Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) is a condition in which individuals physically act out their dreams due to a loss of normal muscle paralysis during REM sleep. While this may sound like a harmless sleep issue, RBD is, in fact, one of the most powerful early warning signs of serious neurodegenerative disease.
A condition that might indicate PD, dementia and MSA
In particular, isolated RBD (iRBD) - meaning RBD in the absence of diagnosed neurological disease or other known triggers, is now recognized as the prodromal (early, before diagnosis) stage of α-synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Nearly 75% of people with PD, and over 90% of those with DLB or MSA, report having had RBD symptoms for years prior to their diagnosis. On average, iRBD can precede clinical diagnosis by up to 15 years.
Long-term studies show that individuals with iRBD convert to a clinically manifested α-synucleinopathy (mostly PD, DLB, or MSA) at a rate of about 6% per year, with over 90% converting within 15 years. This gives us a unique opportunity for early intervention and treatment of neurodegeneration in its nascent stages.
A window to delay or prevent disease outbreak
iRBD affects ~1% in the population >50–60 years, translating to at least ~14,000 individuals in Norway. Because of the long window before diagnosis, high predictive value, and relatively mild symptoms early on, people with iRBD are now considered ideal candidates for neuroprotective clinical trials - that is, studies aimed at delaying or preventing the onset of PD and related diseases.
There are several advantages in testing neuro-protective therapies on patients with iRBD, rather than manifest PD, DLB, or MSA:
- A long prodromal time window offers the opportunity for early intervention, while there is still time to prevent irreversible degeneration.
- High potential for disease modification due to early intervention, before runaway and possibly irreversible processes have taken hold. For instance, a treatment that slows disease progression by ~30% could provide at least 6–10 total extra years without severe disability.
- Less treatment interference: absence of symptomatic dopaminergic therapy interfering with the effects of the trials.
While some may raise ethical concerns about informing people of their risk, the global medical consensus now strongly supports transparency. iRBD is not merely a risk factor; it is already a sign of ongoing neurodegeneration. Informing patients empowers them to make choices about preventive care and participate in trials that could benefit themselves and others.
Moreover, trial participation offers concrete benefits:
- Awareness and empowerment to participate in preventive trials: iRBD is not a risk factor, but a prodromal stage of PD, DLB, or MSA. Thus, a person with iRBD is already suffering from ongoing neurodegeneration. For those reasons, the current consensus in the global medical community is that patients with iRBD should always be informed of their risks to enable informed decision-making regarding participation in neuroprotective trials.
- Access to specialized care: Research studies provide regular follow-up with a clinical neurologist, a service not typically available to individuals with iRBD. Most individuals with iRBD remain undiagnosed until pronounced neurodegenerative symptoms manifest, commonly leading to a delayed diagnosis of α-synucleinopathy and delayed initiation of supportive/symptomatic management. Early identification and regular monitoring will help address dysfunction associated with prodromal symptoms and lead to an early diagnosis of PD, DLB, or MSA, enabling early initiation of supportive treatment.
- Management of symptoms: individuals with prodromal α-synucleinopathy may experience a variety of symptoms including anxiety, depression, constipation, mild cognitive impairment, autonomic dysfunction, and gradually increasing signs of parkinsonism. Furthermore, iRBD can cause considerable somatic and psychological distress, with violent dream enactments leading to potential injuries for the patients or their partners. The substantial impact on the quality of life for both the patient and their partners underscores the need for early and effective management. As such, RBD trials not only contribute to the scientific understanding of α-synucleinopathies but also directly benefit participants by enhancing their quality of life and health outcomes.
The future of neurodegenerative disease research and care
By identifying and monitoring individuals with iRBD, we can both advance scientific understanding of α-synucleinopathies and improve health outcomes for patients and their families. For all these reasons, we believe that iRBD trials are not only ethically justified – they are essential to the future of neurodegenerative disease research and care.
Text by Johannes J. Gaare & Charalampos Tzoulis, March 2025.
Related information:
Article in Bergens Tidende (Norwegian, for subscribers): Han vil forebygge Parkinson. Det er aldri gjort før.
Current clinical studies, now recruiting participants:
NAD-RBD: A Randomised Double-blind Trial of NAD Replenishment Therapy to Prevent α-Synucleinopathies
NOR-RBD: A Longitudinal Cohort and Clinical Trial Platform for Prodromal α-Synucleinopathies