title: Neuropsychological performance in LRRK2 G2019S carriers with Parkinson's disease.
abstract: BACKGROUND
  Ashkenazi Jewish (AJ) LRRK2 carriers are more likely to manifest the postural instability gait difficulty (PIGD) motor phenotype than non-carriers but perform similarly to non-carriers on cognitive screening tests.
  
  
  OBJECTIVE
  To compare the cognitive profiles of AJ with Parkinson's disease (PD) with and without LRRK2 G2019S mutations using a comprehensive neuropsychological battery.
  
  
  METHODS
  We administered a neuropsychological battery to PD participants in the Michael J. Fox Foundation AJ consortium. Participants (n = 236) from Beth Israel Medical Center, NY, Columbia University Medical Center, NY and Tel Aviv Medical Center, Israel included 116 LRRK2 G2019S carriers and 120 non-carriers. Glucocerbrosidase mutation carriers were excluded. We compared performance on each neuropsychological test between carriers and non-carriers. Participants in New York (n = 112) were evaluated with the entire battery. Tel Aviv participants (n = 124) were evaluated on attention, executive function and psychomotor speed tasks. The association between G2019S mutation status (predictor) and each neuropsychological test (outcome) was assessed using linear regression models adjusted for PIGD motor phenotype, site, sex, age, disease duration, education, Unified Parkinson's Disease Rating Scale (UPDRS) Part III, levodopa equivalent dose, and Geriatric Depression Score (GDS).
  
  
  RESULTS
  Carriers had longer disease duration (p < 0.001) and were more likely to manifest the PIGD phenotype (p = 0.024). In adjusted regression models, carriers performed better than non-carriers in Stroop Word Reading (p < 0.001), Stroop Interference (p = 0.011) and Category Fluency (p = 0.026).
  
  
  CONCLUSIONS
  In AJ-PD, G2019S mutation status is associated with better attention (Stroop Word Reading), executive function (Stroop Interference) and language (Category Fluency) after adjustment for PIGD motor phenotype.
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. Electronic address: rna2104@columbia.edu.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Mejia-Santana
authors.affiliation: Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; School of Health Related Professions, Ben Gurion University, Beer Sheba, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Mirelman
authors.affiliation: The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.affiliation: The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Raymond
authors.affiliation: The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Palmese
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Caccappolo
authors.affiliation: Departments of Genetics and Genomic Sciences and Neurology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Ozelius
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Genetics Institute, Tel Aviv Sourasky Medical Center, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Clark
authors.affiliation: Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.affiliation: The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
mesh_terms: D000368:Aged; D005260:Female; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Genetics; LRRK2; Neuropsychological tests; Parkinson