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Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations.
Mov Disord. 2013 Dec; 28(14):1966-71.MD

Abstract

The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n = 97) and non-carriers (n = 391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P < 0.001), were more likely to be women (51.5% vs. 37.9%; P = 0.015), and more often reported first symptoms in the lower extremities (40.0% vs. 19.2%; P < 0.001). In logistic models that were adjusted for age, disease duration, sex, education, and site, carriers were more likely to have lower extremity onset (P < 0.001), postural instability and gait difficulty (PIGD) (P = 0.043), and a persistent levodopa response for >5 years (P = 0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment.

Authors+Show Affiliations

Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24243757

Citation

Alcalay, Roy N., et al. "Parkinson Disease Phenotype in Ashkenazi Jews With and Without LRRK2 G2019S Mutations." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 28, no. 14, 2013, pp. 1966-71.
Alcalay RN, Mirelman A, Saunders-Pullman R, et al. Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord. 2013;28(14):1966-71.
Alcalay, R. N., Mirelman, A., Saunders-Pullman, R., Tang, M. X., Mejia Santana, H., Raymond, D., Roos, E., Orbe-Reilly, M., Gurevich, T., Bar Shira, A., Gana Weisz, M., Yasinovsky, K., Zalis, M., Thaler, A., Deik, A., Barrett, M. J., Cabassa, J., Groves, M., Hunt, A. L., ... Marder, K. S. (2013). Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Movement Disorders : Official Journal of the Movement Disorder Society, 28(14), 1966-71. https://doi.org/10.1002/mds.25647
Alcalay RN, et al. Parkinson Disease Phenotype in Ashkenazi Jews With and Without LRRK2 G2019S Mutations. Mov Disord. 2013;28(14):1966-71. PubMed PMID: 24243757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. AU - Alcalay,Roy N, AU - Mirelman,Anat, AU - Saunders-Pullman,Rachel, AU - Tang,Ming-X, AU - Mejia Santana,Helen, AU - Raymond,Deborah, AU - Roos,Ernest, AU - Orbe-Reilly,Martha, AU - Gurevich,Tanya, AU - Bar Shira,Anat, AU - Gana Weisz,Mali, AU - Yasinovsky,Kira, AU - Zalis,Maayan, AU - Thaler,Avner, AU - Deik,Andres, AU - Barrett,Matthew James, AU - Cabassa,Jose, AU - Groves,Mark, AU - Hunt,Ann L, AU - Lubarr,Naomi, AU - San Luciano,Marta, AU - Miravite,Joan, AU - Palmese,Christina, AU - Sachdev,Rivka, AU - Sarva,Harini, AU - Severt,Lawrence, AU - Shanker,Vicki, AU - Swan,Matthew Carrington, AU - Soto-Valencia,Jeannie, AU - Johannes,Brooke, AU - Ortega,Robert, AU - Fahn,Stanley, AU - Cote,Lucien, AU - Waters,Cheryl, AU - Mazzoni,Pietro, AU - Ford,Blair, AU - Louis,Elan, AU - Levy,Oren, AU - Rosado,Llency, AU - Ruiz,Diana, AU - Dorovski,Tsvyatko, AU - Pauciulo,Michael, AU - Nichols,William, AU - Orr-Urtreger,Avi, AU - Ozelius,Laurie, AU - Clark,Lorraine, AU - Giladi,Nir, AU - Bressman,Susan, AU - Marder,Karen S, Y1 - 2013/10/15/ PY - 2013/05/10/received PY - 2013/07/11/revised PY - 2013/07/28/accepted PY - 2013/11/19/entrez PY - 2013/11/19/pubmed PY - 2014/7/30/medline KW - LRRK2 KW - Parkinson KW - genetics KW - postural instability and gait difficulty SP - 1966 EP - 71 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov. Disord. VL - 28 IS - 14 N2 - The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n = 97) and non-carriers (n = 391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P < 0.001), were more likely to be women (51.5% vs. 37.9%; P = 0.015), and more often reported first symptoms in the lower extremities (40.0% vs. 19.2%; P < 0.001). In logistic models that were adjusted for age, disease duration, sex, education, and site, carriers were more likely to have lower extremity onset (P < 0.001), postural instability and gait difficulty (PIGD) (P = 0.043), and a persistent levodopa response for >5 years (P = 0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/24243757/Parkinson_disease_phenotype_in_Ashkenazi_Jews_with_and_without_LRRK2_G2019S_mutations_ L2 - https://doi.org/10.1002/mds.25647 DB - PRIME DP - Unbound Medicine ER -