Characterizing mild cognitive impairment in incident Parkinson disease
The ICICLE-PD Study
Abstract
Objective:
To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers.
Methods:
Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Consenting individuals underwent structural MRI, lumbar puncture, and genotyping for common variants of COMT, MAPT, SNCA, BuChE, EGF, and APOE. PD-MCI was defined with reference to the new Movement Disorder Society criteria.
Results:
The frequency of PD-MCI was 42.5% using level 2 criteria at 1.5 SDs below normative values. Memory impairment was the most common domain affected, with 15.1% impaired at 1.5 SDs. Depression scores were significantly higher in those with PD-MCI than the cognitively normal PD group. A significant correlation was found between visual Pattern Recognition Memory and cerebrospinal β-amyloid 1–42 levels (β standardized coefficient = 0.350; p = 0.008) after controlling for age and education in a linear regression model, with lower β-amyloid 1–42 and 1–40 levels observed in those with PD-MCI. Voxel-based morphometry did not reveal any areas of significant gray matter loss in participants with PD-MCI compared with controls, and no specific genotype was associated with PD-MCI at the 1.5-SD threshold.
Conclusions:
In a large cohort of newly diagnosed PD participants, PD-MCI is common and significantly correlates with lower cerebrospinal β-amyloid 1–42 and 1–40 levels. Future longitudinal studies should enable us to determine those measures predictive of cognitive decline.
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Information & Authors
Information
Published In
Copyright
© 2014 American Academy of Neurology.
Publication History
Received: July 12, 2013
Accepted: October 11, 2013
Published online: December 20, 2013
Published in print: January 28, 2014
Disclosure
A. Yarnall is supported by grants from the Lockhart Parkinson's Disease Research Fund and MJFF. She has received honoraria from Teva-Lundbeck and sponsorship from Teva-Lundbeck, UCB, GlaxoSmithKline, Genus, and AbbVie for attending conferences. D. Breen is supported by a grant from Big Lottery Fund/Parkinson's UK, has received a Raymond and Beverly Sackler Studentship, and received honoraria from UCB. G. Duncan is supported by a grant from the Lockhart Parkinson's Disease Fund and has received sponsorship from UCB and Abbott for attending conferences. T. Khoo has received honoraria and educational grants from Teva-Lundbeck and Hospira and sponsorship from GSK and UCB for attending conferences. S. Coleman, M. Firbank, and C. Nombela report no disclosures. S. Winder-Rhodes is supported by a Merck Sharp and Dohme Studentship. J. Evans has received honoraria from UCB. J. Rowe is supported by the Wellcome Trust (088324), Medical Research Council, NIHR, Parkinson's UK, Evelyn Trust, and James S. McDonnell Foundation. B. Mollenhauer has received honoraria from Teva Pharmaceuticals, Orion Corporation, and GSK. She is an associate editor for the Journal of Alzheimer's Disease. She holds or has pending patents re: method of differentially diagnosing dementias; novel ELISA-based quantification of α-synuclein proteins in CSF and peripheral blood products using 384-well plates; and microRNA expression profiling of CSF. She serves as a consultant for Bayer Schering Pharma AG and receives research support from Teva Pharmaceutical Industries Ltd., Desitin Pharmaceuticals, GmbH, Boehringer Ingelheim, GE Healthcare, MJFF, the American Parkinson's Disease Association, and the Stifterverband für die Deutsche Wissenschaft (Dr. Werner Jackstädt-Stipend). N. Kruse reports no disclosures. G. Hudson is supported by a Parkinson's UK Senior Fellowship. P. Chinnery is a Wellcome Trust Senior Fellow in Clinical Science and a UK NIHR Senior Investigator. He receives additional support from the Wellcome Trust Centre for Mitochondrial Research, the Medical Research Council Centre for Translational Muscle Disease research, the Association Française contre les Myopathies, and EU FP7 TIRCON, and the NIHR Newcastle Biomedical Research Centre. J. O'Brien has acted as consultant for GE Healthcare and TauRx, and has been on the advisory board for Lilly, Novartis, and Nutricia. He has received grants from Lilly and received