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Fixel-Based Analysis Reveals Tau-Related White Matter Changes in Early Stages of Alzheimer’s Disease

Ahmadi, Khazar LU ; Pereira, Joana B. LU ; van Westen, Danielle LU orcid ; Pasternak, Ofer ; Zhang, Fan ; Nilsson, Markus LU ; Stomrud, Erik LU orcid ; Spotorno, Nicola LU and Hansson, Oskar LU orcid (2024) In Journal of Neuroscience 44(18).
Abstract

Several studies have shown white matter (WM) abnormalities in Alzheimer’s disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic... (More)

Several studies have shown white matter (WM) abnormalities in Alzheimer’s disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations in Aβ-positive patients with mild cognitive impairment compared to control groups. Metrics derived from DKI, and FW-DTI showed similar alterations whereas WM degeneration detected by DTI was more widespread. Tau-PET uptake in medial temporal regions was only correlated with reduced FC mainly in the parahippocampal cingulum in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Despite the spatially extensive between-group differences in DTI-metrics, the link between WM and tau aggregation was only revealed using FBA metrics implying high sensitivity but low specificity of DTI-based measures in identifying subtle tau-related WM degeneration. No relationship was found between amyloid load and any diffusion-MRI measures. Our results indicate that early tau-related WM alterations in AD are due to macrostructural changes specifically captured by FBA metrics. Thus, future studies assessing the effects of AD pathology in WM tracts should consider using FBA metrics.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, diffusion tensor imaging, fixel-based analysis, memory, white matter
in
Journal of Neuroscience
volume
44
issue
18
article number
e0538232024
publisher
Society for Neuroscience
external identifiers
  • pmid:38565289
  • scopus:85192020183
ISSN
0270-6474
DOI
10.1523/JNEUROSCI.0538-23.2024
language
English
LU publication?
yes
id
9ee57644-6711-4f22-baf1-59bd4d4f079a
date added to LUP
2024-05-16 14:34:00
date last changed
2024-05-30 20:27:08
@article{9ee57644-6711-4f22-baf1-59bd4d4f079a,
  abstract     = {{<p>Several studies have shown white matter (WM) abnormalities in Alzheimer’s disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations in Aβ-positive patients with mild cognitive impairment compared to control groups. Metrics derived from DKI, and FW-DTI showed similar alterations whereas WM degeneration detected by DTI was more widespread. Tau-PET uptake in medial temporal regions was only correlated with reduced FC mainly in the parahippocampal cingulum in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Despite the spatially extensive between-group differences in DTI-metrics, the link between WM and tau aggregation was only revealed using FBA metrics implying high sensitivity but low specificity of DTI-based measures in identifying subtle tau-related WM degeneration. No relationship was found between amyloid load and any diffusion-MRI measures. Our results indicate that early tau-related WM alterations in AD are due to macrostructural changes specifically captured by FBA metrics. Thus, future studies assessing the effects of AD pathology in WM tracts should consider using FBA metrics.</p>}},
  author       = {{Ahmadi, Khazar and Pereira, Joana B. and van Westen, Danielle and Pasternak, Ofer and Zhang, Fan and Nilsson, Markus and Stomrud, Erik and Spotorno, Nicola and Hansson, Oskar}},
  issn         = {{0270-6474}},
  keywords     = {{Alzheimer’s disease; diffusion tensor imaging; fixel-based analysis; memory; white matter}},
  language     = {{eng}},
  number       = {{18}},
  publisher    = {{Society for Neuroscience}},
  series       = {{Journal of Neuroscience}},
  title        = {{Fixel-Based Analysis Reveals Tau-Related White Matter Changes in Early Stages of Alzheimer’s Disease}},
  url          = {{http://dx.doi.org/10.1523/JNEUROSCI.0538-23.2024}},
  doi          = {{10.1523/JNEUROSCI.0538-23.2024}},
  volume       = {{44}},
  year         = {{2024}},
}