Project Overview
Isolated REM sleep behavior disorder (iRBD) is a sleep condition where people physically act out dreams because the normal muscle “paralysis” of REM sleep is lost. It is confirmed by an overnight sleep study with video monitoring. iRBD matters because it is one of the strongest known early warning signs for future synucleinopathies (brain diseases linked to abnormal buildup of the protein alpha-synuclein) especially Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) (and less often multiple system atrophy, MSA). The challenge is that, even after an iRBD diagnosis, we still cannot reliably tell who is heading toward PD versus DLB, when conversion will occur, or which brain mechanisms drive these different outcomes.
Using brain MRI, our team has already shown that iRBD is not a “silent” stage: measurable brain changes are present years before diagnosis. Across large datasets, we found evidence of early tissue loss, inflammation-related tissue changes, and altered waste-clearance signals. Together, these findings suggest that multiple biological processes are already active in the prodromal phase. However, one major mechanism remains poorly understood at scale in iRBD: brain iron biology, despite strong links to oxidative stress and cell-injury pathways implicated in synucleinopathies.
This project will address that gap using quantitative susceptibility mapping (QSM), an MRI method derived from a special multi-echo scan that is strongly influenced by iron (and, in the opposite direction, by myelin). QSM provides a practical, non-invasive way to study iron-linked brain biology in living people.
We will do this work within iSYNC, the large international iRBD MRI collaboration led by our lab, which brings together sleep-study-confirmed iRBD participants, matched healthy controls, and long-term clinical follow-up to see who later develops PD, DLB, or related conditions.
Partners & Donors
Azrieli Foundation
