title: Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease: ICICLE-PD study.
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 3 T 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.
authors.affiliation: 1 Department of Psychiatry, University of Cambridge, UK.
authors.forename: Elijah
authors.initials: E
authors.lastname: Mak
authors.affiliation: 1 Department of Psychiatry, University of Cambridge, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: 2 Wolfson Brain Imaging Centre, University of Cambridge, UK.
authors.forename: Guy B
authors.initials: GB
authors.lastname: Williams
authors.affiliation: 3 Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Firbank
authors.affiliation: 3 Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Lawson
authors.affiliation: 3 Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Yarnall
authors.affiliation: 4 Medicine of the Elderly, Western General Hospital, Edinburgh, UK.
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Duncan
authors.affiliation: 5 Brain and Mind Institute, University of Western Ontario, London, Canada 6 Department of Psychology, University of Western Ontario, London, Canada.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Owen
authors.affiliation: 7 Griffith Health Institute and School of Medicine, Griffith University, Gold Coast, Australia.
authors.forename: Tien K
authors.initials: TK
authors.lastname: Khoo
authors.affiliation: 8 Division of Brain Sciences, Imperial College London, London, UK 9 Department of Clinical Medicine, Positron Emission Tomography Centre, Aarhus University, Denmark.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.affiliation: 10 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK 11 Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK 12 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: James B
authors.initials: JB
authors.lastname: Rowe
authors.affiliation: 13 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.affiliation: 3 Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.affiliation: 1 Department of Psychiatry, University of Cambridge, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
keywords: Parkinson’s disease; dementia; neurodegeneration; neuroimaging