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. 2025 Sep 26;29(5):298.
doi: 10.1007/s11325-025-03479-w.

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

Jung-Ick Byun  1 , Jun-Sang Sunwoo  2 , Jung-Won Shin  3 , Tae-Joon Kim  4 , Jin-Sun Jun  5 , Chul-Ho Sohn  6 , Hongyoon Choi  7 , Jung Hwan Shin  8 , Han-Joon Kim  8 , Won Chul Shin  1 , Ki-Young Jung  9   10
Affiliations

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

Jung-Ick Byun et al. Sleep Breath. .

Abstract

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.

Keywords: DTI-ALPS; Longitudinal; Neurodegeneration; Phenoconversion; REM sleep behavior disorder.

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Conflict of interest statement

Declarations. Ethics approval: This study was conducted in line with the principles of the Declaration of Helsinki and were approved by the institutional review board of the Seoul National University Hospital and Kyung Hee University Hospital at Gangdong (IRB No. 1702-150-835 and 2017-04-001, respectively). Consent to participate: All participants provided written informed consent. Conflict of interest: JIB is supported by the National Research Foundation of Korea (NRF) (No. 2020R1C1C1013160). JSS, JWS, TJK, JSJ, CHS, HC, JHS, HJK, WCS, and KYJ declare no conflicts of interest in the context of this paper.

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