Cognitive and behavioral symptoms in Parkinson's disease patients with the G2019S and R1441G mutations of the LRRK2 gene

Parkinsonism Relat Disord. 2015 May;21(5):494-9. doi: 10.1016/j.parkreldis.2015.02.019. Epub 2015 Mar 2.

Abstract

Objective: To compare the cognitive and psychiatric status of patients with Parkinson's disease related to the G2019S and the R1441G mutations of the LRRK2 gene (LRRK2-PD) and idiopathic Parkinson's disease (iPD) patients.

Methods: We examined cognition and psychiatric symptoms in 27 patients with LRRK2-PD (12 G2019S and 15 R1441G) and 27 iPD patients.

Results: The groups were similar in age, education, disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale (UPDRS) II-IV; however, the LRRK2-PD showed less impairment on UPDRS-I (2.0 ± 1.7 vs. 4.2 ± 2.8, p = 0.003). The LRRK2-PD presented less frequent subjective cognitive complaints (18.5% vs. 63.0%, p = 0.002), and mild cognitive impairment or dementia (25.9% vs. 59.2%, p = 0.027). They also showed less impairment on scales for general cognition (Mattis dementia rating scale 131.2 ± 10.9 vs. 119 ± 24.0, p = 0.022), episodic verbal memory (Rey's auditory verbal learning test, immediate recall 39.2 ± 9.5 vs. 27.6 ± 12.8 p < 0.001, delayed recall 7.2 ± 3.7 vs. 4.7 ± 4.0 p = 0.022), and the Neuropsychiatric Inventory (9.7 ± 9.2 vs. 20.5 ± 14.3, p = 0.004, significant differences for apathy and hallucinations). The LRRK2-PD subjects were less frequently treated with antipsychotic medication (0% vs. 25.9%, p = 0.010). There were no significant differences between G2019S and R1441G mutation carriers.

Conclusions: Mutations of the LRRK2 gene might cause PD associated with less cognitive and neuropsychiatric impairment as compared to iPD.

Keywords: Cognitive impairment; Familial; LRRK2; Neuropsychiatry; Parkinson's disease; R1441G mutation.

MeSH terms

  • Aged
  • Behavioral Symptoms / diagnosis
  • Behavioral Symptoms / epidemiology
  • Behavioral Symptoms / genetics
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / epidemiology
  • Cognition Disorders / genetics*
  • Female
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Protein Serine-Threonine Kinases / genetics*

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases