Measurement of Longitudinal β-Amyloid Change with 18 F-Florbetapir PET and Standardized Uptake Value Ratios
Open accessAbstract
UNLABELLED: The accurate measurement of β-amyloid (Aβ) change using amyloid PET imaging is important for Alzheimer disease research and clinical trials but poses several unique challenges. In particular, reference region measurement instability may lead to spurious changes in cortical regions of interest. To optimize our ability to measure (18)F-florbetapir longitudinal change, we evaluated several candidate regions of interest and their influence on cortical florbetapir change over a 2-y period in participants from the Alzheimer Disease Neuroimaging Initiative (ADNI). METHODS: We examined the agreement in cortical florbetapir change detected using 6 candidate reference regions (cerebellar gray matter, whole cerebellum, brain stem/pons, eroded subcortical white matter [WM], and 2 additional combinations of these regions) in 520 ADNI subjects. We used concurrent cerebrospinal fluid Aβ1-42 measurements to identify subgroups of ADNI subjects expected to remain stable over follow-up (stable Aβ group; n = 14) and subjects expected to increase (increasing Aβ group; n = 91). We then evaluated reference regions according to whether cortical change was minimal in the stable Aβ group and cortical retention increased in the increasing Aβ group. RESULTS: There was poor agreement across reference regions in the amount of cortical change observed across all 520 ADNI subjects. Within the stable Aβ group, however, cortical florbetapir change was 1%-2% across all reference regions, indicating high consistency. In the increasing Aβ group, cortical increases were significant with all reference regions. Reference regions containing WM (as opposed to cerebellum or pons) enabled detection of cortical change that was more physiologically plausible and more likely to increase over time. CONCLUSION: Reference region selection has an important influence on the detection of florbetapir change. Compared with cerebellum or pons alone, reference regions that included subcortical WM resulted in change measurements that are more accurate. In addition, because use of WM-containing reference regions involves dividing out cortical signal contained in the reference region (via partial-volume effects), use of these WM-containing regions may result in more conservative estimates of actual change. Future analyses using different tracers, tracer-kinetic models, pipelines, and comparisons with other biomarkers will further optimize our ability to accurately measure Aβ changes over time.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
For florbetapir, the reference region consisted of the whole cerebellum, the pons/brainstem region, and eroded cortical white matter as this composite region has produced more reliable results in longitudinal analyses.
“For florbetapir, the reference region consisted of the whole cerebellum, the pons/brainstem region, and eroded cortical white matter as this composite region has produced more reliable results in longitudinal analyses49.”
From Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity (2017) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., Szoeke, C., Macaulay, S. L., Martins, R., Maruff, P., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70044-9 · Cited by 2,279 · see citing works
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065 · see citing works
Use of Florbetapir-PET for Imaging β-Amyloid Pathology
Clark, C. M. (2011) · JAMA · doi:10.1001/jama.2010.2008 · Cited by 1,117 · see citing works
PET imaging of amyloid deposition in patients with mild cognitive impairment
Forsberg, A., Engler, H., Almkvist, O., Blomquist, G., Hagman, G., Wall, A. E., Ringheim, A., Långström, B., & Nordberg, A. K. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.03.029 · Cited by 725 · see citing works
