[18F]AV-1451 clustering of entorhinal and cortical uptake in Alzheimer's disease

Jennifer Lynn Whitwell, Jonathan Graff-Radford, Nirubol Tosakulwong, Stephen D. Weigand, Mary Margaret Machulda, Matthew L. Senjem, Christopher G. Schwarz, Anthony J. Spychalla, David T Jones, Daniel A. Drubach, David S Knopman, Bradley F Boeve, Nilufer Taner, Ronald Carl Petersen, Val Lowe, Clifford R Jr. Jack, Keith Anthony Josephs

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Abstract

Objective: To use a cluster analysis of [18F]AV-1451 tau-PET data to determine how subjects with Alzheimer's disease (AD) vary in the relative involvement of the entorhinal cortex and neocortex, and determine whether relative involvement of these two regions can help explain variability in age and clinical phenotype in AD. Methods: We calculated [18F]AV-1451 uptake in entorhinal cortex and neocortex in 62 amyloid-positive AD patients (39 typical and 23 atypical presentation). tau-PET (positron emission tomography) values were normalized to the cerebellum to create standard uptake value ratios (SUVRs). tau-PET SUVRs were log-transformed and clustered blinded to clinical information into three groups using K-median cluster analysis. Demographics, clinical phenotype, cognitive performance, and apolipoprotein e4 frequency were compared across clusters. Results: The cluster analysis identified a cluster with low entorhinal and cortical uptake (ELo/CLo), one with low entorhinal but high cortical uptake (ELo/CHi), and one with high cortical and entorhinal uptake (EHi/CHi). Clinical phenotype differed across clusters, with typical AD most commonly observed in the ELo/CLo and EHi/CHi clusters, and atypical AD most commonly observed in the ELo/CHi cluster. The ELo/CLo cluster had an older age at PET and onset than the other clusters. Apolipoprotein e4 frequency was lower in the ELo/CHi cluster. The EHi/CHi cluster had the worst memory impairment, whereas the ELo/CHi cluster had the worst impairment in nonmemory domains. Interpretation: This study demonstrates considerable variability in [18F]AV-1451 tau-PET uptake in AD, but shows that a straightforward clustering based on entorhinal and cortical uptake maps well onto age and clinical presentation in AD. Ann Neurol 2018 Ann Neurol 2018;83:248–257.

LanguageEnglish (US)
Pages248-257
Number of pages10
JournalAnnals of Neurology
Volume83
Issue number2
DOIs
StatePublished - Feb 1 2018

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Cluster Analysis
Alzheimer Disease
Apolipoprotein E4
Entorhinal Cortex
Neocortex
Phenotype
Age of Onset
Amyloid
Positron-Emission Tomography
Cerebellum
Demography

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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[18F]AV-1451 clustering of entorhinal and cortical uptake in Alzheimer's disease. / Whitwell, Jennifer Lynn; Graff-Radford, Jonathan; Tosakulwong, Nirubol; Weigand, Stephen D.; Machulda, Mary Margaret; Senjem, Matthew L.; Schwarz, Christopher G.; Spychalla, Anthony J.; Jones, David T; Drubach, Daniel A.; Knopman, David S; Boeve, Bradley F; Taner, Nilufer; Petersen, Ronald Carl; Lowe, Val; Jack, Clifford R Jr.; Josephs, Keith Anthony.

In: Annals of Neurology, Vol. 83, No. 2, 01.02.2018, p. 248-257.

