Abstract
Pathological alterations in Alzheimer's disease (AD) begin several years prior to symptom onset. Cortical mean diffusivity (cMD) may be used as a measure of early grey matter damage in AD as it reflects the breakdown of microstructural barriers preceding volumetric changes and affecting cognitive function. We investigated cMD changes early in the disease trajectory and evaluated the influence of amyloid-β (Aβ) and tau deposition. In this cross-sectional study, we analysed multimodal PET, DTI, and MRI data of 87 participants, and stratified them into Aβ-negative and -positive, cognitively normal, mildly cognitively impaired, and AD patients. cMD was significantly increased in Aβ-positive MCI and AD compared with CN in the frontal, parietal, temporal cortex, hippocampus, and medial temporal lobe. cMD was significantly correlated with cortical thickness only in patients without Aβ deposition but not in Aβ-positive patients. Our results suggest that cMD is an early marker of neuronal damage since it is observed simultaneously with Aβ deposition and is correlated with cortical thickness only in subjects without Aβ deposition. cMD changes may be driven by Aβ but not tau, suggesting that direct Aβ toxicity or associated inflammation causes damage to neurons. cMD may provide information about early microstructural changes before macrostructural changes.