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Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
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Identifying Distinct Spatiotemporal Patterns of Juxtacortical Microstructure in Alzheimer Disease Using Diffusion
Junfang Zhang1,2, Xinyuan Yang1, Yan Wang3
1Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Radiology
|October 7, 2025
Summary
Free water fraction (FWF) is elevated in Alzheimer disease (AD) and linked to amyloid-beta and tau pathology. Distinct FWF progression patterns correlate with specific cognitive deficits, offering potential imaging insights for AD.
Area of Science:
- Neuroimaging
- Alzheimer's Disease Research
- Biomarker Discovery
Background:
- Free water fraction (FWF) is an emerging imaging biomarker for Alzheimer disease (AD).
- Understanding FWF's role in AD progression and its association with core neuropathologies is crucial.
Purpose of the Study:
- To investigate juxtacortical FWF in individuals with AD and normal cognition.
- To assess the relationship between FWF, neuropathologic severity (amyloid-beta and tau), and neurodegeneration.
- To characterize the spatiotemporal patterns of FWF changes using advanced MRI and PET imaging.
Main Methods:
- A prospective study analyzed diffusion MRI for FWF, 18F-florbetapir PET for amyloid-beta (Aβ), and 18F-MK-6240 PET for tau in 359 participants.
- Two subtype and stage inference (SuStaIn) models were employed: one analyzing FWF change, the other integrating FWF and Aβ.
- Statistical analyses included FDR correction to evaluate associations between FWF, Aβ, tau, and cognitive performance.
Main Results:
- Participants with AD exhibited significantly increased juxtacortical FWF compared to controls (FDR-corrected P < .001 to P = .049).
- Elevated FWF correlated with higher global cortical Aβ and tau deposition (FDR-corrected P < .001 to P = .04 for Aβ; P < .001 to P = .01 for tau).
- Two distinct FWF spatiotemporal trajectories were identified: an 'orbitofrontal-first' subtype associated with smaller hippocampal volumes and worse cognition, and an 'amyloid-first' subtype linked to higher amyloid levels and reduced cortical thickness.
Conclusions:
- Juxtacortical FWF is elevated in AD and associated with key AD pathologies (Aβ, tau) and neurodegeneration markers.
- Distinct spatiotemporal progression patterns of FWF are linked to differential cognitive performance profiles.
- FWF represents a promising imaging biomarker for characterizing AD subtypes and progression.
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