" In this longitudinal study, we have shown for the first time that magnetic susceptibility changes are predictive of future cognitive and motor outcomes in PD."

MR susceptibility measures the iron content indirectly.

The primate study by ATH demonstrated that motor function was recovered by reducing iron content with Iron chelator ATH434.

This new paper is a human study, however. It tells us that the bigger the iron content is the more rapidly the clinical outcomes get worse. In other words, they should get ATH434 as soon as possible, IMO. But nothing is simple and we need to wait, perhaps first up to April in spite I waiting for interim results already within 2.5 months, in March.

Mov Disord

. 2024 Jan 3.

doi: 10.1002/mds.29702. Online ahead of print.

Longitudinal Associations of Magnetic Susceptibility with Clinical Severity in Parkinson's Disease

George E C Thomas ¹, Naomi Hannaway ¹, Angelika Zarkali ¹, Karin Shmueli ², Rimona S Weil ^{1 3 4}

Affiliations expand

• PMID: 38173297

DOI: 10.1002/mds.29702

Abstract

Background: Dementia is common in Parkinson's disease (PD), but there is wide variation in its timing. A critical gap in PD research is the lack of quantifiable markers of progression, and methods to identify early stages of dementia. Atrophy-based magnetic resonance imaging (MRI) has limited sensitivity in detecting or tracking changes relating to PD dementia, but quantitative susceptibility mapping (QSM), sensitive to brain tissue iron, shows potential for these purposes.

Objective: The objective of the paper is to study, for the first time, the longitudinal relationship between cognition and QSM in PD in detail.

Methods: We present a longitudinal study of clinical severity in PD using QSM, including 59 PD patients (without dementia at study onset), and 22 controls over 3 years.

Results: In PD, increased baseline susceptibility in the right temporal cortex, nucleus basalis of Meynert, and putamen was associated with greater cognitive severity after 3 years; and increased baseline susceptibility in basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was associated with greater motor severity after 3 years. Increased follow-up susceptibility in these regions was associated with increased follow-up cognitive and motor severity, with further involvement of hippocampus relating to cognitive severity. However, there were no consistent increases in susceptibility over 3 years.

Conclusions: Our study suggests that QSM may predict changes in cognitive severity many months prior to overt cognitive involvement in PD. However, we did not find robust longitudinal changes in QSM over the course of the study. Additional tissue metrics may be required together with QSM for it to monitor progression in clinical practice and therapeutic trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.