Here is another gray matter paper, and now in PD patients. Not in MSA patients, but it is IMO clear that gray matter atrophy is also present in MSA brains. I believe that ATH434 will also affect the gray matter, not only "MSA Atrophy Index: composite z-score of putamen, GP,
cerebellum and brainstem vs. healthy age-matched population". Gray matter atrophy could perhaps explain even more clearly the changes in UMSARS than the MSA Atrophy Index (??). Think about writing, cleaning, cutting food, dressing, walking, etc. Gray matter is important in all these functions.

Behav Brain Res

. 2025 Aug 5:491:115654.

doi: 10.1016/j.bbr.2025.115654. Epub 2025 May 22.

Grey matter loss across deteriorating cognitive stages in Parkinson's disease

M Chondrogiorgi ¹, L Astrakas ², A Zikou ³, M I Argyropoulou ³, S Konitsiotis ⁴

Affiliations Expand

• PMID: 40412557

DOI: 10.1016/j.bbr.2025.115654Free article

Abstract

The purpose of the present study was to depict the pattern of grey matter (GM) abnormalities in patients with Parkinson's disease (PD) and various stages of cognitive decline. GM changes were investigated with the use of voxel-based morphometry in three age-matched groups consisted of PD patients with normal cognition (PD-NC, n = 20), mild cognitive impairment (PD-MCI, n = 20) and dementia (PDD, n = 21). The Parkinson's disease-cognitive rating scale (PD-CRS) was used for the neuropsychological assessment of the subjects and to define patient groups. GM atrophy was observed in the PD-MCI group in right middle and inferior temporal gyri and in the PDD group in right thalamus and hippocampus both compared to PD-NC group. Regression analyses retrieved significant associations among total, cortical, and subcortical PD-CRS scores and GM volume in multiple areas, with an exceptionally stable finding being the correlation of striatal atrophy with deteriorating cognitive function. Significant associations were also observed between GM volume in specific regions and the performance of patients in particular PD-CRS items. The study findings reveal a central role of striatal atrophy in the PD-related cognitive decline. Degenerative changes in temporal regions could contribute to MCI, while hippocampal and thalamic atrophy are proposed to accompany the transition to dementia.