Clinical Role of Brain PET in Alzheimer Disease in the Era of Disease-Modifying Therapies

References

1. 1.↵
   2024 Alzheimer’s disease facts and figures. Alzheimers Dement 2024;20:3708–821 doi:10.1002/alz.13809

   CrossRefPubMed
2. 2.↵
   1. Rabinovici GD,
   2. Gatsonis C,
   3. 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;321:1286–94 doi:10.1001/jama.2019.2000 pmid:30938796

   CrossRefPubMed
3. 3.↵
   1. Jack CR, Jr.,
   2. Bennett DA,
   3. Blennow K, et al

   ; Contributors. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018;14:535–62. PMCID: PMC5958625 doi:10.1016/j.jalz.2018.02.018 pmid:29653606

   CrossRefPubMed
4. 4.↵
   1. van Dyck CH,
   2. Swanson CJ,
   3. Aisen P, et al

   . Lecanemab in early Alzheimer’s disease. N Engl J Med 2023;388:9–21 doi:10.1056/NEJMoa2212948 pmid:36449413

   CrossRefPubMed
5. 5.↵
   1. Sims JR,
   2. Zimmer JA,
   3. Evans CD, et al

   ; TRAILBLAZER-ALZ 2 Investigators. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 2023;330:512–27 doi:10.1001/jama.2023.13239 pmid:37459141

   CrossRefPubMed
6. 6.↵
   1. Pemberton HG,
   2. Collij LE,
   3. Heeman F, et al

   ; AMYPAD Consortium. Quantification of amyloid PET for future clinical use: a state-of-the-art review. Eur J Nucl Med Mol Imaging 2022;49:3508–28 doi:10.1007/s00259-022-05784-y pmid:35389071

   CrossRefPubMed
7. 7.↵
   1. Thurfjell L,
   2. Lilja J,
   3. Lundqvist R, et al

   . Automated quantification of 18F-flutemetamol PET activity for categorizing scans as negative or positive for brain amyloid: concordance with visual image reads. J Nucl Med 2014;55:1623–28 doi:10.2967/jnumed.114.142109 pmid:25146124

   Abstract/FREE Full Text
8. 8.↵
   1. Sabri O,
   2. Sabbagh MN,
   3. Seibyl J, et al

   ; Florbetaben Phase 3 Study Group. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer’s disease: phase 3 study. Alzheimers Dement 2015;11:964–74 doi:10.1016/j.jalz.2015.02.004 pmid:25824567

   CrossRefPubMed
9. 9.↵
   1. Salloway S,
   2. Gamez JE,
   3. Singh U, et al

   . Performance of [¹⁸F]flutemetamol amyloid imaging against the neuritic plaque component of CERAD and the current (2012) NIA-AA recommendations for the neuropathologic diagnosis of Alzheimer’s disease. Alzheimers Dement (Amst) 2017;9:25–34 doi:10.1016/j.dadm.2017.06.001 pmid:28795133

   CrossRefPubMed
10. 10.↵
    1. Mintun MA,
    2. Lo AC,
    3. Duggan Evans C, et al

    . Donanemab in early Alzheimer’s disease. N Engl J Med 2021;384:1691–704 doi:10.1056/NEJMoa2100708 pmid:33720637

    CrossRefPubMed
11. 11.↵
    1. Budd Haeberlein S,
    2. Aisen PS,
    3. Barkhof F, et al

    . Two randomized phase 3 studies of aducanumab in early Alzheimer’s disease. J Prev Alzheimers Dis 2022;9:197–210 doi:10.14283/jpad.2022.30 pmid:35542991

    CrossRefPubMed
12. 12.↵
    1. Rabinovici GD,
    2. Knopman D,
    3. Arbizu J, et al

    . 2024 updated appropriate use criteria for amyloid and tau PET in Alzheimer’s disease. Butl Hosp Mem Aging Progr 2024;17:1–71
13. 13.↵
    1. Pittock RR,
    2. Aakre J,
    3. Castillo AM, et al

