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Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis
Background: Mild cognitive impairment (MCI) is a condition with diverse causes and clinical outcomes that can be categorized into subtypes. [(18)F]THK5351 has been known to detect reactive astrogliosis as well as tau which is accompanied by neurodegenerative changes. Here, we identified heterogeneou...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874013/ https://www.ncbi.nlm.nih.gov/pubmed/33584247 http://dx.doi.org/10.3389/fnagi.2020.615467 |
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author | Lee, Hyun Jeong Lee, Eun-Chong Seo, Seongho Ko, Kwang-Pil Kang, Jae Myeong Kim, Woo-Ram Seo, Ha-Eun Lee, Sang-Yoon Lee, Yeong-Bae Park, Kee Hyung Yeon, Byeong Kil Okamura, Nobuyuki Na, Duk L. Seong, Joon-Kyung Noh, Young |
author_facet | Lee, Hyun Jeong Lee, Eun-Chong Seo, Seongho Ko, Kwang-Pil Kang, Jae Myeong Kim, Woo-Ram Seo, Ha-Eun Lee, Sang-Yoon Lee, Yeong-Bae Park, Kee Hyung Yeon, Byeong Kil Okamura, Nobuyuki Na, Duk L. Seong, Joon-Kyung Noh, Young |
author_sort | Lee, Hyun Jeong |
collection | PubMed |
description | Background: Mild cognitive impairment (MCI) is a condition with diverse causes and clinical outcomes that can be categorized into subtypes. [(18)F]THK5351 has been known to detect reactive astrogliosis as well as tau which is accompanied by neurodegenerative changes. Here, we identified heterogeneous groups of MCI patients using THK retention patterns and a graph theory approach, allowing for the comparison of risk of progression to dementia in these MCI subgroups. Methods: Ninety-seven participants including 60 MCI patients and individuals with normal cognition (NC, n = 37) were included and undertook 3T MRI, [(18)F]THK5351 PET, and detailed neuropsychological tests. [(18)F]Flutemetamol PET was also performed in 62 participants. We calculated similarities between MCI patients using their regional standardized uptake value ratio of THK retention in 75 ROIs, and clustered subjects with similar retention patterns using the Louvain method based on the modularity of the graph. The clusters of patients identified were compared with an age-matched control group using a general linear model. Dementia conversion was evaluated after a median follow-up duration of 34.6 months. Results: MCI patients were categorized into four groups according to their THK retention patterns: (1) limbic type; (2) diffuse type; (3) sparse type; and (4) AD type (retention pattern as in AD). Subjects of the limbic type were characterized by older age, small hippocampal volumes, and reduced verbal memory and frontal/executive functions. Patients of the diffuse type had relatively large vascular burden, reduced memory capacity and some frontal/executive functions. Co-morbidity and mortality were more frequent in this subgroup. Subjects of the sparse type were younger and declined only in terms of visual memory and attention. No individuals in this subgroup converted to dementia. Patients in the AD type group exhibited the poorest cognitive function. They also had the smallest hippocampal volumes and the highest risk of progression to dementia (90.9%). Conclusion: Using cluster analyses with [(18)F]THK5351 retention patterns, it is possible to identify clinically-distinct subgroups of MCI patients and those at greater risk of progression to dementia. |
format | Online Article Text |
id | pubmed-7874013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78740132021-02-11 Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis Lee, Hyun Jeong Lee, Eun-Chong Seo, Seongho Ko, Kwang-Pil Kang, Jae Myeong Kim, Woo-Ram Seo, Ha-Eun Lee, Sang-Yoon Lee, Yeong-Bae Park, Kee Hyung Yeon, Byeong Kil Okamura, Nobuyuki Na, Duk L. Seong, Joon-Kyung Noh, Young Front Aging Neurosci Neuroscience Background: Mild cognitive impairment (MCI) is a condition with diverse causes and clinical outcomes that can be categorized into subtypes. [(18)F]THK5351 has been known to detect reactive astrogliosis as well as tau which is accompanied by neurodegenerative changes. Here, we identified heterogeneous groups of MCI patients using THK retention patterns and a graph theory approach, allowing for the comparison of risk of progression to dementia in these MCI subgroups. Methods: Ninety-seven participants including 60 MCI patients and individuals with normal cognition (NC, n = 37) were included and undertook 3T MRI, [(18)F]THK5351 PET, and detailed neuropsychological tests. [(18)F]Flutemetamol PET was also performed in 62 participants. We calculated similarities between MCI patients using their regional standardized uptake value ratio of THK retention in 75 ROIs, and clustered subjects with similar retention patterns using the Louvain method based on the modularity of the graph. The clusters of patients identified were compared with an age-matched control group using a general linear model. Dementia conversion was evaluated after a median follow-up duration of 34.6 months. Results: MCI patients were categorized into four groups according to their THK retention patterns: (1) limbic type; (2) diffuse type; (3) sparse type; and (4) AD type (retention pattern as in AD). Subjects of the limbic type were characterized by older age, small hippocampal volumes, and reduced verbal memory and frontal/executive functions. Patients of the diffuse type had relatively large vascular burden, reduced memory capacity and some frontal/executive functions. Co-morbidity and mortality were more frequent in this subgroup. Subjects of the sparse type were younger and declined only in terms of visual memory and attention. No individuals in this subgroup converted to dementia. Patients in the AD type group exhibited the poorest cognitive function. They also had the smallest hippocampal volumes and the highest risk of progression to dementia (90.9%). Conclusion: Using cluster analyses with [(18)F]THK5351 retention patterns, it is possible to identify clinically-distinct subgroups of MCI patients and those at greater risk of progression to dementia. Frontiers Media S.A. 2021-01-26 /pmc/articles/PMC7874013/ /pubmed/33584247 http://dx.doi.org/10.3389/fnagi.2020.615467 Text en Copyright © 2021 Lee, Lee, Seo, Ko, Kang, Kim, Seo, Lee, Lee, Park, Yeon, Okamura, Na, Seong and Noh. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Lee, Hyun Jeong Lee, Eun-Chong Seo, Seongho Ko, Kwang-Pil Kang, Jae Myeong Kim, Woo-Ram Seo, Ha-Eun Lee, Sang-Yoon Lee, Yeong-Bae Park, Kee Hyung Yeon, Byeong Kil Okamura, Nobuyuki Na, Duk L. Seong, Joon-Kyung Noh, Young Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis |
title | Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis |
title_full | Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis |
title_fullStr | Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis |
title_full_unstemmed | Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis |
title_short | Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis |
title_sort | identification of heterogeneous subtypes of mild cognitive impairment using cluster analyses based on pet imaging of tau and astrogliosis |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874013/ https://www.ncbi.nlm.nih.gov/pubmed/33584247 http://dx.doi.org/10.3389/fnagi.2020.615467 |
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