Summary: Two major international imaging studies demonstrate that brain biomarkers can forecast whether people with isolated REM sleep behavior disorder (iRBD) will later develop Parkinson’s disease or dementia with Lewy bodies (DLB). Advanced MRI techniques show that reduced glymphatic circulation predicts a higher risk of Parkinson’s, while increased free water in the basal nucleus of Meynert strongly predicts conversion to DLB.
Conducted across multiple countries, these are the largest MRI studies to date in patients with polysomnography‑confirmed iRBD. Their findings point toward earlier diagnosis, targeted monitoring, and the potential for preventive therapies before irreversible neurodegeneration occurs.
Key facts
- Parkinson’s predictor: Reduced glymphatic fluid circulation (lower DTI‑ALPS index) was associated with a roughly 2.4‑fold increased risk of developing Parkinson’s disease.
- DLB predictor: Elevated free water in the basal nucleus of Meynert was linked to an approximately eightfold greater risk of conversion to dementia with Lewy bodies.
- Clinical impact: For the first time, imaging biomarkers can help distinguish which neurodegenerative outcome is likely years before clinical symptoms appear.
Source: University of Montreal
An international team led by Université de Montréal medical professor Shady Rahayel reports a major advance in predicting neurodegenerative disease trajectories.
Using two complementary multicenter studies, researchers can now identify, years in advance, which individuals with isolated REM sleep behavior disorder—iRBD—are most likely to develop Parkinson’s disease or dementia with Lewy bodies (DLB). iRBD causes people to act out their dreams, often with loud vocalizations or violent movements that can injure bed partners.
“This is more than restless sleep—it’s a clear neurological warning sign,” said Rahayel, a neuropsychologist at the Centre for Advanced Research in Sleep Medicine, Sacré‑Cœur Hospital, Montreal.
About 90% of people diagnosed with iRBD eventually develop a synucleinopathy such as Parkinson’s disease or DLB. Until now clinicians could not reliably predict which disease would develop in a given patient or when conversion would occur.
First biomarker: predicting Parkinson’s disease
The first study, led by Université de Montréal doctoral student Violette Ayral and published in Neurology, included 428 participants from Canada, the United States, France, the United Kingdom and Czechia. Researchers evaluated the brain’s glymphatic system—a network that clears metabolic waste during sleep, including proteins implicated in neurodegeneration.
Using diffusion tensor imaging along the perivascular space (DTI‑ALPS), the team measured fluid movement near the lateral ventricles in 250 patients with polysomnography‑confirmed iRBD and 178 healthy control subjects, with an average follow‑up of six years.
The primary finding was that a lower left‑hemisphere DTI‑ALPS index—indicating reduced glymphatic circulation—was associated with a 2.4‑fold higher risk of developing Parkinson’s disease over time. No similar association was found for conversion to DLB.
“The left‑sided asymmetry mirrors the clinical pattern in early Parkinson’s, where motor symptoms often start on one side of the body,” said Ayral. This is the first robust evidence that MRI‑measured glymphatic dysfunction can serve as a prognostic biomarker for Parkinson’s in patients with iRBD.
Second biomarker: predicting dementia with Lewy bodies (DLB)
The second study, led by doctoral student Celine Haddad and published in Alzheimer’s & Dementia, examined 438 participants from the same international cohort. Investigators focused on the basal nucleus of Meynert—a brain region critical for attention and cognition—and measured the amount of free water, defined as water not constrained by cells and therefore indicative of microscopic tissue changes such as inflammation or early cell loss.
After a median follow‑up of roughly 8.4 years, participants who later developed DLB had substantially higher free water levels in the basal nucleus of Meynert. That elevation corresponded to an approximately eightfold increase in the likelihood of converting to DLB, and proved more sensitive than traditional measures of brain atrophy for predicting this outcome.
“This marker detects very early tissue changes, well before clinical symptoms arise,” said Haddad, underscoring its potential value in early detection and intervention strategies.
