Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation.
Identifieur interne : 000746 ( PubMed/Curation ); précédent : 000745; suivant : 000747Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation.
Auteurs : Anat Mirelman [Israël] ; Talia Heman ; Kira Yasinovsky ; Avner Thaler ; Tanya Gurevich ; Karen Marder ; Susan Bressman ; Anat Bar-Shira ; Avi Orr-Urtreger ; Nir Giladi ; Jeffrey M. HausdorffSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2013.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Protein-Serine-Threonine Kinases.
- genetics : Gait, Parkinson Disease, Postural Balance.
- physiopathology : Parkinson Disease.
- Accidental Falls, Aged, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Mutation, Phenotype, Risk.
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.
DOI: 10.1002/mds.25587
PubMed: 24123150
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Hausdorff</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Accidental Falls</term><term>Aged</term><term>Female</term><term>Gait (genetics)</term><term>Genetic Predisposition to Disease</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (physiopathology)</term><term>Phenotype</term><term>Postural Balance (genetics)</term><term>Protein-Serine-Threonine Kinases (genetics)</term><term>Risk</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein-Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Gait</term><term>Parkinson Disease</term><term>Postural Balance</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Accidental Falls</term><term>Aged</term><term>Female</term><term>Genetic Predisposition to Disease</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Phenotype</term><term>Risk</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">24123150</PMID><DateCreated><Year>2013</Year><Month>10</Month><Day>29</Day></DateCreated><DateCompleted><Year>2014</Year><Month>06</Month><Day>20</Day></DateCompleted><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>28</Volume><Issue>12</Issue><PubDate><Year>2013</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation.</ArticleTitle><Pagination><MedlinePgn>1683-90</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.25587</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>© 2013 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mirelman</LastName><ForeName>Anat</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; School of Health-Related Professions, Ben Gurion University, Beer Sheba, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heman</LastName><ForeName>Talia</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Yasinovsky</LastName><ForeName>Kira</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Thaler</LastName><ForeName>Avner</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Gurevich</LastName><ForeName>Tanya</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Marder</LastName><ForeName>Karen</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Bressman</LastName><ForeName>Susan</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Bar-Shira</LastName><ForeName>Anat</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Orr-Urtreger</LastName><ForeName>Avi</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Giladi</LastName><ForeName>Nir</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Hausdorff</LastName><ForeName>Jeffrey M</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><CollectiveName>LRRK2 Ashkenazi Jewish Consortium</CollectiveName></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, 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