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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Lower cognitive performance in healthy G2019S LRRK2 mutation carriers
Avner Thaler1, Anat Mirelman, Tanya Gurevich
1Movement Disorders Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, Israel.
Neurology
|August 24, 2012
Summary
Healthy relatives of Parkinson disease (PD) patients carrying the LRRK2 G2019S mutation showed reduced executive function. This suggests potential early cognitive changes in individuals at genetic risk for PD.
Area of Science:
- Neuroscience
- Genetics
- Cognitive Science
Background:
- Parkinson disease (PD) is a neurodegenerative disorder with a significant genetic component.
- The LRRK2 G2019S mutation is a common genetic risk factor for PD, particularly in Ashkenazi populations.
- Assessing cognitive function in at-risk individuals can aid in early detection and understanding of PD pathogenesis.
Purpose of the Study:
- To evaluate the cognitive abilities of healthy first-degree relatives of Ashkenazi PD patients.
- To determine if carrying the LRRK2 G2019S mutation is associated with cognitive deficits.
- To investigate executive function performance in carriers versus non-carriers.
Main Methods:
- An observational study involving 60 healthy first-degree relatives of PD patients.
- Participants were categorized into G2019S carriers (n=30) and non-carriers.
- Cognitive assessment included a computerized program, Montreal Cognitive Assessment, UPDRS Part III, and Geriatric Depression Scale.
Main Results:
- LRRK2 G2019S carriers demonstrated significantly lower scores on a computerized executive function index (p = 0.04).
- Specific executive function tasks, including the Stroop test, also showed significantly poorer performance in carriers (p = 0.007).
- No significant differences were noted in other cognitive domains or depression scores between groups (data not shown).
Conclusions:
- The LRRK2 G2019S mutation is linked to impaired executive function in healthy individuals at risk for Parkinson disease.
- These findings suggest that cognitive alterations may precede the clinical diagnosis of PD in mutation carriers.
- Executive function deficits could serve as an early biomarker for neurodegeneration in LRRK2-associated PD.
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