Objective: To investigate differences in functional connectivity of key autonomic brain structures that distinguish those with orthostatic hypotension (OH) from those without among subjects with Parkinson’s disease (PD).

Background: OH, a sign of severe cardiovascular autonomic dysfunction, affects up to half of people with PD and is strongly predictive of poorer quality of life and prognosis. Several autonomic regulatory regions are identified in the brain, but central nervous system contributions to cardiovascular autonomic dysfunction in PD remains incompletely understood. Pathologic data and our own preliminary data point to a key role of the hypothalamus in autonomic dysfunction in PD.

Method: We are recruiting PD subjects with and without orthostatic hypotension. Demographic information and clinical evaluations are collected. OH is defined by reduction of systolic blood pressure of 30 mmHg, or diastolic blood pressure of 15 mmHg, during a tilt table procedure. Subjects undergo 3T brain MRI including MPRAGE and resting state functional MRI (rs-fMRI) sequences. After a standard pre-processing pipeline and nuisance variable regression, we performed seed-to-voxel correlation analysis, placing seeds in the hypothalamus, comparing functional connectivity of the hypothalamus with other brain regions between PD subjects with OH and those without.

Results: 24 subjects have completed study procedures. Mean age of subjects is 72.6 years (SD 7.2) for subjects with OH and 64.4 years (SD 7.8) for subjects without OH. There are no significant differences in disease duration, MoCA, or MDS-UPDRS part 3 (motor score) between the two groups. We found differences in functional connectivity of the hypothalamus with the anterior cingulate cortex (ACC) in PD subjects with OH compared to those without.

Conclusion: We identified alterations in functional connectivity between the hypothalamus and the ACC, key autonomic regions in the brain, which can distinguish PD subjects with and without OH. Though cardiovascular autonomic dysfunction in PD has been classically attributed to peripheral etiologies, there is increasing evidence of a substantial contribution from key brain regions. This discovery will hopefully lead to an improved mechanistic understanding of this highly prognostic symptom in PD, as well as new therapeutic targets.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-connectivity-of-brain-autonomic-centers-reveals-associations-with-cardiovascular-autonomic-dysfunction-in-parkinsons-disease/