Orthostatic hypotension is not associated with small vessel disease progression or cognitive decline

Introduction: Cerebral hypoperfusion is thought to play an important role in the etiology of cerebral small vessel disease (SVD). Orthostatic hypotension (OH) is assumed to be a cause of cerebral hypoperfusion by causing recurrent hypoperfusion episodes, and might thus be related to progression of SVD. Here, we investigated whether presence of OH is associated with the progression of SVD MRI-markers and cognitive decline over a time period of 9 years in a cohort of sporadic SVD patients.Methods: This study included SVD patients from the RUN DMC study, a prospective longitudinal single-center cohort study. In total, 503 patients were included at baseline (2006), from whom 351 participated at first follow-up (2011), and 293 at second follow-up (2015). During all visits, patients underwent MRI and cognitive testing. Association between presence of OH at baseline and progression of SVD-markers on MRI and cognitive decline over time was estimated using linear mixed-effects models.Results: Of the 503 patients who participated at baseline, 46 patients (9.1%) had OH. Cross-sectional analysis of the baseline data showed that OH was associated with higher white matter hyperintensity (WMH) volume (13 = 0.18, p = 0.03), higher mean diffusivity (MD; 13 = 0.02, p = 0.002), and with presence of microbleeds (OR 2.37 95% CI 1.16-4.68). Longitudinally, OH was however not associated with a progression of total WMH volume (13 = -0.17, p = 0.96) or with higher MD (13 = -0.001, p = 0.49). There was no association between OH and cognitive performance, both at baseline and over time.Conclusion: In this longitudinal observational study, there was no evidence that presence of OH is associated with progression of SVD-markers or cognitive decline over time. Our findings indicate that OH may not be causally related to SVD progression over time