Objective: In the present work, we investigated whether cardiac mitochondrial dysfunction might also be associated with the severity of PIGD symptoms in PD patients.

Background: Mitochondrial dysfunction is a well-recognized contributor to Parkinson’s disease (PD) related central neuromodulatory dysfunction and associated pathogenesis; however, its role in peripheral bioenergetic impairments remains scarcely explored. Cardiac sympathetic denervation is an early sign of PD, preceding both the onset of motor symptoms and nigrostriatal dopaminergic denervation. It has been previously shown to be associated with dopamine-refractory postural instability and gait difficulty (PIGD) symptoms of PD.

Method: Nine PD patients (9 male, age: 67.56±8.66 years) underwent a 20 minute delayed imaging (180 minutes post-injection) mitochondrial complex I [18F]BCPP-EF cardiac PET and structural CT scan. TotalSegmentator was used to obtain volume of interest segmentations from the CT scans. The mean value of the morphologically eroded aorta reference region was used to obtain standardized uptake value ratio (SUVR) parametric images of the heart. Mean SUVR of the myocardium was subsequently extracted, and entered into a linear model predicting Movement Disorder Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) based PIGD score, which was calculated as a sum of items 3.10, 3.11, and 3.12 divided by the maximal possible score of 12.

Results: A statistically significant (R2=0.576, F=9.521, p=0.0178) negative linear correlation was observed between mean myocardial [18F]BCPP-EF SUVR and PIGD scores (β=-0.76 [-1.34,-0.18], p=0.018).

Conclusion: Much like cardiac sympathetic denervation, cardiac mitochondrial dysfunction appears to be strongly associated with PIGD symptom severity. Given the high metabolic demand associated with supporting neurotransmission, it is plausible that cardiac sympathetic denervation might partly stem from an underlying bioenergetic deficit. Though our findings remain consistent with this hypothesis, future joint noradrenergic and mitochondrial PET imaging studies of the heart need to be pursued. Our present findings may inform novel approaches to the development of more effective therapies for these dopamine-refractory PIGD motor features.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cardiac-mitochondrial-complex-i-integrity-predicts-axial-symptom-severity-in-parkinsons-disease/