Neuroimaging of White Matter Integrity in Alzheimer's Disease

Alzheimer’s disease is characterised not only by the accumulation of amyloid plaques and tau tangles in grey matter but also by progressive disruption of white matter pathways that underlie cognitive functions. Neuroimaging techniques, in particular diffusion-weighted magnetic resonance imaging, have enabled the in vivo assessment of microstructural integrity across major fibre tracts. By quantifying parameters such as fractional anisotropy and mean diffusivity, researchers can detect subtle changes in axonal coherence and myelin health that precede overt atrophy. These alterations often emerge in limbic circuits—including the fornix and cingulum bundle—before clinical symptoms manifest, offering a window into preclinical stages of the disease. Multimodal approaches that combine diffusion imaging with measures of cortical thickness or molecular PET biomarkers yield richer characterisations of disease progression and may facilitate early diagnosis, patient stratification and the evaluation of novel therapies. Continued refinement of imaging protocols and analysis methods promises to enhance sensitivity to microstructural change and to translate these insights into routine clinical practice worldwide.

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Neuroimaging of White Matter Integrity in Alzheimer's Disease publication trend

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Technical terms

Diffusion tensor imaging (DTI): An MRI method that measures the directional diffusion of water molecules to infer microstructural properties of white matter.

Fractional anisotropy (FA): A scalar index of how directionally constrained water diffusion is within tissue, with higher values indicating greater fibre coherence.

Mean diffusivity (MD): A measure of the overall magnitude of water diffusion, with increases often reflecting tissue breakdown or increased extracellular space.

Radial and axial diffusivity: Components of mean diffusivity representing diffusion perpendicular (radial) or parallel (axial) to axonal fibres, sensitive to myelin and axonal integrity respectively.

Free-water elimination: An analytical technique that separates extracellular fluid contributions from tissue-specific diffusion signals, enhancing sensitivity to cellular changes.

Tract-based spatial statistics (TBSS): A voxel-wise analytical framework for aligning and comparing diffusion metrics across groups along a common skeletal representation of major fibre tracts.

References

1. Neuroimaging Biomarkers for Alzheimer’s Disease. Molecular Neurodegeneration (2019).
2. Diffusion tensor imaging in Alzheimer's disease: insights into the limbic-diencephalic network and methodological considerations. Frontiers in Aging Neuroscience (2014).
3. White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease. Brain (2018).
4. Relationship Between DTI Metrics and Cognitive Function in Alzheimer’s Disease. Frontiers in Aging Neuroscience (2019).
5. Microstructural white matter alterations in preclinical Alzheimer’s disease detected using free water elimination diffusion tensor imaging. PLOS ONE (2017).