Tracking glymphatic dysfunction in isolated rapid eye movement sleep behavior disorder: a longitudinal neuroimaging study

Purpose: This study aimed to investigate baseline diffusion tensor imaging along the perivascular space (DTI-ALPS) index differences between patients with isolated REM sleep behavior disorder (iRBD) who progressed to a neurodegenerative disease (iRBD-C) and those who did not (iRBD-NC), and to assess the longitudinal changes in the DTI-ALPS index. Methods: We prospectively studied a cohort of 48 iRBD patients (minimum three-year follow-up) and 20 age- and sex-matched Healthy controls. All participants underwent magnetic resonance imaging. The DTI-ALPS index was then calculated and its values were compared among the iRBD-C, iRBD-NC, and control groups. Twenty-nine iRBD patients and 5 controls were rescanned after a mean of 41 months, and during the total follow-up period (mean = 4.5 years), 14 patients converted. Results: The iRBD-C group showed significantly lower DTI-ALPS indices at baseline compared to the control group (left: p = 0.009; right: p = 0.019). However, there was no significant difference between the iRBD-NC group and the control group. Furthermore, the iRBD-C group showed a lower DTI-ALPS index in the right hemisphere than the iRBD-NC group (p = 0.013). The longitudinal analysis showed a reduction in the ALPS index in patients with iRBD bilaterally. The baseline DTI-ALPS index was associated with baseline and longitudinal changes in cognitive function scores. Conclusion: The baseline DTI-ALPS index may be a promising biomarker for predicting iRBD patients at risk for conversion to alpha-synucleinopathy. The decrease in the ALPS index observed over time may reflect progressive neurodegenerative processes.