Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects

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6 Citations (Scopus)

Abstract

As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.

Original languageEnglish (US)
Pages (from-to)1148-1160
Number of pages13
JournalBrain : a journal of neurology
Volume142
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Entorhinal Cortex
Amyloid
Biomarkers
Repression (Psychology)
Verbal Learning
Sex Education
Temporal Lobe
Positron-Emission Tomography
Cognition
Reproduction
Alzheimer Disease
Magnetic Resonance Imaging
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

Keywords

  • amyloid PET
  • cortical thickness, memory
  • flortaucipir PET

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{d82f2c11d1954eb0a41e3d9d70ca5ef0,
title = "Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects",
abstract = "As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.",
keywords = "amyloid PET, cortical thickness, memory, flortaucipir PET",
author = "Knopman, {David S} and Lundt, {Emily S.} and Therneau, {Terry M} and Vemuri, {Prashanthi D} and Val Lowe and Kantarci, {Kejal M} and Gunter, {Jeffrey L.} and Senjem, {Matthew L.} and Mielke, {Michelle M} and Machulda, {Mary Margaret} and Boeve, {Bradley F} and Jones, {David T} and Jonathan Graff-Radford and Albertson, {Sabrina M.} and Christopher Schwarz and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.}",
year = "2019",
month = "4",
day = "1",
doi = "10.1093/brain/awz025",
language = "English (US)",
volume = "142",
pages = "1148--1160",
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issn = "0006-8950",
publisher = "Oxford University Press",
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T1 - Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects

AU - Knopman, David S

AU - Lundt, Emily S.

AU - Therneau, Terry M

AU - Vemuri, Prashanthi D

AU - Lowe, Val

AU - Kantarci, Kejal M

AU - Gunter, Jeffrey L.

AU - Senjem, Matthew L.

AU - Mielke, Michelle M

AU - Machulda, Mary Margaret

AU - Boeve, Bradley F

AU - Jones, David T

AU - Graff-Radford, Jonathan

AU - Albertson, Sabrina M.

AU - Schwarz, Christopher

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.

AB - As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.

KW - amyloid PET

KW - cortical thickness, memory

KW - flortaucipir PET

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