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Overview
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  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Progression In The Lrrk2-asssociated Parkinson Disease Population.

Progression in the LRRK2-Asssociated Parkinson Disease Population.

Rachel Saunders-Pullman1,2, Anat Mirelman3,4,5,6, Roy N Alcalay7

  • 1Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York.

JAMA Neurology
|January 9, 2018

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View abstract on PubMed

Summary
This summary is machine-generated.

Patients with Parkinson disease (PD) and the leucine-rich repeat kinase 2 (LRRK2) G2019S mutation show a slower progression of motor symptoms compared to those without the mutation. This finding aids in understanding PD progression and clinical trial design.

Area of Science:

  • Neurology
  • Genetics
  • Longitudinal Studies

Background:

  • Prospective longitudinal studies on Parkinson disease (PD) progression in patients with the leucine-rich repeat kinase 2 (LRRK2) mutation are limited.
  • Understanding LRRK2-associated PD progression is crucial for designing effective clinical trials.

Purpose of the Study:

  • To compare the longitudinal course of PD in patients with and without the LRRK2 mutation.
  • To investigate if LRRK2 mutation status influences the rate of motor and cognitive decline in PD.

Main Methods:

  • A prospective cohort study of 545 patients of Ashkenazi Jewish descent with PD was conducted between 2009 and 2016.
  • Patients were assessed for the LRRK2 G2019S mutation, and motor function (Unified Parkinson's Disease Rating Scale III) and cognitive scores (Montreal Cognitive Assessment) were tracked over time.

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  • Linear mixed-effects models were used to analyze the rate of change in motor and cognitive scores, adjusting for baseline characteristics.

    • Main Results:

    • The rate of motor decline was significantly slower in patients with the LRRK2 mutation (0.689 points/year) compared to those without (1.056 points/year), with a difference of -0.367 points/year (P=.02).
    • The difference in the rate of cognitive decline between the two groups was not statistically significant (-0.096 points/year vs -0.192 points/year; P=.08).

    Conclusions:

    • The LRRK2 G2019S mutation is associated with a slower rate of motor symptom progression in Parkinson disease.
    • These findings support previous cross-sectional data and provide valuable insights into the clinical heterogeneity of PD.
    • The slower motor progression in LRRK2-mutated PD may have implications for trial design and therapeutic strategies.