honoraria from GE Healthcare and Novartis. T. Robbins consults for Cambridge Cognition and receives royalties for CANTAB. He also consults for Lilly, GSK, Merck, Sharp & Dohme, Shire Pharmaceuticals, Lundbeck, and Teva, and has been in receipt of recent research grants from Lilly, GSK, and Lundbeck. K. Wesnes has for the last 3 years been an employee of Bracket, a division of United BioSource Corporation, which provides services to the clinical trial industry for numerous pharmaceutical companies. D. Brooks is a consultant for GE Healthcare, Shire Pharmaceuticals, and Cytox plc. He has received grants from the EU FP7 programme, MJFF, Medical Research Council, Parkinson's UK, Alzheimer Research UK, Lundbeck Foundation, Danish Council for Independent Research, and GE Healthcare. R. Barker has received grants from NIHR, Wellcome Trust, Cure-PD, Parkinson's UK, Rosetrees Trust, EU-FP7 programme, Evelyn Trust, and MJFF. He has received honoraria from Teva-Lundbeck and GSK in the past 2 years and is co–editor-in-chief for the Archives of Clinical Neuroscience and Rehabilitation and Journal of Neurology and associate editor for the Journal of Parkinson's Disease. D. Burn has received grants from NIHR, Wellcome Trust, GSK Ltd., Parkinson's UK, and MJFF. He has received honoraria from Teva-Lundbeck and UCB in the past 2 years and acted as consultant for GSK and Archimedes. Go to Neurology.org for full disclosures.
Study Funding
The authors acknowledge the study funders, Parkinson's UK, Lockhart Parkinson's Disease Research Fund, and Michael J. Fox Foundation (MJFF). The research was supported by the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust/Newcastle University, and an NIHR Biomedical Research Centre award to the University of Cambridge/Addenbrooke's Hospital. Newcastle University and the University of Cambridge acknowledge the support of the NIHR, through the Dementias and Neurodegenerative Diseases Research Network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
Authors
Author Contributions
Dr. Yarnall, Dr. Breen, and Dr. Duncan were involved with coordination of the study. They were also involved with participant recruitment, clinical assessment, data collection, and statistical analysis, and they drafted the manuscript. Dr. Khoo was involved with the study design and coordination of the study. He was also involved with participant recruitment, clinical assessment, data collection, and manuscript revision. Dr. Coleman was involved with statistical analysis and reviewed the manuscript. Dr. Firbank was involved with MRI data analysis and reviewed the manuscript. Dr. Nombela was involved with data acquisition and reviewed the manuscript. Dr. Winder-Rhodes was involved with data acquisition and reviewed the manuscript. Dr. Evans was involved in data acquisition and reviewed the manuscript. Dr. Rowe was involved with data acquisition and reviewed the manuscript. Prof. Mollenhauer is a principal investigator. She analyzed the CSF samples and reviewed and approved the final manuscript. Dr. Kruse analyzed the CSF samples and reviewed and approved the final manuscript. Dr. Hudson analyzed the DNA samples and reviewed and approved the final manuscript. Prof. Chinnery is a principal investigator. He analyzed the DNA samples and reviewed and approved the final manuscript. Prof. O’Brien is a principal investigator and coapplicant for the funding grant. He was involved in the study supervision and reviewed and approved the final manuscript. Prof. Robbins is a principal investigator, was involved in the study design, and reviewed the manuscript. Prof. Wesnes is a principal investigator, was involved in the study design and statistical analysis, and reviewed the manuscript. Prof. Brooks is a principal investigator and coapplicant for the main funding grant. He was also involved with the study design and reviewed the manuscript. Prof. Barker is a principal investigator and coapplicant for the main funding grant. He was involved with the study design and reviewed the manuscript. Prof. Burn is the chief investigator and main applicant for the funding grant. He was involved with the study design, supervised the study, and reviewed the manuscript.
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