Interactive effect of orthostatic hypotension on gray matter atrophy associated with hyposmia and RBD in de novo Parkinson’s disease

Background Orthostatic hypotension (OH) is a potential modifiable risk factor for cognitive impairment in patients with Parkinson’s disease (PD). Although other risk factors for dementia, hyposmia and REM sleep behavior disorder (RBD), are closely associated with autonomic dysfunction in PD, little is known about how these risk factors influence cognitive function and cerebral pathology. Objective We investigated how these three factors contribute to gray matter atrophy by considering the interaction of OH with hyposmia and RBD. Methods We analyzed cortical thickness, subcortical gray matter volume, and cognitive measures from 78 patients with de novo PD who underwent the head-up tilt test for the diagnosis of OH. Results Whole-brain analyses with Monte Carlo corrections revealed that hyposmia was associated with decreased cortical thickness in a marginal branch of the cingulate sulcus among patients with OH, and cortical thickness in this area correlated with cognitive functioning only in patients with OH. Subcortical gray matter volume analysis indicated that severe RBD was associated with decreased volume in the left hippocampus and bilateral amygdala among patients with OH. Conclusion Even in early PD, OH exerts effects on gray matter atrophy and cognitive dysfunction by interacting with RBD and hyposmia. OH might exacerbate cerebral pathology induced by hyposmia or RBD.