Identification of cholinergic centro-cingulate topography as main contributor to cognitive functioning in Parkinson's disease: Results from a data-driven approach

Sygrid van der Zee; Prabesh Kanel; Martijn L T M Müller; Teus van Laar; Nicolaas I Bohnen

doi:10.3389/fnagi.2022.1006567

Identification of cholinergic centro-cingulate topography as main contributor to cognitive functioning in Parkinson's disease: Results from a data-driven approach

Front Aging Neurosci. 2022 Oct 20:14:1006567. doi: 10.3389/fnagi.2022.1006567. eCollection 2022.

Authors

Sygrid van der Zee^{1

2}, Prabesh Kanel^{1

3}, Martijn L T M Müller^{1

3}, Teus van Laar², Nicolaas I Bohnen^{1

3

4

5

6}

Affiliations

¹ Department of Radiology, University of Michigan, Ann Arbor, MI, United States.
² Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
³ Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, United States.
⁴ Department of Neurology, University of Michigan, Ann Arbor, MI, United States.
⁵ Neurology Service and Geriatric Research Education and Clinical Center (GRECC), Veterans Administration Ann Arbor Healthcare System, Ann Arbor, MI, United States.
⁶ University of Michigan Parkinson's Foundation Center of Excellence, Ann Arbor, MI, United States.

Abstract

Background: Degeneration of the cholinergic system plays an important role in cognitive impairment in Parkinson's disease (PD). Positron emission tomography (PET) imaging using the presynaptic vesicular acetylcholine transporter (VAChT) tracer [¹⁸F]Fluoroethoxybenzovesamicol ([¹⁸F]FEOBV) allows for regional assessment of cholinergic innervation. The purpose of this study was to perform a data-driven analysis to identify co-varying cholinergic regions and to evaluate the relationship of these with cognitive functioning in PD.

Materials and methods: A total of 87 non-demented PD patients (77% male, mean age 67.9 ± 7.6 years, disease duration 5.8 ± 4.6 years) and 27 healthy control (HC) subjects underwent [¹⁸F]FEOBV brain PET imaging and neuropsychological assessment. A volume-of-interest based factor analysis was performed for both groups to identify cholinergic principal components (PCs).

Results: Seven main PCs were identified for the PD group: (1) bilateral posterior cortex, (2) bilateral subcortical, (3) bilateral centro-cingulate, (4) bilateral frontal, (5) right-sided fronto-temporal, (6) cerebellum, and (7) predominantly left sided temporal regions. A complementary principal component analysis (PCA) analysis in the control group showed substantially different cholinergic covarying patterns. A multivariate linear regression analyses demonstrated PC3, PC5, and PC7, together with motor impairment score, as significant predictors for cognitive functioning in PD. PC3 showed most robust correlations with cognitive functioning (p < 0.001).

Conclusion: A data-driven approach identified covarying regions in the bilateral peri-central and cingulum cortex as a key determinant of cognitive impairment in PD. Cholinergic vulnerability of the centro-cingulate network appears to be disease-specific for PD rather than being age-related. The cholinergic system may be an important contributor to regional and large scale neural networks involved in cognitive functioning.

Keywords: PET; Parkinson’s disease; acetylcholine; cognition; neuroimaging.

Grants and funding

P50 NS123067/NS/NINDS NIH HHS/United States