Unveiling hidden neurodegeneration in isolated REM sleep behavior disorder through MRI microstructure and glymphatic...

Area of Science:

• Neuroscience
• Radiology
• Sleep Medicine

Background:

• Isolated REM sleep behavioral disorder (iRBD) is a prodromal stage for synucleinopathies.
• Early detection of neurodegeneration and associated functional changes is crucial for understanding disease progression.

Purpose of the Study:

• To assess microstructural MRI and glymphatic flow alterations in iRBD patients compared to controls.
• To compare iRBD subgroups based on disease severity.
• To investigate correlations between clinical symptoms and MRI findings.

Main Methods:

• 44 iRBD subjects and 52 controls underwent clinical and MRI evaluations.
• Microstructural alterations in gray and white matter were analyzed.
• Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) was used to evaluate glymphatic flow.
• Cluster analysis identified patient subgroups.

Main Results:

• iRBD subjects exhibited poorer sleep quality, reduced manual dexterity, and gait disturbances.
• Alterations were observed in the fronto-parietal gray matter and brainstem/frontal white matter.
• A lower DTI-ALPS index indicated impaired glymphatic function in iRBD patients.
• Worse gray matter changes correlated with poorer manual dexterity, mobility, and sleep quality.
• Cluster analysis revealed subgroups with distinct clinical and DTI-ALPS profiles.

Conclusions:

• iRBD is associated with early neurodegeneration, including microstructural brain changes and impaired glymphatic flow.
• Subtle clinical deficits correlate with specific MRI findings.
• The DTI-ALPS index may serve as a biomarker for glymphatic dysfunction in iRBD.