    . Eligibility for anti-amyloid treatment in a population-based study of cognitive aging. Neurology 2023;101:e1837–49 doi:10.1212/WNL.0000000000207770 pmid:37586881

    CrossRefPubMed
14. 14.↵
    1. Murray ME,
    2. Lowe VJ,
    3. Graff-Radford NR, et al

    . Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum. Brain 2015;138:1370–81 doi:10.1093/brain/awv050 pmid:25805643

    CrossRefPubMed
15. 15.↵
    1. Nasrallah IM,
    2. Wolk DA

    . Multimodality imaging of Alzheimer disease and other neurodegenerative dementias. J Nucl Med 2014;55:2003–11 doi:10.2967/jnumed.114.141416 pmid:25413136

    Abstract/FREE Full Text
16. 16.↵
    1. Villemagne VL,
    2. Barkhof F,
    3. Garibotto V, et al

    . Molecular imaging approaches in dementia. Radiology 2021;298:517–30 doi:10.1148/radiol.2020200028 pmid:33464184

    CrossRefPubMed
17. 17.↵
    1. Clark CM,
    2. Pontecorvo MJ,
    3. Beach TG, et al

    ; AV-45-A16 Study Group. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol 2012;11:669–78 doi:10.1016/S1474-4422(12)70142-4 pmid:22749065

    CrossRefPubMedWeb of Science
18. 18.↵
    1. Ikonomovic MD,
    2. Buckley CJ,
    3. Heurling K, et al

    . Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection. Acta Neuropathol Commun 2016;4:130 doi:10.1186/s40478-016-0399-z pmid:27955679

    CrossRefPubMed
19. 19.↵
    1. Ruan D,
    2. Sun L

    . Amyloid-β PET in Alzheimer’s disease: a systematic review and Bayesian meta-analysis. Brain Behav 2023;13:e2850 doi:10.1002/brb3.2850 pmid:36573329

    CrossRefPubMed
20. 20.↵
    1. Palmqvist S,
    2. Zetterberg H,
    3. Mattsson N, et al

    ; Swedish BioFINDER Study Group. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology 2015;85:1240–49 pmid:26354982

    Abstract/FREE Full Text
21. 21.↵
    1. Knopman DS,
    2. DeKosky ST,
    3. Cummings JL, et al

    . Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1143–53

    Abstract/FREE Full Text
22. 22.↵
    1. Jack CR, Jr.,
    2. Bennett DA,
    3. Blennow K, et al

    . A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016;87:539–47 doi:10.1212/WNL.0000000000002923 pmid:27371494

    CrossRefPubMed
23. 23.↵
    1. Lundeen TF,
    2. Seibyl JP,
    3. Covington MF, et al

    . Signs and artifacts in amyloid PET. Radiographics 2018;38:2123–33 doi:10.1148/rg.2018180160 pmid:30422768

    CrossRefPubMed
24. 24.↵
    1. Clark CM,
    2. Schneider JA,
    3. Bedell B, et al

    ; AV45-A07 Study Group. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 2011;305:275–83 doi:10.1001/jama.2010.2008 pmid:21245183

    CrossRefPubMedWeb of Science
25. 25.↵
    1. Johnson KA,
    2. Minoshima S,
    3. Bohnen NI, et al

    . Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. J Nucl Med 2013;54:1011–13 doi:10.2967/jnumed.113.127068 pmid:23753186

    Abstract/FREE Full Text
26. 26.↵
    1. Barthel H,
    2. Luthardt J,
    3. Becker G, et al

    . Individualized quantification of brain β-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer’s disease and healthy controls. Eur J Nucl Med Mol Imaging 2011;38:1702–14 doi:10.1007/s00259-011-1821-1 pmid:21547601

