Systems fail before molecules spread: A cascading failure model of Alzheimer’s disease

Triangulated surfaces were geneterated to contour the most likely voxels for each structure. This atlas was mapped diffeomorphically onto each scan, and atrophy in aMCI patients relative to controls was quantified through local change in surface area, a technique known as surface diffeomorphometry. Regions with significant differences between groups were identified using permutation testing, controlling for false positives at 5% familywise error rate. Results: Anatomical changes were detected, including atrophy in the transentorhinal / lateral-entorhinal region (p < 1e-6). Conclusions:This atlas based method for probabilistically identifying topographic changes in the MTL identified regions of atrophy consistent with Braak staging for early Alzheimers disease. This method may also be useful for following the longitudinal progression of disease in the context of a clinical trial.