Objective: To investigate the differences in the pattern of nigrostriatal and pontine monoaminergic degeneration patients with de novo Parkinson’s disease (PD), stratified by the presence or absence of preceding REM sleep behavior disorder (RBD) and the duration of preceding RBD.

Background: Isolated RBD is a strong prodromal marker for overt synucleinopathy. More than 70% of patients with isolated RBD undergo phenoconversion within 12 years. However, not all patients develop RBD before the onset of PD. The presence of RBD in PD is associated with a higher prevalence of cognitive impairment, dysautonomia, and a rapid progression of dopaminergic neurodegeneration. A recent model hypothesized that the presence of RBD represents a “body-first” subtype of PD, as opposed to a “brain-first” subtype, where pathology propagates in a bottom-up manner from the periphery through the brainstem, thereby manifesting a more symmetric pattern of nigrostriatal involvement.

Method: Patients diagnosed with de novo PD between 2013 and 2022 and underwent 18F-FP-CIT PET at diagnosis, within two years of onset, at age 60 to 80 were eligible. Patients and caregivers were screened for history of RBD by the question, “Have you / has the patient ever acted out dreams while sleeping?” Those who answered “yes” were considered to have prior history of probable RBD. The patients underwent 18F-FP-CIT PET at a drug-naive status, and regions of interest included the bilateral putamen, caudate, ventral striatum, and the pons and the whole striatum. Indices of asymmetry and rostral-to-caudal ratios were calculated.

Results: A total of 150 subjects were included (52 without preceding RBD; PDRBD-, 98 PDRBD+). The PDRBD+ group had lower 18F-FP-CIT binding in all striatal ROIs and the pons, and lower asymmetry for the putamen and caudate compared to the PDRBD- group. These difference were due to a more severe LAH involvement in the PDRBD+ group. Furthermore, the PDRBD+ patients had lower pontine 18F-FP-CIT uptake after normalizing for the striatal uptakes. When stratified by preceding RBD duration, these characteristics were more prominent in the subgroup of PDRBD+ patients with less than 10 years of RBD history before the onset of PD.

Conclusion: The presence of preceding RBD before the onset of PD may represent a distinct disease subtype, with a more diffuse and severe distribution of the neurodegenerative pathology.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/asymmetric-and-profound-nigrostriatal-dopaminergic-dysfunction-in-parkinsons-disease-with-preceding-rem-sleep-behavior-disorders/