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Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease

A major focus of Alzheimer's disease (AD) research has been finding sensitive outcome measures to disease progression in preclinical AD, as intervention studies begin to target this population. We hypothesize that tailored measures of longitudinal change of the medial temporal lobe (MTL) subreg...

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Autores principales: Xie, Long, Wisse, Laura E. M., Das, Sandhitsu R., Vergnet, Nicolas, Dong, Mengjin, Ittyerah, Ranjit, de Flores, Robin, Yushkevich, Paul A., Wolk, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555086/
https://www.ncbi.nlm.nih.gov/pubmed/32845545
http://dx.doi.org/10.1002/hbm.25151
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author Xie, Long
Wisse, Laura E. M.
Das, Sandhitsu R.
Vergnet, Nicolas
Dong, Mengjin
Ittyerah, Ranjit
de Flores, Robin
Yushkevich, Paul A.
Wolk, David A.
author_facet Xie, Long
Wisse, Laura E. M.
Das, Sandhitsu R.
Vergnet, Nicolas
Dong, Mengjin
Ittyerah, Ranjit
de Flores, Robin
Yushkevich, Paul A.
Wolk, David A.
author_sort Xie, Long
collection PubMed
description A major focus of Alzheimer's disease (AD) research has been finding sensitive outcome measures to disease progression in preclinical AD, as intervention studies begin to target this population. We hypothesize that tailored measures of longitudinal change of the medial temporal lobe (MTL) subregions (the sites of earliest cortical tangle pathology) are more sensitive to disease progression in preclinical AD compared to standard cognitive and plasma NfL measures. Longitudinal T1‐weighted MRI of 337 participants were included, divided into amyloid‐β negative (Aβ−) controls, cerebral spinal fluid p‐tau positive (T+) and negative (T−) preclinical AD (Aβ+ controls), and early prodromal AD. Anterior/posterior hippocampus, entorhinal cortex, Brodmann areas (BA) 35 and 36, and parahippocampal cortex were segmented in baseline MRI using a novel pipeline. Unbiased change rates of subregions were estimated using MRI scans within a 2‐year‐follow‐up period. Experimental results showed that longitudinal atrophy rates of all MTL subregions were significantly higher for T+ preclinical AD and early prodromal AD than controls, but not for T− preclinical AD. Posterior hippocampus and BA35 demonstrated the largest group differences among hippocampus and MTL cortex respectively. None of the cross‐sectional MTL measures, longitudinal cognitive measures (PACC, ADAS‐Cog) and cross‐sectional or longitudinal plasma NfL reached significance in preclinical AD. In conclusion, longitudinal atrophy measurements reflect active neurodegeneration and thus are more directly linked to active disease progression than cross‐sectional measurements. Moreover, accelerated atrophy in preclinical AD seems to occur only in the presence of concomitant tau pathology. The proposed longitudinal measurements may serve as efficient outcome measures in clinical trials.
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spelling pubmed-75550862020-10-19 Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease Xie, Long Wisse, Laura E. M. Das, Sandhitsu R. Vergnet, Nicolas Dong, Mengjin Ittyerah, Ranjit de Flores, Robin Yushkevich, Paul A. Wolk, David A. Hum Brain Mapp Research Articles A major focus of Alzheimer's disease (AD) research has been finding sensitive outcome measures to disease progression in preclinical AD, as intervention studies begin to target this population. We hypothesize that tailored measures of longitudinal change of the medial temporal lobe (MTL) subregions (the sites of earliest cortical tangle pathology) are more sensitive to disease progression in preclinical AD compared to standard cognitive and plasma NfL measures. Longitudinal T1‐weighted MRI of 337 participants were included, divided into amyloid‐β negative (Aβ−) controls, cerebral spinal fluid p‐tau positive (T+) and negative (T−) preclinical AD (Aβ+ controls), and early prodromal AD. Anterior/posterior hippocampus, entorhinal cortex, Brodmann areas (BA) 35 and 36, and parahippocampal cortex were segmented in baseline MRI using a novel pipeline. Unbiased change rates of subregions were estimated using MRI scans within a 2‐year‐follow‐up period. Experimental results showed that longitudinal atrophy rates of all MTL subregions were significantly higher for T+ preclinical AD and early prodromal AD than controls, but not for T− preclinical AD. Posterior hippocampus and BA35 demonstrated the largest group differences among hippocampus and MTL cortex respectively. None of the cross‐sectional MTL measures, longitudinal cognitive measures (PACC, ADAS‐Cog) and cross‐sectional or longitudinal plasma NfL reached significance in preclinical AD. In conclusion, longitudinal atrophy measurements reflect active neurodegeneration and thus are more directly linked to active disease progression than cross‐sectional measurements. Moreover, accelerated atrophy in preclinical AD seems to occur only in the presence of concomitant tau pathology. The proposed longitudinal measurements may serve as efficient outcome measures in clinical trials. John Wiley & Sons, Inc. 2020-08-26 /pmc/articles/PMC7555086/ /pubmed/32845545 http://dx.doi.org/10.1002/hbm.25151 Text en © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Xie, Long
Wisse, Laura E. M.
Das, Sandhitsu R.
Vergnet, Nicolas
Dong, Mengjin
Ittyerah, Ranjit
de Flores, Robin
Yushkevich, Paul A.
Wolk, David A.
Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease
title Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease
title_full Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease
title_fullStr Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease
title_full_unstemmed Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease
title_short Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease
title_sort longitudinal atrophy in early braak regions in preclinical alzheimer's disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555086/
https://www.ncbi.nlm.nih.gov/pubmed/32845545
http://dx.doi.org/10.1002/hbm.25151
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