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

Xie, Long ; Wisse, Laura E.M. LU ; Das, Sandhitsu R. ; Vergnet, Nicolas ; Dong, Mengjin ; Ittyerah, Ranjit ; de Flores, Robin ; Yushkevich, Paul A. and Wolk, David A. (2020) In Human Brain Mapping
Abstract

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,... (More)

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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organization
publishing date
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Contribution to journal
publication status
epub
subject
keywords
ASHS, Brodmann area 35, cross-sectional, entorhinal cortex, hippocampus, longitudinal atrophy, MRI, preclinical Alzheimer's disease, tau
in
Human Brain Mapping
publisher
Wiley-Blackwell
external identifiers
  • scopus:85089859876
ISSN
1065-9471
DOI
10.1002/hbm.25151
language
English
LU publication?
yes
id
2c4e52b5-7d3c-49fb-ba9c-9c6e4578399a
date added to LUP
2020-09-08 14:23:19
date last changed
2020-09-09 06:06:36
@article{2c4e52b5-7d3c-49fb-ba9c-9c6e4578399a,
  abstract     = {<p>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.</p>},
  author       = {Xie, Long and Wisse, Laura E.M. and Das, Sandhitsu R. and Vergnet, Nicolas and Dong, Mengjin and Ittyerah, Ranjit and de Flores, Robin and Yushkevich, Paul A. and Wolk, David A.},
  issn         = {1065-9471},
  language     = {eng},
  month        = {01},
  publisher    = {Wiley-Blackwell},
  series       = {Human Brain Mapping},
  title        = {Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease},
  url          = {http://dx.doi.org/10.1002/hbm.25151},
  doi          = {10.1002/hbm.25151},
  year         = {2020},
}