Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
EJNMMI Research
Published in: EJNMMI Research 1/2013

Open Access 01-12-2013 | Original research

Cortical florbetapir-PET amyloid load in prodromal Alzheimer’s disease patients

Authors: Laure Saint-Aubert, Emmanuel J Barbeau, Patrice Péran, Federico Nemmi, Celine Vervueren, Helene Mirabel, Pierre Payoux, Anne Hitzel, Fabrice Bonneville, Raluca Gramada, Mathieu Tafani, Christian Vincent, Michele Puel, Sophie Dechaumont, Francois Chollet, Jeremie Pariente

Published in: EJNMMI Research | Issue 1/2013

Login to get access

Abstract

Background

Florbetapir (AV-45) has been shown to be a reliable tool to assess amyloid load in patients with Alzheimer's disease (AD) at demential stages. Longitudinal studies also suggest that AV-45 has the ability to bind amyloid in the early stages of AD. In this study, we investigated AV-45 binding and its relation with cognitive performance in a group of patients at the prodromal stage of Alzheimer's disease, recruited according to strict inclusion criteria.

Methods

We recruited patients at the prodromal stage of AD and matched control subjects. AV-45 binding was assessed using an innovative extraction method allowing quantifying uptake in the cortex only. AV-45 uptake was compared between groups in the precuneus, posterior cingulate, anterior cingulate, and orbito-frontal regions. Correlations between AV-45 uptake and cognitive performance were assessed.

Results

Twenty-two patients and 17 matched control subjects were included in the study. We report a significant increase of cortical AV-45 uptake in the patients compared to the control subjects in all regions of interest. Specific correlations were found within the patient group between mean global amyloid cortical load and cognitive performance in three different memory tests.

