Longitudinal Multi-Site Modeling of Brain Atrophy Trajectories Associated with Amyloid and Tau

Amyloid and tau pathogenesis are hallmarks of Alzheimer's disease (AD) and occur before observable volumetric changes in a brain MRI scan. Amyloid beta plaque deposition can occur years before tau accumulation and neurodegeneration, and may be an important predictor of subsequent brain atrophy. In this study, we evaluated T1-weighted MRI data from four longitudinal AD datasets to assess associations between amyloid beta and tau biomarkers and brain atrophy patterns using tensor based morphometry. To account for potential non-linear effects of atrophy over time, we modeled age effects, time interval between subject visits, and the acceleration of atrophy with aging in the context of amyloid and tau positivity. We found that amyloid and tau positivity were both associated with greater atrophy and greater atrophy rates in medial temporal lobe brain regions associated with AD. Furthermore, we found that amyloid and tau positivity were associated with different acceleration patterns, namely that the rate of amyloid-related atrophy decelerated with age while tau-related atrophy rates accelerated.