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Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease: ICICLE-PD study

Lookup NU author(s): Dr Michael FirbankORCiD, Dr Rachael LawsonORCiD, Professor Alison Yarnall, Dr Tien Kheng Khoo, Professor David BrooksORCiD, Professor David BurnORCiD, Professor John O'Brien

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Mild cognitive impairment in Parkinson's disease is associated with progression to dementia (Parkinson's disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson's disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects with newly diagnosed idiopathic Parkinson's disease and 37 healthy matched controls had serial 3T structural magnetic resonance imaging scans with clinical and neuropsychological assessments at baseline, which were repeated after 18 months. The Movement Disorder Society Task Force criteria were used to classify the Parkinson's disease subjects into Parkinson's disease with mild cognitive impairment (n = 39) and Parkinson's disease with no cognitive impairment (n = 66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. At baseline, cases with Parkinson's disease with mild cognitive impairment demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and subjects with Parkinson's disease with no cognitive impairment. Regional cortical thickness at baseline was correlated with global cognition in the combined Parkinson's disease cohort. Over 18 months, patients with Parkinson's disease with mild cognitive impairment demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to those with Parkinson's disease and no cognitive impairment and healthy controls, whereas subjects with Parkinson's disease and no cognitive impairment showed more severe frontal cortical thinning compared to healthy controls. At baseline, Parkinson's disease with no cognitive impairment converters showed bilateral temporal cortex thinning relative to the Parkinson's disease with no cognitive impairment stable subjects. Although loss of both cortical and subcortical volume occurs in non-demented Parkinson's disease, our longitudinal analyses revealed that Parkinson's disease with mild cognitive impairment shows more extensive atrophy and greater percentage of cortical thinning compared to Parkinson's disease with no cognitive impairment. In particular, an extension of cortical thinning in the temporo-parietal regions in addition to frontal atrophy could be a biomarker in therapeutic studies of mild cognitive impairment in Parkinson's disease for progression towards dementia.


Publication metadata

Author(s): Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ, Duncan GW, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn DJ, O'Brien JT

Publication type: Article

Publication status: Published

Journal: Brain

Year: 2015

Volume: 138

Pages: 2974-2986

Online publication date: 14/07/2015

Acceptance date: 05/06/2015

Date deposited: 13/01/2016

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/brain/awv211

DOI: 10.1093/brain/awv211


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Funding

Funder referenceFunder name
Gates Cambridge studentship
NIHR Newcastle Biomedical Research Unit based at Newcastle-upon-Tyne Hospitals NHS Foundation Trust
Parkinson's UK
Alzheimer's Research UK
Lockhart Parkinson's Disease Research Fund
Michael J. Fox Foundation
Newcastle University
NIHR Dementias and Neurodegenerative Diseases Research Network
MC-A060- 5PQ30Medical Research Council of Cognition and Brain Sciences Unit, Cambridge
J-0802Parkinson's UK
JBR 103838Wellcome Trust
RG64473National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and Biomedical Research Unit in Dementia

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