Objective: To explore the interrelation of striatal dopamine, cholinergic basal forebrain volume, brain metabolism, and cognition in PD.

Background: Parkinson’s disease (PD) involves multiple neurotransmitter systems including dopaminergic as well as non-dopaminergic system. Among them, dopaminergic and cholinergic dysfunctions have been reported to be associated with cognitive dysfunction in PD. In addition, patients with PD have a characteristic brain metabolism which correlates with cognitive dysfunction. However, it has not yet been well elucidated how they are correlated with each other and affect brain metabolism and cognition in PD.

Method: We consecutively recruited 172 patients with PD and 40 healthy controls who underwent brain MRI, ¹⁸F-FP-CIT PET, and ¹⁸F-FDG PET. All patients underwent detailed neuropsychological testing. General linear models and mediation analyses were conducted to investigate the association of striatal dopamine transporter availability, basal forebrain (BF) volume, brain metabolism, and cognitive scores.

Results: A significant relationship between the caudate dopamine depletion and atrophy of the posterior BF was found in PD patients. Striatal dopamine depletion were associated with altered brain metabolism in regions where PD patients showed decreased metabolism compared to healthy controls, while atrophy in the posterior BF was associated with reduced brain metabolism in the lateral prefrontal, inferior parietal, lateral temporal cortices and precuneus with a significant interaction between caudate dopamine and posterior BF volume. Caudate dopamine depletion was associated with visuospatial, memory and executive dysfunction, whereas posterior BF atrophy was associated with attention, visuospatial, memory, and executive dysfunction. Visuospatial dysfunction was associated with caudate dopamine depletion and posterior BF atrophy by the mediation of altered brain metabolism, while executive dysfunction was associated with caudate dopamine depletion and posterior BF atrophy both directly and by the mediation of altered brain metabolism.

Conclusion: In summary, our findings suggest that the caudate dopamine depletion and reduced volume of the posterior BF synergistically affect decreased brain metabolism, and both differentially affected cognitive dysfunction in an item-specific manner either directly or by the mediation of decreased brain metabolism.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/striatal-dopamine-and-basal-forebrain-cholinergic-dependent-brain-metabolism-and-cognition-in-parkinsons-disease/