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Cited by 56Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials

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Lu, Ming, Pontecorvo, Michael J., Devous, Michael D., Arora, Anupa K., Galante, Nicholas, McGeehan, Anne, Devadanam, Catherine, Salloway, Stephen P. +45 more·2021·JAMA Neurology
DOI 10.1001/jamaneurol.2020.5505PMC PMC7885097
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Abstract

Importance: Flortaucipir positron emission tomography (PET) scans, rated with a novel, US Food and Drug Administration-approved, clinically applicable visual interpretation method, provide valuable information regarding near-term clinical progression of patients with Alzheimer disease (AD) or mild cognitive impairment (MCI). Objective: To evaluate the association between flortaucipir PET visual interpretation and patients' near-term clinical progression. Design/Setting/Participants: Two prospective, open-label, longitudinal studies were conducted from December 2014 to September 2019. Study 1 screened 298 patients and enrolled 160 participants who had a flortaucipir scan at baseline visit. Study 2 selected 205 participants from the AMARANTH trial, which was terminated after futility analysis. Out of the 2218 AMARANTH participants, 424 had a flortaucipir scan around randomization, but 219 did not complete 18-month clinical dementia rating (CDR) assessments and thus were excluded. In both studies, all participants were diagnosed as clinically impaired, and they were longitudinally followed up for approximately 18 months after baseline. Main Outcomes and Measures: Flortaucipir scans were rated as either advanced or nonadvanced AD pattern using a predetermined visual interpretation method. The CDR sum of box (CDR-SB) score was used as primary clinical end point measurement in both studies. Results: Of the 364 study participants who had readable scans, 48% were female (n = 174 of 364), and the mean (SD) age was 71.8 (8.7) years. Two hundred forty participants were rated as having an advanced AD pattern. At 18 months follow-up, 70% of those with an advanced AD pattern (n = 147 of 210) had 1 point or more increase in CDR-SB, an event predefined as clinically meaningful deterioration. In contrast, only 46% of those with a nonadvanced AD pattern scan (n = 48 of 105) experienced the same event (risk ratio [RR], 1.40; 95% CI, 1.11-1.76; P = .005). The adjusted mean CDR-SB changes were 2.28 and 0.98 for advanced and nonadvanced AD pattern groups, respectively (P < .001). Analyses with other clinical end point assessments, as well as analyses with each individual study's data, consistently indicated a higher risk of clinical deterioration associated with an advanced AD scan pattern. Conclusions and Relevance: These results suggest that flortaucipir PET scans, when interpreted with an US Food and Drug Administration-approved, clinically applicable visual interpretation method, may provide valuable information regarding the risk of clinical deterioration over 18 months among patients with AD and MCI. Trial Registration: ClinicalTrials.gov Identifier: NCT02016560 and NCT03901105.

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  • A study aggregating two Phase II clinical trials with 364 participants showed tau PET provides valuable prognostic information in terms of clinical deterioration over 18 months in MCI and AD.

    “A study aggregating results from two Phase II Clinical trials that have used 18F -flortaucipir PET scans in a total of 364 study participants showed that tau PET provides valuable prognostic information in terms of clinical deterioration over 18 months in MCI and AD [196].”

    From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [196]

    Table 1 (Results > Participant Characteristics; page unavailable) reports 364 pooled participants with MCI or AD. The Conclusions and Methods > Statistical Analysis (pages unavailable) support the prognostic value of flortaucipir PET for clinical decline over 18 months, but the Introduction describes the two studies as phase III, not phase II. (LLM, conf=0.92)

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Authors
Lu, M., Pontecorvo, M. J., Devous, M. D., Arora, A. K., Galante, N., McGeehan, A., Devadanam, C., Salloway, S. P., Doraiswamy, P. M., Curtis, C., Truocchio, S. P., Flitter, M., Locascio, T., Devine, M., Zimmer, J. A., Fleisher, A. S., Mintun, M. A., Collaborators, A., Edmunds, J. S. G., McCandless, B. K., Sam, J. W., DePuey, E. G., Kreychman, A., Benzinger, T., Curtis, C., Olichney, J., Delagandara, J., Doraiswamy, M., Sohi, J., Lefebvre, G., Tariot, P., Garg, P., Russell, D., Kawas, C., Kerchner, G., Korn, R., Kudrow, D., Rabinovici, G., Mocherla, B., Nair, A., Ott, B., Zamrini, E., Sadowsky, C., Salloway, S., Schaerf, F., Shankle, W., Stern, R., Woodruff, B., Wolk, D., Johnson, K., Butler, T., Smith, A., & Rydzewski, B.
Affiliations
  • Avid Radiopharmaceuticals (United States) (US)
  • Butler Hospital, Providence, Rhode Island
  • Duke University (US)
  • Eli Lilly (United States) (US)
  • for the AVID Collaborators
Corresponding author
Lu, Ming
ORCID
Venue
JAMA Neurology
Publisher
American Medical Association (AMA)
Published
2021-04-01
Volume
78
Issue
4
Pages
445
ISSN
2168-6149 (ISSN-L)
DOI
10.1001/jamaneurol.2020.5505
PMC
PMC7885097
OpenAlex
W3131335329
Cited by
56
References
44
Citations by year
2026: 5 · 2025: 11 · 2024: 9 · 2023: 10 · 2022: 16 · 2021: 5
FWCI
7.18
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • JAMA Neurology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Avid Radiopharmaceuticals
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
flortaucipir, tau PET, visual interpretation, Alzheimer's disease, mild cognitive impairment, clinical progression, amyloid PET, tau aggregation, neurodegeneration biomarkers, cognitive decline prediction
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Carbolines, Contrast Media, Female, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Risk Factors, tau Proteins, Disease Progression, Positron-Emission Tomography, Cognitive Dysfunction, Protein Aggregates

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