Characterizing mild cognitive impairment in incident Parkinson disease: the ICICLE-PD study

Research output: Contribution to journalArticle


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.


  • Alison J Yarnall
  • 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
  • ICICLE-PD Study Group
External organisations
  • University of Cambridge
Research areas and keywords


  • Aged, Aged, 80 and over, Amyloid beta-Peptides, Case-Control Studies, Female, Humans, Intermediate Filament Proteins, Male, Middle Aged, Mild Cognitive Impairment, Neuropsychological Tests, Parkinson Disease, Peptide Fragments, Retrospective Studies, Severity of Illness Index, tau Proteins, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)308-16
Number of pages9
Issue number4
Publication statusPublished - 2014 Jan 28
Publication categoryResearch