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

This study aimed at: (1) assessing microstructural MRI and glymphatic flow alterations in isolated REM sleep behavioral disorder (iRBD) subjects relative to controls; (2) comparing sub-groups of iRBD patients with different levels of disease severity; and (3) studying the correlations between clinical alterations and MRI changes. 44 iRBD subjects and 52 controls underwent clinical and MRI evaluations. Gray and white-matter microstructural alterations were studied. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) index was obtained for the evaluation of glymphatic flow functionality. Cluster analysis was applied to divide iRBD patients in sub-groups. IRBD subjects showed worse sleep quality, reduced manual dexterity and gait alterations relative to controls. IRBD had alterations in the gray matter of fronto-parietal lobes and in the white matter of brainstem and frontal lobe, and a lower DTI-ALPS index relative to controls. Correlation analyses in the iRBD group showed that worse gray-matter microstructural alterations correlated with worse manual dexterity, lower peak turning velocity during dual-task mobility and worse sleep quality. Cluster analysis identified two clusters, one with worse clinical, neuropsychological, gait performances and DTI-ALPS index. The study detected early neurodegeneration in iRBD, subtle clinical deficits, microstructural gray/white-matter changes, and lower DTI-ALPS scores hinting at glymphatic dysfunction.