    CrossRefPubMed
27. 27.↵
    American College of Radiology. New IDEAS. https://www.acr.org/Practice-Management-Quality-Informatics/ACR-Bulletin/Articles/March-2021/New-IDEAS Accessed April 24, 2024.
28. 28.↵
    New IDEAS: Imaging Dementia–Evidence for Amyloid Scanning Study. https://www.ideas-study.org/ Accessed April 24, 2024.
29. 29.↵
    Centers for Medicare & Medicaid Services. Beta Amyloid Positron Emission Tomography in Dementia and Neurodegenerative Disease. https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=308 Accessed: April 24, 2024.
30. 30.↵
    Food and Drug Administration (FDA). FDA Grants Accelerated Approval for Alzheimer’s Drug. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug Accessed: April 24, 2024.
31. 31.↵
    Food and Drug Administration (FDA). FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval Accessed April 24, 2024.
32. 32.↵
    1. Cummings J,
    2. Zhou Y,
    3. Lee G, et al

    . Alzheimer’s disease drug development pipeline: 2023. Alzheimers Dement (N Y) 2023;9:e12385 doi:10.1002/trc2.12385 pmid:37251912

    CrossRefPubMed
33. 33.↵
    1. Brier MR,
    2. Gordon B,
    3. Friedrichsen K, et al

    . Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med 2016;8:338ra66 doi:10.1126/scitranslmed.aaf2362 pmid:27169802

    Abstract/FREE Full Text
34. 34.↵
    1. Jack CR, Jr.,
    2. Knopman DS,
    3. Jagust WJ, et al

    . Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013;12:207–16 doi:10.1016/S1474-4422(12)70291-0 pmid:23332364

    CrossRefPubMedWeb of Science
35. 35.↵
    1. Bateman RJ,
    2. Xiong C,
    3. Benzinger TL, et al

    ; Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012;367:795–804 doi:10.1056/NEJMoa1202753 pmid:22784036

    CrossRefPubMedWeb of Science
36. 36.↵
    1. Ossenkoppele R,
    2. Hansson O

    . Towards clinical application of tau PET tracers for diagnosing dementia due to Alzheimer’s disease. Alzheimers Dement 2021;17:1998–2008 doi:10.1002/alz.12356 pmid:33984177

    CrossRefPubMed
37. 37.↵
    1. Busche MA,
    2. Hyman BT

    . Synergy between amyloid-β and tau in Alzheimer’s disease. Nat Neurosci 2020;23:1183–93 doi:10.1038/s41593-020-0687-6 pmid:32778792

    CrossRefPubMed
38. 38.↵
    1. Ossenkoppele R,
    2. Rabinovici GD,
    3. Smith R, et al

    . Discriminative accuracy of [18F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders. JAMA 2018;320:1151–62 doi:10.1001/jama.2018.12917 pmid:30326496

    CrossRefPubMed
39. 39.↵
    1. Palleis C,
    2. Brendel M,
    3. Finze A, et al

    ; German Imaging Initiative for Tauopathies (GII4T). Cortical [18 F]PI-2620 binding differentiates corticobasal syndrome subtypes. Mov Disord 2021;36:2104–15 doi:10.1002/mds.28624 pmid:33951244

    CrossRefPubMed
40. 40.↵
    1. Tezuka T,
    2. Takahata K,
    3. Seki M, et al

    . Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies. Brain Commun 2021;3:fcab190 doi:10.1093/braincomms/fcab190 pmid:34632382

    CrossRefPubMed
41. 41.↵
    1. Chen CD,
    2. Ponisio MR,
    3. Lang JA, et al

    . Comparing tau PET visual interpretation with tau PET quantification, cerebrospinal fluid biomarkers, and longitudinal clinical assessment. J Alzheimers Dis 2023;93:765–77 doi:10.3233/JAD-230032 pmid:37092225

    CrossRefPubMed
42. 42.↵
    1. Dore V,
    2. Bullich S,
    3. Bohorquez SS, et al