Rinne, J. O., Brooks, D. J., Rossor, M. N., Fox, N. C., Bullock, R., Klunk, W. E., Mathis, C. A., Blennow, K., Barakos, J., Okello, A. A., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70043-0 · Cited by 701 · see citing works
Episodic memory loss is related to hippocampal-mediated -amyloid deposition in elderly subjects
Mormino, E. C., Kluth, J. T., Madison, C. M., Rabinovici, G. D., Baker, S. L., Miller, B. L., Koeppe, R. A., Mathis, C. A., Weiner, M. W., Jagust, W. J., et al. (2009) · Brain · doi:10.1093/brain/awn320 · Cited by 684 · see citing works
Self-citationWong, D. F., Rosenberg, P. B., Zhou, Y., Kumar, A., Raymont, V., Ravert, H. T., Dannals, R. F., Nandi, A., Brašić, J. R., Ye, W., et al. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.109.069088 · Cited by 684 · see citing works
Vandenberghe, R. R., Laere, K. V., Ivanoiu, A., Salmon, É., Bastin, C., Triau, E., Hasselbalch, S. G., Law, I. G., Andersen, A., Kørner, A., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22068 · Cited by 649 · see citing works
Lopresti, B. J., Klunk, W. E., Mathis, C. A., Hoge, J. A., Ziolko, S. K., Lu, X., MELTZER, C. C., Schimmel, K., Tsopelas, N. D., DeKosky, S. T., et al. (2005) · PubMed · Cited by 536 · see citing works
Landau, S. M., Breault, C., Joshi, A. D., Pontecorvo, M. J., Mathis, C. A., Jagust, W. J., & Mintun, M. A. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.109009 · Cited by 465 · see citing works
Self-citationBrain β-amyloid load approaches a plateau
Jack, C. R., Wiste, H. J., Lesnick, T. G., Weigand, S. D., Knopman, D. S., Vemuri, P., Pankratz, V. S., Senjem, M. L., Gunter, J. L., Mielke, M. M., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182840bbe · Cited by 406 · see citing works
Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β‐amyloid
Landau, S. M., Lu, M., Joshi, A. D., Pontecorvo, M., Mintun, M. A., Trojanowski, J. Q., Shaw, L. M., Jagust, W. J., & Initiative, F. T. A. D. N. (2013) · Annals of Neurology · doi:10.1002/ana.23908 · Cited by 401 · see citing works
Self-citationJoshi, A. D., Pontecorvo, M. J., Clark, C. M., Carpenter, A. P., Jennings, D. L., Sadowsky, C., Adler, L. P., Kovnat, K. D., Seibyl, J. P., Arora, A., et al. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.111.090340 · Cited by 391 · see citing works
Self-citationAssociation of Lifetime Cognitive Engagement and Low β-Amyloid Deposition
Marks, S. M. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.2748 · Cited by 342 · see citing works
Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI
Initiative, T. A. D. N., Shaw, L. M. J., Vanderstichele, H., Knapik-Czajka, M. E., Figurski, M., Coart, E., Blennow, K., Soares, H. D., Simon, A. J., Lewczuk, P., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0808-0 · Cited by 297 · see citing works
Amyloid PET imaging in Alzheimer’s disease: a comparison of three radiotracers
Initiative, T. A. D. N., Landau, S. M., Thomas, B. A., Thurfjell, L., Schmidt, M. E., Margolin, R. A., Mintun, M. A., Pontecorvo, M. J., Baker, S. L., & Jagust, W. J. (2014) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-014-2753-3 · Cited by 294 · see citing works
Self-citationAmyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline
Doraiswamy, P. M., Sperling, R. A., Coleman, R. E., Johnson, K. A., Reiman, E. M., Davis, M. D., Grundman, M., Sabbagh, M. N., Sadowsky, C., Fleisher, A., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182661f74 · Cited by 228 · see citing works
Self-citationFleisher, A. S., Chen, K., Liu, X., Ayutyanont, N., Roontiva, A., Thiyyagura, P., Protas, H., Joshi, A. D., Sabbagh, M., Sadowsky, C. H., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.04.017 · Cited by 202 · see citing works
Self-citationComparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease
Villemagne, V. L., Mulligan, R. S., Pejoska, S., Ong, K. T., Jones, G. R., O'Keefe, G. J., Chan, J. G., Young, K., Tochon‐Danguy, H., Masters, C. L., et al. (2012) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-012-2088-x · Cited by 190 · see citing works
