[18F]AV-1451 tau-PET and primary progressive aphasia

Keith Anthony Josephs, Peter R. Martin, Hugo Botha, Christopher G. Schwarz, Joseph R. Duffy, Heather Clark, Mary Margaret Machulda, Jonathan Graff-Radford, Stephen D. Weigand, Matthew L. Senjem, Rene L. Utianski, Daniel A. Drubach, Bradley F Boeve, David T Jones, David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack, Val Lowe, Jennifer Lynn Whitwell

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Abstract

Objectives: To assess [18F]AV-1451 tau-PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [18F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [18F]AV-1451, [18F]-fluorodeoxygluclose (FDG)-PET and MRI (magnetic resonance imaging) to differentiate the PPA variants. Methods: We performed statistical parametric mapping of [18F]AV-1451 across 40 PPA patients (logopenic-PPA=14, semantic-PPA=13, and agrammatic-PPA=13) compared to 80 cognitively normal, Pittsburgh compound B-negative controls, age and gender matched 2:1. Principal component analysis of regional [18F]AV-1451 tau-PET standard uptake value ratio was performed to understand underlying patterns of [18F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility. Results: Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA, and agrammatic-PPA. Semantic-PPA and agrammatic-PPA showed milder patterns of focal [18F]AV-1451 uptake. Semantic-PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic-PPA. Agrammatic-PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic-PPA. The principal component analysis of regional [18F]AV-1451 indicated two primary dimensions, a severity dimension that distinguished logopenic-PPA from agrammatic-PPA and semantic-PPA, and a frontal versus temporal contrast that distinguishes agrammatic-PPA and semantic-PPA cases. Diagnostic utility of [18F]AV-1451was superior to MRI and at least equal to FDG-PET. Interpretation: [18F]AV-1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [18F]AV-1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18F]AV-1451 may have clinical diagnostic utility in PPA.

LanguageEnglish (US)
JournalAnnals of Neurology
DOIs
StateAccepted/In press - Jan 1 2018

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Primary Progressive Aphasia
Semantics
Principal Component Analysis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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[18F]AV-1451 tau-PET and primary progressive aphasia. / Josephs, Keith Anthony; Martin, Peter R.; Botha, Hugo; Schwarz, Christopher G.; Duffy, Joseph R.; Clark, Heather; Machulda, Mary Margaret; Graff-Radford, Jonathan; Weigand, Stephen D.; Senjem, Matthew L.; Utianski, Rene L.; Drubach, Daniel A.; Boeve, Bradley F; Jones, David T; Knopman, David S; Petersen, Ronald Carl; Jack, Clifford R Jr.; Lowe, Val; Whitwell, Jennifer Lynn.

In: Annals of Neurology, 01.01.2018.

Research output: Contribution to journalArticle

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title = "[18F]AV-1451 tau-PET and primary progressive aphasia",
abstract = "Objectives: To assess [18F]AV-1451 tau-PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [18F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [18F]AV-1451, [18F]-fluorodeoxygluclose (FDG)-PET and MRI (magnetic resonance imaging) to differentiate the PPA variants. Methods: We performed statistical parametric mapping of [18F]AV-1451 across 40 PPA patients (logopenic-PPA=14, semantic-PPA=13, and agrammatic-PPA=13) compared to 80 cognitively normal, Pittsburgh compound B-negative controls, age and gender matched 2:1. Principal component analysis of regional [18F]AV-1451 tau-PET standard uptake value ratio was performed to understand underlying patterns of [18F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility. Results: Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA, and agrammatic-PPA. Semantic-PPA and agrammatic-PPA showed milder patterns of focal [18F]AV-1451 uptake. Semantic-PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic-PPA. Agrammatic-PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic-PPA. The principal component analysis of regional [18F]AV-1451 indicated two primary dimensions, a severity dimension that distinguished logopenic-PPA from agrammatic-PPA and semantic-PPA, and a frontal versus temporal contrast that distinguishes agrammatic-PPA and semantic-PPA cases. Diagnostic utility of [18F]AV-1451was superior to MRI and at least equal to FDG-PET. Interpretation: [18F]AV-1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [18F]AV-1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18F]AV-1451 may have clinical diagnostic utility in PPA.",
author = "Josephs, {Keith Anthony} and Martin, {Peter R.} and Hugo Botha and Schwarz, {Christopher G.} and Duffy, {Joseph R.} and Heather Clark and Machulda, {Mary Margaret} and Jonathan Graff-Radford and Weigand, {Stephen D.} and Senjem, {Matthew L.} and Utianski, {Rene L.} and Drubach, {Daniel A.} and Boeve, {Bradley F} and Jones, {David T} and Knopman, {David S} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Val Lowe and Whitwell, {Jennifer Lynn}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/ana.25183",
language = "English (US)",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",

