Neuropsychological performance in LRRK2 G2019S carriers with Parkinson's disease

Collaborators, Affiliations

Collaborators

LRRK2 Ashkenazi Jewish Consortium:
Roy N Alcalay, Ming-X Tang, Helen Mejia Santana, Ernest Roos, Martha Orbe-Reilly, Stanley Fahn, Lucien Cote, Cheryl Waters, Pietro Mazzoni, Blair Ford, Elan Louis, Oren Levy, Llency Rosado, Diana Ruiz, Tsvyatko Dorovski, Paul Greene, Lorraine Clark, Karen S Marder, Tanya Gurevich, Anat Bar Shira, Mali Gana Weisz, Kira Yasinovsky, Maayan Zalis, Avner Thaler, Yaacov Balash, Shabtai Hertzel, Ziv Gan Or, Hila Kobo, Ariella Hillel, Anat Shkedy, Avi Orr-Urtreger, Nir Giladi, Andres Deik, Matthew James Barrett, Jose Cabassa, Mark Groves, Ann L Hunt, Naomi Lubarr, Marta San Luciano, Joan Miravite, Christina Palmese, Rivka Sachdev, Harini Sarva, Lawrence Severt, Vicki Shanker, Matthew Carrington Swan, Jeannie Soto-Valencia, Brooke Johannes, Robert Ortega, Laurie Ozelius, Rachel Saunders-Pullman, Deborah Raymond, Susan Bressman

Affiliations

¹ 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.
² Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
³ 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.
⁴ The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
⁵ 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.
⁶ Departments of Genetics and Genomic Sciences and Neurology, Mount Sinai School of Medicine, New York, NY, USA.
⁷ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Genetics Institute, Tel Aviv Sourasky Medical Center, Israel.
⁸ 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.
⁹ 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.

PMID: 25434972
PMCID: PMC4306614
DOI: 10.1016/j.parkreldis.2014.09.033

Neuropsychological performance in LRRK2 G2019S carriers with Parkinson's disease

Roy N Alcalay et al. Parkinsonism Relat Disord. 2015 Feb.

. 2015 Feb;21(2):106-10.

doi: 10.1016/j.parkreldis.2014.09.033. Epub 2014 Nov 20.

Collaborators

LRRK2 Ashkenazi Jewish Consortium:
Roy N Alcalay, Ming-X Tang, Helen Mejia Santana, Ernest Roos, Martha Orbe-Reilly, Stanley Fahn, Lucien Cote, Cheryl Waters, Pietro Mazzoni, Blair Ford, Elan Louis, Oren Levy, Llency Rosado, Diana Ruiz, Tsvyatko Dorovski, Paul Greene, Lorraine Clark, Karen S Marder, Tanya Gurevich, Anat Bar Shira, Mali Gana Weisz, Kira Yasinovsky, Maayan Zalis, Avner Thaler, Yaacov Balash, Shabtai Hertzel, Ziv Gan Or, Hila Kobo, Ariella Hillel, Anat Shkedy, Avi Orr-Urtreger, Nir Giladi, Andres Deik, Matthew James Barrett, Jose Cabassa, Mark Groves, Ann L Hunt, Naomi Lubarr, Marta San Luciano, Joan Miravite, Christina Palmese, Rivka Sachdev, Harini Sarva, Lawrence Severt, Vicki Shanker, Matthew Carrington Swan, Jeannie Soto-Valencia, Brooke Johannes, Robert Ortega, Laurie Ozelius, Rachel Saunders-Pullman, Deborah Raymond, Susan Bressman

Affiliations

¹ 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.
² Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
³ 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.
⁴ The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
⁵ 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.
⁶ Departments of Genetics and Genomic Sciences and Neurology, Mount Sinai School of Medicine, New York, NY, USA.
⁷ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Genetics Institute, Tel Aviv Sourasky Medical Center, Israel.
⁸ 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.
⁹ 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.

PMID: 25434972
PMCID: PMC4306614
DOI: 10.1016/j.parkreldis.2014.09.033

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).

Conclusion: 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.

Keywords: Genetics; LRRK2; Neuropsychological tests; Parkinson.

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References

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Neuropsychological performance in LRRK2 G2019S carriers with Parkinson's disease

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Neuropsychological performance in LRRK2 G2019S carriers with Parkinson's disease

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