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Current Alzheimer Research


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

Research Article

PET-Amyloid After Inconclusive Cerebrospinal Fluid Biomarkers in Clinical Practice. Is it Necessary to Duplicate Procedures?

Author(s): Ismael Carrera-Muñoz, Lucía Triguero-Cueva, Juan C. Romero-Fábrega, Eva M. Triviño-Ibáñez*, Rosa Vilchez-Carrillo, Cristóbal Carnero-Pardo and Manuel Gómez-Río

Volume 17 , Issue 8 , 2020

Page: [698 - 708] Pages: 11

DOI: 10.2174/1567205017666201109092637

Price: $65


Introduction: In the absence of a gold standard for in vivo Alzheimer disease (AD) diagnosis, AD biomarkers such as cerebrospinal fluid biomarkers (CSF-B) and PET-Amyloid are considered diagnostically useful in clinical practice guidelines and have consensual appropriate use criteria (AUC). However, little evidence has been published on their utilization in the clinical setting or on approaches to mismatched results. The objective of this work was to evaluate the use of AD biomarkers in clinical practice, focusing on the implementation of PET-Amyloid in cases of inconclusive CSF-B.

Methods: This naturalistic, ambispective case series included patients fulfilling AUC for CSF-B and PET-Amyloid whose CSF-B results were non-diagnostic (target population), analyzing the diagnostic certainty, the treatment approach, and the relationship between CSF-B and PET-Amyloid results.

Results: Out of 2373 eligible patients, AD biomarkers were studied in 417 (17.6%), most frequently due to cognitive impairment in under 65-year-olds, using CSF-B in 311 patients and PET-Amyloid in 150. CSF-B results were non-diagnostic for 44 patients (52.3% male; aged 60.9±6.6 years), who then underwent PET-Amyloid study, which was positive in 31. A ‘k’ coefficient of 0.108 was obtained between CSF-B and PET-amyloid (54.5% concordance). In multivariate regression analysis, Aβ42 was the only significant predictor (p= 0.018) of a positive PET-Amyloid result. In the target population, PETAmyloid increased diagnostic confidence by 53.7% (p <0.001) and modified the therapeutic approach in 36.4% of cases.

Conclusion: These findings support the duplication of AD biomarkers and demonstrate that the implementation of PET-Amyloid provides an early and certain diagnosis to guide appropriate treatment.

Keywords: Mild cognitive impairment, Alzheimer disease, Alzheimer disease biomarkers, Alzheimer diagnosis imaging, Alzheimer cerebrospinal fluid, amyloid positron emission tomography, appropriate use criteria, clinical utility.

