Longitudinal within-subject MRI analysis detects accelerated atrophy in preclinical Alzheimer’s disease that is invisible to cross-sectional MRI due to high anatomical variability, demonstrating the necessity of longitudinal methods for early detection.

In early Alzheimer’s, abnormal tau proteins clump together in memory-related brain areas, killing nerve cells and shrinking those regions. These changes happen too slowly and too variably between people to see in a single scan, but repeated scans of the same person show the shrinkage getting worse over time. Later, the same process spreads to brain areas that control attention and thinking, making the shrinkage even clearer on follow-up scans.