    . CenTauRz: a standardized quantification of tau PET scans. Alzheimer’s Dement 2023;19:e061171
43. 43.↵
    1. Leuzy A,
    2. Raket LL,
    3. Villemagne VL, et al

    . Harmonizing tau positron emission tomography in Alzheimer’s disease: the CenTauR scale and the joint propagation model. Alzheimers Dement 2024;20:5833–48 doi:10.1002/alz.13908 pmid:39041435

    CrossRefPubMed
44. 44.↵
    Food and Drug Administration. Aduhelm. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761178s005lbl.pdf Accessed October 15, 2023.
45. 45.↵
    Food and Drug Administration. Leqembi. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s001lbl.pdf Accessed October 15, 2023.
46. 46.↵
    1. Zwan MD,
    2. Bouwman FH,
    3. Konijnenberg E, et al

    . Diagnostic impact of [18F]flutemetamol PET in early-onset dementia. Alzheimers Res Ther 2017;9:2 doi:10.1186/s13195-016-0228-4 pmid:28093088

    CrossRefPubMed
47. 47.↵
    1. Collij LE,
    2. Mastenbroek SE,
    3. Salvadó G, et al

    . Regional amyloid accumulation predicts memory decline in initially cognitively unimpaired individuals. Alzheimers Dement (Amst) 2021;13:e12216

    PubMed
48. 48.↵
    1. Chételat G,
    2. Arbizu J,
    3. Barthel H, et al

    . Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer’s disease and other dementias. Lancet Neurol 2020;19:951–62 doi:10.1016/S1474-4422(20)30314-8 pmid:33098804

    CrossRefPubMed
49. 49.↵
    1. Hattori N,
    2. Sherwin P,
    3. Farrar G

    . Initial physician experience with [18F]flutemetamol amyloid PET imaging following availability for routine clinical use in Japan. J Alzheimers Dis Rep 2020;4:165–74 doi:10.3233/ADR-190150 pmid:32715277

    CrossRefPubMed
50. 50.↵
    1. Alongi P,
    2. Chiaravalloti A,
    3. Berti V, et al

    . Amyloid PET in the diagnostic workup of neurodegenerative disease. Clin Transl Imaging 2021;9:383–97 doi:10.1007/s40336-021-00428-x

    CrossRef
51. 51.↵
    1. Collij LE,
    2. Salvadó G,
    3. Shekari M, et al

    ; AMYPAD Consortium. Visual assessment of [18F]flutemetamol PET images can detect early amyloid pathology and grade its extent. Eur J Nucl Med Mol Imaging 2021;48:2169–82 doi:10.1007/s00259-020-05174-2 pmid:33615397

    CrossRefPubMed
52. 52.↵
    1. Paghera B,
    2. Altomare D,
    3. Peli A, et al

    . Comparison of visual criteria for amyloid-PET reading: could criteria merging reduce inter-rater variability? Q J Nucl Med Mol Imaging 2020;64:414–21 doi:10.23736/S1824-4785.19.03124-8 pmid:31089074

    CrossRefPubMed
53. 53.↵
    1. Bischof GN,
    2. Bartenstein P,
    3. Barthel H, et al

    . Toward a universal readout for 18F-labeled amyloid tracers: the CAPTAINs Study. J Nucl Med 2021;62:999–1005 doi:10.2967/jnumed.120.250290 pmid:33712532

    Abstract/FREE Full Text
54. 54.↵
    1. Klunk WE,
    2. Koeppe RA,
    3. Price JC, et al

    . The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 2015;11:1–15 doi:10.1016/j.jalz.2014.07.003 pmid:25443857

    CrossRefPubMed
55. 55.↵
    1. Smith AM,
    2. Obuchowski NA,
    3. Foster NL, et al