Research output: Contribution to journalArticle

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abstract = "Objective: To use a cluster analysis of [18F]AV-1451 tau-PET data to determine how subjects with Alzheimer's disease (AD) vary in the relative involvement of the entorhinal cortex and neocortex, and determine whether relative involvement of these two regions can help explain variability in age and clinical phenotype in AD. Methods: We calculated [18F]AV-1451 uptake in entorhinal cortex and neocortex in 62 amyloid-positive AD patients (39 typical and 23 atypical presentation). tau-PET (positron emission tomography) values were normalized to the cerebellum to create standard uptake value ratios (SUVRs). tau-PET SUVRs were log-transformed and clustered blinded to clinical information into three groups using K-median cluster analysis. Demographics, clinical phenotype, cognitive performance, and apolipoprotein e4 frequency were compared across clusters. Results: The cluster analysis identified a cluster with low entorhinal and cortical uptake (ELo/CLo), one with low entorhinal but high cortical uptake (ELo/CHi), and one with high cortical and entorhinal uptake (EHi/CHi). Clinical phenotype differed across clusters, with typical AD most commonly observed in the ELo/CLo and EHi/CHi clusters, and atypical AD most commonly observed in the ELo/CHi cluster. The ELo/CLo cluster had an older age at PET and onset than the other clusters. Apolipoprotein e4 frequency was lower in the ELo/CHi cluster. The EHi/CHi cluster had the worst memory impairment, whereas the ELo/CHi cluster had the worst impairment in nonmemory domains. Interpretation: This study demonstrates considerable variability in [18F]AV-1451 tau-PET uptake in AD, but shows that a straightforward clustering based on entorhinal and cortical uptake maps well onto age and clinical presentation in AD. Ann Neurol 2018 Ann Neurol 2018;83:248–257.",
author = "Whitwell, {Jennifer Lynn} and Jonathan Graff-Radford and Nirubol Tosakulwong and Weigand, {Stephen D.} and Machulda, {Mary Margaret} and Senjem, {Matthew L.} and Schwarz, {Christopher G.} and Spychalla, {Anthony J.} and Jones, {David T} and Drubach, {Daniel A.} and Knopman, {David S} and Boeve, {Bradley F} and Nilufer Taner and Petersen, {Ronald Carl} and Val Lowe and Jack, {Clifford R Jr.} and Josephs, {Keith Anthony}",
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AU - Whitwell, Jennifer Lynn

AU - Graff-Radford, Jonathan

AU - Tosakulwong, Nirubol

AU - Weigand, Stephen D.

AU - Machulda, Mary Margaret

AU - Senjem, Matthew L.

AU - Schwarz, Christopher G.

AU - Spychalla, Anthony J.

AU - Jones, David T

AU - Drubach, Daniel A.

AU - Knopman, David S

AU - Boeve, Bradley F

AU - Taner, Nilufer

AU - Petersen, Ronald Carl

AU - Lowe, Val

AU - Jack, Clifford R Jr.

AU - Josephs, Keith Anthony

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N2 - Objective: To use a cluster analysis of [18F]AV-1451 tau-PET data to determine how subjects with Alzheimer's disease (AD) vary in the relative involvement of the entorhinal cortex and neocortex, and determine whether relative involvement of these two regions can help explain variability in age and clinical phenotype in AD. Methods: We calculated [18F]AV-1451 uptake in entorhinal cortex and neocortex in 62 amyloid-positive AD patients (39 typical and 23 atypical presentation). tau-PET (positron emission tomography) values were normalized to the cerebellum to create standard uptake value ratios (SUVRs). tau-PET SUVRs were log-transformed and clustered blinded to clinical information into three groups using K-median cluster analysis. Demographics, clinical phenotype, cognitive performance, and apolipoprotein e4 frequency were compared across clusters. Results: The cluster analysis identified a cluster with low entorhinal and cortical uptake (ELo/CLo), one with low entorhinal but high cortical uptake (ELo/CHi), and one with high cortical and entorhinal uptake (EHi/CHi). Clinical phenotype differed across clusters, with typical AD most commonly observed in the ELo/CLo and EHi/CHi clusters, and atypical AD most commonly observed in the ELo/CHi cluster. The ELo/CLo cluster had an older age at PET and onset than the other clusters. Apolipoprotein e4 frequency was lower in the ELo/CHi cluster. The EHi/CHi cluster had the worst memory impairment, whereas the ELo/CHi cluster had the worst impairment in nonmemory domains. Interpretation: This study demonstrates considerable variability in [18F]AV-1451 tau-PET uptake in AD, but shows that a straightforward clustering based on entorhinal and cortical uptake maps well onto age and clinical presentation in AD. Ann Neurol 2018 Ann Neurol 2018;83:248–257.

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