Higher glymphatic system activity is linked to longer prodromal stage in isolated REM sleep behavior disorder: a possible protective factor.
In patients with isolated REM sleep behavior disorder, higher DTI-ALPS indices—indicative of better glymphatic function—were associated with longer prodromal symptom duration and substantially delayed phenoconversion to alpha-synucleinopathy.
What the AI sees
In patients with isolated REM sleep behavior disorder, higher DTI-ALPS indices—indicative of better glymphatic function—were associated with longer prodromal symptom duration and substantially delayed phenoconversion to alpha-synucleinopathy.
Research significance
Points to glymphatic function as a noninvasive biomarker to stratify prodromal PD risk and a plausible, potentially modifiable target (e.g., sleep optimization, AQP4/vascular approaches) for interventions to delay conversion, while noting that causality and therapeutic efficacy remain to be proven.
Source abstract
Isolated rapid eye movement sleep behavior disorder (iRBD) is recognized as a prodromal stage of alpha-synucleinopathies. While glymphatic dysfunction has been investigated in Parkinson's disease, its role in iRBD remains incompletely understood. This study evaluated the association between glymphatic function and the speed-modulating effect to alpha-synucleionpathy conversion. Fifty-six patients (67.2 ± 7.1 [mean age ± SD]) with an iRBD and 48 control subjects (61.5 ± 10.0) underwent brain magnetic resonance imaging. Glymphatic function was evaluated using the diffusion tensor imaging along the perivascular space (DTI-ALPS) method with manual acquisition of the ALPS-index. The mean time from symptom onset to MRI acquisition (T1) was 7.05 ± 5.08 years, while among converters the mean time from symptom onset to phenoconversion (T2) was 11.07 ± 5.68 years. Higher ALPS-index was positively correlated with longer iRBD symptom duration (rho = 0.409, p = 0.002). Although the ALPS-index did not predict phenoconversion in the entire cohort, post-hoc analysis of converters revealed that patients with higher ALPS-index exhibited more than nine years longer time to conversion than patients with lower ALPS-index (χ² = 13.075, p < 0.001). These findings suggest that preserved glymphatic function may be associated with prolonged prodromal stability in iRBD.