Reduced dorsal visual stream α2-adrenergic receptor availability is not associated with visuospatial impairment in Parkinson's disease

Overview & Synopsis

Background: Visuospatial deficits are a common and disabling feature of Parkinson's disease (PD) that are linked to dysfunctions of the dorsal visual stream (DVS) and the cholinergic system. However, a body of evidence also points to the possible role of noradrenergic dysfunction, but direct in vivo evidence has remained lacking until the recent development of molecular imaging techniques. Methods: Thirty PD patients and thirty matched healthy controls underwent PET imaging using [ 11 C]yohimbine, a new radiotracer now available for human use, to quantify α2-AR availability. Visuospatial cognition was assessed using the MoCA visuospatial subscore, the Visual Object and Space Perception (VOSP) Number Location subtest, and the 15-Objects test. Results: Compared with controls, PD patients showed reduced performance on the VOSP Number Location and 15-Objects tests (both p < 0.05). Voxel-wise analyses revealed reduced [ 11 C]yohimbine binding in DVS regions, including the superior parietal lobule, posterior cingulate cortex, and supramarginal gyri (p_FWE < 0.05), but no correlations were observed between α2-AR availability and visuospatial performances. Bayesian analyses provided moderate evidence for the absence of association (BF 01 > 3). Conclusion: Despite reduced α2-AR availability within DVS regions, no significant association was observed with visuospatial performance. These findings do not support a simple direct association between DVS α2-AR availability and visuospatial impairment in this cohort of patients with PD.