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Diffusion MRI tracks cortical microstructural changes during the early stages of Alzheimer’s disease

Spotorno, Nicola LU ; Strandberg, Olof LU ; Stomrud, Erik LU orcid ; Janelidze, Shorena LU ; Blennow, Kaj LU ; Nilsson, Markus LU ; van Westen, Danielle LU orcid and Hansson, Oskar LU orcid (2024) In Brain 147(3). p.961-969
Abstract

There is increased interest in developing markers reflecting microstructural changes that could serve as outcome measures in clinical trials. This is especially important after unexpected results in trials evaluating disease-modifying therapies targeting amyloid-β (Aβ), where morphological metrics from MRI showed increased volume loss despite promising clinical treatment effects. In this study, changes over time in cortical mean diffusivity, derived using diffusion tensor imaging, were investigated in a large cohort (n = 424) of non-demented participants from the Swedish BioFINDER study. Participants were stratified following the Aβ/tau (AT) framework. The results revealed a widespread increase in mean diffusivity over time, including... (More)

There is increased interest in developing markers reflecting microstructural changes that could serve as outcome measures in clinical trials. This is especially important after unexpected results in trials evaluating disease-modifying therapies targeting amyloid-β (Aβ), where morphological metrics from MRI showed increased volume loss despite promising clinical treatment effects. In this study, changes over time in cortical mean diffusivity, derived using diffusion tensor imaging, were investigated in a large cohort (n = 424) of non-demented participants from the Swedish BioFINDER study. Participants were stratified following the Aβ/tau (AT) framework. The results revealed a widespread increase in mean diffusivity over time, including both temporal and parietal cortical regions, in Aβ-positive but still tau-negative individuals. These increases were steeper in Aβ-positive and tau-positive individuals and robust to the inclusion of cortical thickness in the model. A steeper increase in mean diffusivity was also associated with both changes over time in fluid markers reflecting astrocytic activity (i.e. plasma level of glial fibrillary acidic protein and CSF levels of YKL-40) and worsening of cognitive performance (all P < 0.01). By tracking cortical microstructural changes over time and possibly reflecting variations related to the astrocytic response, cortical mean diffusivity emerges as a promising marker for tracking treatments-induced microstructural changes in clinical trials.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, amyloid-β, astrocytes, clinical trials, cortical mean diffusivity
in
Brain
volume
147
issue
3
pages
9 pages
publisher
Oxford University Press
external identifiers
  • pmid:38128551
  • scopus:85186593123
ISSN
0006-8950
DOI
10.1093/brain/awad428
language
English
LU publication?
yes
id
29db7c39-d7bc-4242-bcbc-150558ea65cc
date added to LUP
2024-03-27 10:48:03
date last changed
2024-04-24 14:43:21
@article{29db7c39-d7bc-4242-bcbc-150558ea65cc,
  abstract     = {{<p>There is increased interest in developing markers reflecting microstructural changes that could serve as outcome measures in clinical trials. This is especially important after unexpected results in trials evaluating disease-modifying therapies targeting amyloid-β (Aβ), where morphological metrics from MRI showed increased volume loss despite promising clinical treatment effects. In this study, changes over time in cortical mean diffusivity, derived using diffusion tensor imaging, were investigated in a large cohort (n = 424) of non-demented participants from the Swedish BioFINDER study. Participants were stratified following the Aβ/tau (AT) framework. The results revealed a widespread increase in mean diffusivity over time, including both temporal and parietal cortical regions, in Aβ-positive but still tau-negative individuals. These increases were steeper in Aβ-positive and tau-positive individuals and robust to the inclusion of cortical thickness in the model. A steeper increase in mean diffusivity was also associated with both changes over time in fluid markers reflecting astrocytic activity (i.e. plasma level of glial fibrillary acidic protein and CSF levels of YKL-40) and worsening of cognitive performance (all P &lt; 0.01). By tracking cortical microstructural changes over time and possibly reflecting variations related to the astrocytic response, cortical mean diffusivity emerges as a promising marker for tracking treatments-induced microstructural changes in clinical trials.</p>}},
  author       = {{Spotorno, Nicola and Strandberg, Olof and Stomrud, Erik and Janelidze, Shorena and Blennow, Kaj and Nilsson, Markus and van Westen, Danielle and Hansson, Oskar}},
  issn         = {{0006-8950}},
  keywords     = {{Alzheimer’s disease; amyloid-β; astrocytes; clinical trials; cortical mean diffusivity}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{961--969}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain}},
  title        = {{Diffusion MRI tracks cortical microstructural changes during the early stages of Alzheimer’s disease}},
  url          = {{http://dx.doi.org/10.1093/brain/awad428}},
  doi          = {{10.1093/brain/awad428}},
  volume       = {{147}},
  year         = {{2024}},
}