Objective: To evaluate regional cholinergic correlates of cognitive impairment in newly diagnosed, treatment-naïve Parkinson’s disease (PD) patients.

Background: Mild cognitive impairment (PD-MCI) is a common non-motor symptom in PD and is already present in approximately 30% of newly diagnosed patients. Degeneration of the cholinergic system plays an important role in cognitive impairment in PD, even before the onset of PD dementia. However, it remains elusive whether the cholinergic system functions as a diffuse neuromodulator or a more regional system. Early identification of the regional role in cognitive impairment in PD is of importance for disease prognosis and possible early intervention.

Method: A total of 120 newly diagnosed, treatment-naïve PD patients, with a confirmed presynaptic dopaminergic deficit, were included as part of the Dutch Parkinson Cohort (DUPARC) study. Subjects were categorized as cognitively normal (PD-CN) or PD-MCI based on MDS PD-MCI level II criteria, including an extensive cognitive assessment covering all domains. PD-CN and PD-MCI groups were compared on regional cholinergic innervation as measured using the presynaptic vesicular acetylcholine transporter (VAChT) binding PET tracer [¹⁸F]fluoroethoxybenzovesamicol. In addition, whole-brain voxel based analysis was performed to evaluate regional cholinergic denervation related to specific cognitive domain functioning.

Results: PD-MCI showed significantly reduced VAChT-binding compared to PD-NC. Most prominent regions include the hippocampus, insula, fusiform area and amygdala (p<0.01). A voxel-based correlation showed specific regional cholinergic correlates for every cognitive domain, with partly overlapping topography. Key regions include the cingulate gyrus, insula, hippocampus and thalamus.

Conclusion: This is the first study to extensively evaluate cholinergic innervation in newly diagnosed, treatment-naïve PD patients in relationship to detailed cognitive functioning. Our findings suggest a key role of the cholinergic system already at onset of the disease, with possible cholinergic network functioning to be essential.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-cognitive-impairment-is-associated-with-specific-regional-cholinergic-denervation-in-parkinsons-disease/