HAI Book 2025 - Flipbook - Page 466
Tonietto, Matteo
Impact of ARIA on cerebral volume changes with Gantenerumab
Matteo Tonietto1, Erica Silvestri1, Christopher Belder2,3, Frederik Barkhof2,4, Nick Fox2, Janice
Smith5, Gregory Klein1
1
Research and Early Development (pRED), Hoffmann-La Roche, Basel, CH
Dementia Research Centre, UCL Queen Square Institute of Neurology, London, GB
3
Adelaide Medical School, University of Adelaide, Adelaide, AU
4
Department of Radiology & Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, NL
5
Roche Products Ltd, Hoffmann-La Roche, Welwyn Garden City, GB
2
Introduction: Gantenerumab is a monoclonal antibody targeting aggregated forms of amyloid-beta. The phase III
GRADUATE investigational studies aimed to assess the efficacy and safety of gantenerumab in early AD. Similarly
to other anti-A´ immunotherapies, participants treated with Gantenerumab 1) exhibited accelerated brain volume
loss compared to placebo and 2) in some cases, also developed amyloid‐related imaging abnormalities (ARIA). In
this study, we investigated the relationship between ARIA and brain volume loss.
Methods: Volumetric MRI changes in the whole cortex, white matter, lateral ventricles, and cerebellum regions
were calculated using Tensor-Based-Morphometry and compared between placebo, and gantenerumab-treated
participants both with and without ARIA. Additionally, the study investigated the association between volumetric
changes and the maximum Barkhof Grand Total Scale (BGTS) score of ARIA severity in the ARIA group, as well as
the relationship between volume changes and clinical/cognitive scores in all three groups.
Results: At the end of the study, relative to no ARIA, the group with ARIA showed no significant difference in
whole cortex or white matter volume loss but had greater lateral ventricular volume expansion and lower
cerebellar volume loss (Figure 1).
At week 52, in the ARIA group higher BGTS scores were associated with smaller regional volume changes, and
greater ventricular volume expansion. By the study9s end, only ventricular volume expansion was still associated
with the ARIA BGTS score (Figure 2)
Participants with ARIA exhibited less clinical/cognitive change for the same amount of ventricular expansion
compared to those on Gantenerumab without ARIA and placebo (Figure 3).
Conclusion: ARIA effect on cortical volume change was transient and resolved by the end of the studies. The
lower volume loss in the cerebellum and higher expansion of the ventricles in the ARIA group suggest an alteration
of the CSF dynamics due to ARIA, which was not associated with accelerated clinical/cognitive worsening.
HAI2025 - 466
