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Updated: Jul 7, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Diffusion MRI tracks cortical microstructural changes during the early stages of Alzheimer's disease
Nicola Spotorno1, Olof Strandberg1, Erik Stomrud1,2
1Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, 223 62 Lund, Sweden.
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 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.
Insights
Cortical mean diffusivity, a marker of brain microstructure, increased over time in individuals with amyloid-beta and tau pathology. This finding suggests its potential as an outcome measure in clinical trials for neurodegenerative diseases.
Area of Science:
- Neuroimaging
- Biomarker Development
- Clinical Trials
Background:
- Clinical trials for Alzheimer's disease therapies targeting amyloid-beta have yielded unexpected results.
- Morphological MRI metrics showed increased brain volume loss despite positive clinical effects.
- There is a need for reliable markers of microstructural changes for clinical trial outcome measures.
Purpose of the Study:
- To investigate changes in cortical mean diffusivity over time in non-demented individuals.
- To stratify participants based on the amyloid-beta/tau (AT) framework.
- To assess the potential of cortical mean diffusivity as a marker for microstructural changes in clinical trials.
Main Methods:
- Diffusion tensor imaging was used to derive cortical mean diffusivity.
- A large cohort (n=424) of non-demented participants from the Swedish BioFINDER study was analyzed.
- Participants were stratified according to the Aβ/tau (AT) framework.
Main Results:
- A widespread increase in mean diffusivity was observed over time in temporal and parietal cortical regions of amyloid-beta-positive, tau-negative individuals.
- These increases were steeper in amyloid-beta-positive and tau-positive individuals and independent of cortical thickness.
- Steeper increases in mean diffusivity correlated with changes in fluid markers of astrocytic activity and cognitive decline.
Conclusions:
- Cortical mean diffusivity tracks microstructural changes over time, potentially reflecting astrocytic responses.
- This marker shows promise for monitoring treatment-induced microstructural changes in clinical trials.
- Mean diffusivity may serve as a valuable outcome measure in neurodegenerative disease research.
