Alison J Yarnall1, David P Breen, Gordon W Duncan, Tien K Khoo, Shirley Y Coleman, Michael J Firbank, Cristina Nombela, Sophie Winder-Rhodes, Jonathan R Evans, James B Rowe, Brit Mollenhauer, Niels Kruse, Gavin Hudson, Patrick F Chinnery, John T O'Brien, Trevor W Robbins, Keith Wesnes, David J Brooks, Roger A Barker, David J Burn. 1. From the Institute for Ageing and Health (A.J.Y., G.W.D., M.J.F., D.J.B.), Industrial Statistics Research Unit (S.Y.C.), and Institute of Genetic Medicine (G.H., P.F.C.), Newcastle University; John van Geest Centre for Brain Repair (D.P.B., J.R.E., R.A.B.), Department of Clinical Neurosciences (C.N., S.W.-R., J.B.R.), Behavioural and Clinical Neuroscience Institute (C.N., S.W.-R., J.B.R., T.W.R.), MRC Cognition and Brain Sciences Unit (C.N., S.W.-R., J.B.R.), Departments of Psychiatry (J.T.O.) and Psychology (T.W.R.), University of Cambridge, UK; School of Medicine (T.K.K.), Griffith University, Australia; Paracelsus-Elena-Klinik (B.M.), Kassel, and Göttingen University; Institute for Neuropathology (N.K.), Prion and Dementia Research Unit, University Medical Centre Göttingen, Germany; Centre for Human Psychopharmacology (K.W.), Swinburne University, Melbourne, Australia; and Department of Medicine (D.J.W.), Imperial College London, UK.
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.
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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