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

Neurology. 2014 Jan 28;82(4):308-16. doi: 10.1212/WNL.0000000000000066. Epub 2013 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Case-Control Studies
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / etiology*
  • Female
  • Humans
  • Intermediate Filament Proteins / cerebrospinal fluid
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease / epidemiology*
  • Peptide Fragments / cerebrospinal fluid
  • Retrospective Studies
  • Severity of Illness Index
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Intermediate Filament Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • desmuslin
  • tau Proteins