Objective: To characterize the relationship between anticholinergic burden (ACB), mild cognitive impairment (MCI), and its underlying cholinergic pathology.

Background: MCI is a common phenomenon in PD, associated with poorer quality of life and greater risk of developing PD dementia. A prior study in de novo PD patients identified cholinergic denervation in the left prefrontal cortex, fusiform gyrus, and hippocampal region in people with PD and MCI (PD-MCI) as compared to PD without MCI (PD-NC).[1] Likewise, ACB has been associated with poorer cognitive function in PD.[2]

Method: 56 individuals with PD underwent brain VAChT [18F]-FEOBV PET and MR imaging. The Montreal cognitive assessment (MoCA) was used to assess for MCI, as indicated by a score of less than 26 (PD-MCI = 23, PD-NC = 33). Participants with a score of 3 or greater on the German ACB scale were considered to have high ACB (high ACB = 23, Low ACB = 33). Regional FEOBV bindings were averaged to generate composite left prefrontal cortex and bilateral medial temporal lobes. We examined whether a significant interaction was present between ACB and MCI in yielding lower cholinergic integrity in our regions of interest using a hierarchical linear model comparison.

Results: The interaction model was significantly better at predicting lower cholinergic integrity in the left prefrontal cortex as compared to the null hypothesis model (F = 5.47, p = 0.02, R2 = 0.19). There was no significant effect of MCI on left prefrontal cortex cholinergic integrity among individuals with low ACB (𝛽 = -0.28, p = 0.40). There was no significant effect of ACB on left prefrontal cortex cholinergic integrity among individuals without MCI (𝛽 = 0.39, p = 0.24). However, there was a significant interaction effect (𝛽 = -1.16, p = 0.02) suggesting that cholinergic denervation in the left prefrontal cortex previously associated with MCI in PD might depend on the presence of high ACB.  The interaction model was not better at predicting lower cholinergic integrity in the medial temporal lobe as compared to the null hypothesis model (F = 2.23, p = 0.14).

Conclusion: Our findings suggest that ACB might have adverse effects on the prefrontal cholinergic system and cognitive function in people with PD. Future research should examine whether high ACB leads to longitudinal changes in the cholinergic system or exacerbates pre-existing cholinergic system pathology.

References: 1. van der Zee S, Kanel P, Gerritsen MJJ, et al. Altered cholinergic innervation in de Novo Parkinson’s disease with and without cognitive impairment. Movement Disorders. 2022;37(4):713-723. doi:10.1002/mds.28913

2. Rajan R, Saini A, Verma B, et al. Anticholinergics may carry significant cognitive and gait burden in parkinson’s disease. Movement Disorders Clinical Practice. 2020;7(7):803-809. doi:10.1002/mdc3.13032

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-between-anticholinergic-burden-mci-and-cholinergic-denervation/