Reduced α4β2*–Nicotinic Acetylcholine Receptor Binding and Its Relationship to Mild Cognitive and Depressive Symptoms in Parkinson Disease

TLDR: There is a broad reduction of alpha4beta2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers, and novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD is provided.

Abstract: Context Cognitive or depressive disorders are frequently noted in patients with Parkinson disease (PD) and may be related to altered signaling through α4β2*–nicotinic acetylcholine receptors (α4β2*-nAChRs). Objective To assess the availability of α4β2*-nAChRs and their relationship to mild cognitive and mild depressive symptoms in vivo in patients with PD. Design Crossover comparison between patients with PD and healthy volunteers (control group) using the α4β2*-nAChR–specific radioligand 2-[ 18 F]fluoro-3-(2[S]-2-azetidinylmethoxy)-pyridine (2-[ 18 F]FA-85380) and positron emission tomography. Setting Departments of Neurology and Nuclear Medicine, University of Leipzig, Leipzig, Germany. Participants Twenty-two nonsmoking patients with PD and 9 nonsmoking healthy volunteers. Main Outcome Measures Level of 2-[ 18 F]FA-85380 binding potential (2-FA BP), a measure of α4β2*-nAChR availability. The relationship between severity of cognitive symptoms as rated using the Mini-Mental State Examination and DemTect scale and the level of depressive symptoms as indicated using the Beck Depression Inventory, and 2-FA BP were assessed. Results In patients with PD compared with healthy volunteers, there was widespread reduced 2-FA BP, especially in the midbrain, pons, anterior cingulate cortex, frontoparietal cortex, and cerebellum. In subgroups of patients with PD with possible depression, reduced 2-FA BP was most pronounced in the cingulate cortex and frontoparieto-occipital cortex, whereas in patients with PD with mild cognitive impairment, 2-FA BP was reduced in the midbrain, pons, and cerebellum. In patients with PD, the strongest associations between depressive symptoms and reduced 2-FA BP were noted in the anterior cingulate cortex, putamen, midbrain, and occipital cortex. In contrast, cognitive symptoms correlated only weakly with reduced 2-FA BP in the thalamus, midbrain, temporal cortex, hippocampus, and cerebellum. Conclusions There is a broad reduction of α4β2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers. Reduced α4β2*-nAChR binding in patients with PD within the subcortical and cortical regions is associated with the severity of mild cognitive or depressive symptoms. These results provide novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD.