Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

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

Author(s): Yue Wang, Fanghua Lou, Yonggang Li, Fang Liu, Ying Wang, Li Cai, Marc L. Gordon, Yuanyuan Zhang and Nan Zhang*

Volume 18, Issue 6, 2021

Published on: 01 October, 2021

Page: [523 - 532] Pages: 10

DOI: 10.2174/1567205018666211001113349

open access plus

Abstract

Background: A significant proportion of patients with clinically diagnosed Alzheimer’s Disease (AD) and an even higher proportion of patients with amnestic mild cognitive impairment (aMCI) do not show evidence of amyloid deposition on Positron Emission Tomography (PET) with amyloid-binding tracers such as 11C-labeled Pittsburgh Compound B (PiB).

Objective: This study aimed to identify clinical, neuropsychological and neuroimaging factors that might suggest amyloid neuropathology in patients with clinically suspected AD or aMCI.

Methods: Forty patients with mild to moderate AD and 23 patients with aMCI who were clinically diagnosed in our memory clinic and had PiB PET scans were included. Clinical, neuropsychological, and imaging characteristics, such as Medial Temporal lobe Atrophy (MTA) and White Matter Hyperintensities (WMH) on MRI and metabolic pattern on 18F-labeled fluorodeoxyglucose (FDG) PET, were compared between patients with PiB positive and negative PET results for AD, aMCI, and all subjects combined, respectively.

Results: Compared with PiB positive patients, PiB negative patients had a higher prevalence of hypertension history, better performance on the Mini-Mental State Examination, the Rey Auditory Verbal Learning Test, and the Judgement of Line Orientation, lower score of MTA, and were less likely to have temporoparietal-predominant hypometabolism on FDG PET. Affective symptoms were less common in PiB negative patients diagnosed with AD, and the Animal Fluency Test score was higher in PiB negative patients diagnosed with aMCI.

Conclusion: In patients with clinically diagnosed AD or aMCI, absence of a history of hypertension, deficits in verbal learning and memory, visuospatial function, semantic verbal fluency, presence of affective symptoms, MTA on MRI, and temporoparietal hypometabolism on FDG PET suggested amyloid deposition in the brain.

Keywords: Alzheimer's disease, amnestic mild cognitive impairment, amyloid PET, PiB, cognitive function, neuropsychiatric symptoms, medial temporal lobe atrophy, 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]

© 2024 Bentham Science Publishers | Privacy Policy