Cognitive decline in visuospatial and executive functioning domains is a feature of isolated rapid eye movement (REM) sleep behavior disorder (iRBD). Disease pathology in the serotonergic system may be responsible for the biological basis of certain features of iRBD.

Serotonergic system degeneration is seen in the visuospatial cortex in parkinsonian conditions. We hypothesized that serotonin transporter (SERT) positron emission tomography (PET) ¹¹C-DASB distribution volume ratio (DVR) in iRBD participants will correlate with worse performance on a spatial navigation task evaluating visuospatial abilities and executive functioning.

10 adults (M_age = 72.8±5.3) with iRBD were enrolled in a cross-sectional PET imaging study. Participants completed neuropsychological testing and a spatial navigation task measuring allocentric and egocentric memory separately. Performance on the spatial navigation task was assessed by the participant’s ability to correctly recall the location of landmarks on a two-dimensional map after viewing a walkthrough video of the landscape (allocentric), and their ability to correctly recall the order of turns taken in a walkthrough video of identical hallways (egocentric). Participants also completed ¹¹C-DASB PET imaging to evaluate presence of presynaptic serotonin transporters in various brain regions. We used Spearman’s rank order correlation coefficient to evaluate the relationship between performance on relevant neuropsychological tests and DASB DVR in brain regions of interest.

Performance on these neuropsychology tests and spatial navigation memory tasks do not appear to correlate with serotonergic DASB PET findings in the total cortex, visuospatial cortex, or hippocampus. Although not statistically significant, elevated DASB DVR in the medulla seemed to correlate with worse allocentric performance.

Correlations between visuospatial dysfunction and medullary DASB elevations may reflect early changes in an interconnected serotonergic network linked to visuospatial cognition. Alternatively, these PET findings might reflect a state vs. trait marker for people with iRBD who are at risk for progression to Dementia with Lewy Bodies.