Alzheimer's Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 2016; 12(4): 459-509.
[] [PMID: 27570871]
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.
[] [PMID: 21514250]
Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol 2012; 71(4): 266-73.
[] [PMID: 22437338]
Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement 2015; 11(1): 58-69.
[] [PMID: 24795085]
Atri A. The Alzheimer’s disease clinical spectrum diagnosis and management. Med Clin North Am 2019; 103(2): 263-93.
[] [PMID: 30704681]
Jack CR Jr, Bennett DA, Blennow K, et al. Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018; 14(4): 535-62.
[] [PMID: 29653606]
Jack CR Jr, Bennett DA, Blennow K, et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016; 87(5): 539-47.
[] [PMID: 27371494]
Johnson KA, Minoshima S, Bohnen NI, et al. Alzheimer’s association, society of nuclear medicine and molecular imaging, amyloid imaging taskforce. Appropriate use criteria for amyloid PET: A report of the amyloid imaging task force, the society of nuclear medicine and molecular imaging, and the Alzheimer’s association. Alzheimers Dement 2013; 9: e-1-e-16.
Hornberger J, Bae J, Watson I, Johnston J, Happich M. Clinical and cost implications of amyloid beta detection with amyloid beta positron emission tomography imaging in early Alzheimer’s disease - the case of florbetapir. Curr Med Res Opin 2017; 33(4): 675-85.
[] [PMID: 28035842]
Hansson O, Mikulskis A, Fagan AM, et al. The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer’s disease diagnosis: A review. Alzheimers Dement 2018; 14(10): 1313-33.
[] [PMID: 29940161]
Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst) 2017; 8: 111-26.
[] [PMID: 28603768]
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.
[] [PMID: 24849862]
Shaw LM, Arias J, Blennow K, et al. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimers Dement 2018; 14(11): 1505-21.
[] [PMID: 30316776]
Ceccaldi M, Jonveaux T, Verger A, et al. NEUUS in AD study group. Added value of 18F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study. Alzheimers Dement 2018; 14(3): 293-305.
[] [PMID: 29107051]
Triviño-Ibáñez EM, Sánchez-Vañó R, Sopena-Novales P, et al. Impact of amyloid-PET in daily clinical management of patients with cognitive impairment fulfilling appropriate use criteria. Medicine (Baltimore) 2019; 98(29)e16509
[] [PMID: 31335725]
(a)Martínez G, Vernooij RWM, Fuentes Padilla P, Zamora J, Flicker L, Bonfill Cosp X. 18F PET with flutemetamol for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2017; (11): CD012884
[] ; (b)Martínez G, Vernooij RWM, Fuentes Padilla P, Zamora J, Flicker L, Bonfill Cosp X. 18F PET with florbetaben for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2017; (11): CD012883
[] ; (c)Martínez G, Vernooij RWM, Fuentes Padilla P, Zamora J, Bonfill Cosp X, Flicker L. 18F PET with florbetapir for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2017; (11): CD012216
[] ; (d)Zhang S, Smailagic N, Hyde C, et al. (11)C-PIB-PET for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2014; (7): CD010386
[] [PMID: 25052054]
Colective Proceso Asistencial Integrado. Demencia (PAI). Sevilla: Conserjería de Salud 2002.
Lendínez A, Zunzunegui MV, Iribar C, Carnero-Pardo C, González-Maldonado R. Validación de constructo de la batería abreviada Granada de evaluación neuropsicológica. Rev Mult Gerontol 2000; 10(3): 152-7.
Carnero Pardo C, Sáez-Zea C, Montiel Navarro L, et al. Diagnostic accuracy of the Phototest for cognitive impairment and dementia. Neurologia 2007; 22(10): 860-9.
[PMID: 18040903]
Herukka SK, Simonsen AH, Andreasen N, et al. Recommendations for cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic evaluation of mild cognitive impairment. Alzheimers Dement 2017; 13(3): 285-95.
[] [PMID: 28341066]
Minoshima S, Drzezga AE, Barthel H, et al. SNMMI procedure standard/EANM practice guideline for amyloid PET imaging of the brain 1.0. J Nucl Med 2016; 57(8): 1316-22.
[] [PMID: 27481605]
Sabri O, Seibyl J, Rowe C, Barthel H. Beta-amyloid imaging with florbetaben.Clin Transl Imaging 3 (1):13-26 (2015)J Alzheimers Dis 2020; 73(2): 559-69.
[PMID: 31796674]
Reimand J, Groot C, Teunissen CE, et al. Why is amyloid-β PET requested after performing CSF biomarkers? J Alzheimers Dis 2020; 73(2): 559-69.
[] [PMID: 31796674]
