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February 05, 2019; 92 (6) ArticleOpen Access

Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease

Rik Ossenkoppele, Ruben Smith, Tomas Ohlsson, Olof Strandberg, Niklas Mattsson, Philip S. Insel, Sebastian Palmqvist, Oskar Hansson
First published January 9, 2019, DOI: https://doi.org/10.1212/WNL.0000000000006875
Rik Ossenkoppele
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Ruben Smith
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Tomas Ohlsson
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Olof Strandberg
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Niklas Mattsson
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Philip S. Insel
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Sebastian Palmqvist
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Oskar Hansson
From the Clinical Memory Research Unit (R.O., R.S., O.S., N.M., P.S.I., S.P., O.H.), Lund University, Sweden; Department of Neurology and Alzheimer Center (R.O.), VU University Medical Center, Amsterdam Neuroscience, the Netherlands; Department of Radiation Physics (T.O.), Skåne University Hospital, Lund; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Center for Imaging of Neurodegenerative Diseases (P.S.I.), Department of Veterans Affairs Medical Center, San Francisco, CA.
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Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease
Rik Ossenkoppele, Ruben Smith, Tomas Ohlsson, Olof Strandberg, Niklas Mattsson, Philip S. Insel, Sebastian Palmqvist, Oskar Hansson
Neurology Feb 2019, 92 (6) e601-e612; DOI: 10.1212/WNL.0000000000006875

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Abstract

Objective To examine the cross-sectional associations between regional tau, β-amyloid (Aβ), and cortical thickness and neuropsychological function across the preclinical and clinical spectrum of Alzheimer disease (AD).

Methods We included 106 participants from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study, of whom 33 had preclinical AD (Aβ-positive cognitively normal individuals), 25 had prodromal AD (Aβ-positive mild cognitive impairment), and 48 had probable AD dementia. All underwent [18F]flortaucipir (tau) and structural MRI (cortical thickness), and 88 of 106 underwent [18F]flutemetamol (Aβ) PET. Linear regression models adjusted for age, sex, and education were performed to examine associations between 7 regions of interest and 7 neuropsychological tests for all 3 imaging modalities.

Results In preclinical AD, [18F]flortaucipir, but not [18F]flutemetamol or cortical thickness, was associated with decreased global cognition, memory, and processing speed (range standardized β = 0.35–0.52, p < 0.05 uncorrected for multiple comparisons). In the combined prodromal AD and AD dementia group, both increased [18F]flortaucipir uptake and reduced cortical thickness were associated with worse performance on a variety of neuropsychological tests (most regions of interest survived correction for multiple comparisons at p < 0.05), while increased [18F]flutemetamol uptake was specifically associated with lower scores on a delayed recall memory task (p < 0.05 uncorrected for multiple comparisons). The strongest effects for both [18F]flortaucipir and cortical thickness on cognition were found in the lateral and medial parietal cortex and lateral temporal cortex. The effect of [18F]flutemetamol on cognition was generally weaker and less region specific.

Conclusion Our findings suggest that tau PET is more sensitive than Aβ PET and measures of cortical thickness for detecting early cognitive changes in preclinical AD. Furthermore, both [18F]flortaucipir PET and cortical thickness show strong cognitive correlates at the clinical stages of AD.

Glossary

Aβ=
β-amyloid;
AD=
Alzheimer disease;
ADAS=
Alzheimer's Disease Assessment Scale;
AQT=
A Quick Test for Cognitive Speed;
BioFINDER=
Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably;
FDR=
false discovery rate;
MCI=
mild cognitive impairment;
MMSE=
Mini-Mental State Examination;
PVE=
partial volume effects;
ROI=
region of interest;
SUVR=
standardized uptake value ratio;
TMT-A=
Trail Making Test A

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • The Article Processing Charge was funded by the Swedish Alzheimer’s Foundation.

  • Received March 21, 2018.
  • Accepted in final form October 3, 2018.
  • Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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  • Reader response: Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease
    • Maowen Ba, Neurology Doctor, Department of Neurology, Affiliated Yantai Yuhuangding Hospital of Qingdao University (Yantai, China)
    • , Neurology Doctor, Department of Neurology, Yantaishan Hospital (Yantai, China)
    Published February 26, 2019
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