Objective: To investigate the relationship between striatal dopamine depletion, altered brain metabolism, motor deficits, and cognitive dysfunction in Parkinson’s disease (PD)

Background: PD shows degeneration of dopaminergic neurons and characteristic changes in brain metabolism. However, it has not yet been elucidated how they are correlated with each other and affect PD.

Method: We consecutively recruited 143 patients with PD and 38 healthy controls who underwent both ¹⁸F-FP-CIT PET and ¹⁸F-FDG PET scans. All patients performed the Movement Disorders Society-Unified PD Rating Scale, and 120 patients (83.9%) underwent detailed neuropsychological testing. Partial correlation and mediation analyses were conducted to investigate the association of striatal dopamine transporter availability and brain metabolism with parkinsonism motor subscore or domain-specific cognitive score.

Results: Striatal FPCIT SBR was negatively correlated with the FDG SUVR in the cerebellum, thalamus, hippocampus, amygdala, paracentral lobule, and entorhinal cortex, while it was positively correlated with caudate, lateral frontal and parietal cortices, precuneus, and lateral and medial occipital cortices. As the loss of putaminal FPCIT SBR increased, brain FDG SUVR increased from the paracentral lobule, limbic system to cerebellum and anterior cingulate cortex, while brain metabolism decreased from the lateral temporal to frontal and occipital cortices. In motor aspect, the FDG SUVR in the paracentral lobule completely mediated the association between the putaminal FPCIT SBR and rigidity subscore. The putaminal FPCIT SBR, but not brain FDG SUVR, was directly associated with bradykinesia subscore. The FDG SUVR in the hypermetabolic region was directly associated with axial subscore, while the FDG SUVR in the hypometabolic region completely mediated the association between the caudate FPCIT SBR and axial subscore. In cognitive aspect, the FDG SUVR in the hypometabolic region completely mediated the association between the caudate FPCIT SBR and executive, memory, and visuospatial scores.

Conclusion: Striatal dopamine depletion and altered brain metabolism in PD are closely associated with each other. Change in brain metabolism occurred in a specific spatial pattern, depending on the degree of dopamine depletion. Striatal dopamine depletion and altered brain metabolism differentially affect motor and cognitive dysfunction in an item-specific manner.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-striatal-dopamine-depletion-and-altered-brain-metabolism-on-parkinsons-disease/