Conclusions

These findings suggest that at the prodromal stage of AD, memory decline is linked to an increase of cortical β-amyloid load.
Appendix
Available only for authorised users
Literature
1.
Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P: Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 2010, 9: 1118–1127. 10.1016/S1474-4422(10)70223-4CrossRefPubMed
2.
Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P: Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007, 6: 734–746. 10.1016/S1474-4422(07)70178-3CrossRefPubMed
3.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH: 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: 263–269. 10.1016/j.jalz.2011.03.005CrossRefPubMedPubMedCentral
4.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH: The diagnosis of mild cognitive impairment 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: 270–279. 10.1016/j.jalz.2011.03.008CrossRefPubMedPubMedCentral
5.
Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosen E, Aarsland D, Visser PJ, Schroder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttila T, Wallin A, Jonhagen ME, Minthon L, Winblad B, Blennow K: CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009, 302: 385–393. 10.1001/jama.2009.1064CrossRefPubMed
6.
Wiltfang J, Esselmann H, Bibl M, Hull M, Hampel H, Kessler H, Frolich L, Schroder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P: Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem 2007, 101: 1053–1059. 10.1111/j.1471-4159.2006.04404.xCrossRefPubMed
7.
Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, Brewer JB, Dale AM: CSF biomarkers in prediction of cerebral and clinical change in mild cognitive impairment and Alzheimer’s disease. J Neurosci 2010, 30: 2088–2101. 10.1523/JNEUROSCI.3785-09.2010CrossRefPubMedPubMedCentral
8.
Kemppainen NM, Aalto S, Karrasch M, Nagren K, Savisto N, Oikonen V, Viitanen M, Parkkola R, Rinne JO: Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol 2008, 63: 112–118. 10.1002/ana.21212CrossRefPubMed
9.
Wolk DA, Zhang Z, Boudhar S, Clark CM, Pontecorvo MJ, Arnold SE: Amyloid imaging in Alzheimer’s disease: comparison of florbetapir and Pittsburgh compound-B positron emission tomography. J Neurol Neurosurg Psychiatry 2012, 83: 923–926. 10.1136/jnnp-2012-302548CrossRefPubMedPubMedCentral
10.
Fleisher AS, Chen K, Liu X, Roontiva A, Thiyyagura P, Ayutyanont N, Joshi AD, Clark CM, Mintun MA, Pontecorvo MJ, Doraiswamy PM, Johnson KA, Skovronsky DM, Reiman EM: Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol 2011, 68: 1404–1411. 10.1001/archneurol.2011.150CrossRefPubMed
11.
Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, Dannals RF, Nandi A, Brasic JR, Ye W, Hilton J, Lyketsos C, Kung HF, Joshi AD, Skovronsky DM, Pontecorvo MJ: In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med 2010, 51: 913–920. 10.2967/jnumed.109.069088CrossRefPubMedPubMedCentral
12.
Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, Pontecorvo MJ, Hefti F, Carpenter AP, Flitter ML, Krautkramer MJ, Kung HF, Coleman RE, Doraiswamy PM, Fleisher AS, Sabbagh MN, Sadowsky CH, Reiman PE, Zehntner SP, Skovronsky DM: Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 2011, 305: 275–283. 10.1001/jama.2010.2008CrossRefPubMed
13.
Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, Lopresti BJ, Ziolko S, Bi W, Paljug WR, Debnath ML, Hope CE, Isanski BA, Hamilton RL, DeKosky ST: Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 2008, 131: 1630–1645. 10.1093/brain/awn016CrossRefPubMedPubMedCentral
14.
Saint-Aubert L, Payoux P, Hannequin D, Barbeau EJ, Campion D, Delisle MB, Tafani M, Viallard G, Peran P, Puel M, Chollet F, Demonet JF, Pariente J: MR, 18F-FDG, and 18F-AV45 PET correlate with AD PSEN1 original phenotype. Alzheimer Dis Assoc Disord 2012, 27: 91–94.CrossRef
15.
Saint-Aubert L, Planton M, Hannequin D, Albucher JF, Delisle MB, Payoux P, Hitzel A, Viallard G, Peran P, Campion D, Laquerriere A, Barbeau EJ, Puel M, Raposo N, Chollet F, Pariente J: Amyloid imaging with AV45 ((18)F-florbetapir) in a cognitively normal AbetaPP duplication carrier. J Alzheimers Dis 2012, 28: 877–883.PubMed
16.
Doraiswamy PM, Sperling RA, Coleman RE, Johnson KA, Reiman EM, Davis MD, Grundman M, Sabbagh MN, Sadowsky CH, Fleisher AS, Carpenter A, Clark CM, Joshi AD, Mintun MA, Skovronsky DM, Pontecorvo MJ: Amyloid-beta assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study. Neurology 2012, 79: 1636–1644. 10.1212/WNL.0b013e3182661f74CrossRefPubMed
