Cognitive and motor function in long-duration PARKIN-associated Parkinson disease

JAMA Neurol. 2014 Jan;71(1):62-7. doi: 10.1001/jamaneurol.2013.4498.

Abstract

Importance: Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients.

Objective: Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers.

Design, setting, and participants: Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers.

Main outcomes and measures: Unified Parkinson Disease Rating Scale Part III (UPDRS-III) and Clinical Dementia Rating scores and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS-III scores. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose.

Results: Carriers had an earlier age at onset of PD (P < .001) and were younger (P = .004) at time of examination than noncarriers. They performed better than noncarriers on the Mini-Mental State Examination (P = .010) and were more likely to receive lower scores on the Clinical Dementia Rating (P = .003). In multivariate analyses, carriers performed better than noncarriers on the UPDRS-III (P = .02) and on tests of attention (P = .03), memory (P = .03), and visuospatial (P = .02) cognitive domains.

Conclusions and relevance: In cross-sectional analyses, carriers demonstrated better cognitive and motor performance than did noncarriers with long disease duration, suggesting slower disease progression. A longitudinal follow-up study is required to confirm these findings.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age of Onset
  • Aged
  • Cognition Disorders / genetics*
  • Cognition Disorders / metabolism
  • Cognition Disorders / physiopathology*
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Motor Skills Disorders / genetics
  • Motor Skills Disorders / metabolism
  • Motor Skills Disorders / physiopathology
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein