Cognitive performance of GBA mutation carriers with early-onset PD: the CORE-PD study

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Parkinson disease (PD) is a neurodegenerative disorder with a known genetic component.
• Mutations in the glucocerebrosidase (GBA) gene are associated with an increased risk of developing PD.
• The cognitive impact of GBA mutations in early-onset PD is not fully understood.

Purpose of the Study:

• To investigate the cognitive phenotype of individuals with early-onset Parkinson disease who carry glucocerebrosidase (GBA) gene mutations.
• To determine if GBA mutation status is associated with specific cognitive deficits in early-onset PD.
• To assess the relationship between GBA mutation status and the risk of mild cognitive impairment (MCI) or dementia in PD.

Main Methods:

• Neuropsychological testing and the University of Pennsylvania Smell Identification Test (UPSIT) were administered to participants in the CORE-PD study.
• Participants included GBA mutation carriers and non-carriers, with primary analyses focusing on heterozygous GBA carriers and matched non-carriers.
• Cognitive domains (psychomotor speed, attention, memory, visuospatial function, executive function) were assessed, alongside the Clinical Dementia Rating (CDR) score for clinical diagnoses.

Main Results:

• GBA mutation carriers performed significantly worse than non-carriers on the Mini-Mental State Examination, memory, and visuospatial domains.
• Nonverbal memory performance showed the most pronounced differences between GBA carriers and non-carriers.
• GBA carriers were more likely to have higher CDR scores and a clinical diagnosis of MCI or dementia.

Conclusions:

• Glucocerebrosidase (GBA) mutation status may represent an independent risk factor for cognitive impairment in patients diagnosed with Parkinson disease.
• These findings highlight the importance of genetic screening for GBA mutations in understanding cognitive decline in early-onset PD.