳茨海默病研究

淀粉样蛋白阳性与淀粉样蛋白阴性临床诊断为阿尔茨海默病和遗忘性轻度认知障碍患者的临床、神经心理学和神经影像学特征

摘要

当代阿耳茨海默病研究

淀粉样蛋白阳性与淀粉样蛋白阴性临床诊断为阿尔茨海默病和遗忘性轻度认知障碍患者的临床、神经心理学和神经影像学特征

摘要 Play Pause

Related Journals

Related Books

Related Articles

摘要