Relationship between cortical diffusivity and neuropathological substrates in Alzheimer’s disease

Abstract Background Pathological alterations in Alzheimer’s disease (AD) begin several years before the onset of symptoms. Grey matter mean diffusivity (MD) may be used as a measure of early grey matter damage in AD as it reflects the breakdown of microstructural barriers, which precede volumetric changes and affect cognitive function. In this study, we investigated the changes in MD early on in the disease trajectory, and relate them to the amyloid and tau deposition. Method We analysed multimodal PET, DTI and MRI data of 90 participants, stratified into amyloid‐ß negative and positive, cognitively normal (CN), mild cognitive impaired (MCI) and AD patients. Result We found that MD was significantly increased in Aß‐positive MCI and AD compared with CN in frontal, parietal, temporal cortex, hippocampus, and medial temporal lobe. We also found that cortical MD is significantly correlated with cortical thickness only in patients without amyloid deposition and is not significant in Aß‐positive patients. Conclusion Our results suggest that cortical MD is an early marker of neuronal damage as it is observed simultaneously as Aß deposition and as it is correlated with cortical thickness when there is no Aß deposition. This suggests that cortical MD provides information about early microstructural changes before macrostructural changes.