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

## TL;DR

This study compares brain volume changes in Down syndrome and autosomal dominant Alzheimer's disease before symptoms appear.

## Contribution

The study reveals distinct brain volume decline patterns in Down syndrome and autosomal dominant Alzheimer's disease.

## Key findings

- Down syndrome shows earlier and continuous brain volume decline compared to controls.
- Autosomal dominant Alzheimer's disease shows similar volumes to controls until shortly before symptom onset.
- Amyloid burden similarly affects brain volume decline in both conditions.

## Abstract

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).

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.

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.

ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.

Volume declines before Alzheimer's pathology in Down syndrome.Volume declines shortly before symptom onset in autosomal dominant Alzheimer's.Down syndrome and autosomal dominant Alzheimer's are similarly affected by amyloid.Estimated years to onset of decline outpredicts volume relative to Centiloid.

Volume declines before Alzheimer's pathology in Down syndrome.

Volume declines shortly before symptom onset in autosomal dominant Alzheimer's.

Down syndrome and autosomal dominant Alzheimer's are similarly affected by amyloid.

Estimated years to onset of decline outpredicts volume relative to Centiloid.