PURPOSE OF THE STUDY

To address the lack of understanding of the pathophysiological processes in α-synucleinopathies, we will conduct the NOR-RBD initiative, a multicenter longitudinal cohort study of prodromal disease. We aim to identify, diagnose, and recruit individuals with iRBD, and follow them until phenoconversion. The main goals of the initiative will be:

1. Investigate biomarkers, both biological and imaging based, for their potential in risk stratification and phenoconversion prediction.

2. Investigate the neuropathological processes of early α-synucleinopathy in brain tissue of individuals who died with prodromal disease. Our mechanistic understanding of α-synucleinopathies is lacking due to several key challenges in investigating disease pathogenesis in brain tissue of individuals who died with late-stage disease. Thorough postmortem analyses in individuals with prodromal disease have not been performed, and validated iRBD neuropathology has only reported in a handful of single case reports).

3. Establish a platform of patients with iRBD who can easily be recruited into clinical trials of neuroprotective drugs.

4. Use wearables and similar technologies in concordance with polysomnography (PSG) to develop methods to more easily identify individuals with a high likelihood of RBD in the general population.

In addition, the initiative will also provide individuals with iRBD yearly follow-up with a clinical neurologist. At present, the vast majority of patients with iRBD remain undiagnosed until the other neurodegenerative symptoms become so apparent that they are referred to a neurological outpatient clinic and diagnosed with an α-synucleinopathy. This, however, does not mean these induvials are free of other symptoms during this period. Patients in the prodromal stages of an α-synucleinopathy can suffer from anxiety, depression, constipation, mild cognitive impairment, autonomic dysfunction, and gradually increasing signs of parkinsonism. iRBD can itself also cause considerable somatic and psychological disability for the patients. Dream enactments can be so violent that patients hurt themselves or bed partners, which can result in serious injuries, and the impact on both the patient and their partners quality of life is often substantial. Both RBD and other prodromal symptoms can be managed with medication and/or non-medical measures, and we aim to provide this to a patient group that, as of today, does not receive any follow up from specialized health care providers. In addition, regular follow-up will also allow earlier diagnosis of α-synucleinopathies, meaning that patients can begin receiving symptomatic dopaminergic treatment sooner than they otherwise would have.