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Cholinergic and perfusion brain networks in Parkinson disease dementia

Lookup NU author(s): Dr Sean Colloby, Professor Ian McKeith, Professor David Burn, Professor John O'Brien, Professor John-Paul TaylorORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


OBJECTIVE: To investigate muscarinic M1/M4 cholinergicnetworks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil.METHODS: Forty-nine participants (25 PDD and 24 elderly controls) underwent (123)I-QNB and (99m)Tc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs).RESULTS: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor-naive patients with PDD, implicating limbic-paralimbic and salience cholinergicnetworks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks.CONCLUSION: Dysfunctional limbic-paralimbic and salience cholinergicnetworks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition.

Publication metadata

Author(s): Colloby SJ, McKeith IG, Burn DJ, Wyper DJ, O'Brien JT, Taylor JP

Publication type: Article

Publication status: Published

Journal: Neurology

Year: 2016

Volume: 87

Issue: 2

Pages: 178-185

Print publication date: 12/07/2016

Online publication date: 15/06/2016

Acceptance date: 30/03/2016

Date deposited: 23/09/2016

ISSN (print): 0028-3878

ISSN (electronic): 1526-632X

Publisher: Lippincott Williams & Wilkins, Ltd


DOI: 10.1212/WNL.0000000000002839


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Funder referenceFunder name
Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals
Newcastle University
NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease
Research for Public Benefit
National Institute for Health Research (NIHR)
NHS Foundation Trust
NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals
University of Cambridge
G9817682Medical Research Council UK
WT088441MAWellcome Trust