17.
Fleisher AS, Chen K, Liu X, Ayutyanont N, Roontiva A, Thiyyagura P, Protas H, Joshi AD, Sabbagh M, Sadowsky CH, Sperling RA, Clark CM, Mintun MA, Pontecorvo MJ, Coleman RE, Doraiswamy PM, Johnson KA, Carpenter AP, Skovronsky DM, Reiman EM: Apolipoprotein E epsilon4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiol Aging 2012, 34: 1–12.CrossRefPubMed
18.
Johnson KA, Sperling RA, Gidicsin CM, Carmasin JS, Maye JE, Coleman RE, Reiman EM, Sabbagh MN, Sadowsky CH, Fleisher AS, Murali Doraiswamy P, Carpenter AP, Clark CM, Joshi AD, Lu M, Grundman M, Mintun MA, Pontecorvo MJ, Skovronsky DM: Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer’s disease dementia, mild cognitive impairment, and normal aging. Alzheimers Dement in press
19.
La Joie R, Perrotin A, Barre L, Hommet C, Mezenge F, Ibazizene M, Camus V, Abbas A, Landeau B, Guilloteau D, de La Sayette V, Eustache F, Desgranges B, Chetelat G: Region-specific hierarchy between atrophy, hypometabolism, and beta-amyloid (Abeta) load in Alzheimer’s disease dementia. J Neurosci 2012, 32: 16265–16273. 10.1523/JNEUROSCI.2170-12.2012CrossRefPubMed
20.
Rodrigue KM, Kennedy KM, Devous MD Sr, Rieck JR, Hebrank AC, Diaz-Arrastia R, Mathews D: Park DC: beta-Amyloid burden in healthy aging: regional distribution and cognitive consequences. Neurology 2012, 78: 387–395. 10.1212/WNL.0b013e318245d295CrossRefPubMedPubMedCentral
21.
Sperling RA, Johnson KA, Doraiswamy PM, Reiman EM, Fleisher AS, Sabbagh MN, Sadowsky CH, Carpenter A, Davis MD, Lu M, Flitter M, Joshi AD, Clark CM, Grundman M, Mintun MA, Skovronsky DM, Pontecorvo MJ: Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiol Aging 2012, 34: 822–831.CrossRefPubMedPubMedCentral
22.
Van-der-Linden M, Coyette F, Thomas-Antérion C, Sellal , Poitrenaud J, Gély-Nargeot , Linden JV, Kalafat M, Ergis , Adam S, Agniel A, Baisset-Mouly , Bardet , Desgranges B, Deweer : Neuropsychologie: L’évaluation des troubles de la mémoire: Présentation de quatre tests de mémoire épisodique (avec leur étalonnage). Marseille: Solal; 2004.
23.
Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J: 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: 967–972. 10.1136/jnnp.55.10.967CrossRefPubMedPubMedCentral
24.
Fazekas F, Barkhof F, Wahlund LO, Pantoni L, Erkinjuntti T, Scheltens P, Schmidt R: CT and MRI rating of white matter lesions. Cerebrovasc Dis 2002,13(Suppl 2):31–36.CrossRefPubMed
25.
Sarazin M, Berr C, De Rotrou J, Fabrigoule C, Pasquier F, Legrain S, Michel B, Puel M, Volteau M, Touchon J, Verny M, Dubois B: Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study. Neurology 2007, 69: 1859–1867. 10.1212/01.wnl.0000279336.36610.f7CrossRefPubMed
26.
Wallon D, Rousseau S, Rovelet-Lecrux A, Quillard-Muraine M, Guyant-Marechal L, Martinaud O, Pariente J, Puel M, Rollin-Sillaire A, Pasquier F, Le Ber I, Sarazin M, Croisile B, Boutoleau-Bretonniere C, Thomas-Anterion C, Paquet C, Moreaud O, Gabelle A, Sellal F, Sauvee M, Laquerriere A, Duyckaerts C, Delisle MB, Streichenberger N, Lannes B, Frebourg T, Hannequin D, Campion D: The French series of autosomal dominant early onset Alzheimer’s disease cases: mutation spectrum and cerebrospinal fluid biomarkers. J Alzheimers Dis 2012, 30: 847–856.PubMed
27.
Strauss E, Sherman EMS, Spreen O: A Compendium of Neuropsychological Tests. Oxford: Oxford University Press; 2006.
28.
Barbeau E, Didic M, Tramoni E, Felician O, Joubert S, Sontheimer A, Ceccaldi M, Poncet M: Evaluation of visual recognition memory in MCI patients. Neurology 2004, 62: 1317–1322. 10.1212/01.WNL.0000120548.24298.DBCrossRefPubMed
29.
Lacot E, Barbeau E, Thomas-Anterion C, Basaglia-Papas S, Pariente J, Puel M, Vaurtier S: TOP 12: how to interpret the responses as a measure of collective memory ability? Rev Neuropsychol 2011,4(3):273–283.CrossRef
30.
Mahieux-Laurent F, Fabre C, Galbrun E, Dubrulle A, Moroni C: [Validation of a brief screening scale evaluating praxic abilities for use in memory clinics. Evaluation in 419 controls, 127 mild cognitive impairment and 320 demented patients]. Rev Neurol (Paris) 2009, 165: 560–567. 10.1016/j.neurol.2008.11.016CrossRef
31.
Deloche G, Hannequin D: DO 80: Epreuve de Dénomination Orale d’images. Montreuil: ECPA; 1997.
