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

Neurology. 2012 May 1;78(18):1434-40. doi: 10.1212/WNL.0b013e318253d54b. Epub 2012 Mar 21.


Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD).

Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed.

Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004).

Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Basal Ganglia Diseases / diagnosis
  • Basal Ganglia Diseases / genetics
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / genetics*
  • DNA Mutational Analysis*
  • Dementia / diagnosis
  • Dementia / genetics
  • Depressive Disorder / diagnosis
  • Depressive Disorder / genetics
  • Female
  • Genetic Carrier Screening*
  • Genetic Testing
  • Genotype
  • Glucosylceramidase / genetics*
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Memory Disorders / diagnosis
  • Memory Disorders / genetics
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests*
  • Olfaction Disorders / diagnosis
  • Olfaction Disorders / genetics
  • Parkinson Disease / diagnosis
  • Parkinson Disease / genetics*
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics
  • Ubiquitin-Protein Ligases / genetics
  • beta-Glucosidase / genetics


  • Ubiquitin-Protein Ligases
  • parkin protein
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • beta-Glucosidase
  • Glucosylceramidase