Objective: This study aimed to evaluate the free water in the dorsoposterior putamen of idiopathic REM sleep behaviour disorder (iRBD) patients, which is considered a prodromal stage of synucleinopathies.

Background: Free-water imaging is sensitive to microstructural changes and posterior substantia nigra free water has been suggested as a progression marker of Parkinson’s disease (PD). It has been shown that the loss of nigrostriatal dopaminergic axon terminals occurs before the loss of dopaminergic neurons in the substantia nigra in PD. The dorsoposterior putamen receives dense dopaminergic projections and is severely damaged in the early stage of PD.

Method: Baseline diffusion MRI data from 48 healthy controls (HC), 43 iRBD patients and 48 PD patients were included, while 31 HC and 33 iRBD patients had longitudinal data. Free water values in the dorsoposterior putamen, dorsoanterior putamen and posterior substantia nigra were measured and compared between the groups. In iRBD patients, the relationship between longitudinal changes of free water values and clinical manifestations or dopamine transporter (DAT) striatal binding ratio (SBR) was analyzed. Additionally, the relationships between the baseline free water values and DAT SBR or clinical features were calculated in the iRBD and PD patients.

Results: Baseline free water values were significantly higher in the dorsoposterior putamen and posterior substantia nigra, but not in the dorsoanterior putamen, in iRBD and PD groups than in HC. In iRBD patients, free water values in the dorsoposterior putamen were progressively increased and correlated with the progression of clinical manifestations and DAT SBR in the striatum. Baseline free water in the dorsoposterior putamen was negatively correlated with DAT SBR in the striatum and hyposmia and positively correlated with motor deficits. The power of free water values in the dorsoposterior putamen was 0.909 and 0.746 in discriminating PD and iRBD patients from HC.

Conclusion: This study first demonstrates that free water values in the dorsoposterior putamen are increased cross-sectionally and longitudinally, and associated with clinical manifestations and function of the dopaminergic system in iRBD patients. Our findings indicate that free-water imaging of the dorsoposterior putamen has the potential to be a valid marker of early diagnosis and progression of synucleinopathies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-free-water-in-the-putamen-in-idiopathic-rem-sleep-behaviour-disorder/