Vos SJ, Visser PJ, Verhey F, et al. Variability of CSF Alzheimer’s disease biomarkers: Implications for clinical practice. PLoS One 2014; 9(6)e100784
[] [PMID: 24959687]
Müller EG, Edwin TH, Stokke C, et al. Amyloid-β PET-Correlation with cerebrospinal fluid biomarkers and prediction of Alzheimer’s disease diagnosis in a memory clinic. PLoS One 2019; 14(8)e0221365
[] [PMID: 31430334]
Morbelli S, Bauckneht M, Scheltens P. Imaging biomarkers in Alzheimer’s disease: Added value in the clinical setting. Q J Nucl Med Mol Imaging 2017; 61(4): 360-71.
[PMID: 28750495]
de Wilde A, Reimand J, Teunissen CE, et al. Discordant amyloid-β PET and CSF biomarkers and its clinical consequences. Alzheimers Res Ther 2019; 11(1): 78.
[] [PMID: 31511058]
Lehmann S, Teunissen CE. Editorial: Biomarkers of Alzheimer’s dis-ease: The present and the future. Front Neurol 2016; 7: 158.
[] [PMID: 27729897]
Mattsson N, Andreasson U, Persson S, et al. The Alzheimer’s association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement 2011; 7(4): 386-95.
Carrillo MC, Blennow K, Soares H, et al. Global standardization measurement of cerebral spinal fluid for Alzheimer’s disease: an update from the Alzheimer’s Association Global Biomarkers Consortium. Alzheimers Dement 2013; 9(2): 137-40.
[] [PMID: 23274154]
Reimand J, de Wilde A, Teunissen CE, et al. PET and CSF amyloid-β status are differently predicted by patient features: Information from discordant cases. Alzheimers Res Ther 2019; 11(1): 100.
[] [PMID: 31810489]
Sauveé M. DidierLaurent G, Latarchec C, Escanyé M, Olivier J, Malaplate-Armand C. Additional use of A42/A40 ratio with cerebrospinal fluid biomarkers P-Tau and A42 increases the level of evidence of Alzheimer’s disease pathophysiological process in routine practice. J Alzheimers Dis 2014; 41(2): 377-86.
[] [PMID: 24614902]
Lewczuk P, Matzen A, Blennow K, et al. Cerebrospinal fluid Abeta 42/40 corresponds better than Abeta42 to amiloide PET in Alzheimer Disease. J Alzheimers Dis 2017; 55(2): 813-22.
[] [PMID: 27792012]
Dorey A, Perret-Liaudet A, Tholance Y, Fourier A, Quadrio I. Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. Front Neurol 2015; 6(247): 247.
[] [PMID: 26640457]
Janelidze S, Zetterberg H, Mattsson N, et al. Swedish BioFINDER study group. CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: Better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol 2016; 3(3): 154-65.
[] [PMID: 27042676]
Palmqvist S, Zetterberg H, Blennow K, et al. Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid β-amyloid 42: A cross-validation study against amyloid positron emission tomography. JAMA Neurol 2014; 71(10): 1282-9.
[] [PMID: 25155658]
Hansson O, Seibyl J, Stomrud E, et al. Swedish BioFINDER study group; Alzheimer’s Disease Neuroimaging Initiative. CSF biomarkers of Alzheimer’s disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement 2018; 14(11): 1470-81.
[] [PMID: 29499171]
Kaplow J, Vandijck M, Gray J, et al. Concordance of Lumipulse cerebrospinal fluid t-tau/Aβ42 ratio with amyloid PET status. Alzheimers Dement 2020; 16(1): 144-52.
[] [PMID: 31914216]
Zwan MD, Rinne JO, Hasselbalch SG, et al. Use of amyloid-PET to determine cutpoints for CSF markers: A multicenter study. Neurology 2016; 86(1): 50-8.
[] [PMID: 26468410]
Pontecorvo MJ, Siderowf A, Dubois B, et al. Effectiveness of florbetapir PET imaging in changing patient management. Dement Geriatr Cogn Disord 2017; 44(3-4): 129-43.
[] [PMID: 28787712]
Weidman DA, Zamrini E, Sabbagh MN, et al. Added value and limitations of amyloid-PET imaging: Review and analysis of selected cases of mild cognitive impairment and dementia. Neurocase 2017; 23(1): 41-51.
[] [PMID: 28376695]
Apostolova LG, Haider JM, Goukasian N, et al. Critical review of the appropriate use criteria for amyloid imaging: Effect on diagnosis and patient care. Alzheimers Dement (Amst) 2016; 5: 15-22.
[] [PMID: 28054024]
Paterson RW, Toombs J, Slattery CF, et al. Dissecting IWG-2 typical and atypical Alzheimer’s disease: Insights from cerebrospinal fluid analysis. J Neurol 2015; 262(12): 2722-30.
[] [PMID: 26410752]
Winblad B, Amouyel P, Andrieu S, et al. Defeating Alzheimer’s disease and other dementias: A priority for European science and society. Lancet Neurol 2016; 15(5): 455-532.
[] [PMID: 26987701]

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