Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation

Anat Mirelman, Talia Heman, Kira Yasinovsky, Avner Thaler, Tanya Gurevich, Karen Marder, Susan Bressman, Anat Bar-Shira, Avi Orr-Urtreger, Nir Giladi, Jeffrey M. Hausdorff, Rachel Saunders-Pullman, Vicki Lynn Shanker, Mark Groves, Christine Palmese, Kaili Maloy Stanley, Akhila Iyer, Jeannie Soto-Valencia, Deborah Raymond, Marta San LucianoAndres Deik, Matthew James Barrette, Jose Cabbasa, Lawrence Severt, Ann Hunt, Naomi Lubarr, Rivka Sachdev, Sara Lewis, Laurie Ozelius, Roy Alcalay, Stanley Fahn, Lucien Cote, Paul Greene, Cheryl Waters, Pietro Mazzoni, Blair Ford, Elan Louis, Oren Levy, Ming Xin Tang, Brian Rakitin, Helen Mejia, Ernest Roos, Martha Orbe Riley, Llency Rosado, Carol Moskowitz, Tsvyatko Dorovski, Lorraine Clark, Xinmin Liu, Sergey Kisselev, Itsik Peer, Vladimir Vacic, Yaacov Balash, Shabtai Hertzel, Ziv Gan Or, Anat Bar Shira, Mali Gana Weiss, Hila Kobo, Noa Bregman, Meir Kestenbaum, Talma Hendler, Hedva Lehrman, Einat Even Sapir, Shiran Levy, Anat Shkedy, Maayan Zelis

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine-rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non-carrier patients with PD to better understand the genotype-phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non-carriers were studied. An accelerometer quantified gait under three walking conditions: usual-walking, dual-tasking, and fast-walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub-types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P<0.016). The PD carriers also took longer to complete the Timed Up and Go (P=0.011) and were more likely to report having fallen in the previous year (P=0.018). 64% of the PD carriers were classified as belonging to the postural-instability-gait-difficulty (PIGD) sub-type compared to only 17% of the PD non-carriers (P<0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub-type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation.

Original languageEnglish
Pages (from-to)1683-1690
Number of pages8
JournalMovement Disorders
Volume28
Issue number12
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

Keywords

  • Falls
  • G2019S
  • Gait
  • LRRK2
  • Parkinson's disease

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    Mirelman, A., Heman, T., Yasinovsky, K., Thaler, A., Gurevich, T., Marder, K., Bressman, S., Bar-Shira, A., Orr-Urtreger, A., Giladi, N., Hausdorff, J. M., Saunders-Pullman, R., Shanker, V. L., Groves, M., Palmese, C., Stanley, K. M., Iyer, A., Soto-Valencia, J., Raymond, D., ... Zelis, M. (2013). Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation. Movement Disorders, 28(12), 1683-1690. https://doi.org/10.1002/mds.25587