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TY - JOUR

T1 - [18F]AV-1451 tau-PET and primary progressive aphasia

AU - Josephs, Keith Anthony

AU - Martin, Peter R.

AU - Botha, Hugo

AU - Schwarz, Christopher G.

AU - Duffy, Joseph R.

AU - Clark, Heather

AU - Machulda, Mary Margaret

AU - Graff-Radford, Jonathan

AU - Weigand, Stephen D.

AU - Senjem, Matthew L.

AU - Utianski, Rene L.

AU - Drubach, Daniel A.

AU - Boeve, Bradley F

AU - Jones, David T

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Lowe, Val

AU - Whitwell, Jennifer Lynn

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: To assess [18F]AV-1451 tau-PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [18F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [18F]AV-1451, [18F]-fluorodeoxygluclose (FDG)-PET and MRI (magnetic resonance imaging) to differentiate the PPA variants. Methods: We performed statistical parametric mapping of [18F]AV-1451 across 40 PPA patients (logopenic-PPA=14, semantic-PPA=13, and agrammatic-PPA=13) compared to 80 cognitively normal, Pittsburgh compound B-negative controls, age and gender matched 2:1. Principal component analysis of regional [18F]AV-1451 tau-PET standard uptake value ratio was performed to understand underlying patterns of [18F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility. Results: Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA, and agrammatic-PPA. Semantic-PPA and agrammatic-PPA showed milder patterns of focal [18F]AV-1451 uptake. Semantic-PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic-PPA. Agrammatic-PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic-PPA. The principal component analysis of regional [18F]AV-1451 indicated two primary dimensions, a severity dimension that distinguished logopenic-PPA from agrammatic-PPA and semantic-PPA, and a frontal versus temporal contrast that distinguishes agrammatic-PPA and semantic-PPA cases. Diagnostic utility of [18F]AV-1451was superior to MRI and at least equal to FDG-PET. Interpretation: [18F]AV-1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [18F]AV-1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18F]AV-1451 may have clinical diagnostic utility in PPA.

AB - Objectives: To assess [18F]AV-1451 tau-PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [18F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [18F]AV-1451, [18F]-fluorodeoxygluclose (FDG)-PET and MRI (magnetic resonance imaging) to differentiate the PPA variants. Methods: We performed statistical parametric mapping of [18F]AV-1451 across 40 PPA patients (logopenic-PPA=14, semantic-PPA=13, and agrammatic-PPA=13) compared to 80 cognitively normal, Pittsburgh compound B-negative controls, age and gender matched 2:1. Principal component analysis of regional [18F]AV-1451 tau-PET standard uptake value ratio was performed to understand underlying patterns of [18F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility. Results: Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA, and agrammatic-PPA. Semantic-PPA and agrammatic-PPA showed milder patterns of focal [18F]AV-1451 uptake. Semantic-PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic-PPA. Agrammatic-PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic-PPA. The principal component analysis of regional [18F]AV-1451 indicated two primary dimensions, a severity dimension that distinguished logopenic-PPA from agrammatic-PPA and semantic-PPA, and a frontal versus temporal contrast that distinguishes agrammatic-PPA and semantic-PPA cases. Diagnostic utility of [18F]AV-1451was superior to MRI and at least equal to FDG-PET. Interpretation: [18F]AV-1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [18F]AV-1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18F]AV-1451 may have clinical diagnostic utility in PPA.

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DO - 10.1002/ana.25183

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JO - Annals of Neurology

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SN - 0364-5134

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