The rapid progression of brain atrophy becomes very clear when you compare it with the atrophy in PD patients and with healthy people. This measure is not the main target in ATH434 ph 2 studies but most likely this can also be measured. The main thing in the ph 2 study is the iron content of the brain in the MRI which relates to brain atrophy.

Mov Disord

. 2023 Nov 7.

doi: 10.1002/mds.29633. Online ahead of print.

Progressive Brain Atrophy in Multiple System Atrophy: A Longitudinal, Multicenter, Magnetic Resonance Imaging Study

Florian Krismer ^{1 2}, Patrice Péran ³, Vincent Beliveau ^{1 2}, Klaus Seppi ^{1 2}, Germain Arribarat ³, Anne Pavy-Le Traon ⁴, Wassilios G Meissner ^{5 6 7}, Alexandra Foubert-Samier ^{5 6 8}, Margherita Fabbri ⁹, Michael M Schocke ², Mark Forrest Gordon ¹⁰, Gregor K Wenning ¹, Werner Poewe ^{1 2}, Olivier Rascol ⁹, Christoph Scherfler ^{1 2}

Affiliations expand

• PMID: 37933745

DOI: 10.1002/mds.29633

Abstract

Objective: To determine the rates of brain atrophy progression in vivo in patients with multiple system atrophy (MSA).

Background: Surrogate biomarkers of disease progression are a major unmet need in MSA. Small-scale longitudinal studies in patients with MSA using magnetic resonance imaging (MRI) to assess progression of brain atrophy have produced inconsistent results. In recent years, novel MRI post-processing methods have been developed enabling reliable quantification of brain atrophy in an automated fashion.

Methods: Serial 3D-T1-weighted MRI assessments (baseline and after 1 year of follow-up) of 43 patients with MSA were analyzed and compared to a cohort of early-stage Parkinson's disease (PD) patients and healthy controls (HC). FreeSurfer's longitudinal analysis stream was used to determine the brain atrophy rates in an observer-independent fashion.

Results: Mean ages at baseline were 64.4 ± 8.3, 60.0 ± 7.5, and 59.8 ± 9.2 years in MSA, PD patients and HC, respectively. A mean disease duration at baseline of 4.1 ± 2.5 years in MSA patients and 2.3 ± 1.4 years in PD patients was observed. Brain regions chiefly affected by MSA pathology showed progressive atrophy with annual rates of atrophy for the cerebellar cortex, cerebellar white matter, pons, and putamen of -4.24 ± 6.8%, -8.22 ± 8.8%, -4.67 ± 4.9%, and - 4.25 ± 4.9%, respectively. Similar to HC, atrophy rates in PD patients were minimal with values of -0.41% ± 1.8%, -1.47% ± 4.1%, -0.04% ± 1.8%, and -1.54% ± 2.2% for cerebellar cortex, cerebellar white matter, pons, and putamen, respectively.

Conclusions: Patients with MSA show significant brain volume loss over 12 months, and cerebellar, pontine, and putaminal volumes were the most sensitive to change in mid-stage disease. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.