Chen, K., Roontiva, A., Thiyyagura, P., Lee, W., Liu, X., Ayutyanont, N., Protas, H. D., Luo, J., Bauer, R. J., III, Reschke, C., et al. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.114.149732 · Cited by 158 · see citing works
Self-citationVlassenko, A. G., Mintun, M. A., Xiong, C., Sheline, Y. I., Goate, A., Benzinger, T. L. S., & Morris, J. C. (2011) · Annals of Neurology · doi:10.1002/ana.22608 · Cited by 144 · see citing works
Self-citationBrendel, M., Högenauer, M., Delker, A., Sauerbeck, J., Bartenstein, P., Seibyl, J. P., & Rominger, A. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.11.055 · Cited by 135 · see citing works
Test-retest variability of quantitative [11C]PIB studies in Alzheimer’s disease
Tolboom, N., Yaqub, M. M., Boellaard, R., Luurtsema, G., Windhorst, A. D., Scheltens, P., Lammertsma, A. A., & van Berckel, B. N. M. (2009) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-009-1129-6 · Cited by 76 · see citing works
Tryputsen, V., Initiative, T. A. D. N., DiBernardo, A., Samtani, M. N., Novak, G., Narayan, V. A., & Raghavan, N. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131979 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Karikari, T. K., Pascoal, T. A., Ashton, N. J., Janelidze, S., Benedet, A. L., Rodriguez, J. L., Chamoun, M., Savard, M., Kang, M. S., Therriault, J., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30071-5 · Cited by 1,316 · see citing works
Palmqvist, S., Schöll, M., Strandberg, O., Mattsson, N., Stomrud, E., Zetterberg, H., Blennow, K., Landau, S., Jagust, W., & Hansson, O. (2017) · Nature Communications · doi:10.1038/s41467-017-01150-x · Cited by 911 · see citing works
Self-citationAssociation of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study
Hanseeuw, B. J., Betensky, R. A., Jacobs, H. I. L., Schultz, A. P., Sepulcre, J., Becker, J. A., Cosio, D. M. O., Farrell, M., Quiroz, Y. T., Mormino, E. C., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1424 · Cited by 865 · see citing works
Randomized trial of verubecestat for mild-to-moderate Alzheimer's disease
Egan, M. F., Kost, J., Tariot, P. N., Aisen, P. S., Cummings, J. L., Vellas, B., Sur, C., Mukai, Y., Voss, T., Furtek, C., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1706441 · Cited by 685 · see citing works
Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease
Zhang, H., Wei, W., Zhao, M., Ma, L., Jiang, X., Pei, H., Cao, Y., & Li, H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.57078 · Cited by 689 · see citing works
Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer's disease
Pereira, J. B., Janelidze, S., Smith, R., Mattsson-Carlgren, N., Palmqvist, S., Teunissen, C. E., Zetterberg, H., Stomrud, E., Ashton, N. J., Blennow, K., et al. (2021) · Brain · doi:10.1093/brain/awab223 · Cited by 598 · see citing works
Randomized trial of verubecestat for prodromal Alzheimer's disease
Egan, M. F., Kost, J., Voss, T., Mukai, Y., Aisen, P. S., Cummings, J. L., Tariot, P. N., Vellas, B., van Dyck, C. H., Boada, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812840 · Cited by 545 · see citing works
Longitudinal tau PET in ageing and Alzheimer’s disease
Jack, C. R., Wiste, H. J., Schwarz, C. G., Lowe, V. J., Senjem, M. L., Vemuri, P., Weigand, S. D., Therneau, T. M., Knopman, D. S., Gunter, J. L., et al. (2018) · Brain · doi:10.1093/brain/awy059 · Cited by 452 · see citing works
Palmqvist, S., Mattsson, N., Hansson, O., & Initiative, F. T. A. D. N. (2016) · Brain · doi:10.1093/brain/aww015 · Cited by 400 · see citing works
Palmqvist, S., Insel, P. S., Stomrud, E., Janelidze, S., Zetterberg, H., Brix, B., Eichenlaub, U., Dage, J. L., Chai, X., Blennow, K., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201911170 · Cited by 353 · see citing works
van Oostveen, W. M., & de Lange, E. C. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042110 · Cited by 297 · see citing works
Navitsky, M., Joshi, A. D., Kennedy, I., Klunk, W. E., Rowe, C. C., Wong, D. F., Pontecorvo, M. J., Mintun, M. A., & Devous, M. D. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.06.1353 · Cited by 229 · see citing works
