Cardiac sympathetic denervation and anxiety in Parkinson disease

G Carli; P Kanel; F Michalakis; S Roytman; J L B Bohnen; T P Wigstrom; P Scott; R L Albin; K K Wong; D Raffel; N I Bohnen

doi:10.1016/j.parkreldis.2024.106997

Cardiac sympathetic denervation and anxiety in Parkinson disease

Parkinsonism Relat Disord. 2024 May 3:124:106997. doi: 10.1016/j.parkreldis.2024.106997. Online ahead of print.

Authors

G Carli¹, P Kanel², F Michalakis³, S Roytman³, J L B Bohnen⁴, T P Wigstrom⁴, P Scott⁵, R L Albin⁶, K K Wong⁵, D Raffel⁵, N I Bohnen⁷

Affiliations

¹ Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Functional Neuroimaging, Cognitive, and Mobility Laboratory, Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA. Electronic address: gcarli@med.umich.edu.
² Functional Neuroimaging, Cognitive, and Mobility Laboratory, Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Parkinson's Foundation Research Center of Excellence, University of Michigan, Ann Arbor, MI, USA.
³ Functional Neuroimaging, Cognitive, and Mobility Laboratory, Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
⁴ Functional Neuroimaging, Cognitive, and Mobility Laboratory, Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan, Ann Arbor, MI, USA; University of Michigan Medical School, Ann Arbor, MI, USA.
⁵ Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA; Parkinson's Foundation Research Center of Excellence, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
⁷ Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Functional Neuroimaging, Cognitive, and Mobility Laboratory, Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Parkinson's Foundation Research Center of Excellence, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.

PMID: 38723520
DOI: 10.1016/j.parkreldis.2024.106997

Abstract

Background: Anxiety in Parkinson disease (PD) negatively impacts quality of life. While research predominantly focuses on central nervous system changes, some evidence suggests a connection between peripheral autonomic dysfunctions and PD-related anxiety. The role of the peripheral autonomic nervous system in this context may be overlooked.

Objectives: This study explores the link between anxiety symptoms and cardiac sympathetic denervation in PD using ¹¹C-meta-hydroxyephedrine ([¹¹C]HED) PET cardiac imaging.

Methods: We studied 34 non-demented PD subjects, assessing anxiety levels through the Spielberg Anxiety State-Trait test trait section (STAI-T). Patients underwent comprehensive assessments along with [¹¹C]HED cardiac and [¹¹C]DTBZ brain PET. To identify subdimensions of STAI-T, we employed principal components analysis (PCA). We examined associations between the anxiety subdimensions and two measures of cardiac sympathetic denervation from [¹¹C]HED PET. We utilized correlation and linear regression models for these analyses.

Results: PCA revealed two STAI-T results components: anxiety-depressive and pure anxiety subcomponents. Only pure anxiety significantly correlated with measures of cardiac sympathetic denervation (rhos -0.40, p = 0.018; 0.35, p = 0.043). Regression models confirmed a significant association, with cardiac sympathetic denervation explaining ∼20 % of pure anxiety variance, independent of sex, dopaminergic impairment, and anxiolytic treatments.

Discussion: This study provides preliminary evidence of peripheral autonomic nervous system abnormalities contributing to PD-related anxiety, suggesting dysregulation in peripheral autonomic functions influencing anxiety perception.