Objective: To examine the contribution of the central autonomic network (CAN) to physiologic evidence of autonomic failure in Parkinson’s disease (PD).

Background: Autonomic dysfunction, particularly orthostatic hypotension (OH), is a common non-motor symptom of PD that predicts poor outcomes when symptomatic or asymptomatic. Though peripheral causes of cardiovascular autonomic failure have been highly studied, it remains unclear whether there is a central component to physiologic autonomic failure in PD. The CAN is made up of cortical, subcortical, and brainstem structures involved in autonomic control. Several CAN structures, particularly the anterior cingulate cortex (ACC) and hypothalamus (HTH), are involved in PD pathology.

Method: We prospectively collected clinical data, autonomic reflex testing including tilt table examination, and 3 Tesla brain T1 and resting state functional MRI data in people with PD, with and without orthostatic hypotension, who had no alternative causes of parkinsonism or OH. Functional connectivity was examined through seed-based analysis in major autonomic brain structures that have also been shown previously to be involved in PD pathology. Primary analyses correlated resting state functional connectivity of the ACC and the HTH with presence of orthostatic hypotension. Other regions of interest included brain stem, bilateral hypothalamus, thalamus, insular cortex, precuneus and medial prefrontal cortex. Results are corrected for age and disease duration, and family-wise error corrected for a p<0.05.

Results: A total of 30 PD brain MRIs were analyzed. The age range was 52 – 82 years. 16 participants were women, and 11 were found to have OH on tilt testing. We found that functional connectivity of key brain autonomic structures is altered in PD with orthostatic hypotension compared to those without. Furthermore, severity of systolic blood pressure reduction correlated with functional connectivity of structures that are implicated in PD and in autonomic control.

Conclusion: While peripheral autonomic denervation is important in autonomic dysfunction in PD, we show that CAN function is implicated in the pathophysiology of orthostatic hypotension in PD. Accurate mapping of brain networks involved in autonomic failure can aid the identification of new targets for precision neuromodulation in PD and other neurodegenerative conditions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evidence-of-central-autonomic-network-dysfunction-in-orthostatic-hypotension-of-parkinsons-disease/