title: 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.
authors.affiliation: 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.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Yarnall
authors.forename: David P
authors.initials: DP
authors.lastname: Breen
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Duncan
authors.forename: Tien K
authors.initials: TK
authors.lastname: Khoo
authors.forename: Shirley Y
authors.initials: SY
authors.lastname: Coleman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Firbank
authors.forename: Cristina
authors.initials: C
authors.lastname: Nombela
authors.forename: Sophie
authors.initials: S
authors.lastname: Winder-Rhodes
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Evans
authors.forename: James B
authors.initials: JB
authors.lastname: Rowe
authors.forename: Brit
authors.initials: B
authors.lastname: Mollenhauer
authors.forename: Niels
authors.initials: N
authors.lastname: Kruse
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.forename: Keith
authors.initials: K
authors.lastname: Wesnes
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000209:etiology*; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000453:epidemiology*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D007381:Intermediate Filament Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C430456:desmuslin; D016875:tau Proteins