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Hum Brain Mapp. 2015 Aug;36(8):2980-95. doi: 10.1002/hbm.22822. Epub 2015 May 6.

Aberrant cerebral network topology and mild cognitive impairment in early Parkinson's disease.

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Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
Department of Psychiatry, Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer's Disease Research, Karolinska Institute, Stockholm, Sweden.
Department of Biostatistics, King's College London, London, United Kingdom.
Institute of Psychiatry, King's College London, London, United Kingdom.
NIHR Biomedical Research Centre for Mental Health, London, United Kingdom.
NIHR Biomedical Research Unit for Dementia, London, United Kingdom.
Department of Physics, Soft Matter Lab, Bilkent University, Ankara, Turkey.
UNAM - National Nanotechnology Research Center, Bilkent University, Ankara, Turkey.


The aim of this study was to assess whether mild cognitive impairment (MCI) is associated with disruption in large-scale structural networks in newly diagnosed, drug-naïve patients with Parkinson's disease (PD). Graph theoretical analyses were applied to 3T MRI data from 123 PD patients and 56 controls from the Parkinson's progression markers initiative (PPMI). Thirty-three patients were classified as having Parkinson's disease with mild cognitive impairment (PD-MCI) using the Movement Disorders Society Task Force criteria, while the remaining 90 PD patients were classified as cognitively normal (PD-CN). Global measures (clustering coefficient, characteristic path length, global efficiency, small-worldness) and regional measures (regional clustering coefficient, regional efficiency, hubs) were assessed in the structural networks that were constructed based on cortical thickness and subcortical volume data. PD-MCI patients showed a marked reduction in the average correlation strength between cortical and subcortical regions compared with controls. These patients had a larger characteristic path length and reduced global efficiency in addition to a lower regional efficiency in frontal and parietal regions compared with PD-CN patients and controls. A reorganization of the highly connected regions in the network was observed in both groups of patients. This study shows that the earliest stages of cognitive decline in PD are associated with a disruption in the large-scale coordination of the brain network and with a decrease of the efficiency of parallel information processing. These changes are likely to signal further cognitive decline and provide support to the role of aberrant network topology in cognitive impairment in patients with early PD.


characteristic path length; global efficiency; graph theory; hubs; structural co-variance networks

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