Brain volume trajectories in Down syndrome and autosomal dominant Alzheimer's disease

INTRODUCTION: It is unknown if neurodegeneration trajectories differ between Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD), both of which are genetic forms of Alzheimer's disease (AD). METHODS: We compared brain volumes in DS, ADAD, and unaffected family members serving as controls. Participants underwent magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET), deriving volumetric and amyloid burden, respectively. Nonlinear associations between regional volumes and estimated years to clinical symptom onset (EYO) were evaluated using generalized additive mixed-models. RESULTS: Longitudinal data from 267 controls, 341 participants with DS, and 358 participants with ADAD were included, totaling 1908 scans. DS volumes were lower than ADAD and controls initially and dropped linearly. ADAD had similar volumes to controls until diverging, beginning at EYO -7. Amyloid was negatively associated with volume, with similar slopes in DS and ADAD. DISCUSSION: ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.