Self-citationValidation of amyloid PET positivity thresholds in centiloids: a multisite PET study approach
Initiative, F. T. A. D. N., Royse, S. K., Minhas, D. S., Lopresti, B. J., Murphy, A., Ward, T., Koeppe, R. A., Bullich, S., DeSanti, S., Jagust, W. J., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00836-1 · Cited by 237 · see citing works
Self-citationQuantification of amyloid PET for future clinical use: a state-of-the-art review
Pemberton, H. G., Collij, L. E., Heeman, F., Bollack, A., Shekari, M., Salvadó, G., Alves, I. L., Garcia, D. V., Battle, M., Buckley, C., et al. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05784-y · Cited by 226 · see citing works
Ewers, M., Biechele, G., Suárez‐Calvet, M., Sacher, C., Blume, T., Morenas‐Rodriguez, E., Deming, Y., Piccio, L., Cruchaga, C., Kleinberger, G., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202012308 · Cited by 133 · see citing works
Aβ-amyloid and Tau Imaging in Dementia
Villemagne, V. L., Doré, V., Bourgeat, P., Burnham, S. C., Laws, S., Salvado, O., Masters, C. L., & Rowe, C. C. (2017) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2016.09.006 · Cited by 110 · see citing works
Flortaucipir F 18 quantitation using parametric estimation of reference signal intensity.
Southekal, S., Devous, M. D., Kennedy, I., Navitsky, M., Lu, M., Joshi, A. D., Pontecorvo, M. J., & Mintun, M. A. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.200006 · Cited by 92 · see citing works
Self-citationTract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease
Taylor, A. N. W., Kambeitz-Ilankovic, L., Gesierich, B., Simon-Vermot, L., Franzmeier, N., Araque Caballero, M. Á., Müller, S., Hesheng, L., Ertl-Wagner, B., Bürger, K., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.06.2358 · Cited by 73 · see citing works
Su, Y., Blazey, T. M., Owen, C. J., Christensen, J. J., Friedrichsen, K., Joseph-Mathurin, N., Wang, Q., Hornbeck, R. C., Ances, B. M., Snyder, A. Z., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0152082 · Cited by 56 · see citing works
Self-citationThe association between white matter hyperintensities and amyloid and tau deposition
Alban, S. L., Lynch, K. M., Ringman, J. M., Toga, A. W., Chui, H. C., Sepehrband, F., & Choupan, J. (2023) · NeuroImage: Clinical · doi:10.1016/j.nicl.2023.103383 · Cited by 35 · see citing works
Jagust, W. J., Koeppe, R. A., Rabinovici, G. D., Villemagne, V. L., Harrison, T. M., Landau, S. M., & Initiative, T. A. D. N. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.14165 · Cited by 34 · see citing works
Self-citation
- Authors
- Landau, S. M., Fero, A., Baker, S. L., Koeppe, R., Mintun, M., Chen, K., Reiman, E. M., & Jagust, W. J.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- University of Michigan (US)
- Avid Radiopharmaceuticals (United States) (US)
- Banner Alzheimer’s Institute (US)
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2015-03-05
- Volume
- 56
- Issue
- 4
- Pages
- 567-574
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC5313473
- OpenAlex
- W2257069458
- Cited by
- 364
- References
- 24
- Citations by year
- 2026: 29 · 2025: 39 · 2024: 40 · 2023: 27 · 2022: 40 · 2021: 35 · 2020: 40 · 2019: 35 · 2018: 27 · 2017: 27 · 2016: 19 · 2015: 4 · 2014: 1
- FWCI
- 20.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- amyloid-beta, 18F-florbetapir, amyloid PET, reference region selection, standardized uptake value ratio, subcortical white matter, partial volume effect, cerebellum, passive optical networks, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Brain, Brain Mapping, Cerebellum, Ethylene Glycols, Female, Humans, Image Processing, Computer-Assisted, Kinetics, Longitudinal Studies, Male, Pons, Reference Values, Reproducibility of Results, Biomarkers, Amyloid beta-Peptides, Radiopharmaceuticals, Positron-Emission Tomography, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
