Association of DTI-ALPS Glymphatic Index With Differential Phenoconversion in Isolated REM Sleep Behavior Disorder: A
Violette Ayral1,2, Alexandre Pastor-Bernier1, Véronique Daneault1
1Centre for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, CIUSSS du Nord-de-l'Île-de-Montréal, Quebec, Canada.
Neurology
|September 16, 2025
Summary
Patients with isolated REM sleep behavior disorder (iRBD) have reduced glymphatic function, indicated by a lower DTI-ALPS index. This MRI marker predicts future progression to Parkinson disease (PD) and dementia with Lewy bodies (DLB).
Area of Science:
- Neuroimaging
- Neurology
- Biomarker Discovery
Background:
- Isolated REM sleep behavior disorder (iRBD) is a key prodromal marker for synucleinopathies like Parkinson disease (PD) and dementia with Lewy bodies (DLB).
- Identifying reliable brain biomarkers to predict phenoconversion in iRBD patients is crucial for early intervention.
- Glymphatic system dysfunction is implicated in neurodegenerative diseases, potentially linked to abnormal protein accumulation.
Purpose of the Study:
- To investigate glymphatic function in iRBD patients using Diffusion Tensor Imaging along the Perivascular Space (DTI-ALPS) as a noninvasive MRI biomarker.
- To determine if a reduced DTI-ALPS index in iRBD patients correlates with impaired glymphatic function compared to healthy controls.
- To assess the predictive value of the DTI-ALPS index for future phenoconversion to PD or DLB in iRBD patients.
Main Methods:
- A longitudinal, multicenter cohort study involving 250 iRBD patients and 178 healthy controls.
- Brain MRI scans (T1-weighted and diffusion-weighted) were acquired to compute DTI-ALPS indices.
- Cox proportional hazard models were used to analyze the association between DTI-ALPS and time to phenoconversion.
Main Results:
- Patients with iRBD demonstrated a significantly lower left DTI-ALPS index compared to controls (p=0.043).
- A reduced left DTI-ALPS index was observed in iRBD patients who later phenoconverted to synucleinopathy (p=0.038).
- Lower left DTI-ALPS index independently predicted an increased risk of conversion to PD (HR=2.43, p=0.012).
Conclusions:
- iRBD patients exhibit impaired glymphatic function, evidenced by reduced DTI-ALPS indices.
- The DTI-ALPS index serves as a potential prognostic MRI biomarker for predicting synucleinopathy progression in iRBD.
- This finding supports DTI-ALPS as a valuable tool for risk stratification and monitoring in prodromal synucleinopathies.
