(i)identify associations between demographic, genetic, clinical participant characteristics, and cortical micro- and macro-structural integrity, as measured by GWC and MD, and volume and thickness, respectively (Fig. 1)

(ii)quantify the extent of shared/divergent variance between MRI features reflecting cortical micro- and macro-structural integrity, on a global and regional scale (Fig. 2)

(iii)examine the cross-sectional relation between cortical Aβ burden and MRI features reflecting cortical micro- and macro-structural integrity (Fig. 3)

(iv)approximate the time at which MRI features reflecting cortical micro- and macro-structural integrity become affected relative to clinically meaningful amounts of cortical Aβ aggregates (Fig. 4)

 

Methods

We analyzed cross-sectional harmonized* MRI and amyloid-β (Aβ) positron emission tomography (PET) data from 1323 non-demented AMYPAD participants. Cortical volume, thickness, gray-white matter contrast (GWC), and mean diffusivity (MD) were related to global Aβ burden and estimated time to Aβ-positivity** using regression, correlation, and change-point analyses.

Fig. 1: Global averages of micro- and macrostructural cortex properties are differentially affected by demographic and clinical characteristics

Fig. 2: Global and regional inter-phenotypic correlations

Fig. 3: Global Aβ burden is mostly related to boundary-based measures, less to volume and MD

Fig. 4: AD-related phenotype changes occur earlier for GWC than for macrostructural cortex measures

 

Conclusions

Our findings indicate that cortical microstructural MRI measures, particularly GWC, show patterns that are partially independent from classical morphometric measures such as cortical volume and thickness. Alterations in GWC were detectable years before amyloid-β positivity and cortical atrophy. This positions GWC as a sensitive marker of early brain changes in preclinical Alzheimer's disease.