32.
Dubois B, Slachevsky A, Litvan I, Pillon B: The FAB: a Frontal Assessment Battery at bedside. Neurology 2000, 55: 1621–1626. 10.1212/WNL.55.11.1621CrossRefPubMed
33.
Lezak M, Howieson D, Loring D: Neuropsychological Assessment. 4th edition. Oxford: Oxford University Press; 2004.
34.
35.
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M: Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 2002, 15: 273–289. 10.1006/nimg.2001.0978CrossRefPubMed
36.
Lin KJ, Hsu WC, Hsiao IT, Wey SP, Jin LW, Skovronsky D, Wai YY, Chang HP, Lo CW, Yao CH, Yen TC, Kung MP: Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent–a pilot study. Nucl Med Biol 2010, 37: 497–508. 10.1016/j.nucmedbio.2010.02.003CrossRefPubMed
37.
Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, Schneider JA, Arora A, Carpenter AP, Flitter ML, Joshi AD, Krautkramer MJ, Lu M, Mintun MA, Skovronsky DM: Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 2012, 11: 669–678. 10.1016/S1474-4422(12)70142-4CrossRefPubMed
38.
Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Langstrom B: Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004, 55: 306–319. 10.1002/ana.20009CrossRefPubMed
39.
Tosun D, Schuff N, Mathis CA, Jagust W, Weiner MW: Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment. Brain 2011, 134: 1077–1088. 10.1093/brain/awr044CrossRefPubMedPubMedCentral
40.
Villemagne VL, Pike KE, Chetelat G, Ellis KA, Mulligan RS, Bourgeat P, Ackermann U, Jones G, Szoeke C, Salvado O, Martins R, O'Keefe G, Mathis CA, Klunk WE, Ames D, Masters CL, Rowe CC: Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol 2011, 69: 181–192. 10.1002/ana.22248CrossRefPubMedPubMedCentral
41.
Chetelat G, Villemagne VL, Bourgeat P, Pike KE, Jones G, Ames D, Ellis KA, Szoeke C, Martins RN, O’Keefe GJ, Salvado O, Masters CL, Rowe CC: Relationship between atrophy and beta-amyloid deposition in Alzheimer disease. Ann Neurol 2010, 67: 317–324.PubMed
42.
Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, Mathis CA, Klunk WE, Masters CL, Rowe CC: Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain 2007, 130: 2837–2844. 10.1093/brain/awm238CrossRefPubMed
43.
Resnick SM, Sojkova J, Zhou Y, An Y, Ye W, Holt DP, Dannals RF, Mathis CA, Klunk WE, Ferrucci L, Kraut MA, Wong DF: Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology 2010, 74: 807–815. 10.1212/WNL.0b013e3181d3e3e9CrossRefPubMedPubMedCentral
44.
Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL: Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013, 12: 357–367. 10.1016/S1474-4422(13)70044-9CrossRefPubMed
45.
Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, Coart E, Morris JC, Holtzman DM: Comparison of analytical platforms for cerebrospinal fluid measures of beta-amyloid 1–42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol 2011, 68: 1137–1144. 10.1001/archneurol.2011.105CrossRefPubMedPubMedCentral
Metadata
Title
Cortical florbetapir-PET amyloid load in prodromal Alzheimer’s disease patients
Authors
Laure Saint-Aubert
Emmanuel J Barbeau
Patrice Péran
Federico Nemmi
Celine Vervueren
Helene Mirabel
Pierre Payoux
Anne Hitzel
Fabrice Bonneville
Raluca Gramada
Mathieu Tafani
Christian Vincent
Michele Puel
Sophie Dechaumont
Francois Chollet
Jeremie Pariente
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2013
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-3-43

Other articles of this Issue 1/2013

EJNMMI Research 1/2013 Go to the issue

Original research

Noninvasive k3 estimation method for slow dissociation PET ligands: application to [11C]Pittsburgh compound B

Original research

Influence of rigid coregistration of PET and CT data on metabolic volumetry: a user’s perspective

Original research

11C-LY2428703, a positron emission tomographic radioligand for the metabotropic glutamate receptor 1, is unsuitable for imaging in monkey and human brains

Original research

Radiosensitization of noradrenaline transporter-expressing tumour cells by proteasome inhibitors and the role of reactive oxygen species

Original research

Pulmonary vein isolation in patients with paroxysmal atrial fibrillation is associated with regional cardiac sympathetic denervation

Original research

ELIXYS - a fully automated, three-reactor high-pressure radiosynthesizer for development and routine production of diverse PET tracers