Cholinergic and perfusion brain networks in Parkinson disease dementia

Colloby, S. J., McKeith, I. G., Burn, D. J., Wyper, D. J., O'Brien, J. T. and Taylor, J.-P. (2016) Cholinergic and perfusion brain networks in Parkinson disease dementia. Neurology, 87(2), pp. 178-185. (doi: 10.1212/wnl.0000000000002839) (PMID:27306636) (PMCID:PMC4940066)

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Abstract

Objective: To investigate muscarinic M1/M4 cholinergic networks 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 123I-QNB and 99mTc-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 cholinergic networks. 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 cholinergic networks 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.

Item Type:Articles
Additional Information:Supported by Medical Research Council UK (grant G9817682), the National Institute for Health Research (NIHR), Research for Public Benefit, Wellcome Trust (WT088441MA Fellowship funding J.-P.T.); NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals, NHS Foundation Trust, the University of Cambridge; and The NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease, Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals, NHS Foundation Trust and Newcastle University.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wyper, Professor David
Authors: Colloby, S. J., McKeith, I. G., Burn, D. J., Wyper, D. J., O'Brien, J. T., and Taylor, J.-P.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
College of Science and Engineering > School of Physics and Astronomy
Journal Name:Neurology
Publisher:American Academy of Neurology
ISSN:0028-3878
ISSN (Online):1526-632X
Published Online:15 June 2016
Copyright Holders:Copyright © 2016 American Academy of Neurology
First Published:First published in Neurology 87(2): 178-185
Publisher Policy:Reproduced under a Creative Commons License

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