Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer’s Disease

Eun Chong Lee; Jae Myeong Kang; Seongho Seo; Ha Eun Seo; Sang Yoon Lee; Kee Hyung Park; Duk L. Na; Young Noh; Joon Kyung Seong

doi:10.3389/fnagi.2020.563559

Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer’s Disease

Eun Chong Lee, Jae Myeong Kang, Seongho Seo, Ha Eun Seo, Sang Yoon Lee, Kee Hyung Park, Duk L. Na, Young Noh, Joon Kyung Seong

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman’s correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer’s pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.

Original language	English
Article number	563559
Journal	Frontiers in Aging Neuroscience
Volume	12
DOIs	https://doi.org/10.3389/fnagi.2020.563559
Publication status	Published - 2020 Oct 26

Bibliographical note

Funding Information:
Funding. This study was supported by a grant from the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HI14C1135), a grant from the Brain Research Program of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (No. 2018M3C7A1056889); by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korean Government (MSIT) [No. 2019-0-00079, Department of Artificial Intelligence (Korea University)]; and by Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (No. 2020M3C7A101835721).

Funding Information:
This study was supported by a grant from the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HI14C1135), a grant from the Brain Research Program of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (No. 2018M3C7A1056889); by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korean Government (MSIT) [No. 2019-0-00079,

Publisher Copyright:
© Copyright © 2020 Lee, Kang, Seo, Seo, Lee, Park, Na, Noh and Seong.

Keywords

Alzheimer’s disease
amyloid
cortical thickness
magnetic resonance imaging
positron emission tomography
subcortical shape analysis
tau

ASJC Scopus subject areas

Ageing
Cognitive Neuroscience

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10.3389/fnagi.2020.563559

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title = "Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer{\textquoteright}s Disease",

abstract = "The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer{\textquoteright}s disease (EOAD) and late-onset Alzheimer{\textquoteright}s disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman{\textquoteright}s correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer{\textquoteright}s pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.",

keywords = "Alzheimer{\textquoteright}s disease, amyloid, cortical thickness, magnetic resonance imaging, positron emission tomography, subcortical shape analysis, tau",

author = "Lee, {Eun Chong} and Kang, {Jae Myeong} and Seongho Seo and Seo, {Ha Eun} and Lee, {Sang Yoon} and Park, {Kee Hyung} and Na, {Duk L.} and Young Noh and Seong, {Joon Kyung}",

note = "Funding Information: Funding. This study was supported by a grant from the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HI14C1135), a grant from the Brain Research Program of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (No. 2018M3C7A1056889); by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korean Government (MSIT) [No. 2019-0-00079, Department of Artificial Intelligence (Korea University)]; and by Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (No. 2020M3C7A101835721). Funding Information: This study was supported by a grant from the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HI14C1135), a grant from the Brain Research Program of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (No. 2018M3C7A1056889); by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korean Government (MSIT) [No. 2019-0-00079, Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Lee, Kang, Seo, Seo, Lee, Park, Na, Noh and Seong.",

year = "2020",

month = oct,

day = "26",

doi = "10.3389/fnagi.2020.563559",

language = "English",

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T1 - Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer’s Disease

AU - Lee, Eun Chong

AU - Kang, Jae Myeong

AU - Seo, Seongho

AU - Seo, Ha Eun

AU - Lee, Sang Yoon

AU - Park, Kee Hyung

AU - Na, Duk L.

AU - Noh, Young

AU - Seong, Joon Kyung

N1 - Funding Information: Funding. This study was supported by a grant from the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HI14C1135), a grant from the Brain Research Program of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (No. 2018M3C7A1056889); by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korean Government (MSIT) [No. 2019-0-00079, Department of Artificial Intelligence (Korea University)]; and by Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (No. 2020M3C7A101835721). Funding Information: This study was supported by a grant from the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HI14C1135), a grant from the Brain Research Program of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (No. 2018M3C7A1056889); by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korean Government (MSIT) [No. 2019-0-00079, Publisher Copyright: © Copyright © 2020 Lee, Kang, Seo, Seo, Lee, Park, Na, Noh and Seong.

PY - 2020/10/26

Y1 - 2020/10/26

N2 - The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman’s correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer’s pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.

AB - The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman’s correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer’s pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.

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Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer’s Disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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