Neuroimaging Prodromal Neurodegeneration in Synucleinopathy

Neurodegenerative diseases like Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) have a long prodromal interval, meaning that symptoms have started but the disease is not yet fully developed. This interval is key to developing new preventative treatments, because they can be used at a stage when they are most likely to work. Studying prodromal PD and DLB was limited until the discovery that >80% of people with idiopathic REM sleep behavior disorder (iRBD), a disorder in which people act out their dreams at night, actually have prodromal PD/DLB. This means that studying people with iRBD gives a rare opportunity to directly observe the earliest stages of disease. Although routine clinical scans in PD/DLB are normal, there have been major recent developments. PET and SPECT scanning can find loss of the dopamine system which underlies motor parkinsonism. We have developed a new PET scan of the cholinergic system, to help understand cognitive loss. Also, there are new MRI scan techniques with exciting potential to identify early PD/DLB. We will recruit 40 iRBD patients and 20 controls. They will have a comprehensive clinical prodromal marker assessment as part of our ongoing cohort study (our center has the largest cohort of iRBD patients in the world). All patients will have three different brain scans: a cholinergic PET scan, a dopaminergic PET scan, and an MRI scan that includes three new markers of prodromal PD/DLB. We will follow patients each year, to see the scans predict development of disease over time. So with this study, we will: 1) See if the acetylcholine system is abnormal in early-stage PD/DLB, and if this might explain some of the cognitive changes that happen to our patients. 2) Test three new MRI markers to diagnose early-stage disease. 3) Be able to continue the world’s leading cohort on prodromal PD/DLB, so we can follow-up the many key prodromal markers we’ve already assessed and test new ones as they are discovered.