Objective: To map the relationship between cholinergic activity in Parkinson Disease (PD) and cognitive performance and identify any differences in this relationship in cognitive impairment.

Background: Cholinergic modulation of brain activity is key in cognitive and behavioral function, affecting attention, memory, and sleep. Recent studies link cognitive function and cholinergic signaling, correlating domain performance with mild cognitive impairment (MCI) and controls from a memory clinic¹ and integrity of basal forebrain cholinergic projections in PD. Here, we explore cholinergic signaling’s impact on cognitive performance in PD.

Method: 26 control and 58 PD participants were scanned using the [18F]VAT radiotracer as a marker for cholinergic activity. Scans were reconstructed, motion-corrected, and aligned to structural MRI. Time-activity curves were calculated using FreeSurfer7.3-based regions, partial volume corrected using the geometric transfer matrix method, and binding potentials were estimated using multilinear reference tissue model (MRTM2). Participants underwent cognitive testing to generate population normalized, z-score data for attention, memory, visuospatial skills, executive function, and language domains. Global cognitive status was assessed using the clinical dementia rating scale (CDR) (0: normal cognition; 0.5: MCI; 1+: dementia). Control participants with CDR > 0 and PD participants with dementia were excluded from analysis.

Results: PD participants demonstrated significant, 10-40% lower, [18F]VAT uptake throughout most cortical regions, thalamus, and cerebellum. Frequent, significant correlations between binding potential and attention (R = 0.3-0.5) were observed within PD, with more limited correlations in visuospatial and executive function domains. PD participants with MCI showed more frequent, stronger correlations between binding potential and visuospatial function and fewer, weaker correlations with attention when compared to cognitively normal PD participants.

Conclusion: These findings demonstrate that lower cholinergic tone in PD correlates with cognitive function. Furthermore, [18F]VAT demonstrates differences in association with attention and visuospatial ability that are specific to global cognitive state, suggesting cholinergic activity reflects disease progression. Future work will examine whether differences in cholinergic signaling can predict cognitive decline in PD.

References: 1. Xia et al., Reduced cortical cholinergic innervation measured using [18F]-FEOBV PET imaging correlates with cognitive decline in mild cognitive impairment. Neuroimage Clin. 2022 Mar 24;34:102992. 2. Crowley et al., Basal forebrain integrity, cholinergic innervation and cognition in idiopathic Parkinson’s disease. Brain. 2024 May 3;147(5):1799-1808.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cholinergic-activity-associates-with-cognitive-function-in-pd-using-18fvat/