Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;36(3):642-650.
doi: 10.1002/mds.28360. Epub 2020 Nov 2.

Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

Sygrid van der Zee  1   2 , Martijn L T M Müller  1   3 , Prabesh Kanel  1   3 , Teus van Laar  2 , Nicolaas I Bohnen  1   3   4   5
Affiliations

Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

Sygrid van der Zee et al. Mov Disord. 2021 Mar.

Abstract

Background: The cholinergic system plays a key role in cognitive impairment in Parkinson's disease (PD). Previous acetylcholinesterase positron emission tomography imaging studies found memory, attention, and executive function correlates of global cortical cholinergic losses. Vesicular acetylcholine transporter positron emission tomography allows for more accurate topographic assessment of not only cortical but also subcortical cholinergic changes.

Objective: The objectiveof this study was to investigate the topographic relationship between cognitive functioning and regional cholinergic innervation in patients with PD.

Methods: A total of 86 nondemented patients with PD (mean ± SD age 67.8 ± 7.6 years, motor disease duration 5.8 ± 4.6 years), and 12 healthy control participants (age 67.8 ± 7.8 years) underwent cholinergic [18 F]Fluoroethoxybenzovesamicol positron emission tomography imaging. Patients with PD underwent neuropsychological assessment. The z scores for each cognitive domain were determined using an age-matched, gender-matched, and educational level-matched control group. Correlations between domain-specific cognitive functioning and cholinergic innervation were examined, controlling for motor impairments and levodopa equivalent dose. Additional correlational analyses were performed using a mask limited to PD versus normal aging binding differences to assess for disease-specific versus normal aging effects.

Results: Voxel-based whole-brain analysis demonstrated partial overlapping topography across cognitive domains, with most robust correlations in the domains of memory, attention, and executive functioning (P < 0.01, corrected for multiple comparisons). The shared pattern included the cingulate cortex, insula/operculum, and (visual) thalamus.

Conclusion: Our results confirm and expand on previous observations of cholinergic system involvement in cognitive functioning in PD. The topographic overlap across domains may reflect a partially shared cholinergic functionality underlying cognitive functioning, representing a combination of disease-specific and aging effects. © 2020 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; acetylcholine; cognition; PET.

PubMed Disclaimer

Conflict of interest statement

Relevant conflicts of interests/financial disclosures: Nothing to report.

Figures

FIG. 1.
FIG. 1.
Statistical parametric voxel-based analysis (false discovery rate corrected P < 0.01) of the correlation between vesicular acetylcholine transporter binding and (A) memory domain z scores, (B) executive function domain z scores, (C) attention domain z scores, and (D) language domain z scores controlled for parkinsonian motor impairment and levodopa equivalent dose. L, left; R, right.
FIG. 2.
FIG. 2.
Statistical parametric voxel-based analysis (false discovery rate corrected P < 0.05) of the correlation between vesicular acetylcholine transporter binding and (A) memory domain z scores, (B) executive function domain z scores, (C) attention domain z scores, and (D) language domain z scores controlled for parkinsonian motor impairment and levodopa equivalent dose superimposed on a Parkinson’s disease impairment-related mask. L, left; R, right.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Post B, Muslimovic D, van Geloven N, et al. Progression and prognostic factors of motor impairment, disability and quality of life in newly diagnosed Parkinson’s disease. Mov Disord 2011;26(3):449–456. - PubMed
    1. Lawson RA, Yarnall AJ, Duncan GW, et al. Severity of mild cognitive impairment in early Parkinson’s disease contributes to poorer quality of life. Parkinsonism Relat Disord 2014;20(10):1071–1075. - PMC - PubMed
    1. Aarsland D, Bronnick K, Williams-Gray C, et al. Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology 2010;75(12):1062–1069. - PMC - PubMed
    1. Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003;60(3):387–392. - PubMed
    1. Hely MA, Reid WGJ, Adena MA, Halliday GM, Morris JGL. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord 2008;23(6):837–844. - PubMed

Publication types

Substances