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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.

Publication ,  Journal Article
Lu, M; Pontecorvo, MJ; Devous, MD; Arora, AK; Galante, N; McGeehan, A; Devadanam, C; Salloway, SP; Doraiswamy, PM; Curtis, C; Truocchio, SP ...
Published in: JAMA Neurol
April 1, 2021

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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Published In

JAMA Neurol

DOI

EISSN

2168-6157

Publication Date

April 1, 2021

Volume

78

Issue

4

Start / End Page

445 / 453

Location

United States

Related Subject Headings

  • tau Proteins
  • Risk Factors
  • Protein Aggregates
  • Prospective Studies
  • Positron-Emission Tomography
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lu, M., Pontecorvo, M. J., Devous, M. D., Arora, A. K., Galante, N., McGeehan, A., … AVID Collaborators, . (2021). 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. JAMA Neurol, 78(4), 445–453. https://doi.org/10.1001/jamaneurol.2020.5505
Lu, Ming, Michael J. Pontecorvo, Michael D. Devous, Anupa K. Arora, Nicholas Galante, Anne McGeehan, Catherine Devadanam, et al. “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.JAMA Neurol 78, no. 4 (April 1, 2021): 445–53. https://doi.org/10.1001/jamaneurol.2020.5505.
Lu M, Pontecorvo MJ, Devous MD, Arora AK, Galante N, McGeehan A, Devadanam C, Salloway SP, Doraiswamy PM, Curtis C, Truocchio SP, Flitter M, Locascio T, Devine M, Zimmer JA, Fleisher AS, Mintun MA, AVID Collaborators. 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. JAMA Neurol. 2021 Apr 1;78(4):445–453.

Published In

JAMA Neurol

DOI

EISSN

2168-6157

Publication Date

April 1, 2021

Volume

78

Issue

4

Start / End Page

445 / 453

Location

United States

Related Subject Headings

  • tau Proteins
  • Risk Factors
  • Protein Aggregates
  • Prospective Studies
  • Positron-Emission Tomography
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans
  • Female