Assessment of Bioenergetic Deficits in Patients With Parkinson Disease and Progressive Supranuclear Palsy Using ³¹ P-MRSI

Abstract

Background:Bioenergetic disturbance, mainly caused by mitochondrial dysfunction, is an established pathophysiological phenomenon in neurodegenerative movement disorders. The in vivo assessment of brain energy metabolism by 31phosphorus magnetic resonance spectroscopy imaging could provide pathophysiological insights and serve in the differential diagnosis of parkinsonian disorders. In this study, we investigated such aspects of the underlying pathophysiology in patients with idiopathic Parkinson’s disease (PwPD) and progressive supranuclear palsy (PwPSP).Methods:In total, 30 PwPD, 16 PwPSP, and 25 healthy control subjects (HCs) underwent a clinical examination, structural magnetic resonance imaging, and 31phosphorus magnetic resonance spectroscopy imaging of the forebrain and basal ganglia in a cross-sectional study.Results:High-energy phosphate metabolites were remarkably decreased in PwPD, particularly in the basal ganglia (−42% compared with healthy controls and −43% compared with PwPSP, p<.0001). This result was not confounded by morphometric brain differences. In contrast, PwPSP had normal levels of high-energy energy metabolites. Thus, the combination of morphometric and metabolic neuroimaging was able to discriminate PwPD from PwPSP with an accuracy of up to 0.93 [95%-CI: 0.91, 0.94].Discussion:Our study shows that mitochondrial dysfunction and bioenergetic depletion contribute to idiopathic Parkinson’s disease pathophysiology but not to progressive supranuclear palsy. Combined morphometric and metabolic imaging could serve as an accompanying diagnostic biomarker in the neuroimaging-guided differential diagnosis of these parkinsonian disorders.

Levodopa Impairs the Energy Metabolism of the Basal Ganglia In Vivo

“…None of the above-reported HEP levels showed any significant association with our volumetric data or observed LEDD levels, which aligns well with our previous reports. 9,14,16 In addition, no visit effects were observed for any clinical-or neuroimagingrelated data (in covariate testing).…”

“…Even though DAergic medication was previously discussed as a potential confounder of cerebral metabolism, no 31 P-MRSIrelated studies have assessed the possible influence of L-DOPA on cerebral bioenergetics in a standardized manner. [9][10][11] This previous assumption may have been reasonable because no correlations were shown between depleted HEP levels and LEDD. 9,16 However, our study illustrates that the treatment with L-DOPA can substantially confound metabolic measurements in PwPD.…”

“…[9][10][11] This previous assumption may have been reasonable because no correlations were shown between depleted HEP levels and LEDD. 9,16 However, our study illustrates that the treatment with L-DOPA can substantially confound metabolic measurements in PwPD. 11,17 We demonstrated that exogenously administered L-DOPA strongly interferes with the energy metabolism of the basal ganglia independent of the PD state.…”

“…However, previous studies have often neglected concomitant medication with L-DOPA or the timing between medication intake and neuroimaging assessments. [9][10][11] Until now, no systematic in-vivo evaluation of cerebral bioenergetics following exogenous L-DOPA administration has been performed. Here, we investigate the short-term influence of a standardized, cross-over, double-blinded, and placebo-controlled 200/50 mg L-DOPA on cerebral bioenergetics in PwPD and healthy controls (HCs).…”

High-Throughput CSF Proteomics and Machine Learning to Identify Proteomic Signatures for Parkinson Disease Development and Progression

“…The identification of biomarkers capable of capturing the ever-changing brain state of Parkinson disease (PD) remains a significant unmet need in clinical practice. [1][2][3][4][5] Because PD is heterogeneous and complex, with many intersecting biological processes shaping its pathogenesis, the development of these biomarkers likely necessitates the integration of multiple markers. 6,7 Thus, the "omics" technologies, which have been developing in parallel with rapid progress in analytical technology in recent years, hold considerable promise.…”