Toward precision medicine for neurodegeneration
Together, these two large multicenter MRI studies—each conducted in patients with polysomnography‑confirmed iRBD—provide complementary biomarkers that help predict distinct disease trajectories. Measuring glymphatic function via DTI‑ALPS and assessing free water in the basal nucleus of Meynert can help clinicians forecast whether a patient is more likely to develop Parkinson’s disease or DLB, years before diagnosis.
These biomarkers could enable personalized monitoring plans, guide enrollment in targeted clinical trials, and support earlier intervention aimed at slowing or preventing neurodegeneration. By identifying who is at greatest risk for specific synucleinopathies, care can be tailored and resources allocated more effectively.
“We have long recognized isolated REM sleep behavior disorder as a potent early warning sign for synucleinopathies,” said Rahayel. “Now, with these imaging tools, we can better predict which disease will develop and begin to personalize care and prevention strategies much earlier.”
About this sleep and Parkinson’s disease research news
Author: Julie Gazaille ([email protected])
Source: University of Montreal
Contact: Julie Gazaille – University of Montreal
Image: Image credited to Neuroscience News
Original research (open access): DTI‑ALPS associates with differential phenoconversion in patients with isolated REM sleep behaviour disorder: a multicenter MRI study by Shady Rahayel et al., published in Neurology. This study and a complementary article in Alzheimer’s & Dementia report the DTI‑ALPS and free‑water findings described above.
Abstract
DTI‑ALPS associates with differential phenoconversion in patients with isolated REM sleep behaviour disorder: a multicenter MRI study
Background and objectives
Isolated REM sleep behavior disorder (iRBD) is the most reliable prodromal marker of synucleinopathies such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Identifying brain imaging biomarkers that both predict progression and distinguish likely phenoconversion trajectories remains a major clinical challenge. The glymphatic system plays a central role in clearing interstitial waste during sleep, and glymphatic dysfunction has been linked to abnormal protein accumulation and neurodegenerative processes. Diffusion tensor imaging along the perivascular space (DTI‑ALPS) has emerged as a noninvasive proxy measure of glymphatic function. This study evaluated whether patients with iRBD exhibit reduced DTI‑ALPS indices relative to controls and whether a lower DTI‑ALPS index predicts later conversion to PD or DLB.
Methods
The investigation was a longitudinal multicenter cohort study using T1‑weighted and diffusion‑weighted MRI from patients with polysomnography‑confirmed iRBD and healthy controls recruited across five international centers. DTI‑ALPS indices were calculated from diffusivity measures along projection and associative fiber tracts adjacent to the lateral ventricles. The primary outcome measure was time to phenoconversion to a synucleinopathy. Baseline group differences and clinical correlations were tested with linear models; Cox proportional hazards models assessed whether DTI‑ALPS predicted time to phenoconversion.
Results
The sample included 250 patients with iRBD (mean age 66.5 ± 6.8 years; 87% male) and 178 controls (mean age 65.7 ± 6.8 years; 81% male). Patients with iRBD showed a lower left‑hemisphere DTI‑ALPS index compared with controls. Among 224 iRBD patients followed for an average of 6.1 ± 3.5 years, 65 converted to a synucleinopathy. Converters had a lower left DTI‑ALPS index than nonconverters, and a reduced left DTI‑ALPS index was associated with a higher risk of conversion specifically to Parkinson’s disease (hazard ratio ≈ 2.43). Other diffusion metrics within periventricular regions, including fractional anisotropy and free‑water measures, did not differ between groups in this analysis.
Discussion
Patients with iRBD exhibit reduced DTI‑ALPS indices, consistent with altered glymphatic function. The association between reduced DTI‑ALPS and later conversion to Parkinson’s disease supports the use of this MRI measure as a potential prognostic biomarker for progression in prodromal synucleinopathies. When combined with complementary markers—such as basal nucleus of Meynert free‑water measures—these imaging tools may enable earlier, disease‑specific risk stratification and more personalized approaches to monitoring and early intervention.