    . The RSNA QIBA profile for amyloid PET as an imaging biomarker for cerebral amyloid quantification. J Nucl Med 2023;64:294–303 doi:10.2967/jnumed.122.264031 pmid:36137760

    Abstract/FREE Full Text
56. 56.↵
    1. Olsson B,
    2. Lautner R,
    3. Andreasson U, et al

    . CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 2016;15:673–84 doi:10.1016/S1474-4422(16)00070-3 pmid:27068280

    CrossRefPubMed
57. 57.↵
    1. Lewczuk P,
    2. Beck G,
    3. Esselmann H, et al

    . Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid beta peptides. Clin Chem 2006;52:332–34 doi:10.1373/clinchem.2005.058776 pmid:16449222

    FREE Full Text
58. 58.↵
    1. Pais MV,
    2. Forlenza OV,
    3. Diniz BS, et al

    . Plasma biomarkers of Alzheimer’s disease: a review of available assays, recent developments, and implications for clinical practice. J Alzheimers Dis Rep 2023;7:355–80 doi:10.3233/ADR-230029 pmid:37220625

    CrossRefPubMed
59. 59.↵
    1. Ashton NJ,
    2. Brum WS,
    3. Di Molfetta G, et al

    . Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol 2024;81:255–63 doi:10.1001/jamaneurol.2023.5319 pmid:38252443

    CrossRefPubMed
60. 60.↵
    1. Erickson CM,
    2. Chin NA,
    3. Johnson SC, et al

    . Disclosure of preclinical Alzheimer’s disease biomarker results in research and clinical settings: why, how, and what we still need to know. Alzheimers Dement (Amst) 2021;13:e12150 doi:10.1002/dad2.12150 pmid:33665341

    CrossRefPubMed
61. 61.↵
    1. Yadollahikhales G,
    2. Rojas JC

    . Anti-amyloid immunotherapies for Alzheimer’s disease: a 2023 clinical update. Neurotherapeutics 2023;20:914–31 doi:10.1007/s13311-023-01405-0 pmid:37490245

    CrossRefPubMed
62. 62.↵
    1. Reimand J,
    2. Boon BDC,
    3. Collij LE, et al

    . Amyloid-β PET and CSF in an autopsy-confirmed cohort. Ann Clin Transl Neurol 2020;7:2150–60 doi:10.1002/acn3.51195 pmid:33080124

    CrossRefPubMed
63. 63.↵
    1. Roytman M,
    2. Mashriqi F,
    3. Al-Tawil K, et al

    . Amyloid-related imaging abnormalities: an update. AJR Am J Roentgenol 2023;220:562–74 doi:10.2214/AJR.22.28461 pmid:36321981

    CrossRefPubMed
64. 64.↵
    1. Black RS,
    2. Sperling RA,
    3. Safirstein B, et al

    . A single ascending dose study of bapineuzumab in patients with Alzheimer disease. Alzheimer Dis Assoc Disord 2010;24:198–203 doi:10.1097/WAD.0b013e3181c53b00 pmid:20505438

    CrossRefPubMed
65. 65.↵
    1. Cogswell PM,
    2. Andrews TJ,
    3. Barakos JA, et al

    ; ASNR Alzheimer, ARIA, and Dementia Study Group. Alzheimer disease anti-amyloid immunotherapies: imaging recommendations and practice considerations for monitoring of amyloid-related imaging abnormalities. AJNR Am J Neuroradiol 2025;46:24–32 doi:10.3174/ajnr.A8469 pmid:39179297

    Abstract/FREE Full Text
66. 66.↵
    1. Cogswell PM,
    2. Barakos JA,
    3. Barkhof F, et al

    . Amyloid-related imaging abnormalities with emerging Alzheimer disease therapeutics: detection and reporting recommendations for clinical practice. AJNR Am J Neuroradiol 2022;43:E19–35 doi:10.3174/ajnr.A7586 pmid:35953274

    Abstract/FREE Full Text