Sleep disorders predict Parkinson’s or dementia years ahead

ABSTRACT: Two historical international studies show that brain biomarkers can predict whether people with REM sleep behavior disorder (IRBD) will develop Parkinson’s disease or dementia with Lewy bodies (DLB). Magnetic resonance scans revealed that the reduction of the function of the glyphatic system indicates a higher risk for Parkinson’s, while the increase in free water in the basal core of Meynert predicts the progression to DLB.

These findings come from larger image studies ever performed in patients with IRBD confirmed. The results are paving the way for the previous diagnosis, directed monitoring and preventive treatments before irreversible brain damage occurs.

Key facts

Parkinson’s predictor: Reduced glyphatic fluid circulation doubled Parkinson’s risk. DLB predictor: Greater free water in the basal core of the high DLB risk of Meynert 8 times. Clinical impact: First tools to differentiate the results of the disease years before symptoms.

Source: Montreal University

An international research team led by the medical professor at the University of Montreal, Shady Rahayel, has made a progress in the prediction of neurodegenerative diseases.

Thanks to two complementary studies of UDEM, scientists can now determine, years in advance, that people with a particular sleep disorder will develop Parkinson’s disease or dementia with Lewy bodies (DLB).

Studies focus on Rest sleep behavior disorder (IRBD), a condition in which people shout, attack or act their dreams, sometimes violently enough to hurt a bed couple.

“It’s not just a restless dream, it is a neurological warning sign,” said Rahayel, a neuropsychologist and researcher at the Advanced Research Center in Sleep Medicine at the Sacré-Cœur hospital in Montreal.

Approximately 90 percent of people with this sleep disorder will eventually develop Parkinson’s disease or DLB. Until now, however, it was impossible to know what disease would happen, or when.

First Biomarker: Parkinson Prediction

The first study, led by the Udem doctoral student in Violette Ayral Neurosciences and published in Neurology on September 16, involved 428 participants from five countries: Canada, the United States, France, the United Kingdom and Czech.

He examined the glyphatic system of the brain, a network that clears metabolic waste during sleep, including proteins linked to neurodegeneration. When this system is affected, waste accumulates, which potentially triggers diseases such as Parkinson’s.

Using an advanced magnetic resonance technique known as DTI ALP, researchers measured the circulation of liquids in specific brain regions in 250 patients with IRBD and 178 subjects of healthy control, with an average follow -up of six years.

The key finding: patients with a lower DTI alp index in the left hemisphere of the brain (indicating a reduced circulation of liquids) had 2.4 times more likely to develop Parkinson’s disease in the following years. This link for dementia with Lewy bodies was not found.

“This asymmetry reflects what we see clinically in the first Parkinson, where motor symptoms often begin on one side of the body; it can mark the earliest stage of the disease,” said Ayral.

This is the first evidence that the glyphatic function, measured by magnetic resonance, can predict the progression to that of Parkinson’s, and the largest international study ever performed on this issue between patients with REM sleep disorder confirmed by polysomnography.

Second biomarker: DLB prediction

The second study, led by Udem doctoral student in Neuropsychology Celine Haddad and published in Alzheimer’s & Dementia on September 19, focused on 438 participants of the same five countries as the first study.

A different approach was taken to predict the beginning of the DLB, a condition that combines Parkinsonian symptoms (tremors, stiffness) and symptoms similar to Alzheimer’s (cognitive deterioration, confusion, hallucinations). It is the second most common degenerative dementia after Alzheimer’s.

The researchers measured the amount of “free water”, water not linked by brain cells and capable of flowing freely between them, in the basal core of Meynert, a key region for thought and reasoning. This free water is a sign of early microscopic changes, such as inflammation or cell loss, and serves as an indirect marker of neuronal degeneration.

After a medium tracking of 8.4 years, the results were surprising: the people who developed DLB had significantly higher levels of free water in this region of the brain, which makes them eight times more likely to become this form of dementia. This method was more sensitive than traditional approaches based on brain atrophy.

“The fascinating thing is that this marker collects very early changes, even before the symptoms arise,” said Haddad.

Towards precision medicine

These studies represent the largest international research ever conducted in IRBD patients confirmed by polysomnography, and pave the way for personalized detection tests to predict what disease they will develop before the symptoms appear.

Doctors can adapt medical monitoring to each patient’s trajectory and better direct clinical trials for preventive treatments, researchers say, add that their early intervention model could transform care for neurodegenerative diseases when addressing them before irreversible damage occurs.

“We already knew that Remi Remained Behavior Disorder is a warning signal for these diseases,” Rahayel said.

“What we did not know was who would develop what. Thanks to these complementary studies, we now have tools to predict and customize the attention.”

About this of Sleep and Parkinson’s disease research news

Author: Julie Gazaille
Source: Montreal University
Contact: Julie Gazaille – University of Montreal
Image: The image is accredited to Neuroscience News

Original research: open access.
“DTI-ALPS is associated with differential phenoconversion in patients with Isolated Sleep Behavior Disorder: a multicentric magnetic resonance study” by Shady Rahayel et al. Neurology

Abstract

DTI-ALPS is associated with differential phenoconversion in patients with Sleeping Disorder isolated: a multicentric magnetic resonance study

Background and objectives

Inslated sleep behavior disorder (IRBD) is the strongest prodromic marker of Sinucleinopathies, including Parkinson’s disease (EP) and dementia with Lewy bodies (DLB). Identifying brain biomarkers that predict progression and distinguish phenoconversion trajectories remains a challenge. The glyphatic system is involved in the elimination of interstitial waste, and its dysfunction has been associated with the accumulation of pathological proteins and neurodegeneration.

The image of the diffusion tensioner throughout the perivascular space (DTI-ALP) has been proposed as a non-invasive proxy for glucatic function. The objective of this study was to determine if IRBD patients show a reduced DTI-ALP index compared to controls and if a lower DTI-ALP index predicts a future phenoconversion to PD or DLB.

Methods

We carry out a longitudinal multicentral cohort study using brain magnetic resonance resonance scan of IRBD confirmed by polysomnography and healthy controls recruited in 5 international centers. All participants underwent a weighted magnetic resonance in T1 and weighted by diffusion. The DTI-ALP indices were calculated from the diffusivity throughout the projection and the associative fibers adjacent to the lateral ventricles.

The primary result was the time for phenoconversion to sinucleinopathy. Linear models evaluated the differences of reference groups and clinical correlates, and COX proportional danger models evaluated the predictive value of DTI-ALP for time to phenoconversion.

Results

A total of 250 patients with IRBD (Middle Ages: 66.5 ± 6.8 years were included; 87% men) and 178 controls (65.7 ± 6.8 years; 81% male). IRBD patients showed a lower lower DTI-ALP index compared to controls (average difference = −0.034, 95% IC −0.067 to −0.001; p = 0.043). Of 224 patients with IRBD followed during an average of 6.1 ± 3.5 years, 65 phenoconverted to a sinucleinopathy.

The converters had a lower ITI-ALP index than non-converters (average difference = −0.050, 95% IC −0.098 to −0.003; p = 0.038). The lower left DTI-ALP index was associated with a higher risk of conversion to PD over time (Risk ratio = 2.43, 95% IC 1.13–5.25; P = 0.012). Other dissemination metrics within the periventricular masks, namely, fractional anisotropy, diffusivity metrics and free water, did not differ among the groups.

Discussion

IRBD patients exhibit a reduced DTI ALP index, which suggests an altered glyphatic function. This reduction was associated with the future phenoconversion to the EP, which supports the DTI-ALP index as a possible progression biomarker of MRI prognosis in prodromal sinucleinopathies.